|
|
Blood Safety Transcripts
TABLE OF CONTENTS
Risks of Transfusion, Dr. Busch, 1
Dealing With and Communicating Risk,
Mr. Maibach, 32
Open Committee Discussion,
Mr. Caplan, 53
P R O C E E D I N G S (8:00 a.m.)
MR. CAPLAN: -- first on the risks associated with
transfusion by Dr. Michael Busch, second by Dr. Ed Maibach,
dealing with the topic of how to communicate about risk.
Then we are going to move to readdress the language on the
recommendations that the committee wishes to offer in
response to the questions it has been asked, and we will
work on that for the rest of the morning, or until such time
as we are satisfied that we have language that we are
willing to pass back to the Public Health Service and the
agencies that have asked us to comment on the issue of
hepatitis-C. So, let me at this point turn the forum over
to Mike.
Agenda Item: Risks of Transfusion
DR. BUSCH: Good morning. In a brief half an hour
this morning, I am going to review current risks of
transfusion and actually, this is an outline of the
presentation. I am going to first give you two quick
slides, just to give you an historical perspective about how
much infectious risk the blood supply used to represent
compared to the way we are, and the issues we will be
dealing with this morning.
Then, review briefly the kinds of approaches that
have historically been used to measure risk, and lead you to
what is really, the current only option, which is model
estimates of risk. I will give you data on the current
estimates of risk for the four major viruses that we are
concerned about, and then liberally borrow from the GAO
Report, which is a document that I think each of the
committee members received.
It is really an outstanding effort by these
government individuals to compile estimates of risk, both
for the infectious -- major infectious, and what we might
call minor infectious agents, as well as the noninfectious
risks, and then put all those together and estimate risk for
the general public from transfusions, and then contrast that
with both medical and nonmedical risks in different
settings.
I think it is very useful to briefly present a few
examples about how new initiatives to improve safety further
can be examined and particularly, a couple of slides from
Jim on cost-effectiveness of some of these new initiatives,
and then briefly touch on approaches and viruses and agents
of concern with respect to new and emerging agents.
We will go quickly. Again, all of this material,
a lot of it, I can give you a paper -- in fact, I will
probably give to Paul a recent review paper for distribution
that summarizes all of these risk estimates from our work as
well as point you back to that GAO Report, which is really
outstanding.
Just, again, for retrospective considerations, the
risk of blood with respect to hepatitis, specifically,
hepatitis-C, was in excess of 20% per transfused recipient,
back in the sixties. In the seventies, with introduction of
surface antigen and the concurrent discontinuation of paid
commercial donors, there was a dramatic, nearly two-plus-fold
drop in risk, and then stable risk at around 10% of all
patients getting HCV through the seventies and into the
early eighties, when, serendipitously, the AIDS risk
exclusions resulted in a modest drop.
The evidence came forward that this was a more
significant post-transfusion phenomenon(?), and could be a
more significant problem than previously thought, and the
associations with ALT and anti-corp appreciated. The
introduction of these surrogate tests, and then eventually
the discovery of HCV and progressive improved assays. So,
you see, we are now dealing with risks well below 1%, and
this is what we will be struggling with to estimate today.
For HIV, it is a very different picture. It is
not a longstanding endemic virus, but rather an epidemic
explosion of occult infection in the absence of symptoms for
about five to ten years. First cases of transfusion
transmission documented back in the 1977, 1978 time period,
and then really clearly, now well-documented exponential
rise in risk in some areas, like San Francisco, exceeding 1%
of all units infecting with HIV.
The peak actually occurred in 1983, in the high
risk areas, and declined well before testing became
available, again as a consequence of education efforts and
exclusion efforts. So, this illustrates, as did the
hepatitis-C experience, how measures other than screening --
education, safe donor selection -- can have a dramatic
impact on the safety of the blood supply, well before a
specific agent is appreciated.
In terms of how we can measure today, there are
three sort of approaches, two of them, as I will show you,
somewhat impractical because of the low risk, and yet still
important. One is recipient follow-up, enrolling large
cohorts of recipients prior to transfusion, following them
prospectively for evidence of seroconversion or clinical
disease.
A second is to actually focus on the donor
products that are leaving the blood bank, have been screened
as safe, and one can subject those samples to culture or PCR
to estimate the residual rate of occult infection that is
missed by the standard methodology.
Then third is the approaches using models that
both focus on window period risk, as I will show you, which
rely on understanding the rate of new infections, or
incidence and the duration of the infectious window period,
to estimate the risk of seroconverting donors, but also,
more recently, as I will show, we have added in estimates of
risk due to variant viruses, due to test failure, things of
this nature, to compile an overall modelled estimate of
residual risk.
To illustrate some of the classical approaches,
probably, certainly, the most recent and large-scale study
of recipient seroconversion was one funded by NHLBI and
conducted in the immediate post-HIV period. Over a six-year
period, almost 10,000 recipients and additional non-transfused
patients were enrolled, who were undergoing
cardiac surgery, in the Hopkins, Houston, Ken, Nelson and
colleagues; 120,000 units were transfused into these
recipients. They observed actually six of these patients --
again, they collected pre-transfusion samples, and then
samples six months post-transfusion.
They started with the strategy of testing the six-month
post-transfusion sample. They found eight infected
patients six months post-transfusion, but when they went
back to the pre-bleed, six of those eight were actually
infected prior to the transfusion.
They had six prevalent infections, but they did
have two documented transmissions, both of which were linked
to donors who subsequently seroconverted. And both of these
transmissions occurred in the fairly early phase of the
study, in the late eighties, and before we moved into
contemporary, more sensitive antibody tests, and certainly
prior to antigen screening.
These estimates certainly are out of date, but the
point estimate from this would be basically the two
transmissions over the 120,000 units for one in 60,000, but
an upper confidence bound of about one in 20,000. So, not
terribly reassuring.
This same population of samples from that same
cohort was subsequently tested for HCV and HBV. This slide
summarizes the HCV risk and if you would just focus on this
column, the per unit risk, you can see that, prior to
surrogate tests, a half a percent of these units were
causing recipient seroconversion.
After surrogate tests but before HCV was
introduced, .36%. So, very much the predicted efficacy of
surrogate tests, about a third reduction in risk per unit.
And then, HCV first generation test kicked in, dropping the
risk fairly dramatically to .06 or six per 10,000, which is
a low risk -- one in 1500 -- but this has clearly been
dramatically reduced further by the second generation
assays, which actually detected in clinical trials, one in
1,000 units that were missed by the first gen tests were
detected by the second gen tests, and confirmed by PCR.
This is funny, because actually, that would
suggest that the second gen test picked up more infections
than the first gen test was missing; one in 1,000 is a
bigger number than one in 1500. So, we are dealing now with
residual risks that are so low that studies are having
difficulty matching themselves up.
This just shows HBV now. HBV transmission, same
population of recipient samples. Prior to surrogate
markers, about one in 2,000. Modest drop with anticorin(?)
ALT, perhaps 10%. A more dramatic and somewhat surprising
drop with introduction of HCV, almost a reverse surrogate
effect, where HCV screening dramatically reduced the risk of
HBV transmission, something that is still not explained.
But, very low residual risks from the studies, and those of
that recipient seroconversion study, I haven't got a firm
number, but Paul could probably confirm this, but I would
suspect it probably cost $20 million to conduct over the
course of that five- or six-year period.
In parallel there was a large study in San
Francisco where we actually performed PCR and cultures on
200,000 donations for HIV. Again, you know, probably a $20
million dollar study over the course of five years. Every
donor had an extra tube collected. After the routine
testing was done, the tubes that were screened as safe,
corresponding to safe units, were subjected to pooling of
the cells, eventuating in pools of 50 donor cells each.
Those pools were then tested in parallel by
culture and PCR, and the results of that study, there was a
two-phased component, but the bottom line over the entire
study was, we identified one infected donor who had been
missed by routine screening, over the course of the study,
during the two phases, a total of 200,000 samples.
A confidence interval, an estimate of -- a point
estimate, when you adjust for the pooling issues in the
sensitivity of about one in 160,000. But again, an upper
confidence bound of about one in 25,000, which is not
reassuring to the general public.
Clearly, these approaches are very tedious, very
expensive, for measuring risk, which has led to our
estimating risk through modelled approaches, and as we
realize that there are continued rare transmissions of blood
infectious viruses, despite screening, we can step back and
ask, why does that happen, and that can then let us focus on
estimating the contributions of these various sources of
risk, to the total picture.
In terms of viruses, there are four major
potential reasons for failures. One is pre-seroconversion
window period donations, and we will talk about that. A
second is the concern about viral variants, type O HIV, HCV,
rare variants, things of this nature, that tests are simply
not adequately representative of viral diversity, and so
they miss some rare infections.
A third consideration are what we term atypical or
non-seroconverters, also called silent carriers. This would
be not a problem with the virus being variant, but a person
who is infected and has an unusual or incomplete immune
response, so the virus is a standard strain, but the host
does not form a typical immune response and is a long term
immuno-silent carrier.
Then the fourth consideration is that we simply
screw up, that the markers in the blood and the testing is
performed inaccurately, and as we get into very low residual
risks due to all these other things, you will begin to see
that test error can begin to contribute a significant
contribution to risk, especially with viruses that are very
prevalent, so you have a fair frequency of positive donors
in the tested population, a rare test error occurring on a
highly prevalent virus can begin to contribute
proportionately to some of these other sources of risk.
Window risk, though, has been the major focus of
the last decade and I want to just give you a little bit of
examples of how we approach estimating residual risk from
window period. Basically, this slide summarizes the very
simple relationship that we use to both estimate residual
risk, and to project the value of a new test designed to
reduce the risk.
The residual risk is simply estimated by
multiplying the incidence rate, which is expressed as the
rate of seroconversions over person time of observation in a
population, and we can measure this in the donor pool --
times the infectious window period, or the time prior to
standard seroconversion that the individual is infectious or
viremic.
If we want to evaluate a new test, as we will do
toward the end of the talk, we simply similarly multiply the
incidence rate, the rate of new infections, times the
reduction in the window period that the new test achieves.
What fraction of a year does that new test cut off of that
residual infectious window period?
For the various viruses, we can measure incidence
-- this is data from the red study published in the New
England Journal last year, that estimates the incidence rate
for each of the major viruses that we currently screen for,
and you can see, they range from a low of one in 100,000
person years for HGLV, to incidence rates of about four to
five per 100,000 for HIV and HCV, and actually, not
surprisingly, in the broad public health context, but
somewhat surprising to blood bankers, is that HBV is
actually the most common virus occurring in our donor
population. It is by far the most frequent virus of these
transmitted in the general population. So, we are running
at about one per 10,000 incidence for HBV.
Toxins(?) themselves, but the window period
summary slides here, HIV we believe that there is a phase
prior to detectable RNA, a brief phase during which the
virus is beginning to disseminate at very low levels, so we
have an overall estimate of a 22-day infectious window
period, with RNA becoming detectible and ramping up for
about half of that phase.
Perhaps this theoretical RNA negative infectious
phase is an area of consideration in current
experimentation. Whether this exists or not, whether RNA
screening could eliminate infections is an important
question that is being studied. But RNA can be detected for
usually about three or four days before P-24 antigen is
detected, transiently, then antibody and improved antibody
tests have successfully now detected IGM antibody, and we
will talk a little bit about this when we talk about P-24
antigen screening, but in terms of residual risk, it is this
ten or so -- 10 or 20 day pre-seroconversion window that is
a concern.
For HCV, there is actually a much longer, both
total window from exposure to seroconversion of about 80
days, of which nearly all of that is viremic with high
levels of detectible HCV RNA. Hepatitis-B, we screen for
surface antigen as well as currently anti-corp(?). This I
am sure will be an area of focus for this committee, whether
this test is still worth retaining.
You can detect HBV DNA for in the range of 10 to
25 days prior to surface antigen and seroconverters, and
there is an overall nearly 60-day window between exposure
and when you detect surface antigens. So these are the kind
of window period information that we need to plug into
formulas to estimate residual risk of seroconverters, and
that is simply -- as we showed in that earlier slid --
achieved by multiplying the incidence rate, times the
fraction of a year that the person is in this infectious
window period of 22 days, and you get these estimates of two
per million. So this is where these kind of numbers come
from, through these calculations of this nature and are
subject to confidence considerations, etcetera.
Now, aside from the window period risk, we have to
consider those other three sources. Now, this is a slide
that just illustrates the distribution of HIV subtypes
around the world. As you all know, the U.S. was seeded and
subsequently promulgated Type B infections, really, through
the blood supply and other mechanisms, throughout much of
the developed world. In other areas of the world, though,
in Central Africa, and seeding out into various regions in
Asia, other subtypes are by far predominant. In Central
Africa, Type B is a very rare variant, and you have an
incredible mixture, and really endemic within different
countries, different subtypes.
The greatest concern with respect to subtypes in
our discussion is the failure of some of the tests to detect
some of the variant subtypes, particularly, there was a
problem with HIV-2, which led to the introduction of HIV-1-2
screening tests. It is worth noting that in the last now
seven years of HIV-1-2 screening, there have only been two
HIV-2 infected donors identified in the U.S., both of whom
were detectible by the HIV-1 test that existed. So, in
truth, there has been zero yield in seven years of screening
with these combi-tests, which are substantially more
expensive than HIV-1 tests.
Similar concerns were raised with the outlier
group, O viruses. There was a paper in Lancet about, now,
three or four years ago, documenting that some people
infected with subtype O test negative on the standard HIV-1
and HIV-1-2 screening tests. This in turn led to
surveillance in the U.S. Studies collaborative between CDC,
Red Cross. REDS looked at thousands of people who were
infected with HIV-1, in determinants, etcetera, and failed
to find any HIV group O infected donors.
In a separate study that is ongoing, we have been
doing subtyping on a fairly large number of donors over
time, both going back to early hemophiliacs infected, early
donors during the first six months of screening, and then
more recent, donors about -- now, actually, this is a number
about 500 totally. And in that whole group, we have only
found two variant viruses, a Group A and a Group B, both
arising from recent immigrants from Africa who were clearly
infected heterosexually in their endemic countries.
The subtype surveillance is important, but if we
step back and we ask what the potential contribution of risk
is from something like a Group O -- and I do not have time
to walk through this -- but the bottom line is, that the
risk is extraordinary -- if you take the worst case
scenario, the risk is extraordinarily rare that a group O
infection will slip through.
These viruses are extremely rare, even in Africa.
Their presence in the U.S. is extraordinarily low because
people are not -- in fact, now these people are ineligible.
The FDA issued guidelines which resulted in permanent
deferral, or indefinite deferral of persons coming from
group O endemic countries, so even though they were rare in
the first place in the U.S. donors from these countries, are
now excluded.
And then the tests that we are talking about
actually have only about a 20% failure rate, so even if a
group O infected donor does slip through, most of the time
the tests pick them up. So we end up with an extremely low
contribution to these variants.
If we similarly run the same issues for the other
viruses, the story is pretty much the same. For all the
viruses, the risk due to variants is extremely small, the
possible exception being HGLV-2, we are still using HGLV-1
based assays. There's pending licensure of bona fide HGLV-1-2
combi-test, but there may be a rare miss of HGLV-2 by
the current HGLV-1 based tests.
There was a significant problem with the first
generation HCV test, which has very limited antigen
representation from genotype I missing the other genotypes,
and that was a major reason for the failure of that test was
that is missing non-genotype I infections. So, that has
been fixed, too. So, the issue of variant viruses is one of
constantly chasing and surveillance for these variants;
fixing the tests to detect them, but one that really
contributes very little to current risk, because these
variants are very, very rare.
The third problem is the non-seroconverter, and
there had been reports -- there was an MMWR now almost over
a year ago, and just recently published, the paper that
describes this case in detail of a Utah plasma donor who was
donating and not seroconverting. There have been other
cases like that -- this is another one -- a person who
developed very high titer(?) viremia, and the antibody tests
over the course of a year have just remained borderline
positive and negative. But these cases are extraordinarily
rare, as evidenced by the fact that antigen screening has
not detected any such cases in a year and a half of regular,
prospective screening. So, again, these atypical
seroconverters are rare for HIV, now this is an important
point, because I think this is going to be a major issue for
this committee, in the setting of HCV, there is significant
evidence that there may be a moderate frequency of people
who are PCR-positive, and not seroconverting.
We talked a little bit about this yesterday, the
English experience with doing PCR on their recipients who
screen negative. They found those four or five cases, which
does not surprise me. Actually, Miriam Alter, who is still
here, reported five years ago -- to a lot of criticism --
that she was finding in her studies, cases that were
serologically negative; people presented with community-acquired
non-A, non-B hepatitis, who were testing PCR-positive. And she
reported that at a rate of about 10% of
all the infections did not seem to be seroconverting, which
everybody said, you are crazy.
It turns out, she may be right, and this has
become known, because people have begun to do this large-scale
PCR screening, and there have been several large
studies now in Europe and a recent study in the U.S., both
in the source and the Red Cross whole blood plasma
collection setting, where people have begun to do large-scale
pooled PCR, and there have been no surprises with HIV,
nobody is picking up any, but in contrast with HCV, there
have been substantial pick-ups of PCR-positive, sero-negative
infections.
In the German experience, which is by far the
largest to date, they are doing large pools of 500-plus
samples and then they are breaking those down and finding
the source of the positivity, and then actually
appropriately following the donor, and they are also tracing
the recipients. And in their studies, they have tested over
700,000 samples, this is as of about four months ago, and
they have had problems with false positivity, and samples
that test positive initially and then negative, and they
cannot explain it all, but they were able to actually
identify and firm up and confirm seven positive HBV pools
that track down to single donations and yielded a risk of
one in 100,000, and almost 70 in this period, one in 10,000
HCV infections.
Impressibly, they were able to get follow-up on a
reasonable proportion of these, and three of the five HBV
infections they picked up seroconverted to remain viremic
and did not seroconvert, even to surface antigen, so this
was a very low level PRC positivity undetectable by surface
antigen or anti-corp(?).
With HCV, only two of the 36 seroconverted and 33
remained persistently viremic and seronegative for up to six
months, so very disturbing data, and the question really is,
whether these people were infectious.
In their own look-back studies which were limited,
they could not from prior donations document any infected
recipients from prior donations, from these donors. But
there is data from the U.S., from one of the earlier NHLBI
studies, the TTVS study, where Jim Moseley -- we have gone
back now and tested these samples by PCR. This was a study
in the late seventies and early eighties, where in this
study there were 138 seropositive units that were
transfused, and 110 of those units caused recipient
seroconversion by the second gen test, the third gen test
picked up an additional three units.
There were 113 transmissions that were tracked
from seropositive blood that caused seroconversion in the
recipients, but in addition, there were seven recipients who
seroconverted, but there were no positive donors. And we
have recently gone back and begun to extensively study the
donor units that went into these seven recipients.
One case was found were the third gen test picked
up an implicated donations that probably caused one of these
infections. There were three other cases, though, that were
RNA-positive, and serologically negative that appear to
represent these PCR-positive, antibody-negative infections,
and appear to be associated now with transmission. This
needs to be confirmed and is in the process of being
confirmed in multiple labs with sequencing to confirm that
these were transmissions.
If you take these three transmissions from PCR-positive,
antibody-negative blood, out of a total, then, of
116 transmissions, that is about one in 40 transmissions
tracked to these PCR-positive, sero-negative units. And
that turns out to fit very well with this one in 10,000
frequency. If you multiply one in 40 times the current
prevalence of HCV in the donor pool, which is about, you
know, .2, .3%, you end up about one in 10,000.
This is consistent with the observation of one in
10,000 PCR-positive, sero-negative, and suggests that these
may be transmitting infection. So, this is an area that I
am sure will be a major focus. It has now become the major
driver behind expedited introduction of PCR screening in the
context of pool-testing before we have standard assays.
The last risk source is test error. I do not have
time to go into it, but in a study, we have measured the
rate of test error through tracking subsequent donations
from confirmed positive donors, and figuring out how
frequently do those units test negative when they clearly
were infected, and that turns out to be .067%.
For a test error to be significant, it has to
occur on a positive unit. So, to measure the contribution
of test error, we multiply the error rate times the
prevalence, or the frequency of positive units, and that
gives us the frequency of risk of missing a positive unit
due to error. So, these numbers are small. These are
expressed as per million donations, so the worst case for
HCV, which is a very prevalent virus, is about one in a
million units may sneak through because an error in testing
occurs on a straightforward, positive unit, which is, as we
talk, begins to be a reasonable risk. We cannot just
continue to ignore this, and clearly improvement in methods
of testing automation should be pursued to eliminate test
error to the extent possible.
This is a summary slide that puts together each of
these sources of risk, and again, I have a review that comes
to the same table that I can distribute through Paul. Pre-
seroconversion window period estimates we have just talked
about, immunovariant viruses. These non-seroconverting
carriers, where HCV is the big controversy and if this is
real, maybe one in 10,000 transmissions may be due to these
variants, then you can see that the risk of HCV is
substantially higher, perhaps as high as one in 10,000 or
greater, and that is really the major issue that is the
focus of most blood bankers today, is that residual HCV
risk.
You can see, then, we can derive total risk
estimates. This is nicely summarized, again. Now, I am
going to use four or five slides from the GAO Report
compiled from that, and I really urge you to read just that
first four or five pages of that. I am not going to go
through in detail, I just want to juxtapose these risks with
noninfectious risks and then with other risks.
These are pretty much the same numbers I just
walked through for the major viruses. These are
conservative estimates. They purposely focused on the most
conservative estimates, risks of one in 5,000 for HCV, which
is even higher than I was talking about. One in 450,000 for
HIV, again, a relatively high estimate. One in 50,000 for
HGLV-2, because of those missed infections. So, these are
really high estimates of risk. They also incorporate a risk
of one in a million for HIV. A residual potential risk of
non-ABC, some of which may be HGV, but it is probably a very
nonpathogenic infection. CMV has a low level risk.
We have a total infectious viral risk of about
four per 10,000, which is moderately alarming. For nonviral
risks, there are particular focus on bacterial
contamination, which risk estimates are as high as one in
10,000 for platelet components appear to exist, of low level
bacterial growth in these products that can cause
significant morbidity and rarely mortality in recipients.
T-cruzi(?) is another concern, one in 40,000 potential
risks, although transmissions have yet to be documented in
any prospective U.S. studies. There will be a paper coming
out in JAMA soon with Red Cross experience on this.
If we sum these nonviral and viral risks, we get
five per 10,000. You know, one in 2,000 units cause risk.
But if we translate this out to -- as they do nicely -- to
the number of recipients who survive long enough to acquire
an infection, that translates per year in the whole U.S. in
about seven million recipients, to about 7,000 infected
recipients, and they also go on to evaluate how much chronic
disease burden will this eventuate in? And that is in the
range of 12, 1300 per, again, seven, eight million
recipients. So, fairly low frequency of disease outcome,
but clearly still there are infections transmitted and
diseases resulting.
These are the noninfectious risks, which again the
GAO Report summarizes; ABO incompatibilities, circulatory
overload, things of this nature. And they sum out to a rate
per transfusion of these things happening of three per
10,000 units, with a moderate number of recipients being
exposed and living with these complications, at least
briefly. Many of these are transient. Only about 200 or so
develop significant chronic disease or death, though, as a
consequence of these noninfectious risks.
Then if we sum this up, we have the infectious
risk estimate of five per 10,000, the risk of transfusion
reactions, three per 10,000, for a total risk per unit of
eight per 10,000, nearly one in 1,000 units is associated
with some kind of a risk of an adverse effect. But, again,
if we run the numbers through in terms of number of
recipients, or frequency of recipients who are affected, it
is 2.8 per thousand overall, and who really develop
significant chronic morbidity or potential mortality, they
estimate four per 10,000, or about 1500 per year among the
seven million recipients develop a serious consequence.
Then they go on to nicely -- this is that same
number, we had four per 10,000, which is forty per 100,000.
This is your risk if you are a recipient of a standard four-unit
transfusion of developing significant morbidity from a
blood transfusion.
They then go on to say, now, if you are not going
to get blood for sure. If you are just going into surgery,
then based on the probability that a surgery patient will
get blood, they reduce the risk to five per 100,000, and
then they look at, what is the probability if you are just
somebody currently walking on the street with no plans for
surgery, no chronic bleeding disorder, what is the
probability that you are going to go to surgery or develop
one of these bleeding requiring transfusion problems, and
they get a five per million. This is the risk to the
general person in the population of chronic consequences,
were they to need blood and suffer a consequence of that.
Then they go -- this is that five per hundred
thousand. And then they go to contrast that with other
risks, five per 100,000, if you are a general surgery
patient; 40 per 100,000 if you actually need a blood
transfusion. And then they contrast these blood-related
risks with other health outcome risks. Being in the
hospital and if you get in the hospital, your probability of
dying or disability is 600 per 100,000. If you go through
surgery, just the consequences of surgery is likely to cause
death at a rate of 1300 per 100,000. Injury from a drug
complication during a hospital, 6500 per 100,000. So, we
are dealing with risks a hundredfold that of blood
transfusion for most of these other well-known complications
of being in the hospital.
Then they go further to contrast this risk, again,
of transfusion-related death with other risks of non-hospitalized,
or other problems; malignant tumors, CVA,
etcetera. Again, just to juxtapose this relatively low risk
of transfusion with the much higher risks associated with
many of these other complications, or illnesses.
Then they go on, again, referring you to this
document, because it really does a nice job of this, to
contrast this risk with lots of other just general life
risks. Electrocution, you know, drowning, nine -- so,
tenfold, greater than tenfold higher risk of drowning, in
general, than from transfusion. Stroke, heart disease,
etcetera. So, a nice job of juxtaposing all of these risks.
This is sort of the summary of where we stand
relative to those other risks, and I am sure we will hear in
the next talk about how we should try to be comfortable or
not comfortable with these considerations.
I just want to briefly touch on other approaches
and just highlight a few examples of how we can try to make
things better, but we often are trying to make things better
where the risk is so low that we actually perturb the fabric
of safety and make things worse, or could make things worse.
So, approaches to reducing risks, these low level risks,
involve trying to improve screening, education, enhance
screening through the blood tests themselves, increased
regulatory oversight, pathogenic inactivation, which is on
the forefront, and I am sure, again, another issue will come
to this committee but brings with it low level exposures to
potential carcinogens, etcetera. And then obviously,
reducing allogeneic exposures to autologous, or reducing
blood usage, but that begins, as this again, GOA document
shows, the benefit to most patients who need blood of
getting blood is so enormous, that as you begin to consider
not giving these people blood, you really can potentially
harm these people much, much more than exposing them to
these low risks.
Just one example, a paper that is in press now,
where we have looked at the impact of excluding donors --
this has to do with CJD, and because CJD has mostly been
documented in older people, there have been proposals and in
fact in some plasma centers they do not draw blood from
people over 50. And this has led to consideration in the
whole blood setting, of stopping collecting blood, or
selectively only drawing certain types of blood units, from
younger donors. And the truth is, younger donors have much
higher incidence of all of these major viral transmissions,
so with this study, what we did was to evaluate what the
impact of exclusion of older donors was on the net rate of
new infections for the known viruses.
It turns out, if you exclude donors over 50, you
would increase the risk of the major viruses by 10 to 20%,
because you would perturb the blood supply mix, you would
move it more towards younger, riskier, donors, and your
older, safer donors with respect to these sexually-transmitted,
drug-transmitted risks, begin to be pulled out
of your blood supply. So, this is just an example of how
the mix of donors in the blood supply can be perturbed
toward increasing, quote, safety, for an agent that may not
even be transmitted by blood, with the negative effect of
increasing the risk, for agents that we know are being
transmitted by blood.
Another example is moving to new tests, and we can
add tests, like P-24 antigen or RNA. There is concern that
adding these tests will recruit new donors who are at risk
to be tested because they cannot get these tests anywhere
else. Fortunately, that has not happened, but in fact,
also, these are very expensive tests, and Jim AuBuchon and I
did an analysis of the cost-effectiveness of adding P-24
antigen, or RNA PCR, and the bottom line is, as I think Jim
showed yesterday, is the P-24 antigen estimate was a little
over $2 million, RNA PCR over a $1 million per qualle(?), so
very high numbers. This was on the assumption that we would
predict -- that we would pick up as predicted in the range
of five to ten infections per year.
The truth is, in the first year of screening well
over ten million -- this is the Red Cross experience -- but,
there has only been one infected donor found in the entire
national screening program. In fact, in the first year and
a half, in the whole blood sector, probably 18 million units
have been tested of whole blood, and only one infected, true
infected donor.
These other numbers represent all the horrendous
problems with false positivity that we have had to deal
with. None of these people are infected. We have had to do
large PCR studies on all the people who were negative on the
confirmatory tests, etcetera, but the bottom line is, that
the yield was much, much lower than we even projected, and
there was extensive criticism that these projections were
underestimates. So we can put a lot of resources to try to
improve safety, with very little bang for the buck.
This is, again, a slide in a review that Jim has
developed and I participated in that is coming out in Annals
of Internal Medicine very soon, of the overall risk and
cost-effectiveness of blood initiatives, and again,
contrasting many of these blood initiatives, such as antigen
testing, anti-corp(?) testing here, P-24 testing, ALT
screening of donors. Contrasting these, solvent detergent
plasma, viral inactivation method, with the other commonly
accepted interventions that are going on, and just
illustrating that we are really beginning to get out of the
envelope of reality in some of the things that people are
doing to try to reduce risk.
Finally, just a list of the new agents. I do not
have time to go into these, but a lot of things down the
pipeline of concern, and everybody is out there to discover
the next agent and to try to prove that it is a blood safety
risk, because that is the political hot button. So,
everybody who discovers a new virus immediately tries to
document a transmission of this or that.
There was just a recent case of HHGV-8, where an
in vitro transmission of the virus from a healthy donor --
this is a very common virus -- to cell culture, resulted in
the inference that the blood supply is at risk for this, and
now we are having to do large studies on HHV-8. So, most of
these agents, you know, through surveillance studies, are,
one, extremely rare. Transfusion transmission has never
been documented. And even if they are infectious, the risk
of disease is very low. So, we have to begin to try to put
the same numbers on these things. And you can imagine the
risks being so low that the studies must be quite large and
intricate to be able to try to estimate the consequences of
these things.
But we do have good strategies. Over the last
year, there has been good efforts to develop strategies to
measure the consequences of new agents through monitoring
donor recipient populations, understanding the transmission
routes in the non-transfusion settings, and implementing
national surveillance of cases to understand whether
transmission is from blood. So, I will conclude there,
thank you.
MR. CAPLAN: Questions for Mike before he runs
off?
PARTICIPANT: Mike, if I could just reiterate one
point that you showed up there about the ABO errors and
mistransfusions, just so that the committee is aware of this
and the relative magnitude, because we are often talking
about, as Mike has talked about, what more we can do, or
what fancy new technology we can bring in to make the blood
supply just a little bit safer. And every year in this
country, we kill two dozen patients because they get the
wrong unit of blood due to an entirely preventable human
error. We do not need a PCR test, we do not need any new
fancy approach to that, we just need good practice and
traditional checking and make sure things are done right the
first time to prevent a very preventable and disastrous
consequence.
PARTICIPANT: Mike, have you calculated, or has
Jim calculated, dollars per qualle for HCV RNA testing?
DR. BUSCH: Not as yet. I think -- one thing I
did not mention, it is impressive to actually benchmark each
of these new efforts against the current standard testing.
HIV antibody testing is extraordinarily cost-effective. HCV
antibody testing actually more than pays for itself. It has
a very negative dollars per qualle. It is preventing so
many transmissions that the antibody test is extremely
effective.
The issue is, you talk about adding a new test,
almost always it will never replace the old test, because
you are basically trying to pick up window phase or occult
infections, but some people who are sero-positive may test
negative on a virus detection assay, so you have to keep the
antibody test in place. So the cost-effectiveness. The
cost is borne by the infrequent, incremental detections, the
rare pick-up.
It would be a good one to do. We have the outcome
measures, and only in the last six months have people begun
to recognize and acknowledge that there may be this pick-up
rate of one in 10,000. So, I think we could probably do a
good number on that now.
MR. CAPLAN: Okay. I am going to ask Dr. Maibach
to come down. While he is approaching the podium, one of
the things that I wanted to alert the committee to is, we
will spend a little bit of time trying to think about the
structure of the report next, and I think the discussion I
have had with some of the committee members makes me think
that it might be reasonable -- and I would like you to be
thinking about this a little bit -- to use the first draft
that Dr. Hoots put together, sort of the template, not that
Dr. Kenner's insights will not go down in human history as
valued, but it may be more useful just to go with that as
the document we are kind of working on and editing and
building around. So, think about that a little bit before
we get back to the discussion of recommendations.
Dr. Maibach is going to talk to us about
communication of risk.
Agenda Item: Dealing With and Communicating Risk
MR. MAIBACH: I really enjoyed the last
presentation for a number of reasons; one, I am totally
uninformed on most of these issues, and secondly, it was a
very nice presentation of a substantial amount of
quantitative risk information. And, in many ways, I am sure
that my presentation will be the only one in two days that
is completely devoid of numbers. And actually, I am going
to go -- rather than start with my first slide, I am going
to briefly reflect on my last slide for a moment, my final
point on my final slide, and that is that, people simplify,
and our job, in communicating complex risk information is to
help them simplify appropriately.
It is a basic truism of human cognition that we --
that -- well, A, people are phenomenally adept at processing
a lot of information, but by virtue of the overload
phenomenon, we automatically invoke biases, heuristics and
biases that allow us to deal with complex information in a
rapid fashion, so, i.e., we simplify. And the big challenge
in doing risk communication effectively is understanding
those heuristics and biases that we apply, so we can
understand how to help people simplify appropriately.
One of the fundamental observations in risk
perception is that we have a tendency to overestimate
uncommon risks; i.e., in this example, the risks of dread
disorders associated with blood transfusions, and we
underestimate risks that are actually quite common to us;
i.e., for hypertensive and perhaps the risk of stroke, or
for a smoker, the risk of lung cancer or other dread
disorders. And that is sort of a fundamental paradox of
risk communication. We overestimate the unlikely, we
underestimate the likely.
That paradox is a direct consequence of the fact
that risks are not unidimensional; namely, they do not go
from the remote to the highly likely; that we do not
perceive risks on a single dimension, but rather we perceive
risks along a variety of different dimensions, or we respond
to risks along a variety of different dimensions. Depending
on which cognitive researcher you are paying attention to,
that number of dimensions might be seven, or five, or nine,
or what have you, but the basic point is that risks are not
unidimensional. The way in which we respond to risk is
really a direct function of where the risks fall along those
various dimensions.
Risks that are perceived to be greater tend to
have these attributes. Risks that are involuntary; i.e.,
imposed on us by external forces, as opposed to imposed on
us by our own decisions or lifestyle choices tend to be
perceived as greater, and therefore, we are more likely to
respond to them with what risk perception researchers call
outrage.
Risks that are uncontrollable, i.e., beyond our
control, again, we are more likely to see those as greater.
Risks that are unfair, namely, where I, as the individual,
do not accrue the benefit of taking the risk, but the
benefit is accrued elsewhere, the whole issue of
environmental equity in environmental health is a nice
example of that, namely, communities where there is risk
imposed on them by virtue of where they live, but the
benefit of those risks, for example, the corporate profits
are going elsewhere.
Risks that are unfamiliar tend to be more dreaded,
simply because we do not understand what the risk is really
implying. Risks that lead to a dreaded condition are seen
as living larger in our minds. Risks where there is
uncertainty about the risks, i.e., when the experts cannot
really explain to us what the consequences -- with any
certainty -- what the consequences of those risks really
are. Those loom larger in our minds.
Similarly, risks where there are potentially
catastrophic consequences, i.e., when many people will have
the potential to be affected simultaneously, as opposed to a
single individual. And finally, risks that are memorable.
If you think of the great catastrophes of our times, Three
Mile Island is a single instance, that invokes -- it very
readily invokes some mental heuristics that are quite
frightening and therefore lead to greater perceptions of
risk.
Coming back to the point that our job is to help
people simplify appropriately, we might be persuaded
inappropriately to use qualitative expressions of risk, as
opposed to quantitative; such as, likely, very likely,
highly probable. The problem with this approach is that
there are very good studies documenting that people
interpret those qualitative expressions of risk very
differently. So, the confidence interval around the
quantitative expression associated with the term, likely,
for example, is as low as 30 to 40% and as high as 90 to
95%, depending on the individual who is responding. So, it
is certainly not a good way to communicate with any
precision, what we are really implying as a magnitude of a
risk.
Conversely, is the fact that most people have a
very difficult time understanding quantitative expressions
of risk; namely, all of those numbers that we just saw, the
average viewer, the average listener, myself included, has a
really difficult time wrestling with those and putting them
in context to what the risk means to us as individuals.
Fortunately, there is some literature indicating
that visual representations of risk, believe it or not, the
kind of thing that you see in U.S.A. Today, are actually
perhaps the best strategy for conveying complicated risk
information. And moreover, when visual representations have
corresponding qualitative and quantitative expressions of
risk, i.e., when the text matches the visual and numbers are
included in both the visual and the text, that allows people
to get the best sense -- if, by best I mean, most accurate
sense -- of what is attempting to be conveyed about the
risk.
People value a given piece of risk information
more when they perceive the source of that information to be
credible; i.e., disinterested, personally or professionally,
disinterested in the outcome. Industry is often greatly
perplexed by the fact that, even when they attempt to be
forthcoming with risk information, they are typically viewed
as being suspect in the whole process. The information,
even if it is generate by external scientists, is perceived
to be not credible.
Government sources, on the other hand, are
generally perceived to be credible, although as you all
know, as time goes on, even government information is
increasingly seen as suspect. But credibility is clearly
the key to taking risk information on its face value.
Somewhat associated with that is the fact that
people value information that is perceived to be certain.
No one likes uncertainty. And when we present risk
information with uncertainty, which unfortunately, as you
all know, is almost always the case, we are rarely certain
about the risk information we have -- was struck in the last
presentation by the degree of certainty that was being
implied, and perhaps that is because you-all have been on
this for so long -- but typically, when there is full
disclosure, you have to disclose the fact that you are not
fully certain about your risk estimates. And when you do
that, people tend to either be suspicious of the source of
the information; they feel you are withholding knowledge
that you genuinely have, but do not want to be forthcoming
about, simply because the audience will not like the
implications; i.e., why don't they just tell me, what are
they hiding?
In addition, if the recipient of the information
is suffering from a risk that is not self-imposed; i.e.,
externally imposed, to the degree that the information is
presented as being uncertain, they will tend to lay blame on
the communicator or on whatever source they perceive to be
causing the risk, and they will lay blame and want to do
finger-pointing as opposed to do problem-solving.
Conversely, if the recipient is the cause of the
risk, they will tend to discount the risk; i.e., again, the
smoker situation. It is not really as risky as they are
telling me it is.
Perhaps the most important point I want to make
today is that, people are generally motivated to reduce
risks that they face, but that is, I say, generally, because
simply because you perceive a risk, and even if you are
motivated to reduce that risk, does not necessarily mean an
individual will change their behavior to actually mitigate
risk. And there is an enormous literature on behavior
change that really speaks to this point. There are numerous
different reasons why people who appreciate their own risk,
who are motivated to reduce their risk, simply do not, or
are incapable of taking action to reduce the risk. And
therefore, it is risk communication -- the efficacy of risk
communication should not be judged, based on its ability to
change people's behavior. That is an unfair evaluation
criteria.
Instead, it should be judged on its ability to
impart an accurate understanding of the risk, that is really
the ultimate criterion against which risk communication
should be judged. Beyond that, risk communication can be
judged by its ability to facilitate reaching a good
decision. What constitutes a good decision for an
individual, is simply beyond appreciation of the
communicator, or the communicating organization.
Individuals have many different contingencies in their
lives, and are going to have to consider all of those
contingencies when deciding how to react to risk
information. And therefore, again, the point is, do not
judge the consequence of risk communication based on the
action, but based on how well-informed people are, and the
degree to which the information has facilitated them to make
a good decision, based on what they value.
One common, very common technique, in attempting
to communicate risk information is by making comparisons to
other risks. The irony in this is that it can either be one
of the most helpful risk communication strategies, or one of
the most harmful risk communication strategies, depending on
how you actually go about making comparisons.
The seven dimensions of risk that I introduced
earlier, when we make risk comparisons among two risks, or
between two risks, that have different dimensional profiles,
people will reject those comparisons, and therefore, not
only gain absolutely nothing from the risk comparison, but
will essentially discredit the communicator.
Conversely, if we are able to identify risks,
known risks, risks that we understand because we have a lot
of experience with them, that have a similar dimensional
profile to the risk that we are trying to communicate about,
that can be a very, very useful risk communication tool, but
it is -- given the fact that there are at least seven
different dimensions that we have to consider -- not at all
a straightforward process. Namely, when we make these
comparisons, we have to be very careful, we have to be very
measured in the comparisons we make.
A number of other ways of conducting comparisons,
however, are more helpful, and perhaps more straightforward;
namely, comparing the risk with its benefits, and an example
commonly in the lay literature right now, or the popular
press, is hormone replacement therapy, for post-menopausal
women. And, yes, there are undoubtedly risks associated
with hormone replacement therapy. Conversely, there are
also benefits associated with hormone replacement therapy.
The best way to communicate about those risks is to
communicate them in juxtaposition to the potential benefits.
It is a much more balanced way of communicating, because it
helps people understand the information more thoroughly.
Similarly, comparing the risk in question to risks
associated with the alternatives; again, back to the hormone
replacement therapy example. There is clearly a risk of not
taking hormone replacement therapy by post-menopausal women,
and understanding the risks of taking action, versus the
risks of not taking action, is a very nice way to help
people really place the decision that is in front of them in
context.
Finally, in some situations, you can compare the
risk to natural background levels of the disorder in
question. So, for example, cancer clusters, I mean, there
will always be a background level of leukemia in any
community, and the concern is exposure from an old plant
that has been shut down, and there is fear of a cancer
cluster. It is very helpful to compare the level of
expected leukemia in a given cancer, compared to that
actually found.
To sort of bring this to closure at the most
simple level, there are a number of ways we know about that
are sort of tried and true in terms of improving risk
communication. One of those is to provide the information
from a variety of perspectives, including both relative and
absolute risk, humanizing the estimates of risk; i.e., do
not simply present numbers, but present how people figure
into those numbers. One in 1,000 people are expected to
come down with the disorder, or one in 10,000 people, or one
in 100,000 people, and this is equivalent to. Definitely,
you need to include people in the equation, because that is
how we think. That is the basis on how we make decisions,
because we, after all, are people.
As I have already made the point, that it is very
helpful to compare the risks we are trying to communicate
about with similar risks. Risks, i.e., with similar risk
profiles.
Be clear about the degree of certainty in your
risk estimates. I have already said that uncertain
information can be more volatile. On the other hand, if
risk information is presented with certainty, and it is in
fact uncertain, that is the most volatile potential
situation, because that is where lots of suspicion tends to
be brought in, and a lot of finger-pointing and blaming.
A very important point is, use language that is
appropriate for your audience. Rarely is scientific jargon
appropriate for communicating risk information. One of my
own -- sort of a related point, and an area in which I had
the opportunity to do some research was, understanding of
consent forms as an example of language that is typically
inappropriate for the audience. Most patients are incapable
of understanding consent forms the way they are typically
written. The risk information is absolutely presented there
in excruciatingly painful detail. Unfortunately, it is
presented in such a way that the person who we are
attempting to inform, is incapable of understanding. We
have to go to great pains to use language that is
appropriate to our audience, even if that entails research
to understand what language is appropriate for a given
audience.
I come back, again, in conclusion, to my opening
point, and that is, that people simplify, and our job is to
help them simplify appropriately. It is a basic human
process to simplify information so that we can get through
our day and get the things done that we need to do. If we
really want people to be informed, we, as the communicators,
have to go through all of the machinations required to
understand how to help people simplify appropriately.
Are there any questions?
PARTICIPANT: That was an excellent presentation.
I really enjoyed it because we are trying to communicate
this type of information to the lay public, and politicians
all the time, and we find it very difficult, not to mention,
reporters.
When you said that we should not measure, or we
should not judge our communication by its ability to change
behavior, but then you said that, you should look at whether
or not a good decision is made, as to whether we
communicated effectively. Isn't that, then, the same thing?
In other words, in the current context, we are attempting to
get individual -- we want to notify individuals in one way
or another, that they may have been exposed to an infection
by nature of the fact that they had a blood transfusion.
And whether or not we can evaluate the types of notification
that we use is questionable, but if we attempted to do that,
one way we would evaluate it is by whether or not they went
to see a physician, or got testing. Well, that is a
behavior, in essence, so what is the best way, or can you
put that in a different context for me, or give me an
example?
MR. MAIBACH: The question was, if we are not to
evaluate the efficacy of risk communication based on the
resultant behavior change, isn't it comparable to say that
we are evaluating based on imparting an accurate
understanding of the risk? I think I misstated the
question, but I understand the nature, and I will address
it.
If the objective of the communication is to convey
to people who may have been exposed to infected blood, that
they may have been exposed to infected blood there, and they
should seek medical evaluation, the evaluation criterion for
that should be, did they understand what you were intending
to communicate? It should not be, did they seek medical
consultation? The reason I say that is, because your job as
the communicator is simply to ensure that they got the
message.
The reasons that they might not seek medical
evaluation is, they may be fearful of doctors. They might
not be able to afford medical care. There are a hundred
different reasons why they might not seek a medical consult.
All of those have to be somebody's concern, but they are not
your concern as the communicator of the risk information.
And if your communication is deemed as faulty for not
getting people into a medical consult, well, then that just
simply makes you the scapegoat for why the situation is not
improving.
My point is, that if you have done your job; i.e.,
the person is truly informed that they are at risk and they
have a balanced appreciation of their risk, then you are off
the hook and somebody else is now on the hook, if they do
not move into the healthcare setting. And my whole point is
that that is an appropriate way to judge sort of a risk
management scenario.
PARTICIPANT: So, how do you evaluate whether or
not an individual has perceived accurately the message that
you intended to get to them, to communicate?
MR. MAIBACH: There are ways. Ideally, you create
a risk communication approach, and you test it with a
limited number of individuals. You really get involved.
You interview them, you ask questions from every possible
angle to ascertain the fact that they really understand the
risk. That they are using that risk information to make a
judgment that makes sense in the context of their lives, and
then you go public with your risk communication campaign.
And then you may want to do the subsequent step of
evaluation, which is, you know, on some population basis,
make sure that people actually got the risk communication
that you intended they would receive, and just as your test
subjects responded appropriately to it, your population --
some sample of the population is responding appropriately to
it. If you have gone through all of that, then I would
maintain that your risk communication program was an
unqualified success.
MR. CAPLAN: Let's go to the next (inaudible).
PARTICIPANT: I think there are those times when,
however well we try to communicate risk to populations,
there are those other competing forces that are generated by
the media that sometimes tends to sensationalize or
misinform or confuse the issue, and coupled with that is
what seems to be at least in some communities, and it
relates to some of the points that you were making about
some of the environmental concerns, in particular, that
there is a growing cadre of attorneys that are very quick to
move into communities, and to take their own information and
to find their own list of experts, that come and also try to
take a message that is counter to what one is trying to
communicate. How does one try to reconcile some of those
tensions and confusions?
MR. MAIBACH: That is the art of communication
rather than the science of communication. What I have
attempted to present this morning really is the science,
based on cognitive psychology, and an understanding of how
people process risk information.
The art of communication, on the other hand,
really involves how to work, how to do media outreach, so
that journalists understand what you are trying to
communicate, and are able to faithfully reproduce at least
the core message that you as the scientist feel must be
communicated, which goes a long way towards diffusing
opportunists and moreover, an environment, a community
environment, in which opportunists can take advantage of
alienation and suspicion.
I have the privilege of working with the CDC on a
number of HIV communication issues, and we have been
particularly concerned -- this is just by way of example --
we have been particularly concerned over the past year,
about a potential misunderstanding of the development of
combination therapies for HIV infection, and specifically,
we were worried that there might be members in certain high
risk communities who would sort of backslide behaviorally
because they interpret this as being a cure for AIDS, and
therefore, they do not have to be quite as vigilant anymore.
We talked both to individuals at risk about their
behavior in focus group settings, and we did an analysis of
the media, content analysis. Much to our delight, the
message as transmitted through the media, was transmitted
with almost perfect fidelity; namely, these are not cures,
these are wonderful breakthroughs. They are very hopeful.
But more is not known about them than is known about them.
And they should never be misunderstood to imply the fact
that you need not be vigilant anymore. And, moreover, we
were extremely heartened to find out that members of -- in
this case, we were focus-group interviewing gay and bisexual
men, virtually without exception, they understood that to be
the case. They did not see combination therapy as a cure,
and they claimed, at least, that not in their wildest dreams
would they abandon their safe sex practices because of the
development of these combination therapies.
MR. CAPLAN: To Jim?
DR. AUBUCHON: This committee is faced with
several different approaches, potential approaches to be
used to patients who may have been transfused with units
that may have transmitted, or may have exposed them to a
particular viral agent in the past.
We have some choices including, probably, a direct
letter saying, you received a transfusion and we have reason
to suspect the unit that you personally got, versus more
general public service announcements, just saying that, if
you were transfused in the past, you are at some risk. Do
you have any comments about the relative efficacy of
creating the desired type of behavior in the recipient of
that message?
MR. MAIBACH: I am under the impression that there
are studies that have actually looked at this question. The
National Center for Health Statistics, as you know, conducts
a number of national sort of assessments of our health
status, and in the process of doing that, the results from
physical examination and blood work-ups and what have you,
often they detect disorders, and have the ethical obligation
of informing the participant that, in fact, they may have
this disorder. And I know that they have been involved in
some tests of a variety of different strategies. I honestly
cannot tell you the outcome. I can, however, give you my
judgment as a person who does communication on health issues
full-time, and that is, the same message through multiple
channels inevitably has a more positive outcome. So, if
there were, to the extent to which it is made -- the
information is made available to the general public in a
broad fashion, namely, a campaign fashion, you will have an
audience who are better able to understand, when they
receive a letter, indicating that they in fact may have been
exposed. But, perhaps even more importantly, is the fact
that the way that letter is written, I would say that the
specific language used is going to be all-important in
determining how people respond to it. Language, a letter
that is written in medical jargon will certainly confuse,
alienate, cause a lot of unnecessary fear, and may
consequently, ironically, wind up producing less desirable
action as a result.
DR. AUBUCHON: But just in general, if you had a
choice for a health-related concern, would a direct letter
be more effective, or an overall campaign that would raise
public awareness about a potential risk be more effective?
MR. MAIBACH: If I could only choose one, I would
go for the direct letter, but if I could change the
scenario, I would say, public communication, direct letter,
as well as professional education, because often, that is
the person -- health professionals will be the first group
turned to for additional information, and when you have
synergy among the message in all three, you are going to get
the best outcome.
MR. CAPLAN: Let's do one more over here, Bill.
DR. HOOTS: I am concerned about how you translate
very low or infinitesimal risk to individuals. Do you -- I
mean, would you advise saying, alright, your chances of --
because obviously, part of a physician's and a healthcare
provider's role is reassurance, when it is appropriate to
reassure. Do you put it in a context of something that you
think you understand mathematically, but maybe infer
differently by different people, like you said? Well, your
chances of this occurring are about like your chances of
winning the Lotto today. Or, do you take it more toward the
absurd, and something that probably is far beyond their
expectation of occurring, to get the point across that it is
exceedingly low, even if the numbers do not quite match up?
MR. MAIBACH: The example -- the risk comparison
you just made, your chances of a disorder from a blood
transfusion is equivalent to your chance of winning the
Lotto today, would be an awful risk comparison, for a
variety of reasons. One is that, they are fundamentally
different behaviors. One is a risk imposed upon you,
literally, while you are probably anesthetized and out on
the table, and the other is something that you choose, a
risk you choose to take yourself, moreover, with great hope
that it is going to be your ticket to the big time, and
quitting that job, and moving to Florida. So, that is a
risk communication that is almost certain to be rejected.
Conversely, or sort of alternatively, if you could
find a risk that was well understood but equally improbable
-- and it really does not matter if it is one in a million
or one in ten million, or even one in a trillion, I do not
know, that might be too remote, but for example, the risk of
being struck by lightening -- this is totally off the top of
my head, it might be that the risk for being struck by
lightening might be seen as comparable to the risk of a
transfusion-related disorder, simply because those are both
things that are imposed on you, from externally. I do not
know, I would have to -- clearly, there are many different
dimensions we have to consider.
DR. HOOTS: Right. And the problem I think that
you run into is, if you use an analogy like that, it may
actually, because of their own cognition, or having just
read stories of three people who got hit by lightening,
exaggerate the risk to them. If you go more towards the
relative absurd, something you know they have not heard to
have occurred, because it has not occurred within aeons, is
that -- even though it is mathematically less accurate, is
it both appropriate --
MR. MAIBACH: I would say that, as long as they
really understand the risk you are comparing it to.
Understand it, and feel comfortable with the fact that it is
an extremely improbable event. But you can reiterate that
in a number of ways, namely, using appropriate visuals that
represent the minuscule nature of the risk, using language
that is consistent with the visual, and using the numbers as
well. I mean, people are not totally incapable of
understanding one in a million, but they are much more
likely to misunderstand one in a million, if all you are
telling them is, one in a million.
MR. CAPLAN: Okay, thank you very much.
MR. MAIBACH: Thank you.
Agenda Item: Open Committee Discussion
MR. CAPLAN: Let me ask Paul if he could put Dr.
Hoots' original draft back up on the overhead. I asked
Steve Nightingale if he would help us out, too, in working
the overhead. I hope you have a pen and some blank sheets
there.
Let me say a few words about our work for the next
couple of hours. You remember, we have been tasked, asked
by the agencies and the White House, and indeed by Congress,
to do what we can to make sure that people who are exposed
to hepatitis-C, or face the risk of being exposed to
hepatitis-C, know about these risks, understand them, and
that we are charged to come up with recommendations to the
agencies, that they can really put into practice as policy.
I mean, if you were trying to think of, what is the guiding
theme for us, it is to come up with recommendations that
they can put into practice.
There are a range of questions that have come up,
some of which we have been asked about, some of which we
have not, and that is why I am not putting the original
questions back up on the overhead, because we have kind of
come a distance in the two meetings. I have a proposal
about the structure of this.
I think the Hoots draft, as we started to
formulate it, is very good. And I think there is much to
commend sticking with many of the things that are said in
there, although I suspect we are going to want to add and
debate a bit about some of these points, but I think we
might think about a structure that went as follows.
Something like, in front of what is up here, a
little bit of what I am going to call, for want of a better
term, a preamble, and that gets to the issue of, why are we
doing this, some of which is captured in recommendations
here. See that recommendation two, it says the advisory
committee is dedicated to expanding the public trust about
safety. I might move that more to the preamble. That is
not a recommendation, it is a reason why we are meeting, why
we are trying to make some recommendations, why we are
trying to talk about things. And I have actually drafted up
a little bit of language of some other things that might go
in this brief preamble, but the first part might be, why
now? Why are we meeting? What are we trying to achieve?
We want to cement the public trust. We want to make sure
that people are informed to the extent they can be and so
forth.
A second section then might be, facts. When I was
thinking about this last night, taking my own assignment
seriously, something I am not sure how many of the rest of
you did, but when I was thinking about this last night, I
thought, well, one way to capture some of the reasons why we
are trying to struggle with a policy change at the present
time is because there are certain facts that are mercurial,
and I could mention a couple of them.
There is a new accurate test in 1992. There is
new information about lifestyle that might be relevant to
prevention. There is new information about therapies.
There is new information, in fact, about risk. There may be
new information about new tests coming down the road, PCR-based
testing and so on. I've got five or six facts that
would make, I think, some sense to people as to why we are
saying, well, we did not do this, this, or this in the past,
but maybe we are going to do this now. They are not
principles, they are basic facts that have shifted about
where we are with respect to hepatitis-C. Then I think we
could move to some principles, maybe two of those will
survive. We could add one or two others if appropriate, and
then into the recommendations.
The first thing I would like to have you comment
on -- I know it is a little bit hard to wrestle with this as
a structural feature -- is, whether that seems like a
reasonable structure to raise the recommendations? I am not
proposing a GAO-length report here, I think for policy
purposes, we have to keep ourselves succinct. I take
seriously the advice from the previous speaker that we have
to simplify in order to be heard. I do not know what
language we should learn in order to be heard, but we have
to simplify anyway. So, maybe a preamble-type statement, a
couple of paragraphs, two or three. Six or seven facts
about where we are at with hepatitis-C. Things that have
changed that have made it important to think about what we
want to do now. Some principles to follow. And then the
recommendations. Does that seem like a structure that
people are comfortable with? So, it would run, basically,
preamble, facts, principles, recommendations, is what the
thing looks like.
We could put that up there, Steve, as a -- what I
would like to do, then, if it is alright with you, is just
maybe start, not with the preamble, but I actually wanted to
start with the facts.
One of the little lessons I have learned over the
years about values in policy is, if you can get agreement on
the facts, you can sometimes move toward consensus faster
than if you try and argue about principles first. So, in
the spirit of respect for the empirical, here are just six
facts, or six areas of empirical information that I thought
were important in thinking about why we might, as a nation,
want to change our practices, or what we do with respect to
hepatitis-C.
The first is, the emergence of a reliable test to
detect hepatitis-C in 1992. It seems as if we have the
second generation hepatitis-C test and that shifts the
nature of the ability to detect this problem in the blood
supply of hepatitis-C.
The second fact I would say, is the availability
of new knowledge about risk and transmission. And I noted,
one of the things that seemed to me to be important is that
as we have heard presentations about the differences that
might occur in blood transfusion versus parenteral-acquired
hepatitis-C, there is new information coming out, it may not
stand the test of time, but there are new suggestions about
course of disease, risk of transmission, risk to health of
someone who has hepatitis-C, how long the disease may lie
dormant and then suddenly activate. These kind of facts are
relevant. They may not have been known in 1987. They are
known in 1997. So, facts about probability of harm to the
individual who is infected, information about transmission.
Third fact. So, fact one, Steve, was just the
emergence of a reliable test in 1992. Availability of new
knowledge about risk in transmission. The third fact is, we
know that there seems to be much greater risk to people who
received transfusions prior to 1992. We kept saying that
yesterday as something we needed to grapple with, and decide
how to deal with it, but there it is, it is a fact, and it
is something we know now, partly due to the emergence of
that test, that we have a much safer blood supply in terms
of hepatitis-C than we did.
A fourth fact, new knowledge about prevention
through lifestyle change. I sometimes think of this as the
don't drink fact, but there may be other lifestyle things.
We have had a little bit discussion about sexual practices,
and other things that people might do, but certainly, in the
area of alcohol use, based on some of the testimony we heard
at the last meeting, there is a suggestion that certain
lifestyle changes might be important.
PARTICIPANT: The effect of outcomes on
(inaudible).
MR. CAPLAN: Effective outcome, yes.
PARTICIPANT: [Comment off microphone.]
MR. CAPLAN: Fifth fact, certainly one that is
very relevant here, the availability of new therapies. So,
this is our interferon, maybe other things as well, but this
is different. It is certainly a material fact that makes us
think perhaps it is time to revisit the policy about
hepatitis-C.
The sixth that I could come up with was the
emergence of new techniques for assessing hepatitis-C. This
is the new PCR technology that looms. It is part of the
reason why, even though Mike has pointed out a number of
times that it may not make obvious sense why we are doing,
or talking about prospective look-back right now, maybe it
does if we are going to pick up more cases than we did not
see, and some of the information you actually gave us, Mike,
this morning, kind of makes me think that there may be new
technologies that are leading us to detect hepatitis-C in
ways that we could not do even a year or two ago. Or, will
be able to do a year or two from now which might change our
record keeping and look-back, and practices.
So, those seem to me, those are the facts that I
generated in the privacy of my own slumber. Some of you may
want to add to those, but they seem to me to make -- if I
was trying to explain in simple language to an agency or a
congressman or a person from the general public, well, why
change the policy now? Why are we talking look-back, or
announcements or something? Some of these facts seem to me
to be the driving force behind that. It is not that we just
woke up one day and said, let's change the policy. It is
because we have this information that is making us want to
rethink, perhaps, how we have done things to date.
I am certainly open to altering those facts or
adding to them, or changing them. But, anyway, I thought
that might be a way for us to get going in terms of the
next, let's say, before we get to the break.
PARTICIPANT: [Comment off microphone.] The
Army's therapy (inaudible) is inadequate.
MR. CAPLAN: Yes.
PARTICIPANT: The epidemiology, as we discussed
yesterday, is not entirely worked out, it is a debate, how
many individuals are going to move towards end stage in a
relatively 10 to 20 year period, versus 40 years? So, there
-- I think it is important to also state in the fact
situation, that there are still some unknowns.
MR. CAPLAN: How would you want to -- I understand
what you are asking, I am just trying to think how to put
that. There is -- I mean, in one sense we could say, I
mentioned interferon. I should not neglect the fact, by the
way, we did have a ton of testimony last time. This is not
what you are asking, but I remind you, we did hear about
liver transplant last time as a therapeutic modality, from
Dr. Hoofnagle(?), and the prospect is there, one might say
that, new therapies and new knowledge about epidemiology may
be changing. I mean, that it is emerging, put it that way.
PARTICIPANT: There is rapid development of new
knowledge -- recognition of rapid development of new
knowledge in this field.
MR. CAPLAN: And you were talking about the trials
that you are running on different types of interferon and so
on, so it seems as if there is a shift in thinking
epidemiologically, and the prospects for even more improved
therapies may be in the offing, which will lead to some
policy changes. We might try a rapidly advancing knowledge
base, leading to the prospect for new intervention, and
better understanding of the epidemiology of the disease.
Dr. Guerra.
DR. GUERRA: I think a couple of other facts, one
is that it seems to be more prevalent in men than women, and
two, that it leads to serious liver disease at a relatively
young age.
MR. CAPLAN: Do you think those are new facts
relative to what was understood about hepatitis-C, let's
say, pre-19 -- I mean, is this part of this new
epidemiological understanding?
DR. GUERRA: It seems to me that, as we gather
more information, we are finding that the median age is
really quite young.
PARTICIPANT: I think one of the things that is
really important here is, not only do we recognize our
charge here with respect to transfusion, but how great this
disease is in terms of the number of people infected totally
in the country. We need to put that in relationship.
People need to know that there are in excess of four million
people infected. Transfusions represent a certain part of
that, but we do not want to lose sight of all the other
people and what we can do in terms of having them recognize
the need for them to be tested.
MR. CAPLAN: The way to put that is, if you are
amenable to this is, we did say yesterday that we have now
recognized that hepatitis-C is at epidemic levels, and it is
clear that the nation is going to move to try and grapple
with this health challenge, and this becomes a part of that,
and that is another reason why we are rethinking what we are
doing here, because we are not treating this as somehow a
transfusion-related problem only. It is unfolding against
the backdrop of the hepatitis-C challenge that is just out
there generally, and this has to become part of that.
I think that is true, that is a fact that is
absolutely moving this along, so we might put it, it is four
million people affected, Steve, but it is also, with efforts
being made to grapple with that epidemic, and so this, the
fact here is that we are trying to grapple with this problem
as part of the overall attempt to deal with this --
recognize -- now recognized epidemic of hepatitis-C.
We keep using that four million, I keep wanting to
say, at least four million. All those numbers of the
institutionalized and so on yesterday made me think that is
the conservative four million. Yes, Tricia.
MS. O'CONNOR: Just a small point here, but -- and
I am not saying it is a new fact, but in terms of this word,
epidemic, I would say, as opposed to HIV, HCV is something
that has been endemic in the population for a long period of
time, and it is only with the availability of these new
tests that we have the -- you know, can detect it, and
measure it in some way and follow its natural history in a
much more precise way than we would previously. Because HIV
and HCV are very different because of HIV being recently
introduced and truly taking on an epidemic course.
MR. CAPLAN: The recognition of a problem as
opposed to the emergence of a problem. Jim?
DR. AUBUCHON: Would the committee be comfortable
in adding to this list of facts that, the recognition that
traditional look-back methodologies have limited
effectiveness and/or efficiency?
PARTICIPANT: I would not agree to that.
MR. CAPLAN: I was tempted to put into this list
of facts, something about a recognition that record-keeping
and the American health system is less than optimal, leaves
something to be desired, could be better? I did not quite
know how to phrase it. I know what --
PARTICIPANT: (Inaudible) limitations of record-keeping --
MR. CAPLAN: There are severe limitations on --
PARTICIPANT: (Inaudible) recognition of severe
limitations in record-keeping.
MR. CAPLAN: Yes. By the way, I was not sure, and
just as a matter of fact clarification for me, did I hear
yesterday that there was a seven-year legal requirement to
keep records, or that is just convention, that a lot of
places throw things out after about seven years? Does
anybody know what the real --
PARTICIPANT: (Inaudible) real element there of --
MR. CAPLAN: Yes. Jay, do you know?
PARTICIPANT: A lot of establishments are required
to keep records for five years, however what was at issue
yesterday was the length of record-keeping by hospitals, and
that is much more variable.
MR. CAPLAN: Right. But is it -- there is no
seven-year statute or --
PARTICIPANT: There are hospital records that --
not to my knowledge.
MR. CAPLAN: Yes, it is not like the IRS or
something, we have to keep tax records for years and so
forth. Yes. Well, at any -- be that as it may, record-keeping
certainly does leave something to be desired, or has
limits that have to be recognized, and that may be a way to
bridge this issue. Ron.
DR. GILCHER: I want to come back to what Mary
said. I think it is really important that hepatitis-C has
been endemic in the population, but we did not have a way to
recognize that until just recently. And I am going to shift
gears for a second and go to HTLV in Japan, exactly the same
thing. What was recognized for a long time was the leukemia
that occurred from it, and ultimately that led to the
discovery of the retrovirus that caused it. But what I am
really leading up to is, the Japanese have in fact found a
way to intervene and in a matter of two generations they
expect to eliminate this virus from their population, simply
by preventing the vertical transmission, that is, breast
feeding.
Really, what I am saying is, it is important, what
Mary said, but also that we now have a way of detecting it,
and potentially interventional therapy could eliminate this
from the population. So it goes, again, beyond the
transfusion-transmission portion.
MR. CAPLAN: I think we do have to get that
phrasing right. It is that we have a situation in which we
can now detect the fact that four million people are
affected, as opposed to the emergence, the burst of some
sort of epidemic.
I would say the second part of what you are
saying, Ron, I am trying to capture with this phrasing of
evolution of new knowledge and the prospect for new cures.
It is basically, there is a hope, not just a fear, a hope
that maybe we could intervene to do things that would reduce
viral load, or allow people to clear the virus and so on,
either with some current therapies, but more likely with
some emerging therapies.
DR. GILCHER: But, what I am saying are initially
two things. Not only the chance to cure the disease with
the new therapies, but also to prevent further transmission
of this disease within the population, because we did not
know that in the past, that is why it is endemic. And now
we have a way to prevent further transmission, not only cure
those potentially who have it.
MR. CAPLAN: Mike.
DR. BUSCH: Yes I would suggest perhaps two
different areas of facts, bullets if you will, one HCV
general fact, most of these are that, the level of
endemicity, the ability to now detect the virus, all the
issues about available treatments, understanding of natural
history.
Then a second which is the issues related to
transfusion and HCV, which could talk in a little bit more
detail about how the risk has actually been reduced over the
last several decades, since 1992, with the availability of
the current generation, test risk is exceedingly small, get
into the issues about ability to track recipients is
problematic due to issues such as availability of records,
etcetera. And perhaps get into some of the issues in a
comfortable fashion that Jim raised, about mechanisms to
communicate historical risks are problematic, and the
options are --
MR. CAPLAN: Certainly could sort some of these
facts along those lines. Let me just suggest this, so that
we do not proliferate facts, always feared by philosophers.
Proliferate opinions, not facts. What I would like to see
us do maybe a little bit is steer ourselves by the facts
that are new or materially relevant to explain to someone,
not part of this group, sitting on the outside, why did you
take a look now? Why were you revisiting this? I am
certain there are a bunch of facts we could get into about
the tests and so on and their accuracy and what could be
done. I am not sure that is what I set up the problem is
with. It is sort of, drive it with the facts that tell
somebody, why are you taking a look at this now? What
shifted, what changed, what is it that is making you rethink
this situation?
I think if we do that, the public, the agencies,
congress will be in a position to understand, oh, well, they
did not have these practices in place before, was that
because they were venal, is that because they were stupid,
is that because they did not care? I suspect not, I think
it is partly -- well, a lot because, we've got a factual
situation that is evolving, and that is what I would use to
edit what we have in this section, sort of driving it by,
here is what made us think that it was time to rethink our
public policy, rethink the challenges that PHS faces and so
on. Other things that you might want to get up there. Yes,
Bill.
DR. HOOTS: But just in terms of kind of
constricting some of these to put up, up higher, up on the
list, really, the ability to test accurately that allowed to
actually classify and clarify and characterize the endemic.
And a lot of the things that are below the black dash mark
up there, are things that actually come under that context,
and could actually be listed at --
MR. CAPLAN: Under there, or part of that.
DR. HOOTS: As in number seven, just in terms of,
because that really -- I think understanding just how big an
endemic this really is, is clearly driving -- one of the
things that is driving our decision-making.
MR. CAPLAN: Yes. And it is clear -- I think that
is right. I think part of the push to grapple with this
now-detected problem, generally speaking, of hepatitis-C is
fueling attention back to, so what about the transfusion-related
causes, but without the former, I would not have a
look so much at the latter, and so I think that is right.
We have to capture that as relevant here. Others?
PARTICIPANT: Just a question about order. If you
put 1992 first, my first reaction would be, well, what have
you been doing for the last five years? So, while
everything there is right, perhaps not focusing on 1992 as
the very first thing we put out.
MR. CAPLAN: Yes, I thought of that. It did make
me think sometimes, what are we doing with it? On the other
hand, I am certainly willing to drop it down. I have no
love of that being the number one fact, but the -- I think
what happens in part with these new tests is, you get them,
they disseminate, people understand them, they trust -- it
sort of, it appears in 1992, but it kind of absorbs or what
I guess the technology calls, diffusion. It takes awhile,
but I understand what you are saying.
PARTICIPANT: We know that, but the public does
not, necessarily.
PARTICIPANT: [Comment off microphone] by the new
test.
MR. CAPLAN: Starting in 1992, something like
that. Yes, Dr. Guerra.
DR. GUERRA: Part of the epidemiology discussion
also relates to, what do we know about the distribution of
this virus around the world? And we heard some
presentations from some developed countries, but what is the
rest of the information that is out there?
MR. CAPLAN: Yes, Jim?
DR. AUBUCHON: If I could suggest that there is an
element of timeliness related to the fact that the NIH
consensus recommendations, only just issued in March of
1997, providing a firmer underpinning to directing people
toward testing and possible therapy.
MR. CAPLAN: That is certainly true, and we could
list it as an issue there, that we have had the emergence of
a consensus report, that has made specific recommendations,
and that is driving us to reexamine. I think I could -- I
think that is probably true, too. That is part of that
general recognition of the epidemic and where this fits in.
But the appearance of a major consensus report is certainly
a relevant fact.
PARTICIPANT: I think it is important to recognize
that no therapy was available until 1995(?), that is when it
was licensed, and the fact is that, at that point in time it
was licensed for the treatment of non-A, non-BC, because we
had retrospectively, basically, looked at those patients,
and that was with the first gen test, and they looked to be
C patients.
I think the intervening time between 1992 and 1997
has been a time of data-gathering, to see, indeed, if this
therapy, although not what we would like it to be, had real
efficacy, I mean, in the sense that the original trials did
demonstrate efficacy, but as we began to be able to look at
the virus itself, to see whether we could eradicate the
virus, which is the gold standard.
So, there is a period of time in there where we
had a therapy that was being used, and undoubtedly
benefitted people, but now we can actually look at the virus
and say, yes, the virus is gone, and based on this premise,
we hope, as Dr. Gordon said yesterday, that you will not
have any more sequelae in this disease. So, I think that,
you know, you can explain that five-year period between the
NIH consensus conference and 1992, and I think therapy has
really been used since about 1995 when we could look at the
virus, in that era when we were really able to do PCR and
some other things, and see that we could eradicate the
virus, and that there was a long-term benefit for this
therapy.
That somewhat explains why the --
MR. CAPLAN: Hence, the time.
PARTICIPANT: -- tests, the therapy, and the
virus, do not all fit together.
MR. CAPLAN: Yes. I am not ignoring that, I am
just trying to -- I am mulling over a way to get that
clearly put in there. One of the things we will do is, as
we come up toward the break here, I am going to ask Steve if
he could just meet during the break with maybe Mike and me,
and we could see if we could recast some of these -- get the
language sorted out a little bit in there. Yes.
PARTICIPANT: Yes, I think we also heard yesterday
that there seems to be perhaps a natural shedding of the
virus in the very young individuals. I wonder if that is an
acceptable fact. That the younger the individual is, that
they seem to perhaps have a natural resolution of the
infection and seem fine. Wasn't there about a 10 or 15% I
think --
MR. CAPLAN: Self-clear?
PARTICIPANT: Self-clear.
MR. CAPLAN: What I would say there is, I think we
may want to capture this by, new understanding of the course
and incidence of the disease, somewhere in there. That we
understand more about its natural history, basically, that
sometimes it goes into remission, sometimes it goes away,
none of this understood before.
Let me see if I can sort of shift gears off this
fact discussion. Steve, if you would, why don't you put the
Hoots draft back up there for a second? Having now attained
clarity about the way the world is, perhaps we are in a
better position to look at some of the principles and
recommendations that we were talking about at the last
meeting.
I have one suggestion, which is that we are going
to move statement two out to a more preamble, or
introductory-type statement. It seems to me -- I have one
other suggestion about the draft as it is there now. See
recommendation three? Or, excuse me, principle three. It
says, all recommendations made by the advisory committee
should be ever-mindful of a wise stewardship about the
public monies and energies.
I know what we are talking about here. I think
what we need is language in those principles, that actually
are principles directed to the agencies, not to us. This is
a binding principle forever, to make the committee behave in
a certain way. That is nice, but my suggestion is, we now
want to get all those principles in the form that says, all
recommendations, or all actions taken by government agencies
should be ever-mindful of the wise stewardship requirement,
we are not obligating ourselves, we want to tell them what
to do in terms of policy, so that is an obvious change I
thought of that we could stick in there. I do not think the
principle is bad.
I had one other one, that we are basically
following these principles out there, two of them there now,
if we do that, which is that there is an old ethics
principle that says, treat like cases alike, and it has come
up a couple of times. Dr. Penner addressed it yesterday
when he said, well, we cannot discriminate against some
people just because they are unlucky, they have records,
they do not have records. They are in a situation where
they could be traced, they are not.
I think we might want to go with a principle that
says -- do not write this yet, Steve -- but it is to the
extent possible, people who have -- who are known to have
received, or been exposed to, hepatitis-C through
transfusion, should expect fair and equitable treatment. In
other words, what we are going for is, some affirmation
that, if they are not able to pay, if they cannot afford --
Well, remember we were yelling yesterday, but we
have to say something that says, geez, you cannot just say
to everybody, well, you know, maybe you were infected.
Sorry you cannot pay for tests, sorry you cannot get
treatment. Sorry the health system is not what it should
be, see you later, but we told you. We want to make sure
that we have a principle in here that says, every measure
must be taken not only to inform people, but to treat them
fairly and equitably and to get the access to the services
they need, or something like that. I am struggling for a
principle that commits us to, not just leaving people
hanging out there with a warning and then -- not that this
does not happen in the healthcare system, but, yes, Jim?
DR. AUBUCHON: Relating to your redirection of
principle number three toward the agencies that would be
implementing these recommendations, can I toss the hot
potato to our colleagues from the FDA? Because the word
from the FDA has been that, they are not allowed to regard
cost when making recommendations. They will focus only on
the safety of the blood supply, or safety of recipients. So
the recommendation, if just issued in that form from us to
them, would not be able to be implemented by them. Am I
reading your philosophy correctly?
PARTICIPANT: I will comment on that. I think you
are, the answer to your question is, yes. And in fact, one
of the founding reasons for this particular advisory
committee was to get a broader scope, other than the Blood
Products Advisory Committee, which had in the past
considered some of the issues, and then was redirected to
strictly deal with the scientific facts, and not to look at
the economics of the situation. It does put us in a bit of
a Catch-22, to be quite honest.
PARTICIPANT: Also, with regard to redirecting it
back to the government agencies, I am not sure that it would
totally leave the committee off the hook, in the sense that,
no, the committee does not have direct command of a certain
dollar amount of money that can be dispersed in a way that
we might, the committee might see fit, but I think the
public is looking to us to come up with recommendations that
are viewed as fair, reasonable, practical, prudent, and I
think there is some -- in considering that, there is some
element of cost, you know, because you have to consider, I
think the committee has to consider -- as Kathy said, I
mean, we have that duty, I guess, or responsibility to -- it
is not going to be, certainly, the driving force, but it is
a consideration, because if you recommend -- the committee
recommends something that could translate into billions of
dollars; you know, let's send a letter to every person who
got a transfusion from -- I am going to say something really
unrealistic -- 1970, you know, when the risk was truly quite
risky. Then that could ultimately translate into a lot of
dollars. I see the committee -- you know, I am sure the
committee, can we get entirely off the hook?
MR. CAPLAN: No, but a thought on --
PARTICIPANT: Yes, well, just kind of where this
came from is, out of our committee title. I mean, we are
not only safety, but also availability, and tied up in the
concept of availability are resources and energies. And
that is kind of why that is in there, just to make sure that
we have to balance, always, but always err on the side of
safety, but still balance the completeness of availability
of these life-saving therapies. And products.
If we go to the extreme on safety, there is always
(inaudible) this, because we as a government, or we -- well,
not, we, but, well, actually, I guess we are government
employees in this context -- but, government agencies go to
the extreme, even the FDA, and I think, certainly in the
context of BPAC(?) and everything else, FDA has always said,
yes, safety, but there has always been the concept of
availability, and availability, I do not think you can
separate from energies and resources.
MR. CAPLAN: Mike, then Eric.
DR. BUSCH: Yes, I think all of these issues here
in one, two, three, should really be a part of the preamble,
the mission of this committee. And in fact, the preamble, I
would suggest, might be something that we would develop
which would be a common preamble to all of the issues this
committee addresses in the future, and then the facts
related to specific issues that we are dealing with, and
then the principles, how our mission uses these facts to
develop principles related to the specific question at hand,
and then the recommendations.
I do not know that any of these up here, perhaps
other than this (inaudible) obligation to try to get to
everybody, but maybe basically, we try to translate the
principles, using the facts into the principles specific to
this issue. But I think all of these could nicely fold into
the preamble, in that sense that, you know, the requirement
or the need to deal with stewardship, etcetera, is very
appropriate for our committee to acknowledge it as our
responsibility.
MR. CAPLAN: Eric?
DR. GOOSBY: I was just going to say a similar
thing, so I will just abbreviate it. The committee is
charged to come up with what the collective consensus is on
these issues, with the commitment to being clear in
articulating, once that decision has been made, I think the
risk that is still afforded the individual around whatever,
you know, blood element you are considering. That is such a
fundamental prerequisite to the activity or work of the
committee, that you are committed to a clear articulation,
delineation, of the risk, once you have decided what is the
reasonable activity, okay, in terms of the look-back, how
far, what you are going to look at.
Hand-in-hand with that is that there be a clear
communication of, at that point, the afforded risk. So, a
commitment to what Dr. Maibach was referring to in his
discussion, to communicate once that final decision has been
realized by the committee, what the afforded risk is, I
think is what you are being asked to do. And that could be
a generic thing that could go over in a preamble, as Michael
was saying.
MR. CAPLAN: Alright, I have a suggestion just for
fun. We are getting out to the break, and that would be a
time for great minds to meet. Let's gamble on something.
Let's take a look at the actual, substantive,
recommendations that are on the rest of this sheet, just to
get us to be able to talk a little bit about something when
we get out there, if we haven't got enough to say about
facts or principles, or what might be in the preamble.
Let's do them one at a time. There is a
recommendation there about perspective recipient
notification, being implemented forthwith. I am just
curious to see, just on that recommendation one, does that
hold up, are people still comfortable with that? Are there
any refinements of language that come to mind about that
particular proposal? Sorry, times up.
PARTICIPANT: Well, I think the concept of
prospective look-back to seroconverting donors, the truth
is, if you do the numbers and you run the experience, it is
extremely low yield, but it is a safety valve to unsafety,
and perception is good, so I think we have to do this.
PARTICIPANT: I agree. My only comment was one of
wording, the second-to-the-last line, be notified to
facilitate HCV testing, and potential treatment of the
recipient. It is not so much the units that we are worried
about at that point, we want to test and possibly treat the
recipient, exposed to -- potentially exposed recipient.
MR. CAPLAN: Carolyn(?), I see your hand up there?
DR. JONES: I had a comment, and it was not
confined to item one (inaudible). If we want to have a
general preamble that sort of is the committee's (inaudible)
or what our position is going to be, or policies, or what
our structure is going to be for addressing blood issues. I
think it would be more appropriate to move number four, your
additional one, down to the recommendations section and say
that, if we have some perspective notification of
recipients, or we have some sort of look-back, that there is
some sort of requirement, moral obligation, to allow these
people, or to provide people who do not have access to
medical care, some sort of treatment or follow-up testing.
I think that should be a part of the recommendation, rather
than in the upper section.
MR. CAPLAN: Yes, that makes sense to me.
PARTICIPANT: We have not talked about the
recipients here, and this is in the prospective aspect. And
at one time we discussed the possibility of having an
educational program for patients who are hospitalized who
may -- or who have received blood products. In other words,
the onus should be placed on the hospitals to provide some
instruction for individuals as to risk factors, when they
are going to receive the blood, or, if they have received
the blood. That would be one element that I had considered
adding in there.
MR. CAPLAN: Did you mean to add that to one?
PARTICIPANT: It would be at one or two, could
even be at two, because that is part of the educational
program.
MR. CAPLAN: Why don't you scrawl on the bottom
down there, Steve, see under three, you can put three-B or
something. Let's see, I better phrase that. The importance
of enhancing consent on the part of blood recipients.
Knowledge or -- and while that is moving up there, let me
ask if --
PARTICIPANT: May I add one more on that, before
we get off of it, and that was, the possibility of obtaining
a blood sample on that patient who does receive blood for
testing for hepatitis-C. I would like the group to think
about that. It would be, we always get the blood sample for
type and cross-match. We could set aside that sample, and
the HCV assay could be obtained. So that we would have
documentation, then, of whether the patient was positive to
begin with. Then that would give us the alternative, or the
option, of obtaining a sample of six months or wherever, to
determine whether the patient had contracted hepatitis-C.
PARTICIPANT: [Comment off microphone.]
PARTICIPANT: Pardon? It would be a baseline
blood sample.
PARTICIPANT: How long would the hospital keep
that?
PARTICIPANT: They would not have to keep it, they
would run it.
PARTICIPANT: They just test it.
PARTICIPANT: Anybody who gets blood should have
an HCV test done.
PARTICIPANT: Why limit it to HCV?
PARTICIPANT: You wouldn't have to, you could get
it broader than that, but I think, specifically, we are
trying to address this problem, that is why I bring it up.
But the testing that would be done, at least would document
whether a patient is coming in with HCV. If they had
received the blood, or even beforehand. Then one has the
option of going back, if you find that the donor was
positive, at a subsequent testing, of going back and saying,
well, this individual was negative to begin with, and we
know when the patient received the blood, therefore, if the
patient is positive now, six months later it must have been
due to the blood -- or, is more likely due to the blood
product, that is all.
MR. CAPLAN: Carolyn, and then Mike?
DR. JONES: It sounds good in the abstract, but I
think there are some privacy issues related to doing that,
and I do not know that we want that information just --
DR. BUSCH: It would be the same as when we are
doing the biochemical profiles. It would be information
that would be available to the patient, and it is obvious
the hepatitis-C business would be typically what we obtain.
PARTICIPANT: You know, that speaks to a much
broader public health case-finding program. The prevalence
of HCV in hospitalized patients, we saw some data yesterday
that was just startling, it was like 20-some percent. So --
in your transfused population. Pre-transfusion, you are
going to have anywhere from a 2 to 20% prevalence, just a
background prevalence of the infection. And the incidence
in the community, hepatitis, in the general population, let
alone in hospitalized non-transfused patients, is probably
one or two logs greater than the risk of blood.
So, even if you had a seroconversion that
occurred, you know, it is not to my mind presumptive
evidence that a transfusion of current screened blood caused
that. And just the logistics, I mean, basically what you
are talking about doing is implementing on a routine basis,
the Hopkins Houston Study that I alluded to, which focused
two or three hospitals, cost $20 million over the course of
two or three years to conduct that kind of activity. It is
a massive undertaking. You have to then manage those
infections.
MR. CAPLAN: One way to handle this, if we are not
ready to get agreement on whether it is a good idea to seek
baselines, is that we certainly could ask the agencies to
explore the desirability of having a baseline. I mean, we
can come back to that one, that may not be -- if it is up
for both privacy and cost concerns, we can certainly ask
that it be explored.
PARTICIPANT: Which agency would have jurisdiction
over the samples from a hospital patient?
MR. CAPLAN: Over exploring that one? I have no
idea.
PARTICIPANT: I submit that if I were the surgeon,
I would want to know whether my patient was hepatitis-C-positive
to begin with, before I take him into surgery.
PARTICIPANT: This is getting into whether or not
all hospitalized patients should be tested for HIV, as well.
PARTICIPANT: Right, right.
PARTICIPANT: And a whole list of other
infections, which has not generally been the public health
perspective that the country has used, so I am very antsy
about -- and anxious about moving in that direction.
Clearly, hepatitis-C infection in the community needs to be
recognized, there needs to be increased awareness on the
public's and provider's, healthcare provider's parts to pick
up hepatitis-C, but I am not sure that we want to recommend
essentially a nationwide screening program for hepatitis-C.
The CDC might want to do that, but I think that is beyond
our purview.
PARTICIPANT: [Comment off microphone.]
Recommendation number one up there, one of the situations
that is not outlined is, what do you do if there is not a
prior negative test?
PARTICIPANT: [Comment off microphone.]
PARTICIPANT: What if it was a donor that last
gave before testing was implemented, and so on. I mean,
there's --
PARTICIPANT: [Comment off microphone.]
MR. CAPLAN: Comment on that, what if we have a
donor who has come back after six years, or a long time ago,
or never?
PARTICIPANT: In the context of HIV look-back, the
same issue was encountered, and we recommended a five-year
retrospective search, based on the five-year requirement for
record-keeping. But I think that the practical limit for
how far back to go is availability of records, and a choice
can be made whether to arbitrarily limit it to some number
of years, or whether to recommend a minimum number of years,
or as long as records permit.
MR. CAPLAN: One of the things I think we are
going to run into when we get down to the next page of our
recommendations, which I would like us to take one look at,
just before we go out of here, if you could flip that
recommendation forward.
PARTICIPANT: [Comment off microphone.]
MR. CAPLAN: No, I am going to come back to that,
but it is in the spirit of this, how far back should we
look? One of the things that is up there is, we do not
recommend targeted look-backs (inaudible) transfused prior
to 1990. I expect us to have a big, knock-down, drag-out
about whether that sentence stays there, but one way to be
consistent is, just as you look at this number four language
that was up there before, if we are going to use terms like,
as records permit, or as documents permit, that may -- if we
do that here, I want you to think about, that maybe the
answer to what to do under number one, that is what I was
getting at.
If we go with a standard that says, well, we are
just going to look back according to some time limit, five
years, seven years, ten minutes, whatever it is, as a way to
think about possible look-back obligations, to be
consistent, one possibility is that we say, you have to look
back to the extent to which records are available, or
records make that possible. So if that is how we are going
to go, we may want to be consistent about that. Because I
am leading toward thinking, the language I would like to see
personally in one is, to the extent records permit, without
getting into the five-year -- so, it may be different,
depending on who it is and where it came from. Military may
be different from the average hospital.
PARTICIPANT: As a hospital, that is blessed with
an excellent record-keeping system, that language could
conceivably cause me to go back into the 1960s.
MR. CAPLAN: Before.
PARTICIPANT: Because we have the capability of
doing that, and I am not sure that is really worthwhile, but
if that is the recommendation of this committee, I will
probably feel compelled legally to do that. So, I would
prefer that the committee take its responsibilities of
stewardship, and set some reasonable time limit, but
specific time limit, as to how far to go back.
MR. CAPLAN: You are going to be in that category
that we saw from those slides of Britain, where there were
those outliers marching back into the late sixties and so
on? Yes, Paul.
PARTICIPANT: I guess somewhat in the same tone, I
hoped this would not happen, but I would not like to create
the perverse incentive, which would then say, do not keep
records. So, I have added, the availability of records
permit, within a period of seven years, or -- we can say
whatever years we are willing to accept, but I think
something like that -- would that give you a limitation that
would allow you not to go back to 1944?
MR. CAPLAN: Mike?
DR. BUSCH: Yes, I think all these times -- there
is a whole separate issue besides record availability, which
is, the relative risk, and the risk in the pre-1990 and
potentially, 1990 to 1992 period, was so much substantially
greater than today, and the look-back I see as kind of the
contemporary way to deal with rare risk, whereas the major
effort that we have been talking about is to focus, to try
to find the majority of people who were exposed in that
earlier period, and even if records were available prior to
that date, the yield of that process, in terms of the
proportionate number of infected people and absolute number
per dollars is going to be so much lower.
I think drawing that line at about five years or
seven years, is consistent with that date of 1990 to 1992,
when the risk during that early period was substantially
greater, and a different message needs to be, a different
strategy needs to be pursued to detect those people.
PARTICIPANT: And that gets to number three, and
actually, what I was going to propose in three is, make it
much more aggressive, to see if the committee would go
along, in context of the dialogue we had yesterday about
this very issue, which is that, every effort -- first of
all, number three, I would change to begin with.
Identifying all significantly at-risk individuals, or
individuals at significant risk, and not exclude -- I mean,
include -- being all-inclusive, not just people who have
been transfused.
But, for the transfused individuals, that efforts
in number two, or number three, that three-B which John was
talking about, be undertaken to identify by whatever
educational means necessary, individuals within the United
States who have been transfused, for advisement to come in
for testing for HCV. Which would cover all the ones --
MR. CAPLAN: Let's hold on that for a second now.
I know we will get some discussion of that.
PARTICIPANT: But it is directed in -- I mean,
obviously, you do not have -- if you are going to do that,
you have thrown a much wider net, and you do not have to go
to esoteric details about the record-keeping, how far back
it goes.
MR. CAPLAN: Let me ask this. And I will drive
you forward with the prospect of letting us break. Would we
agree just for now on recommendation one, for the twelve
months prior to a situation we do not have it, that people
ought to trace records back, at least for five years? I
mean, is that a cut-off that you can all -- it will get us
towards this notion of, as records permit, for up to five
years, is that a reasonable --
PARTICIPANT: No.
MR. CAPLAN: No? What would you want to see
there?
PARTICIPANT: I think the records do go back
beyond that. I think blood centers have records that will
go back to 'way beyond that, certainly since the inception
of our blood center. On the other hand, the limiting factor
is the hospital.
PARTICIPANT: [Comment off microphone.]
PARTICIPANT: That is going to vary, then,
somewhere probably around the seven-year -- five- to seven-year.
MR. CAPLAN: Want to make it seven?
PARTICIPANT: Seven?
PARTICIPANT: At the hospital level.
PARTICIPANT: Probably be more reasonable. My
hospital keeps it about seven.
MR. CAPLAN: So, let's put -- at least we will
answer it in the spirit of that. We have also opened the
door to this notion, which I was hoping we would get to a
little bit of linking look-backs to some notion of record
availability. So, why don't we take our break? What we
will do is, during the break, Steve and maybe Paul, Mike and
anyone else who wants to, can peer at that first sheet of
the facts. We will probably try and rewrite that overhead
for you to take a look at when I come back, then we will
return back to the recommendations. Work those over a bit
more, and oddly enough, following in some logical sequence,
we will decide what we want to do and then come up with a
preamble to justify it. A little humor there for you to
take away. Alright.
[Brief recess.]
MR. CAPLAN: -- get back underway. If I can get
the committee back. What I asked an elite corp of
wordsmiths to do during the break, was to try and compact
some information in the interest, again, having taken some
of the admonitions we heard about -- be simple -- seriously.
What you see up here is an attempt to take some of
our fact discussion from the morning, put it into both a
preamble and fact statement. This would come in front of
the recommendations. It is carrying a lot of weight in a
relatively small number of words.
It may not have all the details of your particular
fact that you were enamored of before the break up there,
however, the driving purpose at this point in the document
is to both explain why now, to somebody who might not be so
certain about why we are thinking about changing public
policy with respect to hepatitis-C, and narrow it down to
those facts that people can manage, in a relatively simple
dose. Steve, do you want to read that thing? We recruited
you for your penmanship and --
PARTICIPANT: I didn't have to have penmanship to
take this job. The introduction of a new [comment off
microphone] improved blood test for hepatitis-C virus in
1992, has substantially reduced the risk of acquiring this
disease from transfusion. Subsequent experience with this
test has revealed the following.
Number one, about four million in the U.S. are
infected.
Number two, many are unaware of their infection
because of [comment off microphone.]
Number three, [comment off microphone] causes
cirrhosis, liver failure, and hepatocellular carcinoma.
Four, the risk of HCV (inaudible) prior to the
introduction of the improved HCV test.
The availability of new therapies and knowledge
reinforces the concept that blood recipients have the right
to know the risks associated with transfusion of blood and
blood products and, specifically, any unique risks related
to the (inaudible) quality of blood products they received.
That (inaudible).
MR. CAPLAN: And so, what we are trying to do here
is say, in an, again, compact form, here is the situation
that has shifted? This is a factual summary about why we
are rethinking what our duty is to those who have received
blood. We are trying to also put it in the context of the
general awareness of hepatitis-C, which did not exist prior
to the availability of tests, and maybe we have said enough
here, too, I hope, about the availability of new therapies
and new knowledge, without detailing it, to let people know
that that is also fueling our interest in making these
recommendations.
The point is, I am not saying we cannot wordsmith
or ask questions about whether this is right or whether you
liked something else better, but please keep in mind, as we
try to do this, that I think succinct is going to be
important, and I think the reason for picking out facts, is
not that we just know information, but it is to present the
facts that have made us offer the recommendations. That is
what we are trying to do is, link the one to the other.
Let's go to Trish and then we will just start coming around.
DR. O'CONNOR: One concern of the statement of the
blood test in 1992 reducing the possibility of transfusion,
and then about four million people in the U.S. are infected,
to me, implies that they all got it from the transfusion,
and that is a concern.
PARTICIPANT: -- from a variety of cause
(inaudible) --
MR. CAPLAN: Yes, go ahead, Keith.
PARTICIPANT: One way to go would be to go from
generic, in terms of this preamble to specific (inaudible).
MR. CAPLAN: Could do it that way.
PARTICIPANT: Because and then, the other thing
that we did not put in here that we had (inaudible) list(?),
was to the benefits of changing lifestyles and the potential
benefits of (inaudible) should be included as well.
MR. CAPLAN: That is what I was hoping -- the
availability of new therapies and knowledge --
PARTICIPANT: Oh, okay.
MR. CAPLAN: I am fishing in there about
lifestyles, I do not know how much we have to spell it out
there. Maybe we do. I am actually editing myself here, in
the interests of fairness. Let's see, Mary?
PARTICIPANT: Just a couple of thoughts, one is,
about the statement that is number one. I think you could
clarify -- add a clarification for Trish's point, which is a
good one, by simply stating that, about four million persons
in the U.S. are infected, of whom 7% acquire their infection
-- are estimated to have acquired their infection through a
transfusion. So, that would provide some information and
provide the clarification --
MR. CAPLAN: I see a lot of heads nodding on that,
that seems --
PARTICIPANT: One other comment in that sort of
introductory phrase, from which these one, two, three, four
statements follow. I am not sure if it is a bit of an
overstatement to say, the introduction of this test
substantially reduced the risk of acquiring disease, because
I think as Mike Busch's presentation showed us, there are a
lot of other things that happened in the seventies and
eighties that really impacted on risk reduction for HCV,
through transfusion.
The test allowed us to identify with more
precision, who was infected. So, it -- I think -- and that
may not be the best way to state that, but that is what I
think the test allowed us to do.
PARTICIPANT: [Comment off microphone.]
MR. CAPLAN: Has contributed substantially to.
PARTICIPANT: [Comment off microphone.]
MR. CAPLAN: Yes, it is certainly causally there
as a -- why don't we try, Steve, has contributed
substantially to a reduction? It probably did do that, no?
PARTICIPANT: I am not sure it did(?). Actually,
the test in 1992 did not have much of an impact itself on
the reduction in the risk --
MR. CAPLAN: You think it was still the behavior
before?
PARTICIPANT: -- from transfusion. The major
reduction really even took place prior to 1990.
MR. CAPLAN: You mean, from the big [simultaneous
discussion] --
PARTICIPANT: That is right. So, by the time 1990
and the test came in, the risk was already below 1%. And we
are talking about risks in 1980, of 10 to 20%, so, you know,
that is just not really the issue.
MR. CAPLAN: Alright. Let's do it then, has
contributed substantially to the ability to detect.
PARTICIPANT: Exactly.
MR. CAPLAN: Contributed substantially to the
ability to detect.
PARTICIPANT: One option would be to have a first
sentence relating to the fact that, you know, over the last
several decades, the number of measures that have reduced
the risk, and then the second sentence could be, in 1992,
the development of a very accurate test, both reduced the
risk substantially, and allowed us to address many of these
other questions.
PARTICIPANT: That takes it away from what you are
trying to do here, which is, to define the reasons for
proceeding at this point. And I think you want to make a
strong impact at this level, don't you?
MR. CAPLAN: I do not want to assign magical
powers to the test that it cured people, I understand that.
What I am trying to say, I think is, that because the
ability is there to detect the disease much more accurately,
that has led us to want to take a look again.
It is not -- I mean, yes, true the disease
incidence was dropping. I remember that big dive in the
curve prior to 1990, but I think it is this ability to
detect that has us in a corner(?), moving here right into
this group(?).
PARTICIPANT: [Comment off microphone.]
MR. CAPLAN: Not only that, but that is one of the
factors. Yes, (inaudible).
PARTICIPANT: I personally like Mike's
introductory statement at the beginning of the fact, I think
that would show where we have been going over the last
several decades, and that this has been a focus of blood
bankers for some time.
I would also suggest that at the end of these
facts, to state something such as, therefore, it is entirely
appropriate that the first action of this committee, the
first consideration of this committee, has been to look at
hepatitis-C risks in transfusion recipients.
In order to clarify that we have not -- as several
of us discussed at the break -- we have not been around for
20 years, waiting for this to happen. We are a new
committee, this was the first thing on our agenda, and we
are dealing with it.
MR. CAPLAN: Yes. Alright, I may actually ask
Mike if he could take his pen out right now and try and
craft that first two sentences. He can slip it quietly to
Jim, then we can get it up on the board. I love this
editing on the fly type thing, wonderful thing. I will have
other assignments for more of you later in a minute. Write
the Magna Carta.
Any other comments on other aspects of what is up
there, does that seem to capture enough to get us set up for
the recommendations? What we are looking for here is
something that would be, again, pretty simple statement.
Here is why we convened, here is what we are
doing, we are not sort of laying on the tasks, per se, but
these are the facts, and a little bit of history that led us
to make these recommendations. So, we are moving that way.
We have kind of excised principles, moving them
more toward the recommendations, to the extent we have them,
and that -- we are producing a document that is certainly
under ten pages at this point, which I think is good, maybe
under five, depending on how things go.
The idea now is to preamble it, set it out with
the facts, and then move to the recommendations. That is
the structure you have, just so you have it in your head
here. Mary?
PARTICIPANT: Fact number three, HCV is a major
cause of cirrhosis, liver failure, and hepatocellular
carcinoma. I believe that is a bit of an overstatement, and
I would ask others who perhaps have more technical expertise
to suggest a rewording, but, I think that somewhat
overstates.
PARTICIPANT: One of the major causes for death --
PARTICIPANT: It could be -- you could just say it
is a major cause of chronic liver disease, or a major cause
of liver disease -- well, actually, it is a major cause of
chronic liver disease, is what it is. And the problem here
probably is more with the hepatocellular carcinoma, it is
not a major cause of liver cancer in the United States. It
may be in other countries, but not -- it is a major cause of
other liver-related problems, but not liver cancer. So --
and it is certainly the leading reason for liver transplant.
So, you might say, chronic liver disease and liver failure.
PARTICIPANT: I think what Marian is saying, I
agree with Marian in that what she is saying, it is a major
cause of chronic liver disease, and I think the wording in
that could be used, which can result in liver failure, in
cirrhosis, liver failure, hepatocellular carcinoma, and
certainly, it is in this country, if you want to use that
word, major cause of liver transplantation. So, I think
that chronic liver disease is what we want to get at, that
is its major cause, or, it is a major cause of, and then
say, which can result in the following things that you have
listed.
MR. CAPLAN: And that is chronic liver disease.
PARTICIPANT: Chronic liver disease, right. And I
think what Leonard was telling us yesterday, is that he is
beginning to agree, and the data is saying, that
approximately 20% of these patients will, over the course of
their disease, develop cirrhosis, which then can result in
these other sequelae.
MR. CAPLAN: -- cirrhosis, liver failure, if we
can keep the hepatocellular carcinoma -- and I think that
will do it, that is fine. Others?
PARTICIPANT: Yes, possibly, the second [comment
off microphone] -- some (inaudible) certain (inaudible).
MR. CAPLAN: The question here is, do you want to
say something about spontaneous remission, sudden -- no,
okay.
PARTICIPANT: I think that dilutes the message.
PARTICIPANT: It is also a small fact. I mean,
you are talking about -- firstly, you are not saying in
there, how many people develop chronic infection to begin
with, you are just saying, this is the number of chronically
infected people, and the number who actually resolve, the
percentage could be 15%, you know, it could be as high as
30%, as Leonard pointed out, in one population.
The confidence interval around that, whatever it
is, it is a minority of those infected and again, it is too
much information, I think, for what you want to get across
here.
MR. CAPLAN: In writing these kinds of things, in
a group, one of the things that you want to do is you want
to pull this off when it looks like exhaustion is leading
people to a certain kind of agreement. So, after Ron, I am
going to ask Steve to take this away as a preamble that
might work, and I want to go back to those recommendations,
which is the nuts and bolts of what we have to do in the
next hour. And bang those around for awhile.
PARTICIPANT: Art, I would propose a new first
sentence to be added in front of the first sentence that is
up there, something to this effect. The recognition of
hepatitis-C, previously called non-A non-B hepatitis, as a
major cause of chronic liver disease in the United States,
has been facilitated by the development of a specific test
for hepatitis-C infections.
Then we can say the introduction, so that we are
putting the focus on the recognition of hepatitis-C, and
then we go to the introduction. So, the sentence I am
proposing would precede the introduction.
PARTICIPANT: That is a good point. (Inaudible)
infections. I also rewrote the first couple of sentences.
MR. CAPLAN: Still busy? I was going to ask you
about that assignment.
PARTICIPANT: Maybe I will read it. It is,
progressive measures over the past two decades have
dramatically reduced the risk of HCV infection from
transfusions. The introduction of the improved HCV test in
1992 has almost eliminated the risk of acquiring HCV from
transfusions, and has allowed for accurate detection of
infection in exposed patients.
MR. CAPLAN: Comments? Attempts to merge? I like
those two sentences that Mike just generated. Steve, while
you are copying that over, why don't we follow my plan of
putting the recommendations back up that we started to
evolve? I was going to suggest that two facts -- or two,
sort of facts come out here.
One is, we were talking at the break, some of us,
and somebody said, well, to what extent do we want to get
specific about our recommendations? Do we want to say that
it is PSAs and they should be broadcast between midnight and
six, or you know, make sure that it is in five major
languages, and six other linguistic groups? And I think the
answer to that is, no.
We could ask for something like the following, if
you wanted to. I mean, we are giving advice to the Public
Health Service and the agencies. We could say, look, we
would like to see a report about how you are going to
implement this by time X to take these recommendations
forward.
The committee would be very interested in having
some ideas about what you think is a -- based upon your
opportunity to do it more than in two days, a good education
campaign for healthcare workers, or a good education
campaign to reach out to donors.
I am not saying we cannot be somewhat specific,
but some of it we can say, look, work on it, and we want to
take a look at it. That is fair game to do. So that is one
issue. How specific are we getting? How fine-tuned? My
inclination is to be broad, but it is fair to ask agencies
to work together to come up with a statement back about what
they propose to do.
PARTICIPANT: I agree with that, but I would want
to add in, maybe also, some plan for evaluation of
effectiveness. That should be in the front end.
MR. CAPLAN: Then some of us were kicking around
at the break one other issue, which I do think is important.
It is not part of our recommendations up here yet. It has
to do with look-back and records which we are going to,
obviously, talk a little bit more about, about contacting
people and to what extent we do or do not want that to
happen as part of looking backwards.
I think it is important to understand, at least my
understanding is -- and people who know much more about this
should correct me -- but, what I believe to be true is,
records are often destroyed or disappear between a blood
bank and the hospital, coming from blood bank distribution
to the hospital, about where units went, after five, seven,
eight years.
Individuals, patients, have records about their
healthcare that are kept more than five or seven years in
most cases, in fact, I believe they are probably kept
forever in a lot of places. If you wanted to know whether
you had gotten a transfusion, because you were not certain,
or you were young, you could ask to see your records and
come, if you will, upstream.
You could go back to your original patient records
and say, did I get a blood transfusion when I was a neonate,
or when I was in this car accident, that I did not know
about? And we could ask people, or tell people, if you are
concerned about this, you might want to find out from your
records or talking with your doctors about whether you ever
had a blood transfusion, and it in theory could be done.
It would probably be expensive and a complete pain
in the neck for the hospital to go drag it out, but you
could get it. It is not true to say, there is no means of
getting information, the way I understand it, for an
individual who wanted, and was concerned about blood
transfusion in the 1980s or 1970s, to find out the answer to
that.
It is true that if we are going to use tracking
blood from the center to the hospital, there is a disconnect
in the ability to do that after a period of time. But it is
not true that there is no information anywhere that somebody
could, you know, oh, let me make up a hypothetical person,
say, a lawyer, could -- track back from records back to
receiving blood from a person who turned out to be infected
with hepatitis-C.
We do have to grapple with that fact. I do not
think we want to tell the American people, we are being
honest and being fair with you and then say, well, I am
sorry, if it is more than seven years, your records are gone
and that is too darned bad. That is not quite true. It is
just that one type of information moving from blood
distribution out to the hospital is ragged, after a certain
period of time, but there is information that they could use
to build facts, I believe, coming in the other direction.
Does that seem factually true?
PARTICIPANT: Yes, that is correct. Yes, the --
the disconnect, or the raggedness, as you used the term, is
probably in the transfusion service records going far back,
because the blood center would be able to say where they
sent the blood.
MR. CAPLAN: Sent the units, yes.
PARTICIPANT: Right. But knowing which patient
received a particular unit will fall apart, the further back
you go, yes.
MR. CAPLAN: Mike?
DR. BUSCH: Right, and to enumerate another
scenario, as our experience in San Francisco and I think
generally, the transfusion services destroy the linkage
records with respect to the blood component that came from a
particular unit, but they usually have records as to which
people were transfused in their hospital.
The other strategy that has been pursued with
limited effectiveness is the transfusion service sending
letters to all transfused patients, not enumerating,
discriminating, which have gotten blood from a particular
patient, but focusing with letters, the campaign on people
who indeed did get transfused. The truth is, that program
had a very low response and very low yield of tested people,
and of those tested, you know, only 3 or 4% were infected,
but that is another -- there are multiple options.
PARTICIPANT: I think this relates to the worried
patient that we talked about yesterday, with Dr. Robinson,
and one of the things that we might keep in mind is, rather
than tell a patient to go track his transfusion records, if
he has reason to believe he was transfused and is worried,
the NI(?) HCV testing is really pretty simple and you go,
find out if you are NI(?) HCV-positive, and that pretty much
ends your worry, if you will. And that is a reasonably easy
way to do it, rather than trying to track back through a
hospital, where the records are in a storehouse someplace
that you cannot get at them.
We might want to consider that in the counselling
of patients, that maybe sometimes it is easier just to go
get checked, if you are worried, if you are a worried
patient.
MR. CAPLAN: Well, one of the things that I think
we can anticipate happening after today's meeting, is that
announcements are going to go out to the United States
saying, this group met and said, there was a problem of
exposure prior to 1991, 1992, and that people should talk to
their doctor, people might want to know if they were
transfused. That could lead to a burst of phone calls prior
to the CDC's massive educational teleconference experience,
which I believe is impending, but has not happened yet.
In other words, people are paying attention to
what we are doing right now and may want to go out and ask
questions, so it is important, I think, that we do not stir
people to action tomorrow morning, in terms of firing off
questions, since we are talking publicly here now.
What we are saying is, there is an issue. It has
to be talked about with your doctor, but I would suggest
that one of the first recommendations we have to put up
there, if I was going to re-prioritize these is, this
business about educating medicine and the healthcare field,
to be ready to field these questions, like the one you are
saying, I mean, the appropriate thing to the worried, well
may be for the doctor to say, well, then, we will do the
test, if you are worried about this. And then, if you are
not infected, we are done. If you are, then maybe you do
want to drag your hospital records out, or see what
happened, or something like that.
If we do not have that loop closed, we are going
to be in big trouble. So, my next comment is, it seems to
me the number one recommendation that we ought to move to --
and I am sort of speaking to the gallery here as well -- is
that, we have to make a very strong -- it is recommendation
two, I guess, becomes recommendation one.
That we have to implement, as soon as possible, a
systematic program to educate -- I was going to say,
healthcare providers, not just medical care -- this is
fighting words -- but, healthcare providers, to the
appropriate assessment of individuals at risk, as defined in
the consensus conference.
If that does not happen, there is going to be
trouble. I mean, we will make trouble just by having our
little meeting finished today, because people are going to
turn on the TV tonight and say, oh, well, I better go call
my doctor and -- that is going to be trouble.
That is the first step, the first thing I think we
ought to emphasize is that we have to get a person on the
other end who can answer that. If we do that, that may
solve some of the worried issues about, was I transfused and
so on. An appropriately informed physician, nurse, should
be able to do that. I would argue that, let's make that
number one, and just for that reason.
PARTICIPANT: Art, do you want to add in anything
about counseling in that statement number one, or --
MR. CAPLAN: Yes.
PARTICIPANT: -- leave it separate?
MR. CAPLAN: Where does that go?
PARTICIPANT: [Comment off microphone.]
MR. CAPLAN: Assessment and counselling of
individuals, yes. I think we solved the problem of number
two, in terms of that time limit we were talking about of
looking back the seven years. I think that does become
relevant, relative to those kinds of records. Number three,
we did not talk about much. It is time to say a few words
about it.
PARTICIPANT: I just will reiterate what I said
before the break, which is, I would like to rephrase,
identifying all or every possible individual at significant
risk for hep-C. And add a caveat that says that individuals
determined to be at risk, should be tested.
MR. CAPLAN: Where do you want to put that? I
lost -- it is other strategies?
PARTICIPANT: [Simultaneous discussion] --
sentence.
MR. CAPLAN: Individuals determined to be at risk
should be urged to seek testing?
PARTICIPANT: Right. Should be tested, either
one. It could be the provider who determines the risk, or
it could be the patient that determines it.
MR. CAPLAN: Comments?
PARTICIPANT: Should be provided an opportunity
for testing. Then they could decide whether they wished to
or not. That also puts the mandate on providing some means
of getting the test done(?).
MR. CAPLAN: Alright, I can see a sentence that is
at the end of three, that individuals be provided with the
opportunity for testing. That individuals at risk be
provided with the opportunity for testing.
PARTICIPANT: Is that meant to imply that the
testing is provided by the government? I think you need to
be pretty specific about what you are recommending here.
MR. CAPLAN: I -- that issue, I am waiting to get
to with baited breath. When we had our little moral
principle about fair access, which we have to come back to
in a second here. But before staggering toward that, I
heard absolutely no sentiment for what is up there as three
and three-quarters. It seemed to fall aside, am I correct
on that?
PARTICIPANT: I am too close to read it,
unfortunately.
MR. CAPLAN: Can you read that three and three-fourths again?
PARTICIPANT: Three and three-fourths is a
recommendation to obtain specimens from recipients of
transfusion for documentation of HCV status, or perhaps
other infections [comment off microphone.]
MR. CAPLAN: This foundered on the rocks of making
a public health recommendation that might be too broad for
us right now. It might be a good idea, maybe, but it seemed
to fall apart a little bit on worries about privacy and
worries about cost, and worries about whether that was just
worth doing as a baseline thing right now.
The obligation of providers to provide adequate
informed consent for transfusion recipients seems to me to
be fine, do we want to keep that, or is that apple pie-ish,
and -- Yes.
PARTICIPANT: It would have been a good idea ten
years ago, but today, I think most hospitals do use some
type of informed consent for transfusion, and frankly, the
risks for hepatitis-C now are incredibly small, so there is
not a whole lot to inform about, and it is unlikely that the
current risk is going to dissuade anyone who really needs a
transfusion, or should not dissuade anyone who really needs
a transfusion.
MR. CAPLAN: So, what do you think about three and
a half there?
PARTICIPANT: Yes, I do not recall whether that is
listed, though, on most of the documents that are handed the
individuals who sign off on this. Do you recall, Jim --
DR. AUBUCHON: Every hospital handles informed
consent for transfusion differently. NHLBI did put out a
booklet a number of years ago that listed risks and
alternatives, and hep-C was listed as one of the risks,
actually, in much greater numerical predominance than we now
have.
MR. CAPLAN: Alright, I guess I will take the
Chair's prerogative on this one, as I don't hear enough --
it is going to take more enthusiasm than that to keep that
one up there.
Alright, let's slide to four.
PARTICIPANT: Art?
MR. CAPLAN: Yes.
PARTICIPANT: Is there any -- future deliberations
of this advisory committee, I am not particularly
comfortable with that. Can't we make a more definitive
statement right now -- [comment off microphone.] It's the
second line.
PARTICIPANT: [comment off microphone] makes it
this committee's responsibility.
PARTICIPANT: How about [comment off microphone]?
MR. CAPLAN: I think that was just procrastinating
until this meeting, is what that was.
PARTICIPANT: Yes, yes. Actually, there is
probably a period there -- [simultaneous discussion].
PARTICIPANT: -- recommendation. That is how I
thought.
PARTICIPANT: But we are coming up with language
that [comment off microphone].
PARTICIPANT: This might be an ideal place to put
-- when that was written, obviously, we were in a great
state of ambivalence. But this might be a good place to put
developed, period, or developed by, with, the follow-up --
you know, the tracking and reporting mechanism (inaudible)
of what the outcomes of these strategies are.
MR. CAPLAN: The(?) developed -- [simultaneous
discussion]. So, in other words, identifying.
PARTICIPANT: Well, why not -- maybe we should
acknowledge that these other strategies for identifying
individuals have been examined (inaudible). I mean, that is
what we have done, we have really considered the options
that we have toward finding these people, and maybe that
should be a clear statement.
We have examined the historical experience with
approaches for identifying individuals at risk, in
collaboration with PHS. And this has led to, now, what we
should come forward with as these following specific
recommendations.
PARTICIPANT: Could I ask a question? When you
say, other strategies for identifying individuals, I am
actually -- I read that -- I actually interpreted that one
way when I first read it, and now I am interpreting it a
second way, and now I am not sure what you meant by it.
Do you mean, other strategies, or strategies other
than public awareness campaigns, and look-back, for persons
exposed to transfusions, or are you referring to
identification of other individuals at risk? Because the
vast majority of individuals at risk in the United States,
are at risk not because of transfusions, but because of
other exposures.
PARTICIPANT: Right, and that was the original
intent(?).
PARTICIPANT: And it seems to me that, in a public
health context, our responsibility is to -- if we are going
to have a public awareness campaign -- is to include all of
those at substantial risk, including transfusion recipients.
PARTICIPANT: Well, that was the original intent,
actually.
PARTICIPANT: And so, now, we are getting away
from that aspect, by virtue of three and four, whereas I
thought perhaps maybe three and four need to be combined and
include, you know, this, we recommend a public awareness
campaign, you know, that --
MR. CAPLAN: Well, you know, what I think is
becoming clear to me is that three might want to be
revisited in a second, after we talk about four, because
what I understood three to mean was, other strategies for
identifying people who might have been exposed through blood
transfusion, and somehow integrated with efforts on
hepatitis-C more generally, looking -- remember that talk
about the push to take on the challenge of hepatitis-C and
make sure it was integrated with what we were trying to do
with blood transfusions. So, I understood it in the first
sense that you were talking about, Marian, in A.
PARTICIPANT: Oh, okay. Yes, I see.
MR. CAPLAN: But maybe -- maybe let's just hold
off on three for a second, and let's wrestle with four
again, if we can pull that first sheet off entirely, Steve.
We can come back to three in a little bit, and see if we
still need it at all. Let's see what we do with this. We
have really been tottering up to it, and it is time to just
go full bore.
Right now it says, no targeted look-back prior to
1990. That is certainly an interesting phrase. I would
like just some discussion to open this up, about whether we
still want to stand with the policy that is articulated
there.
PARTICIPANT: Whether we stay with that or not, I
think that there has to be some provision provided for these
individuals who feel that they may have been transfused, and
may have this HCV, and make sure that they understand that
they can still come in and be tested. So that they do not
feel excluded from that. And make sure that it is
communicated in some kind of way that --
We have not discussed who is going to pay for
these tests, but I think that is going to be an issue, also.
There are going to be many individuals who will not be able
to pay for this test, and unless they know prior to this,
that they can come and get this test without worrying about
paying for it, then we are dealing with another issue here
(inaudible).
MR. CAPLAN: Yes, Carolyn.
DR. JONES: [comment off microphone] continue to
address that?
MR. CAPLAN: Yes, in fact it was -- it was
ambiguous enough so that it both did that and also did this
integrated thing. We also had a principle drop out from the
earlier slide which said, there is an obligation to make
sure that people have fair access. Some bright person has
said, to who, who is obliged? But, yes, the issue of who is
paying and who is ensuring that this happens is out there.
DR. JONES: I am not so sure from the discussions
we have had here that (inaudible) completely (inaudible)
belong there. I think (inaudible) recommend (inaudible).
Correct me if I am wrong.
PARTICIPANT: I think that is the line in the sand
here, and we may as well get at it. I mean, I think
everybody should be clear now as to the yield and the
reality of doing that kind of targeted look-back, and the
process -- you know, a lot of work will go into just the
blood center records review, and then that will dead end at
the hospitals, because there's no records, and it will dead
end at patients on downstream. And I think you are hearing
the blood bankers who are -- I would recommend that we not
do that. That we not proceed to any targeted notification
of recipients who got blood prior to 1992, prior to
effective screening.
Other people are echoing the issue that we cannot
withhold what might be of value to some subset of these
patients who would eventually, at the end of that process,
get that notification. I do not know whether a vote of the
committee -- but that to me is a very clear distinction that
we have very divided opinions of.
PARTICIPANT: At the moment, number four and the
new number two leave me somewhat confused as to what it even
is that is on paper and that we are considering, because
number two talks about a prospective look-back, which to me
as a blood banker, if I were implementing it, would mean
that only today, and henceforth, when we find someone who
for the first time is HCV-antibody-positive, would we
initiate a look-back.
Then, in number four, we talk about for persons
transfused prior to 1992, they would not be part of the
look-back, but certainly, prior to 1990, they would not be
part of the look-back. So, I would not -- if I were charged
with implementing it right now as it stands on paper, I
would be confused as to what I should be doing. And I --
MR. CAPLAN: The only group that would get a
direct look-back, the way I understand what we have written
so far is, right now. Prospective look-back. That seems to
me to be what number two says. So, if you did not get a
blood transfusion in 1998, or 1997, as far as I can see,
there is no recommendation in here at all saying, look-back
to anybody.
We did talk about whether we wanted to cover that
period, 1992 to here and now, with look-back. And there is
this issue about, what do we want to do prior to 1992, 1991,
or 1990, depending on how you define it. But the way I read
what is in there right now, just so we are all clear, we
have not told anybody to do directed look-back, except
contemporaneously.
PARTICIPANT: [comment off microphone] -- if
someone came in today, a donor, who is HCV-positive for the
first time, and they have had a negative donation some time
ago, number two does not say that the recipients of that
previous intervening donation [comment off microphone.]
MR. CAPLAN: Excuse me, with that -- yes, with the
rider, yes, it does. Number two does say that, up until
five years --
PARTICIPANT: But if -- yes, but the problem is,
that if a donor came in in 1995, or 1993, and tested
positive and had given in 1992, we are not covering that.
PARTICIPANT: No, it does not say that.
PARTICIPANT: I think I would recommend the
distinction be, what kind of blood was transfused? That if
you have blood that had been screened with second gen, that
you would not do look-back -- I mean, sorry.
You would do look-back on recipients,
seroconverters, as far back as second gen screening was in
place. Prior to that point, prior to March of 1992, these
other modalities of tracing recipients are the approaches.
So, look-back would stop at the point of introduction of
second gen screening.
MR. CAPLAN: It does not say that yet.
PARTICIPANT: It does not say that yet. Right.
PARTICIPANT: Well, I agree with Mike, with the
addition that I would like to see, in keeping with what we
said -- or what we were just debating about in number three,
is that anyone transfused prior to gen II, be tested for
HCV, if they have not been previously tested. Be offered
testing, again, you know, I mean, not mandated. Obviously,
we cannot do that, anyway, but I mean, be offered testing.
So, look-back for anyone who had generation II
testing, of the donor that [comment off microphone.] And
then, anyone else be offered testing.
MR. CAPLAN: John.
DR. PENNER: I think if we get back to that 1988
transfusion recipient, and how we are going to identify him.
And I guess I have not heard specifically why aren't we
going to go and track that -- let that individual of 1988
know? And I am hearing two things. One, it is
inconvenient, low yield. And low yield to me means cost.
So it is saying, it is too costly to let these people know.
MR. CAPLAN: But I do not think low yield means
cost, it means that only a very small fraction of the
recipients in 1988 who got HCV from blood transfusions will
be traceable. It is the proportion of infected people from
blood that we can find through that program. That is what I
mean by low yield.
PARTICIPANT: But then those who you are able to
trace, are going to be missed, right?
MR. CAPLAN: But then there is the
misunderstanding that we are doing this program and that
this is the way we are going to find you. So we actually
dilute out the public health message, because they think,
oh, well, if I really have it, they are going to come at me
with this other thing, but the truth is, from our analyses,
only perhaps 5% of all the infected people in 1988 will be
found through this tracking mechanism.
PARTICIPANT: But we have heard from our
publicists, that the best way to get at this is by several
messages. To get a direct letter, as well as the public.
So, if we rely on his recommendation, we would say, we
should try to notify these individuals at least by look-back,
as well as by public announcement.
MR. CAPLAN: I would recommend doing it from
anybody who got transfused, try to get letters out to those
people. I think there at least you are going to get
everybody who got transfused with a letter. And then you
have most people getting multiple messages. You do not have
an extremely small fraction getting this message that in
truth is a very costly and low yield program.
PARTICIPANT: But then you are withholding
information from one individual who has been exposed.
MR. CAPLAN: Correct.
PARTICIPANT: Specifically. And you are saying,
you are never -- as an agency, don't really -- we will make
the decision for you. We are not going to let you have this
information, because we do not think it is good(?)
enough(?).
MR. CAPLAN: You are not going to embark on that
program that will identify that recipient.
PARTICIPANT: That's right. But that recipient
has information that has some meaning to him or her, and
would have meaning to their lifestyle and their future
management. And you are not allowing them access to the
information that is there.
PARTICIPANT: I believe this can be handled a
couple of ways, because it is so difficult to get the people
further back. If the overall health message to the
community-at-large, and the training of the doctors is good
enough, you will pick up a lot of the people that way,
because they will see the general message. They may say,
oh, I did have a transfusion, or I better check with the
doctor. Will we miss some people? Yes. But at least you
are going at it from two perspectives, rather than just
trying to use a letter, or just a limited public service.
MR. CAPLAN: Yes, Jim.
DR. AUBUCHON: I think we should recognize that
any of the avenues that we try will have holes in it.
Clearly, public service announcements are not going to
stimulate everyone to check their medical records, or to
have an HCV test. Look-back, as a program, has many
inherent flaws in it, primary of which, that the donor has
to return on a subsequent donation, and be tested and fall
positive for HCV.
We have continually improved the donor historical
screening questions over the years, as Mike showed the
effect of, and that has resulted in the culling out of many
donors who otherwise would have been tested and found to be
HCV-positive. We will never be able to identify their
previous donations to write the fabled look-back letter.
I agree with Mike that we should not leave the
public the impression from a public service campaign that,
if they do not get a letter from their hospital, that they
are off the hook, and they do not need to be concerned about
it. If the patient had been transfused at a time when there
was substantial risk of HCV transmission, whether you want
to say before 1990 or 1992, we can debate. But if their
transfusion occurred during that time, they should check out
whether or not they are HCV-positive.
MR. CAPLAN: One of the things we talked about
doing, and even though I was yelling about not being too
specific, is to put in here something about all physicians
should ask their patients if they had a transfusion prior to
-- or physicians and nurses. We could add that. That is
specific, but it is another way to reinforce that that be
routinely part of practice.
PARTICIPANT: Then you could add in there, and
then offer them testing, and that would be part of that.
MR. CAPLAN: More discussion. Let's let this go,
since it is important, a little while longer in the
discussion, about the look-back. I think the case is there
to try to make the strongest case about notifying to say,
well, you knew that I was exposed from a donation. You knew
who the donor was.
It is material to me to know that I got this
infection, not because I used drugs or because I engaged in
sexual practices, but because of blood. That would make me
feel better about myself. I am not that interested in how
much it costs and how hard it is, if you know it, you should
go back and tell me. That is about as strong a case as I
can make. Why didn't you?
You have the records, you know where it is, it is
relevant to me, the origin of transmission does matter to
me. It may not matter to my treatment, it may not matter to
my testing, but it matters to me to know how this happened
to me, says somebody. That is about the best case I can see
for doing look-back that says, it happened this way, and you
got it that way.
PARTICIPANT: I have been writing. For
individuals transfused prior to 1992, we recommend that
testing for HCV-antibody be undertaken. Identification of
these individuals through a targeted look-back is not
recommended as the primary method of look-back.
Educational campaigns targeted to the public-at-large,
selected high risk communities, and providers, is
recommended as the primary form of look-back for these
individuals, and that really encompasses, then, everything
that we have been trying to say and does not leave any -- it
allows both to occur, but we make a recommendation as a
primary and in a sense as a secondary.
PARTICIPANT: I would suggest you be very careful
on the use of your term, look-back. Look-back refers to a
very specific mechanism, okay? So, what you mean when you
use that term, look-back and all those others, is really
your primary or secondary method of identification, not
look-back, actually.
PARTICIPANT: Correct.
PARTICIPANT: Only because in the end, we should
be clear about our terms.
MR. CAPLAN: If I am a recipient of blood from
1986, and I say, well, I have had a test, and I want to know
how I came to get hepatitis-C. I did not know I had it and
now I see I have it. Can I stride off to my blood bank, or
hospital, and demand a look-back in the sense in which you
are talking about it, now? In other words, could I activate
-- what you are talking about, Ron.
Could I say, look, I want you to track this back,
because I am going to prove to my spouse, or I am going to
prove to my mother, that I got this through a blood
transfusion, and that is what I want to do, and I am telling
you, look back. Tell me how I got this.
PARTICIPANT: I would not call that look-back,
either. That is a case investigation. You get yourself a
lawyer and we will do that for you, no problem. That is the
mechanism where that linkage will occur downstream. I mean,
this, why don't we do this or that, has no implication on
whether there will be (inaudible), because those linkages
can be obtained.
That is very simple. If you come in and say, I
was transfused this date -- it is a very simple track to see
whether we have ever subsequently identified a donor who has
given a unit of positive blood. That takes ten minutes.
PARTICIPANT: I would just like to point out that
there is an inconsistency between recommendation three(?)
and recommendation number four, either as written or as
rephrased by Dr. Gilcher.
If it is 1997, and you do seven years of look-back,
you are back to 1990. If, on the other hand, you are
recommending that you do not do a directed look-back prior
to 1992, you have two years of inconsistency that you need
to address.
The situation gets even more confusing with the
period that the committee has not yet addressed, which is
what to do between 1992 and 1997. I assume that has not
been forgotten.
PARTICIPANT: I think Dr. Busch addressed that,
but we have been throwing lots of things about here. I
believe the concept was that, we would perform a look-back,
based on all donors found to be hepatitis-C antibody-positive,
with second generation, or subsequent testing.
And that once the donor had been identified as second
generation or later positive, we would then look backwards
in our records and identify recipients back to some date.
And we could say, 1992, we could say, 1990, we could say,
1980. But, we would use as the trigger mechanism for the
look-back, a second generation confirmed test -- I am sorry,
supplementally supported test. And then look backwards to
some date.
PARTICIPANT: I agree that that was as stated by
Dr. Busch, that directed look-backs be triggered by
generation II tests. I would assert that it has not been
clarified whether those are confirmed or unconfirmed.
I would further assert that this language in
number four, or Dr. Gilcher's language, focuses on when the
recipient was transfused. That is independent of when and
by which test the donor was screened.
That changes things, because you are saying not to
do the look-back if the date of transfusion antecedes 1992.
That is a second, completely independent concept. And it
does render inconsistent the effect of recommendation two.
In recommendation two, a seven-year look-back is
triggered by a generation II reactive donor. That could go
back to 1990. However, it is being stated in number four,
that if the transfusion occurred in 1992, do not do the
directed look-back. So, they are not in fact consistent,
although I agree with what you stated as the criterion. I
would suggest that the committee needs to decide whether the
criterion is a test in 1990, a test in 1992, or a confirmed
test, and we have not talked about how and when. That
ambiguity is still unresolved.
PARTICIPANT: If I am hearing right, then, we are
disregarding all of the testing that was done between 1990
and 1992, because it is only 50% positivity. And we are
doing that because we are going to lose 50% or, as I still
hear it, it is going to be more costly for each individual
that we identify.
PARTICIPANT: The other distinction, I think, is
again, the risk to recipient prior to 1992 was substantial.
The risk since then is two orders of magnitude lower. And
it is that message that I think -- I think dovetails nicely
with the decision to only do look-back to units that were
transfused prior to the introduction of the second gen test.
Because those people prior to that point, irrespective of
our look-back, a lot of first time donors were coming in who
never came back and were transmitting. Those people had
substantial risk that we will never be able to get to them --
that a substantial proportion will never be traceable
through targeted look-back.
So, those people prior to 1992 deserve a message
that catches everybody and says, everybody was at risk and
everybody should be tested. Whereas, subsequent to that
point, we are not going to give those people that message.
Post-1992, mid-1992, the blood is relatively safe. You do
not need to get tested routinely. And what we have during
that period of people who received second gen screened
blood, we have this safety belt of trying to get the rare
transmissions through this look-back.
PARTICIPANT: Why not do both look-back, though,
and the general, as was suggested, for those individuals
prior to 1992?
PARTICIPANT: Well, if you do it for the people
who come in, in let's say, 1993, test positive, and then
they gave units prior to 1992, that is basically the same
thing as when we first introduced the first gen test in
1991, and then you do it to the ones prior to that. And
then you go, why not just --
PARTICIPANT: So long as you have a test that is
50% positive, there is a high risk, then, that that
individual will have been infecting.
PARTICIPANT: I do not disagree in the slightest.
The risk of a recipient of unscreened blood, getting blood
from somebody who is subsequently confirmed positive, is
very high. And there is no question about that.
PARTICIPANT: So, why aren't we going to notify
those individuals?
PARTICIPANT: Because it is extraordinarily
ineffective and low yield from the perspective of the
proportion of exposed people found.
PARTICIPANT: But those individuals were found.
PARTICIPANT: They have not been found, they are
not known, and the question is, do we begin the process --
PARTICIPANT: But if they are found, and you
expect that they will be found, then you have to say, it was
important to them. But it still comes back to me as you are
saying, it is too costly to do this. And that is the only
reason that we are not going to look back further.
PARTICIPANT: I am the one that is -- well. I am
very interested in cost-effectiveness, I am very interested
in cost, but I am not focusing on cost here. I am trying to
focus on yield, and how we can identify the people who are
really at risk, because a number of individuals will never
be told that they got a unit, that they were at risk for
getting HCV. We depend on the look-back program, and I
think -- I agree with Mike. We do need to be clear as to
where the risk changed, and have a specific program targeted
for specific years of transfusion.
If we try to -- whether we use 1990 or 1992, we
can argue about, but before a specific date, we need to be
very clear, we are not doing look-back before this date.
You cannot depend on us to tell you that you are at risk.
Listen to this public service announcement. You are at
risk, go do something about it. After that date, the risk
is lower. We have a system where we can manage a targeted
look-back, and in that time period, we can provide some
information for patients. And you can depend on us to tell
you.
PARTICIPANT: One case of data that we saw
yesterday that is worthy of comment. The relative
prevalence of HCV in first time or one-time donors versus
repeat donors I think was 13-fold. So there is 13 times as
many infections in the people who never come back, as in
those who are these repeat donors who we are screening
again. Those people were never going to trigger the look --
those people were giving blood. All along they have been
giving blood, and never coming back. And they are never
going to trigger a look-back.
PARTICIPANT: Well, I am talking about the
individuals who actually were infected, and that you are
going to pick up by going -- by doing a look-back. Those
individuals are there, and you are denying them information
-- [simultaneous discussion] --
PARTICIPANT: There are some there, but they
represent [simultaneous discussion] --
PARTICIPANT: -- that has meaning to them, by
saying, it is not important for us to give that information.
MR. CAPLAN: Just for my clarification here, it
seems to me, two issues up on the table. One is, if we say
that a second generation test is where we do look-back, and
that is the trigger, does that handle the consistency
question we were asked about by Dr. Epstein?
PARTICIPANT: The clarification is that, one, the
second generation test triggers a look-back; only people who
are confirmed positive. And two, is that the look-back will
only proceed back to the recipients of second gen screened
blood. So, it will only go back as far as the people who
got that kind of blood. Because prior to that point, one,
is we are talking about seroconverters, but prior to that
point, the risk was so high that this whole other strategy
is playing in. So, I think those two points make it
consistent.
MR. CAPLAN: And let me ask then the second
question, just for Keith or anybody who wants to jump in on
this, if we were to say, our reasons for not doing look-back
prior to 1992, are that we feel we are going to miss too
many people. Not that it costs too much, or not that it is
a pain in the neck, but because there are a lot of single
donors that are lost forever to -- could have exposed folks.
What we want is a very aggressive campaign to let
everybody know, prior to 1992, who got a transfusion, that
they may have been at risk, and that would include, not just
the public service announcements, but change in medical
practice to make sure that every physician and nurse asked
about this, as part of a routine question or physical, maybe
also, putting in some sort of notices at hospitals. I mean,
up on the wall.
What we are talking about is a serious push to let
folks know the best way to let the most people know who
might have been exposed is simply to really undertake a huge
outreach campaign through providers and through public
service and general media announcement. It does not get to
my issue about how I got this, and my right to know that.
It does trade it for, there are so many people that might be
at risk that we could not pick up by tracking back, that we
better spend the resources doing general physician education
and general public health outreach. Is that roughly where
we are at, with that?
Somebody mentioned, just to toss it up and I was
curious. We could have letters written to every person who
had a blood transfusion in the United States, prior to 1992.
Yes? That is another kind of notification, it is a lot of
stamps, but --
PARTICIPANT: Actually, that was kind of the
compromise that I was going to propose, which is, make first
of all, semantic distinction between look-back and risk
notification. Look-back, define look-back precisely as Mike
and Jim defined it. And then say, we are advocating a risk
notification program for people who received transfusions.
That would include a letter notifying them that they
received blood, a blood transfusion, during a time of risk.
Of significant risk. Maybe not high risk, but of
significant risk. And that we recommend that they be
tested.
PARTICIPANT: That program, I should give you the
numbers, because this -- one issue is, this was HIV, which
obviously should have triggered a lot more concern in
patients' minds than HCV. The other is, the time period of
risk was much more discrete, and the time when this effort
was undertaken was relatively soon after the time period of
risk. But at UCSF, 17,000 people received such a letter.
So the whole, you know, transfusion service, history of
transfusions was scanned and they identified 17,300 people
who -- they were discharged from the hospital after getting
transfused.
Only 808 people responded to those letters, and of
those -- which is 4.4%. And only 15% of the estimated
12,000 recipients. And of those, they only identified, I
think, about 15 infected people with HIV. This was a major
area of focus in the late eighties, and the American
Hospital Association recommended against broad scale
implementation of that program. This was at the same time
as the national recipient notification effort in the late
eighties was undertaken vis-a-vis risk of HIV from
transfusion.
So, the program, the recipient programs, are not
high yield and, from many people's perspective, cost-effective, either.
PARTICIPANT: I do not think anything you do with
respect to look-back or letters are going to be the kinds of
yields that we would like to see, but either you are going
to have to do, or think about doing a targeted look-back, or
a general letter to those folks who have been transfused.
It is easier to send a letter informing people of
a risk. And if they do not take advantage of it, you are
still going to have the public service announcements. You
are still going to have several modes of attack to these
people, and you can take a horse to water, but you cannot
make it drink, but our obligation is to inform these people
that there is a risk associated with them being transfused
prior to the time that reasonable testing had been
implemented. And that is the only obligation that we have.
We cannot force these people to go in and be
tested. Even if the yield is low, we have addressed our
obligation, and if folks choose not to be tested, that is
their choice. But we have to do something. Either we do
the targeted look-back, which will be a problem for blood
banks, for hospitals, and so on. I mean, either way, we are
going to end up spending money that is going to have, not
the kind of yield we would like, but something is better
than nothing.
MR. CAPLAN: Well one other way to -- I mean, I do
not want to get into the details of the UCSF thing. The
idea here is, of course, obviously, we have learned to do
these things in tandem. Not just the letters but the public
service announcement and the medical question being a
routine part of a physical and a properly prepared health
establishment to answer these questions. I will be moving
to this country whenever it exists.
The fact is, too, that if we look at the outreach
effort, the situation is such that with the potential for
cures, and with the potential for lifestyle information,
that might justify the expenditure. The other side of it
is, you have something to offer. It is not just a letter
saying, hey, bad disease, may have it, do not want to
communicate it. It is, bad disease, something might be
done, and you might want to alter your lifestyle. So, the
momentum that comes behind a letter campaign could be
different, potentially.
PARTICIPANT: Well, and it also gets to the issue
of shifted risk, because unlike look-back which takes
energies, significant energies, away from personnel within
the blood banking community, with computers, I mean, it is
pretty easy to put out a standardized form letter, so that
it really comes to a dollar issue, not an energy issue.
I think that that is a major advantage, and
probably still has about -- still will -- I do not know
this, but I would guess it has the likelihood of uncovering
people for follow-up and testing, to a degree that is every
bit as effective as look-back during the period prior to
1992. And probably more.
MR. CAPLAN: Mary, then over to Paul.
PARTICIPANT: I guess I would like to seek some
clarification, because I think the committee should be -- at
least I do not have as clear an understanding of what the
impact of that kind of a recommendation would be, you know,
a more general letter notification. Are you --
Will we be recommending that hospital transfusion
services search their records, and identify people who have
a blood transfusion during some period of time, and as
opposed to HIV, where we have kind of a sense as to when
that was introduced into the blood supply?
We do not have that luxury, if you will, for HCV.
It has been endemic for decades. So, transfusion services,
then, would have to compile lists of all people who had a
transfusion dating back some period in time, and then, use
addresses that they might have had, you know, X-number of
years ago --
I am trying to sort of operationally translate
this recommendation into steps so at least it is clear to
me, because right now, I apologize, but it is not entirely
clear as to how that would be done.
MR. CAPLAN: Actually, you are going to laugh when
I give you this answer. I think what the committee will do
is say, the agencies have to work together -- if it goes
with this recommendation -- to find a means to notify all
recipients of blood, to the extent possible, prior to 1988,
that they are at risk and need to go talk to their doctor.
Then we will be waiting to find out what course of operation
-- how that goes.
In other words, I do not think we are going to go
today and say, here is this database. Find that mailing
list. Go out and -- the charge will be, we think there is
an obligation to let those at risk know. It looks like the
yield of trying to do it specifically from infected donors
to those who got their units prior to 1988, is just going to
give low yield, but a general notification followed up with
a comprehensive campaign involving docs and PSA, and
whatever else we can think of, that is the way to go do it,
in tandem. Plus the prospect of some benefit for you.
Lifestyle or maybe therapeutic intervention.
That is how I see the package coming. It is
moving more towards saying, that has to be then
operationalized, not here, over at CDC, NIH, FDA.
PARTICIPANT: You said something about, the
agencies would have to develop a plan? A plan --
MR. CAPLAN: To make that happen. Or a set of
recommendations that they would send out. In other words, I
do not think we are going to get, today, out of this group,
the information about how often have the mailing lists been
updated, what has the Oklahoma blood bank got that, I don't
know, the transfusion service at Irwin does not, I do not
know.
We will not know, but there are going to be some
general recommendations about, try to make this happen.
That will have to be put into a policy or a plan at that
point, is how I see that going. Although I may be alone in
this vision.
PARTICIPANT: I think, probably the experience
with this letter(?) activity is what I just told you. That
is the total world experience with trying to send letters to
transfusion recipients in a broad fashion. I think it is a
worthwhile effort to try to pursue that strategy as a pilot
study, but I would recommend that we recommend that they
explore this option in addition, as a potential feasible
option, to find these patients.
PARTICIPANT: My thought(?) was going on the exact
same vein, and that, if I am following what John is saying,
we are really trying to get to the most people, and I think
there is some significant question as to whether this type
of letter is (inaudible). I go give blood, or receive blood
today, and I move tomorrow, and now we are talking about
people who had blood decades ago, and we are assuming we are
going to find them.
I think that maybe the word, pilot, that Mike just
mentioned -- what is the effective yield of the direct
letter, and if that yield is crappy, then John's point
becomes more and more relevant all the time of, we have to
try to get to as many people out there as we can, and it is
easy for us here to say, let's send this letter, but who the
heck is going to get it?
PARTICIPANT: [comment off microphone.] -- and
healthcare (inaudible) period of time, over years, most
likely, as the knowledge evolves. It has to be part of it,
it has to be a cornerstone of this whole approach and I
think we are more or less agreed that a targeted look-back
from the point of view of the introduction of the second
generation screening (inaudible), does make sense, so what
we are debating is, prior to that, and education has to be
part of it.
PARTICIPANT: It seems to me we are talking about
perhaps something similar to notify all of the troops in the
Gulf War that you may have been exposed to nerve gas, and
withholding the information that those within five miles of
it were exposed critically, and we are not going to notify
them, specifically.
We are withholding information from people that
you already have the information for, you are not going to
allow them to have. And they have a right to have it. We
say that in our premise, to begin with, that we are going to
try to give all the information that we have, and this is
where it differs from, I think, what Ed is saying, is that
we have specific information that belongs to that
individual, and we are unwilling to provide that information
because it is too costly.
MR. CAPLAN: Let's go over to Ron.
DR. GUERRA: Some points that I think need to be
clarified. First of all, as one goes into the past, risk
increases. In other words, the risk of hepatitis-C was
actually far greater in 1970, than it was in 1990. And I
think we need to put that into perspective.
The second point is, and I want to clarify this.
The hospital blood banks, most of them, do not have the
records in the blood bank of who was transfused. Most of
the blood banks in the hospitals have kept information on
who the problem patients were, because I have been an
inspector for the ABB in the past, and clearly, that is what
they retain, if that is even retained. So, there is no way,
going to the blood bank, that we could get a list of
transfusion recipients that goes into the distant past.
The last point that I want to make is that one
method here should not preclude the other, and the statement
that I have given to Steve and I have modified it with what
Marian had said, so to speak, encompasses this, and I would
just like to put it up at this point. It is not the final
statement, if you could read that, or if you would like me
to read it.
PARTICIPANT: For individuals transfused prior to
1992, we recommend the testing for HCV antibodies be
undertaken. Identification of these individuals through a
targeted look-back (inaudible) is not recommended as the
primary method of identification. Educational campaigns
targeted to the public at large and selected high risk
communities and survivors is recommended as the primary form
of identification of these individuals.
DR. GUERRA: That really encompasses everything
that is being said and it does not preclude one form over
the other in terms of looking back, where records do exist.
PARTICIPANT: Then you are going to disregard two
years' worth of information from the laboratory tests that
(inaudible) provided, that would identify more selectively a
small group of individuals who were exposed.
DR. GUERRA: No, I am not precluding -- I am not
saying that one should not do the other. I am just saying
what we would recommend as a primary.
PARTICIPANT: Yes, but they are not going to do
the targeted look-back.
DR. GUERRA: Not recommending it. It does not
say, we are not doing it, it is saying, not recommending it
as the primary form of identification. Are you --
PARTICIPANT: That almost reads as though, if you
are not recommending it, then it is not going to be
(inaudible).
DR. GUERRA: No, that is not the intent of what I
have written, and -- I mean, are you concerned, John, with
the 1990 to 1992 time frame?
PARTICIPANT: Yes, the assay when it was first
installed in 1990, we have that -- that is the data, I think
we are looking at. So, those tests that were positive
during that time, we now have a look-back that we are not
proceeding with. You are saying, we will disregard that
testing.
DR. GUERRA: No, I am definitely not saying that
we should disregard that. That is not intended or implied
by what I have written.
MR. CAPLAN: Just so I am clear, could we -- is
there a position about this, what if we changed that date up
there until 1990, I mean, just erased 1992 and made it 1990,
and took the look-back requirement, targeted look-back
requirement for that interval to include both the one and
two tests?
I mean, we are sort of rattling around on this --
one of the reasons I am inclined to think about this is, it
seems to me that is where the record-keeping is still going
to make it feasible. Beyond that, we start to get into this
antsy area of, what is the yield and what have we got, even
if we are trying hard to do it, it starts to -- then we are
back, more than seven years, and things get -- so would that
--
PARTICIPANT: Again, you have two issues, as Jay
enumerated. You have the donations triggering it, and then
you have the recipients of those kind of screened products.
In terms of donations triggering it, the downside of going
prior to second gen, is the test was less sensitive, less
specific, you did not have a supplemental to discriminate,
so you will be triggering look-backs from the first gen test
that will -- half of them will be nonspecific, and you will
be creating anxiety, etcetera, those issues.
The other is that the people who got blood between
1990 and 1992 had virtually a zero risk, and -- I am sorry,
had a substantial risk, and this look-back will only find a
proportion of them, so there is the issue that those people
do need to get the public health campaign, because they did
have risk, and we are not going to find most of them through
targeted look-backs.
MR. CAPLAN: I understand that, but in a way, if
we went to the 1990-1992 and included them in, wouldn't that
give us what some of you are talking about, which is the
ability to see how that look-back went? In other words,
that could, in a sense, function as the pilot.
If we said, today, well, we have this inaccurate
test and we do not want people to just rely on the notion
of, they looked back, did not look back. We are going to
give them the public health message, anyway, that prior to
1992 you should get a test.
We will send that message, anyway. But, in that
1990 to 1992 window, we will make every effort to do the
targeted look-back, and we will see how it goes. De facto,
we have a pilot there. I mean, we will know pretty quickly,
or relatively quickly, if there is any point in doing this.
It may be a position that lets us at least not saddle the
system of trying to either find people from 1945, and so
forth, and at the same time, gives us some idea of whether
there is any point at all.
I mean, is that -- I understand what the pluses
and minuses are in terms of looking to the false positives
and so on, but it may still give us a means by which we are
exploring in a reasonable way, with reasonable records still
around, what people might want to know.
PARTICIPANT: -- 1990 or 1992 as the date of
transfusion.
MR. CAPLAN: It is the 1990 date of donation.
Donors would be in before --
PARTICIPANT: -- hepatitis-C --
PARTICIPANT: -- say someone came in in --
PARTICIPANT: In 1990.
PARTICIPANT: -- 1990.
PARTICIPANT: That was the first generation test.
PARTICIPANT: Okay, if someone tested -- say,
someone came in in 1992, or 1991 --
PARTICIPANT: In 1991?
PARTICIPANT: And tested positive.
PARTICIPANT: Okay, there is a 50% chance that
that test --
PARTICIPANT: And they had --
PARTICIPANT: -- would be truly positive, and not
a false negative.
PARTICIPANT: And so you decide to do look-back.
PARTICIPANT: And we look back.
PARTICIPANT: And say, the last time that person
gave was 1988. Would you go back to those 1988 recipients,
or do you cut it off at 1990, being --
PARTICIPANT: We would go back -- [simultaneous
discussion].
PARTICIPANT: So, what if he had given in 1988?
PARTICIPANT: That is the whole game of look-back,
that is not a pilot at all, that is the whole game. Yes,
but we would go back.
PARTICIPANT: So, it is just standard look-back.
PARTICIPANT: That is it.
PARTICIPANT: We can always do more. We will
never be able to do everything for all patients. If we want
to consider including in look-back those donations that were
found positive in first generation testing, where there was
about a 50% probability that the donor was truly infected,
well then, why don't we also do look-back on the surrogate
testing we were doing in the last half of the 1980s?
Because about 30% of those individuals who were core-positive
and/or ALT-positive, were truly infected with non-A, non-B hepatitis.
They were not great tests, they were
the best that we had available at that time. But, we have
gone from a 50% probability to a 30%, well, that is not that
different.
So, where do we draw the line? And I do not think
anyone is thinking that it is reasonable to use surrogate
testing, and I think we have to bite the bullet and say, we
feel this is the appropriate point.
I would be willing to -- I mean, philosophically,
I guess, since I typically could see some benefit to
extending the look-back to transfusions to 1990, based on
second generation testing. In other words, a donor donating
in 1992 or 1993 might have donated in 1990 to 1992, and we
would look back on those transfusions during that time. But
to go further back, probably has low yield. We are dealing
with now records that are a decade old, difficult finding
patients, and relatively very little return for a lot of
effort.
PARTICIPANT: Practically speaking, if we agreed
on a date today, how quickly could this actually begin? Are
we talking 1998 or 1999 before we actually have a broad
reach out to the public, which then really takes us out of
that seven-year record-keeping?
MR. CAPLAN: I have no idea, except to say, if
anything happened before 1998, of any nature, I would be
very surprised about it. So, I will say there is going to
be at least some time lag of that nature.
PARTICIPANT: Well, it just seems from what Jim
has said, and also just the practicalities of getting this
implemented, that 1992 probably makes better sense.
PARTICIPANT: The ALT test is not specific though,
Jim, and you know(?) it(?). And there is specificity in the
hepatitis-C first generation, (inaudible) 50%. The ALT is
nonspecific for just about everything that comes up,
including walking up the stairs fast. So I do not think one
can really use that as a reasonable look-back procedure,
whereas I think we can take a look at a specific test, for
50% specificity, and consider that it would be useful.
PARTICIPANT: What concerns me, John, about the
first generation tests, is if there is a substantial number
of individuals tested with that procedure, who are actually
infected, that were not picked up, so, the potential there
is, a recipient of the unit who is actually infected, might
be aware of, well, look-back has taken place during this
particular period of time, and I am fine.
I really think that the 1990-1992 period is a --
it is a problematic one, and I particularly like Ron's
terminology here, from the point of view of not the primary
method of identification, because it is certainly a useful
tool, but it is not the only tool, or the key tool here.
PARTICIPANT: I still am looking at this from a
personal view of an individual, that you are withholding
information --
PARTICIPANT: But you could get false information.
PARTICIPANT: That is alright, but that is up to
that individual to decide, when you give them the
information, that it may be false, it may be true. But you
have to give them at least the option of making a decision.
If they do not have the information, they do not get the
decision.
That hearkens back to the syphilis trials, as you
remember. We just will not tell you that you are positive
for syphilis, and we will just kind of watch you. This is
the same sort of approach that we have here (inaudible). We
have a situation where you do not have any knowledge of what
has gone on that would indicate that you are at higher risk
than someone else.
MR. CAPLAN: Carolyn.
DR. JONES: I disagree, because if we had some
other sort of programs(?) here [comment off microphone], you
are not denying them information, you are only denying them
information about a particular unit that may have infected
them, and that is not -- you are not going to give them a
donor's name or anything.
What you are doing, is informing them that there
was a risk associated with the transfusion. You cannot even
say for sure if they were transfused with a positive unit,
whether they actually came down with HCV. So, I mean, what
information are you denying them?
We are saying, there was a risk associated with
transfusion at that time. Go get tested. I do not see what
you are denying them.
PARTICIPANT: Yes, because it is a general
information, whereas you have specific information on a
test(?) (inaudible) for that individual. And I think that
is going to give rise to some real problems, legally, and I
can see individuals saying that, I now am tested positive,
you gave me a general statement in the community newsletter
that came through that said, anybody who has received blood
and so on and so forth should be tested, but you also had
knowledge that I was at a much higher risk than somebody
else, than my neighbor, who got a blood transfusion. And I
just overlooked that, because I did not get that information
that I was maybe at a 50% higher risk for getting it than
anybody else.
MR. CAPLAN: That is the point I was going to
stress. The question is, if you know that you have a
positive unit, and you have some test indication, plus
records, it is not just the test, but it is the records, the
ability to find it.
Do we feel some obligation to say, not only should
you get tested, because you were at risk prior to the
availability of a very reliable test, but we know, in our
records here, that Mr. X was positive, and we tested and
found out that there was some higher chance that you could
have been infected; we have to tell you that.
My interest in feeling obligated to get that path
closed down is beginning to diminish, the further back we go
in time, because I am becoming persuaded that that is just
not the route to do it. The records, the moving, the phone
numbers, the mailing addresses, things start to fall apart.
I am not sure in this 1990, 1992 window area, that
we shouldn't or couldn't, if we wanted to, and I am not sure
whether it is donation date or transfusion date, still, I
hear that, but nonetheless the general question is, if I
know that you have been exposed to a transfusion that had
hepatitis-C in it, because I had some means of testing that,
not ALT, but the first generation test, and it is in my
records, would I want someone to call me up and let me know
or try to find me?
To me, that is the bottom line of that push, and
when we cannot call me up or find me anymore, then I think
we have to be very aggressive about just letting you know,
hey, hepatitis was a big problem in blood transfusions prior
to this testing. We do not who is at special risk, you are
all at equal risk, go get tested. It is when there is more
information that somebody might have that says, you are at
risk because of what I know that is in the record, that
triggers some duty to disclose. So, that is why I am still
hung up.
If we could push past or resolve the 1990, 1991,
1992 issue, in terms of how that goes, I suspect, if we get
consensus there, we might agree that all we can expect
people to reasonably do before that date, is not really look
back, and maybe not mail -- I am not sure we haven't knocked
the mailing to the transfusion recipients out. But that
massive notification of, folks have to know that before we
could test for this, there was a big hepatitis problem out
in that blood supply, and you really have to get in there
and talk to your doc and your doc has things that they can
tell you about.
By the way, Trish, that campaign to educate the
doctors, if we really say that has to come first, that takes
us 'way into 1998, by the way, just as a -- if you are doing
that first so they can answer the questions that they get,
and what are my options, and so forth, we are into 1998,
somewhere. Mike?
DR. BUSCH: Yes, just to pursue your sort of
spirit of compromise in exploring this interval period. One
could make the argument that there was HCV testing beginning
in 1990, and there may have been a perception put out in the
community that blood was safer then. So for that purpose,
to consider overlapping time periods where the general
campaign really extends to 1992, because we know there was
substantial risk through to 1992, but that indeed the look-back
program extend back to first gen screened blood.
That both potentially, the people who were
identified obviously by second gen once implemented, but
even during the first gen screening period, the
seroconverting repeat donors, you would go back to their
prior, first gen screened blood, blood transfused since
implementation in 1990, and track records for those. The
records are probably mostly there. You will get a higher
yield, as Jim showed, from that more recent period, but that
we abort the process at unscreened blood.
That unscreened blood, even though recognized
right up front that unscreened blood has a substantial risk,
probably a higher risk than the screened blood, but the
process just falls apart, as you said --
MR. CAPLAN: The moral difference is -- if I can
talk that way for a second -- weirdly, we know there is more
risk before the test, but the converse is, there is more
obligation to say something because of the test. I mean, it
comes -- the more you know, the more you have some duty to
tell somebody what you know.
When you do not know anything except that the risk
is worse, then I think you are diminished and your
obligation -- you cannot sort of go find anybody and tell
them anymore than, gosh, there was a big huge risk that has
been going down like this on a curve, but if you look at the
fifties and sixties and seventies, 20% -- whatever it was --
it was really risky out there and you want to pay attention
to that.
But when we tested, even in a crude way, we got
information. We have some of that. We have some duty to
let you know or try to find it. That is what I am fishing
for here. It is not that I do not understand very well that
folks are not off the hook because they did not get a good
test or even a half-baked test. They were probably the most
risky group of all, but when we have test results, that is
what you were fishing for with that analogy about
withholding information.
PARTICIPANT: Yes [comment off microphone.] If
the information is there, you are obligated to provide it to
the public. And if the information is not there, you are
not. So then you are safe.
PARTICIPANT: I guess the issues that I am hearing
here are, if -- well, number one, it is -- I think we need
to decide upon a date, and depending upon that date, I am
hearing the issues of, there may not be records available
for persons. I am hearing also, financial impact that it
would have, and also, ethical responsibilities that we may
have. And I think we have to go back to ourselves and ask
ourselves the question, if we choose one date over the
other, are we being ethically responsible to the American
public?
What if we choose the 1992 date over the 1990
date, if the American public understands that there was at
least a test, the generation one test in 1990, what is going
to be our answer to them to say, we have chosen one over the
other?
PARTICIPANT: As a parent with two children who
get a lot of transfusions, what I would like to see is, when
it is all said and done and the American public realizes why
we recommended certain procedures and not others, I think
that we have to consider how we answer them in that regard.
I also think that when we start talking about the
low yield, as a parent, that does not have much meaning to
me, and I understand your end of it, and the cost effects of
it, but also, the people that we do identify, will at least
have the knowledge available to them, and if we agree that
we are not going to reach everyone, do we not have an
obligation to at least notify the ones that we can?
Part of what I am sensing out of this is that, you
know, it is like if we had a vaccination for a disorder, but
it is so costly that, unless we are able to identify enough
people to make it worthwhile making this vaccination, then
we are not going to put it out to the public. And I mean,
the public's perceptions since the HIV problem has changed,
and I think if we educate them properly, and give them the
tools, whether they use all those tools or not is not our
part of this.
Our part of it is making sure that if the
information is available, we do our very best to get it to
as many people as we can, whether the yield is low or not, I
think the quality of those people that we do reach, the
quality of life that we are helping them with is
substantial, and I do not think that they are going to be
upset with you because -- you know, it is just a matter of
the quality of life of the people we can reach.
When we start talking about numbers, then as a
parent, I have a problem with that. I understand that,
sitting here on this committee, but as someone who, if I
were not here and I heard about this years and years later,
I would have a definite problem with all of this.
I just think that we have to reach the people we
can, and not worry so much about yield, because the people
we do reach will be the ones that will thank you, and the
ones that we cannot reach, no matter what we come up with at
this point, I do not see us finding a way to reach everyone.
So, I think we do have to reach whomever we can, however we
can.
MR. CAPLAN: Well, let me put on my stovepipe Abe
Lincoln hat and say, how about if we tried a statement that
we recommend for individuals transfused prior to 1992, that
they be tested? I think that is a very radical
recommendation, but maybe one you want to go with.
That we say, in the interval, once the appearance
of a hepatitis-C-specific test appeared, we recommend look-back
that would be generation I- and II-driven -- is what is
going on here, with the notion that the obligation is, if
you have the results, you are going to try and track them
back as far as you can, so I think we are in the 1990 to
1997 period there.
That we recommend prior to 1990, almost what the
language is here, the targeted look-back is not the primary
way to go, but that a massive public health outreach and
healthcare educator program is the way to go, to let those
people know what is going on. Is that a -- that is not
quite English, but are those the elements?
PARTICIPANT: How could you do look-back prior to
1990, if there was no test -- [simultaneous discussion] --
PARTICIPANT: You have to understand that the
blood centers have records going back to the sixties,
fifties. So, as soon as we decide to do what you just said,
we would go to all the records of all the HCV-reactive
donors, starting with first gen testing, and then the
confirmed positive with second gen.
We would go back and determine which of those
donors had prior donations. We would go back to all the
records of prior donations, dating back to the sixties,
fifties. We would then have to disseminate to the hospitals
the list of all the components that were issued at those
hospitals over the past few decades.
It is up to the hospitals to individually
determine which records they can then trace. So, they have
to go through a process that is a huge undertaking. The
scope of this, what we are talking about now, is probably a
hundredfold that of the entire HIV look-back program that we
undertook in the mid-eighties that tipped the boat to near
sinking in many transfusion services.
What we are describing is a massive program that
we are arguing is a very low yield program, and you are
saying, do it anyway. Some of you are saying, do it anyway.
It is going to get a few people on the back end and it is
worth getting those few people. That is the question at
hand. Is it worth that?
MR. CAPLAN: More comments.
PARTICIPANT: (Inaudible) with the obligation.
The testing was done, and therefore you have to follow up.
And information must be made available. I think you could
construct some limits on what the hospitals have to do, and
I think the hospitals actually will construct limits on what
they will do. But also, I have seen what happens in the
hospitals when they do the look-backs, and also, I have seen
what happens when we do that in our Red Cross centers, and I
think it is doable, but it is a pain.
PARTICIPANT: Your comment yesterday -- well, two
responses. One is, your comment yesterday that the cost
will be passed on. That is no longer the case. We are into
managed care. The price of blood used to be $100, it is now
$80 and driving -- due to the HMOs driving, so there is no
pass-down of costs, there is contractions of service that(?)
we(?) see(?).
If you juxtapose -- again, assuming that there are
limited resources, to me, if you juxtapose -- if I were a
transfuser and my child was transfused in the mid-1980s, and
I were to weigh the probabilities that that child, if
infected, would be found and notified and tested through a
broad public health message versus look-back, there is only
at best a 5% chance, if he got the infection from a
transfusion in 1985, that that will be eventually found
through a targeted look-back. If you run the numbers, and
you can walk through that.
I think there is a much better probability that he
will be found as a consequence of an effective, broad public
health notification to recipients, the things that -- the
other issues we have talked about, much more probability
that he will be tested. And I think that is the way to go,
and I think we are wasting our resources with this double
effort, where one is so much poorer than the other.
PARTICIPANT: As a blood product consumer every
week, I am conflicted here. But I honestly have to say
that, if I had a real specific, directed message, that
anybody that is a blood product user, or anybody that had a
transfusion, needs to go get tested.
I would be more comfortable with that, than I am
after hearing all the data, depending on some blood bank, or
some hospital, or infusion service, to tell me that I had a
specific lot or product that potentially was contaminated.
Again, I am conflicted, but I would feel much more
comfortable -- if you have any question at all that you had
a transfusion, for whatever period, you need to get tested.
And that we spend our resources letting the public know
that, because the other side of the coin is, only 5% of
those that have HCV, as we have heard in testimony, or 8%,
are by transfusion. And we have an obligation to let those
that are affected otherwise -- if you will, that they have
to be aware of this condition as well.
So, as a blood product consumer, I am -- again, I
would rather just go down and get tested and make sure
everybody in my community who has (inaudible) anti-trypsin
deficiency, gets tested, and we probably all have.
PARTICIPANT: But you are very knowledgeable about
this, John, so I think you are coming at it from a different
--
PARTICIPANT: That is true.
PARTICIPANT: As we all are here. But about the
cost factor, maybe just a perspective on cost, and we talked
about this a little bit at the break. The cost of blood has
gone down, as we said, to $80, and there is a lot of
pressure on blood. This is a lifesaving commodity. What
does it cost us to give an antibiotic program to an
individual? Some of our antibiotics are running $1,000 a
day.
I ordered antithrombyn-free concentrate for a
patient the day before I left, $2,000 worth, as a lifesaving
precaution, one shot. Our hemophilic population are getting
$800 to $1000 worth of product for an acute bleed. And
blood is very inexpensive when it comes down to the fact
that it is $90, or whether it is $100. And I was very
strongly in favor of a $40 -- and keeping the price down
when I was overseeing my Red Cross responsibilities. But I
have come the other way around and realize how inexpensive
this product is, in comparison to everything else that is
lifesaving, that we are providing our patients in the
hospital.
It is a negligible cost when we consider it, and
the fact that we can provide a very clean -- with respect to
reducing some of the infectivity -- and it is going to cost
us another $10, I think is something we need to get out of
our minds. Most of us were brought up in the era of turning
the lights off when we left a room, and I think maybe we
still have that kind of concept. But I have been willing to
extend my thoughts on this to the fact that we do need to
perhaps price blood much higher. It is more important to
have it as safe as we can get it, and safety means that we
are going to have to add more cost.
PARTICIPANT: And John's concern about depending
on a transfusion service to notify him that he might have
received a unit that could have transmitted an agent, I
think is an appropriate one. Not that blood bankers are
cavalier or that they are not trying to do the best job
possible, but there are limits and constraints put on their
operation.
I just recently completed a survey through the
College of American Pathologists which has not yet been
published, that inquired of hospital transfusion services
what their budget had looked like over the last several
years, and whether they had had to make changes in their
operation.
Of the responding laboratories, 15% noted that
their -- I am sorry; 21% noted that their budget had been
restricted, reduced, out of proportion to any changes in
their workload, over the last two to three years. So, 21%
have seen a contraction in the amount of resources they have
available, and in fact, 8% noted that because of those
restrictions, they have had to make changes in their
operations, that in the opinion of the pathologist or the
laboratory supervisor, reduced the safety of transfusion at
their institution.
Now, that is worrisome, if just with ongoing
operations, these laboratories are having to cut corners to
the point where they are having a riskier operation, now, on
top of that, we are going to be asking them to perform some
type of look-back procedure. Many of these hospitals, that
is going to be a manual procedure; in any case, it is going
to very labor-intense.
The hospital administration is not going to
provide extra staff to do that, and the patients in the
operating room and the emergency room are still going to
need transfusing. Someone is going to be doing double duty,
trying to do too many things at a time that could lead to an
avoidable error that has been caused by our good intentions
of trying to get information out to patients.
MR. CAPLAN: Let me try this. Sense(?) of the
meeting, nonbinding. Just on the issue of, should we ask,
or look-back, from donors, who are positive by, let's call
it, hepatitis-specific test, 1990 to the present. As part
of our recommendation.
I think we are going to have no problem saying we
recommend that everybody get the test. It seems to me, we
probably are not going to have a problem saying, prior to
1990, it is going to have to be a massive campaign and
well-structured thing. I think we have the two ends of that
recommendation running.
What I want to get is a sense by hand -- I will
not hold you to it, you can change -- would you favor a
recommendation right now that said, in the period 1990 to
1998, given what we know about cost, burden, yield,
obligation to tell when you have these results, that we
include a recommendation to look back for any donor who
tested positive in that time?
That is not exclusive of the public health
campaign. We know we are going to miss -- they are going to
be subject to that, anyway, but I am asking about, as a
supplementary strategy in that 1990 to the present strategy.
Well, we have test results that indicate there is a unit
that is positive, do we have to look back and find out who
else might have been exposed to the donor of that blood?
Not all can vote who are sitting around here, but
of those who are on the committee proper, how many would
favor including that now, that provision? You have to put
them up 'way high. We won't hold you; you can even close
your eyes. Against? Uncertain, indifferent, no -- Okay.
PARTICIPANT: Art, let me make sure that I
understood what you said. The period that is creating the
problem for us is obviously the 1990 to 1992, that is where
we are hung up. Are you recommending that both targeted
look-back and educational campaigns be utilized as primary
methods for that group?
In other words, we say that we are going to put
equal --
MR. CAPLAN: Equal emphasis?
PARTICIPANT: Equal emphasis in that time period.
Is that what I hear you saying?
MR. CAPLAN: Yes. That we would do both. We had
test results. We could probably get someplace with the
record. And we would do the same public education -- they
would be told to get a test, anyway. They would be told
that there is risk in the blood supply. They would be told
that it was 50% accurate. You are not safe because you did
not test positive in this interval, blah, blah, blah.
The question is, do we include that along -- I
have to say, by the way, the sense that I am getting here is
that there is still not strong sentiment from the committee
to include that as a co-equal way to do this right now, just
for the sense of the meeting, so far.
PARTICIPANT: Kind of gets back to what I said
before, since this is obviously the impasse area. I would
be very much in favor of being very intensive in identifying
any type of risk to transfusion group, during this time.
Because I really believe that, if we -- you know, that the
yield is suspect enough that any resources we can to get
everyone identified -- and that is the reason I originally
proposed the mailing, who was transfused at all, is more
likely to get those people into identified HCV-positive
status, if they truly are, and into therapy, than the
targeted look-back.
I really think that, from a physician's
perspective, I would rather see more people get more care
out of this, than if we have to make tough choices, rather
than saying, well, we got a little bit closer to identifying
the actual ones who some test said was accurate, when it may
not have been.
The reason I am so leaning towards really -- and I
think maybe one of the ways we could get past the impasse is
to say, because this is a problematic era, during which we
had something that may or may not -- I mean, it may have
been better than nothing, but it certainly was not what it
was to become.
That we could apply more resources during this
time, along with the blanket educational programs, to
identify those individuals, across the board, who are at
risk. And then, ease backward, knowing that it does not
make any sense to do that for people who were transfused in
1981, because we will never get their addresses. But we
probably do have addresses, as we have already said, during
that period, and if we took a lot of intensive effort to
identify everyone who was transfused and get them tested, we
could come closer to solving this impasse, I think.
PARTICIPANT: I guess I am moving much in the same
direction. I am very sympathetic to the points that John
has been trying to make all morning long, but we -- I guess,
my economics training tells me that no matter how badly we
want two primary strategies, that in reality, that is not
going to happen.
Then I listen to the types of things like Jim and
others have said, that if we devote a whole lot of resource
to something that is not going to work, will that then
diffuse the effectiveness of the type of thing that Keith
has just described? And I guess my leaning -- you notice my
hand did not go 'way up when you asked -- my leaning towards
what Keith was saying, let's really get big barrels, and
this educational campaign that we are talking about in this
area(?), and as I mentioned earlier, my concern about
whether we are going to find people.
Yes, I think we will find more people in the 1990
to 1992 than in the eighties, and maybe we can be more
effective there, and it is in that spirit that I would tend
to say, let's not push back to 1990, but stick with 1992.
PARTICIPANT: That section [comment off
microphone] --
MR. CAPLAN: Just their accuracy, or lack thereof.
Alright. Let me try --
PARTICIPANT: I will just state again something
that Jim reiterated, the suggestion that we do look back
from second gen screened blood, which would include the
prospective look-back beginning back -- you know, to
seroconversion beginning back from 1992, but would also
include tracing back to recipients of first gen screened
blood, who got blood that was detected as infected after the
second gen test, which is about one in 1,000 units.
That would basically give us an overlap for that
period of 1990 to 1992, when there was transmissions going
on, some people may not get the full message because they
will think that was screened blood, I do not need to worry.
So, for that phase, we do do a look-back to first gen
screened blood that was negative, that was picked up when
the second gen test was introduced.
It then gets us also to the issue that the people
who we are doing look-back on, are people who have a
supplemental test to target that, to the specific period.
Some level of overlap coverage for that problematic period.
But would not go back -- I would propose it not trigger from
first gen screened donations for which there is no
supplemental.
In addition, it would not extend back to
recipients of first gen unscreened blood. It would only go
as far back as 1990, when first gen screening was
introduced, and the major thrust of our education would be
to the pre-1990, but bring along also the 1990 to 1992
people for general testing recommendations.
MR. CAPLAN: Go ahead. Keith.
PARTICIPANT: One of the questions that Carolyn
raised yesterday after we met, there is another group here
that we have kind of ignored in a way, in terms of, if we
put them in or do not put them in in terms of look-back, but
suppose we decide to go with the 1992 rigid cut-off?
There are still the donors who are identified.
Whether you do look-back or not, if they truly are positive,
those people are accessible a lot of times in a way that
even the recipient may be much more difficult to achieve.
Could we also go after that group, in that gray range we are
talking about? Because -- in other words, they are probably
positive. They need the same counseling, they need the same
further testing, if they have not already had it. Do blood
banks have the names of those donors? Could we identify --
PARTICIPANT: Those people, we have been obligated
and have notified those people all along. So they are
always told they are deferred from donating, they are told
they are positive, they are told the data we have and
referred to physicians.
PARTICIPANT: Oh, okay. That's good. So they are
always told why they were deferred?
PARTICIPANT: Yes.
PARTICIPANT: Okay, alright, that is good.
MR. CAPLAN: Mike, can you put that proposal
forward again, that we would only do look-back with a
confirmed test on the gen I group, is that what you were
saying, basically?
DR. BUSCH: Right, right, that we would -- look-back
would be -- would commence with the introduction of
second gen screening donations, and the second gen confirmed
positive donations would trigger a look-back, be it to
prior, second gen negative donations, which would be
seroconverters, or to the recipients of first gen screened
units for when the test was first introduced. Over that
first year or two there were large numbers of donors who had
been previously giving regularly, who had been negative on
the first gen, who were picked up and confirmed positive.
Rate of about one in 1,000.
What I am proposing is that, during that period,
we would notify the recipient, trigger the look-back to
attempt to notify the recipients of first gen screened blood
from those second gen pick-ups. But that that would stop at
the point of unscreened blood. So it would only go back to
recipients who got blood since May of 1990, when the first
gen test was introduced.
MR. CAPLAN: Let me try to tax Steve's ability.
New slide up. The reason I am going to ask you for a new
overhead here is, I want to see if I can get this into a --
Mike might even want to write it himself if he is so
inclined up there, but the idea is, if you take the
bookends, of what we had up on Ron's proposal, and agree
that we are going to call(?) for the testing before and that
we have a strategy about outreach for the pre-1990s.
What I want to do is get a vote, again, sense of
the meeting, about this proposal, because if that becomes
the middle package for how look-back goes, then I think we
have a -- we can pull these apart or list these separately,
but we may be somewhere. If it is not, we will have to go
back and debate a bit more, but let me tell you this. I am
not going to call for a final vote, I am going to let us
take a break. But if we get close to agreement on this,
then we can reconsider it and finalize it when we come back.
I apologize, by the way, to those in the group who
do not think that the look-back issue is the nub of what is
going on here. There may be some of you saying, yes, that
is the least of our worries, but we will take the meeting
and just continue with it, the other issues, other things
that you may want to get on there as recommendations when we
come back, so we will just plod on.
If we do not get to the post-lunch topic and
speakers, if we get consensus, and get this written up in a
form that we can understand, that will be fine. We will
pick up what to do next the next time we meet. Alright, so
one last time of trying to see if --
PARTICIPANT: Okay, actually, I would recommend
outreach extend through 1992, that that gives us the
overlap, so that continues -- the targeted look-back be
undertaken for donations confirmed positive with second --
who are detected by the second gen EIA, and confirmed by
appropriate supplemental testing since 1992. So, it
triggers on the donations that are confirmed since
introduction of second gen in mid-1992, that this targeted
look-back extend to, as far as first gen screened blood
only. So, back only as far as May 1990.
MR. CAPLAN: Do I understand what we are going to
be asked to see if we agree or not? All clear on this?
Okay, how many people would be willing to go with --
PARTICIPANT: -- (inaudible) for an example. So,
there are two relevant examples. The first is, we have been
screening with first gen for several years, we have just
introduced the second gen test, and a couple of months later
a donor comes in and is screened positive and confirmed
positive. And that donor had been giving first gen blood,
and the test was missing them. That was happening at a rate
of about one in 1,000.
So, because we are concerned that people who got
first gen screened blood, one, we think we have a relative
potential of getting to those people; and two, we are
concerned that they would have a mixed message. We were
giving them screened blood, they would think they were
relatively safe, so for that period, we would go back to
those screened units. But if that donor had also given into
the eighties, what I am proposing is that we not continue
that look-back trigger to the hospitals, prior to May 1990,
when unscreened blood was given.
The other issue is, the donors who have continued
to give and were second gen negative on several occasions,
and now they seroconvert in 1985 or in 19 -- sorry, 1995 or
2,000. Those will routinely trigger the look-back per FDA's
recommendation that you would go back, as far back as one
year prior to the most recent second gen screened negative
blood.
PARTICIPANT: If they do not have a second
generation screened blood?
PARTICIPANT: They don't trigger --
PARTICIPANT: If they go back -- if they gave a
unit in 1985 or in 1988?
PARTICIPANT: My proposal would be, no look-back
to units given prior to -- to units given prior to first gen
screening.
PARTICIPANT: But, how far do you (inaudible) go
back --
PARTICIPANT: May 1990. No recipients will be
triggered --
PARTICIPANT: So, the donor that is positive in
1992, you are not going to go check out individuals who
received blood that he gave in 1988.
PARTICIPANT: That is the proposal, right. That
we would have the overlap period where we would have both
targeted look-back and the education campaign for that
period of 1990 through 1992, but that it would not extend
back. Otherwise, if you are not going to -- if you are
going to say, just trigger by second -- and trigger by first
as well -- not trigger by first, 90-plus percent of the
donors who were infecting recipients prior to 1990, were
picked up by the first generation test which, if you believe
that is necessary, then you have to trigger it from first
gen donors, as well.
PARTICIPANT: Yes, but you have gaps. You have
people who came in in 1992, and their last donation was
1987. What are you going to do with those?
PARTICIPANT: Those people will be tackled through
the broad education campaign, because the records are not
there --
PARTICIPANT: [Simultaneous discussion] --
specific information for them.
PARTICIPANT: We are drawing a line, that is
right.
PARTICIPANT: You are drawing a line, and -- you
are drawing a line because it is going to cost more --
MR. CAPLAN: Well, let's see how many --
PARTICIPANT: And so it is a cost basis that you
are dealing with right here.
MR. CAPLAN: Let's see how many folks favor
drawing a line in this place -- sense of the meeting again.
How many can go with the look-back for the second generation
test, plus the look-back to confirm first gen tests by a
second generation test, as the overlap period for where the
look-back period is? That particular line.
PARTICIPANT: I need to state that again. I think
you just misstated it. What is stated here is correct, that
we would trigger targeted look-back for donors detected by
the second gen test, that that would only extend back as far
as transfusions from donations that were screened with the
first gen test.
MR. CAPLAN: Agree? Hands? Disagree? Hands?
Looking for a sense. Okay. Alright, let's revisit, we may
be staggering toward a destination that no one can remember
where we are going anymore, so what I would like you to do
is be back in this room in 45 minutes. Short lunch. Got to
come back, though.
[Whereupon, at 1:00 p.m., recess was taken until
1:45 p.m. that same day.]
A F T E R N O O N S E S S I O N (1:45 p.m.)
MR. CAPLAN: Take your chairs. Somebody said to
me during the lunch break, they know we are building toward
a proposal to look at, again, about narrowing the time
period at which look-back might be done, but somebody else
did say to me, they had lost a little bit of track about
what some of the other recommendations were, and in
particular, we did have two versions of a preamble put up on
the table. I think Ron had some language, and then Mike
Busch had some language, that were opening sentences. And I
do want to make sure we get back to those.
What I have in mind for our last hour -- and then
I am also told, since I did a little surveying around lunch
-- is that everybody is leaving. So, we will get to
consensus in the next hour. I warned our speaker for the
afternoon that we would not be able to get to them. We will
take the hour and march toward this modicum of agreement of
recommendations, but what I will do is, Steve and I -- did
Steve ever come back? No, he left. That's alright.
We will work with Paul to get typed up the
recommendations that we have here. We will send them out to
you for a final look-see, and then finalize them that way.
I am not going to try and commit you to what gets put on the
overhead. They are hard to read. The penmanship is fuzzy
and things get changed. So, we will try to edit them back
into a usable form.
Having said all that, why don't we see -- I know,
Mike, you must have been trying at lunch to polish that
language a little bit on the issue. Why did I know this was
true? And you could actually -- why don't we read it? We
are still on recommendation four, it is what I call the
middle sentences.
You will recall we said, HCV testing ought to be
recommended for everybody as a beginner, and we were trying
to do the major public health outreach and educational
campaign to get people prior to 1990 as points of consensus,
I think, and we are still in the sandwich here of
recommendation four.
PARTICIPANT: Right. One here is basically a
restatement of what you just said, although again, I think
that should continue to include recipients through the
second gen test introduction in March 1992. The PHS
education campaign.
Then the second issue which, through some
discussion of sort of compromise and I think appropriate
rationalization of, can you or can't you draw lines at
certain places? We have made a modification to what was on
the table before. Basically, it is proposing to implement a
targeted look-back program, triggered by donors detected as
HCV-confirmed positive by second gen screening supplemental
testing, which was introduced in March 1992.
There is a minor detail here that the supplemental
test was not approved until early 1993, but most blood banks
did have access to that, so most of your second gen screen
donations were confirmed. One probable scenario would be if
you did not have confirmatory, you perhaps would have to
notify, based on the screening. But optimally, you would
have confirmatory tests.
Then, who would be notified is the three bullets
below that. Clearly, you would notify per, you know, the
earlier discussion, recipients who had gotten prior second
gen negative units. And this would be the second gen
seroconverters, and this would be what would continue
henceforth.
The second group we discussed was actually going
back and notifying recipients who got first gen EIA-negative
units. That would be the recipients between 5/90 and the
introduction of second gen testing.
And then the third group of recipients that could
be triggered from these confirmed positive donors would be
recipients who got unscreened blood prior to 5/90. And in
discussion right after we broke, it was felt that stopping
at 5/90, when you have already initiated the identification
of the confirmed positive donor, you have looked at his
donation history records, and then you have a history of his
having donated in 1990, 1991, but also back in 1989 and
1988.
To draw that line is somewhat arbitrary when you
have that information in front of you, so perhaps an
appropriate compromise would be to extend this second gen
triggered look-back to recipients of unscreened blood.
Now, just a general opening the door to all prior
donations creates somewhat of the uncertainty as to how many
of these products are going to be traceable, etcetera, so
actually in discussion with Dr. Epstein at lunch, he felt
that perhaps, per FDA's usual recommendations, that
extending back to some reasonable time period, but not
indefinitely, would be appropriate, and putting a front-end
bound on that of 1985 or 1987 might be reasonable.
MR. CAPLAN: Comments? Again, remember, we are
trying to balance very important, two sets of principles
here, which you have heard again and again, that what we are
trying to do is decide if we have knowledge from tests, that
someone may have been exposed to a donor who is infected, to
what extent do we want to push for a tracing -- I do not
want to call it a look-back anymore -- tracing back
strategy, for that exposure, when the two types of tests
existed.
I think, you know, the political, the moral
question, the PR question is, if you knew something, why
didn't you go back and find the people that had been
exposed? We have to be prepared to answer that question.
This is an attempt to lay out at least a strategy that says,
in some areas, we are going to look, in others, maybe
drawing a line that is somewhat arbitrary, we are going to
go with a bigger outreach campaign. So that is what we are
struggling with.
I think that just to put the heat on us, yet
again, we will be asked by some, why didn't you just look at
anyone who might have been exposed when you knew it? That
is a moral question, and we have to be prepared to answer
that question, if that is not what we do. And, at the same
time, we also have to be prepared to answer the question,
why are you making us look, if the yield is low, if the
costs are high, if the records stink, why don't you do it
some other way?
We are trying to balance in there, don't ask us to
do what we cannot do at one end. Why didn't you do what you
should have done if people knew, at the other end?
Somewhere in between is what this is working to answer, is
the way I would put it.
Any other -- aside from that brilliant comment? I
do not have a sense, and I am really looking to the blood
bankers here about the time limit issue, which has become
issue C about looking back to the unscreened thing, we are
going to draw that. I know there is not a right answer
here, it is just an answer, but --
PARTICIPANT: Considering this, I think, from the
blood bankers' perspective, one, this is a fairly enormous
task. We have to go back to all of the donors found.
Probably in an average blood center of 100,000, we are
probably talking about tracing back and finding the records
on about 5 to 10,000 donors who have been detected as HCV-confirmed
positive, identifying the subset of that group who
were repeat donors prior to that, through the computers,
generating lists of their prior donations, tracking back
through archived records to determine where those products
went, and compiling notification lists to the hospitals, of
all of the products that went to their hospitals from these
donors who have been now found as confirmed positive.
It is a large undertaking. The issue of whether
you draw the line and stop that process at 1990 versus 1987,
versus 1985, versus indefinitely, for the blood centers, it
is modest additional work the further back you go, but I
think the issue really becomes at the hospitals at that
point.
Once we have started to track these records, we
can basically go back and find these archived -- I need to
go back to my own center and find out what the impact would
be, but I really think the burden here, if we are going to
move through, and we are talking specifically about how far
to extend it back, is going to be on the hospital's --
particularly concerned that a hospital has a blanket
understanding that they do not have records prior to some
date, but they are getting these notifications from us about
transfusions prior to that date. They have certain
liabilities and efforts that they consider they might have
to undertake to go beyond any reasonable effort, to ask the
hospital folks to comment on.
PARTICIPANT: Well, to put a number on this, we
are probably looking at, if we talk, let's say, 1987 as a
cut-off date, I am working off the top of my head here. But
we are probably dealing with about a quarter of a million
tracings that hospitals will have to do. That is, they will
be notified of about a quarter of a million components, that
they will have to go back through their records, a large
share of them being manual records, to identify the
recipients, and then initiate the notification by letter or
however they will do it.
PARTICIPANT: That is nationally.
PARTICIPANT: Nationally. And if the FDA, in
providing recommendations, guidelines, or regulations as to
how this is to be done, implements it in the way that HIV
notification, look-back notification, is to occur, it is a
substantial process, because we are required to make at
least three attempts at notification, if I remember
correctly, within a defined amount of time. And this could
be -- if we were to be required to do this, or if that were
the standard of practice to do this for HCV, it could be a
substantial undertaking for hospitals. Not one that is not
worthwhile, understand.
PARTICIPANT: Clearly, Jim, the link is broken --
the three blood bankers are speaking here. The link is
broken at the hospital transfusion service level, and they
will not be able to track back that 250,000 components.
The blood centers will be able to notify the
hospital that the link is broken, unless they actually went
to the patient files, which are on microfilm -- and that
truly would be an impossible job, and I would never
recommend that -- so, I do not think we are going to see the
hospitals being able to track back this number of
components.
MR. CAPLAN: One thing we can do, if we want to
draw a line, somewhat arbitrarily, about 1985, 1987, with
this look-back, coming back again, the trigger being still,
the gen II test confirm, which still leaves some window of
people that we know something about, maybe not well. I just
want to remind you of all that, that we have not -- that we
have decided we are not hunting for it all. But, we could
say -- I hate to be temporizing about this -- but, our
recommendation is now that we launch this undertaking, that
we watch what happens here, and we are going to revisit this
and see if the entire hospital, blood bank, United States
health system, collapsed, under the duress of trying to meet
this requirement.
If it does not, we could then extend that look-back
to the other population we have been talking about, or
we could say, go back to 1906, and continue on. This has
been a wonderful demonstration of your efficacy -- in other
words, I have to say in all honesty as I look at this, some
people have said, can't we pilot, can't we check? Couldn't
we see?
Well, I think the American people will probably
want to know that, if we knew that some of them were exposed
to infected blood, that we did what we could to tell them.
I personally am going to find it hard to say, I knew you
were exposed, even in a probablistic way, and I did not tell
you. That makes me uncomfortable. But, I am much more
comfortable if I say, well, I have a two-pronged strategy.
I am going to make a big push on the public health side, and
I am going to take this on as my trace-back, and we will see
what we get.
I mean, we could say, this is our attempt to sort
of reach a balance, and if it is getting us where we need to
be in terms of letting folks know that hepatitis-C is
something they have to worry about, okay. If it turns out
to be something that is implementable before the year 2,000
and carries forward, okay. But it may still leave us a
little bit of room to come back and then add to or follow-up
on it, depending upon the cost and the precision and the
real impact of those public health outreach efforts.
If they do not work; if no one spends any money on
the PSAs, if there is no budget put forward, despite what we
have to say about doctor education that really dents(?) in
there, we could be back here saying, well we have to do more
tracing. The other is a failure.
In other words, I am hopeful that some of what we
are hoping is going to happen will happen, but if it did
not, we could come back and say, well, we went halfway down
a road and we are ready to finish the trip now, because we
did not get where we were supposed to be. So, we may ponder
that as something to bring into this discussion.
PARTICIPANT: If you raise the issue about who is
going to allocate money for these various efforts, who is
going to pay for the look-back effort? There is a huge
amount of expense there. I would have to calculate it out,
but it is in excess of several hundred million dollars.
Are hospitals going to be expected to bear this?
Do blood centers have to just eat what it cost them?
Obviously, if you are tracing back a quarter of a million
donations, that is a lot of person hours, a lot of time and
effort, not to mention just stamps and stationery. Is this
something that the hospitals just have to swallow?
MR. CAPLAN: Mike(?), you know, I will tell you
what my answer is to that, too, is the cost issues have come
up sometimes about access or getting testing or who is
carrying the load for either the public health outreach
campaign that we call upon the agencies to implement and
coordinate, or these kinds of trace-backs.
It seems to me that what we have to do is decide
what we think ought to happen. At that point, we will let
the agencies, the White House and Congress, the lobbyists,
whoever, battle it out. And I mean that in all sincerity.
We will not do it as soon as we leave this room with a set
of recommendations, phones will go off and people will start
to say, well, what can we do to avoid getting this cost
stuck on our plate? And I wish all of them well, but my
attitude is, we should decide what we want done, and then
the chips will fall.
I think we should send a clear message about that
hepatitis-C testing, that that -- to put that up there and
say, and you know, we hope it happens, is not enough. That
we have to send that out as a major public health challenge
that ought to be addressed by this country, and we think
that that testing ought to be available.
I am perfectly willing to say that that ought to
happen, and that we urge the White House, the agencies,
Congress, to make it happen, but in all honesty, we will not
sort out the, who is going to pay for this, and we should
not. It is not even our -- yes, Trish?
DR. O'CONNOR: I had a question. Were you
suggesting with this, I guess sort of a huge pilot, that we
just do A and B and [simultaneous discussion] --
MR. CAPLAN: No, no, the whole thing, but watch
it. That we are monitoring and evaluating to see what is
really happening here, so that we know, if we have put our
eggs in the basket of the pre-1990 look-back, and no look-back
is happening, that is going to change my thinking about
the duty to inform.
I mean, if it just does not happen, I am going to
be very nervous that people are not getting the information
they want, because no one made a sincere effort that we are
going to go back and urge tracing to eternity. I mean, I
would, not we would, I would. John?
PARTICIPANT: We have already heard from the
British and the Canadians, that it did not sink their ship,
despite some of the critical nature of some of their
budgeting problems, so it does not seem to me that it is
that overwhelming in comparison, and the fact that they have
already accomplished this on their own, and that we are kind
of just following along, seems to me that if we do not do a
pretty good job and a thorough job, it is going to look very
sad that we could not keep up with the other members of the
world.
PARTICIPANT: Could I clarify what we mean by
test, when we talk about test recipients? Does this mean
that, for those recipients that do not have private
healthcare, that there will be some mechanism that they will
be able to get a test performed? Is that what we are
proposing?
MR. CAPLAN: We are not proposing the mechanism,
but we are saying there is a -- there should be an effort
made to make sure that that testing can be done.
PARTICIPANT: What we are basically saying is,
that the private healthcare, and/or some other mechanism,
should allow every patient who is identified, or who was
part of this group that was contaminated, post the people we
are looking back at, should be able to get a test. That is
what we are saying.
PARTICIPANT: Okay. I agree. I just wanted to
clarify it.
MR. CAPLAN: I think that is in a word,
aggressive.
PARTICIPANT: One question I have had throughout
the day is whether -- we have heard the CDC's sort of plans
for this national hepatitis testing or information strategy,
and one option that is attractive would be to fold this
recipient piece into that. It is an existing mechanism,
presumably funded, presumably there is testing on the heels
of that.
The caution or concern about that is that the
recipient piece of that should be small, because it is a
small piece of the total HCV risk. So, the other option
would be to argue that we need a separate recipient-specific
public health campaign that is perhaps piggybacked or on the
heels of that, but I think that is an issue that perhaps PHS
can deal with, but I think our group would recommend that it
be a focused recipient piece, and not simply a small piece
in the bundle of HCV planned already.
MR. CAPLAN: Well, let me see if I can be
parliamentarian for a second here. Are people interested in
voting on that at this point, or would you like to have a
little more discussion?
PARTICIPANT: [Comment off microphone.] -- very
serious consequences and (inaudible) pretty much part of
(inaudible). I just wonder if you couldn't in some way try
to connect this part of (inaudible) campaign (inaudible) so
that when we take the story about the hepatitis-C virus
(inaudible) right to conclusion and we have recognized
across all sectors of the communities, this is now another
virus (inaudible), because otherwise, we effectively will
have had a national (inaudible) hepatitis-C (inaudible)
campaign, my kids are protected against it.
It just occurred to me and I am a little bit
concerned that maybe we need to add one other(?)
dimension(?) to this(?).
MR. CAPLAN: Probably not bad for preamble
language, too, in terms of saying, again, we know there has
been a lot of attention to this, but this is a special area.
Hepatitis-C, here we go. Again, once we say that, we can
certainly expect that the agencies, as they try to implement
the public health dimension of this, are going to wrestle
with that very problem.
That is going to be there for them as a major
challenge. Because I do think a lot of people hear,
hepatitis, hepatitis, and assuming they have had one
negative hepatitis test for some hepatitis virus, will
assume they are done with all of this, and we are going to
have to explain that in clear language. Not us, I mean, as
this gets implemented.
PARTICIPANT: But I think it is incumbent on us to
inform them (inaudible) statement(?) (inaudible).
MR. CAPLAN: I am seeing some, put it to a vote
sentiment here by expressions. Alright. What you are being
asked to do is approve maybe with some minor wordsmithing,
as things go along, or dissent from, this proposal, that we
seek out aggressively to know the test recipients transfused
prior to March 1992, through PHS physician and public
education campaigns.
We may actually -- you can make a note of this,
Steve -- put in something like that the financial means be
made available to allow people to get that testing. We can
add that so that we are clear that that is what we were
talking about. Or that, whatever. The financial obstacles
be eliminated or reduced, to the extent they exist.
Implement the targeted look-back program triggered
by donors detected as HCV-confirmed positive by second gen
screening and supplemental testing. And -- I will not read
the rest of it, but with these qualifications, and I think
what I heard was -- although I am open to this -- the vote
will be actually on drawing the line on 1987, unless someone
wants to pipe up. And the justification for drawing it at
1987 is partly due to where other record look-backs of this
type have been, but acknowledging that it is somewhat
arbitrary.
Alright. In favor. Opposed. Abstain. Is that
an opposed or abstain, I jumped fast.
PARTICIPANT: Abstain.
MR. CAPLAN: Abstain. Alright. Let's do it again
by count. I think I am actually going to record this vote.
All in favor. Opposed. Abstain. One, alright. What did
you get?
PARTICIPANT: Eleven(?), zero and one.
[Whereupon, the motion proposed by the Chairman
was passed unanimously by a vote of hands.]
MR. CAPLAN: I am in a state of shock here, since
I had not expected to get that thing off the page. We will
go back and fold that into the language that Ron gave us,
too, Steve, if you can remember this, on this
recommendation. We will try and wordsmith that to make them
come together. And again, on recommendation four, which is
what we are still talking about, we will make this part of
something that we will send out to you to just make sure you
knew exactly what the language was.
If we could, then, let's go back to that first
sheet, recommendations one, two, three, and also, Steve,
keep handy a blank one, because I have a feeling we may hear
a couple of other recommendations.
Let's revisit for a second, recommendation three,
which we did clearly establish before the lunch break that
no one knew what it meant anymore. It is a valued
recommendation, it is an important one. We do not know what
it means, and I guess I want to put the question, are we
getting rid of recommendation three completely? Is there
something there that we were trying to say that we have not
said very well? Mike?
DR. BUSCH: Well, my thought was that perhaps this
could be a preamble point to what other recommendations we
just voted on, stating that we have reviewed the range of
strategies available for identifying individuals at risk and
propose -- in collaboration with all experts in Public
Health Service, and based on deliberations, propose the
following, and then that leads into the recommendations.
MR. CAPLAN: Yes, Keith?
PARTICIPANT: I would like to include testing of
people who for some reason -- and there will be a lot -- who
do not come through the look-back. That we recommend they
be tested -- (inaudible).
MR. CAPLAN: That is up in -- that is in the first
part of that next statement. Yes, it just fell over to the
--
PARTICIPANT: Okay, sorry.
MR. CAPLAN: Alright, we can use three, then, as a
little bit of boilerplate to set up what will now become
recommendation three, as this is now numbered. Do you want
to say -- let me just ask you again to revisit, briefly
recommendation one. Implementing a program to educate
providers of medical care in the appropriate assessment and
counseling of individuals at risk.
We talked a little bit before about that this
should proceed, I believe, or that this has to happen very,
very quickly. If we are going to be having people coming in
for a testing and look-back and so forth, and asking
questions -- I mean, it is going to happen so quickly.
It is going to happen tonight when these news
things get on the air about people calling their doctor but,
do we need to say anything more about the speed? Do we want
to see this plan presented to us at a future meeting? Would
that be appropriate? And we have not said anything here
about evaluation or audit of the activity. Well, in fact, I
will propose that we add that this educational program be
monitored and assessed in a timely fashion.
PARTICIPANT: With regard to our education
program, one of the things that I see in the patients is
that they may have dual problems. They have been
transfused, and they may be remote IV drug abusers.
I think it is very important as part of this, when
we are reaching transfused patients, to also advise them,
there are other high risk behaviors, that even though they
may not have been infected by transfusion, they could have
been infected by some other lifestyle that they have
indulged in in the last 20 years. So, I think it is
important to get that in there, as well, because more of
these patients, I think, will have been infected by their
lifestyle, like IV drug abuse, remotely, than would probably
have gotten it from transfusion.
PARTICIPANT: There is also the group -- we might
want to say something about, you may not be completely --
you may not know exactly if you were transfused or not. If
you were in any of the following high risk groups for
transfusion, please consult with your physician about
possible testing. Like, prematurity, etcetera. I mean, I
don't know if you have an exhaustive list, but --
MR. CAPLAN: Do you think it necessary that we do
this on a -- do you want to get this specific in the
recommendation, or do we want to see what they bring us
back, in terms of how they decided to implement here?
PARTICIPANT: Well, I don't know. Maybe singling
out prematurity as special, or a low birth rate, infants as
a special issue is not appropriate, but my personal
experience is that, there are a lot of babies, particularly
who were born peri- or pre-HIV, who got (inaudible)
transfusion, may not have been aware of. They may know they
were born premature, because obviously, their parents --
MR. CAPLAN: Well, how about this? We -- Steve,
one recommendation that we did not put up there yet, which
we had talked about is, the obligation -- the need to inform
people that they may have received a transfusion, and that
they may want to talk to their doctor about finding out how
they could establish whether they did or not.
PARTICIPANT: This sounds good. You know, what is
currently number one here, could perhaps just be expanded.
I think it clearly should be the first statement coming
after our statement of facts, that we recommend that there
be implemented a broad program to educate about appropriate
assessment, counselling, and then perhaps a second sentence,
this program should include specific information about the
risks of transfusion over time for HCV, and subgroups of
patients who are at risk of having been transfused.
Then, what we are doing with the next piece that
was on the other page, is we are going on to the specific
additional focused public campaign that should target
recipients, above and beyond this general implementation
planned already, I think.
MR. CAPLAN: I don't know if you followed that,
but, Steve, that was a -- emendation. The issue of alerting
people to the possibility that they may have undergone a
transfusion and the need to counsel about that. And the
need to make sure they understand what other behaviors might
put them at risk, if I was capturing your point, too. Those
are -- we will add those in under --
PARTICIPANT: The other point is, what is
currently number two here, I could argue is actually
subsumed under what we already have in that other piece, but
I also think it could and maybe should stand alone, as a
third bullet under that other piece of our recommendations.
It would come after the piece about, this committee has
considered strategies for identifying -- and(?) we
recommend. This would be one of perhaps three pieces there.
MR. CAPLAN: Yes, I understand what you are
saying. All that would mean is just moving that particular
strategy for individuals at risk under, to go along with the
others. We can do that, too, that is fine. It will be so
simple. We will have one giant recommendation in a second,
just with many subpoints.
Are there other recommendations -- oh, no.
Actually, before I do that. Are people comfortable -- I am
going to ask for a vote -- on recommendation, what is now up
there as number one, about the implementation of the
program, the counseling -- oh, and the assessment. I
forgot. Assessment, a timely assessment of this education
program should be on there, too.
Here, we are asking you for a little bit of a vote
on some vague language, but -- I mean, we have notes up
there, but the spirit of it is, to get this education
program going forthwith, but the agencies work to establish
this. That it be both there to assess and counsel. Let
people know about ways in which they could have been put at
risk in the past; that is, transfusions they did not know
about. Ways in which they could have been put at risk right
now or in the past by lifestyle, and then to assess this
effort to make sure that it really is doing what it is
supposed to be doing.
In favor? Opposed? Alright, I actually got a
unanimous one there.
[Whereupon, the motion proposed by the Chairman
was passed unanimously by a vote of hands.]
MR. CAPLAN: Having tested our penmanship beyond
belief, why don't we put a blank one up there and see if
there is anybody who wants to add any other proposed
recommendations? Maybe I shouldn't have forced a blank one
up there --
PARTICIPANT: Art, it occurs to me that maybe --
and I am sure that probably the agencies, especially the
CDC, will ultimately be coming out with some
recommendations, but the first one that gets out to the
public is the one that is going to probably raise a lot of
questions.
One of the questions that will invariably come up,
that we are going to need to be prepared to field is, how do
you deal with the circumstances that affect those
individuals that are very close to someone that fits into
the risk categories?
The newborn infant of a mother who is HCV-positive
and, you know, fits into the category, well, we have done
the look-back, find her to be HCV-infected. Can she
breastfeed? So, I mean, there has to -- it seems to me to
be that one other section that at least opens up the
opportunity to build in those other considerations.
MR. CAPLAN: Yes --
PARTICIPANT: Not included under assessment and
(inaudible).
MR. CAPLAN: There is a tendency here to want to
make sure that we -- well, let me put it this way. We will
not necessarily have to spell out some of these points in
the recommendation, but what we will do is send the
transcript along with the recommendations, so that the kind
of specific points that were originally thought about or
reflected about, will be on the record.
If we try to do each one of these, we will wind up
-- the recommendations will get lost, but we have taped and
will transcribe everything, so when we pass the
recommendations along, a lot of this is going to be captured
in there. I got asked -- I keep reporting to you, my big
empirical studies --
The other thing I did not tell you was, the three
cases that I found where the doctors did not know what to
counsel, one of the things that was of concern to the people
was, could they maintain sexual relationships with their
partners, I mean, knowing that they were -- so, and I think
that was a question that the doctors were not prepared to
answer for them.
There is breastfeeding and might I have a problem
if I go to the health club and all these other kinds of
questions are going to come flying out. They have to be
addressed, that is exactly the sort of thing that people are
going to ask, and that is what I am a little nervous that
our physicians are not yet in a position to give good advice
about right now. Dana?
MR. KUHN: I do not know if this has anything to
do with the hepatitis, but I have heard a lot in these
discussions that we were having problems with the record-keeping.
I do not know, maybe this is going to be something
in the future that we would want to look at, to include, or
encourage blood establishments, hospitals, however, through
whatever mechanisms, to keep longer -- records for a longer
period of time, considering that other epidemics or endemics
are possible. And if that would even help future look-backs,
or notifications.
MR. CAPLAN: Comments?
PARTICIPANT: [Comment off microphone.]
MR. CAPLAN: I am just giving Steve a minute to
catch up there. On the issue of, do we want to say
something about records? There is certainly no reason why
this body cannot make recommendations based on hepatitis-C
about record-keeping, or the need to set up a system that is
as good as it can be in terms of finding out about
infectious diseases.
I do not think we have to link it to hepatitis-C,
we could. We had a little discussion, you will recall,
about CJD at the last meeting, and there are other bacterial
things and so on, where people have raised issues about
record-keeping and information.
The only reason I am hesitating to put it in here
is, I guess I see us today as just sort of trying to
address, to the extent we can, the hep-C issues, but I do
not mind at all coming back at a future meeting, to the
issues of records and information.
PARTICIPANT: I agree with that. I think we
should come back, because I think there are a number of
issues that we have not even touched on that need to be.
MR. CAPLAN: Any other potential recommendations
about hepatitis-C, specific? One of the things that we did
say was that, we would be concerned about making sure that
obstacles to testing, to counseling, were minimized, and
that is in our recommendation in terms of aggressive
efforts.
Do we want to say something that stands out as a
recommendation on that? One of the things that will jog
your politicians is if you make a special point of
recognizing that there are obstacles out there in the
current healthcare system, both to testing, to counseling,
to tracing, to many things.
I mean, my personal inclination is to try and
bring that out, that every effort be made to minimize
obstacles, and everyone will stand up and salute that and
say, yes, every effort should be made to minimize obstacles.
The question is, do we want to put it in there so we can
hold people to account, to find out what they did? Maybe we
can have a few congressmen in for testimony. Keith?
PARTICIPANT: Do we want to say that this is --
rather than lose everything by saying it belongs to
everybody, actually say, it does belong to everybody, but
there has to be a concerted effort by the government, the
private sector, the whole healthcare delivery system to
[comment off microphone] stating that everybody and
therefore nobody is going to take responsibility. But at
least it singles out that it is not likely to occur until
every one of those components is in agreement, and is
cooperative.
MR. CAPLAN: Yes.
PARTICIPANT: We have now identified these people.
What are we going to do with them? The NIH consensus makes
some statements around offering therapy, and I think it is
unreasonable to identify people, if we are not going to do
something about them and determine whether they are
appropriate for therapy. And this, then, gets into our
healthcare system again.
MR. CAPLAN: Certainly, an appropriate therapy up
to that list of, minimize obstacles to testing, counseling,
and appropriate therapy. And even, I might add -- you do
not have to say this, but I can -- even to access to
clinical trials, which is, I know from my own healthcare
center, getting to be an increasing pain in the neck about
finding out who is going to pay for the clinical trial type
thing, that is getting to be a big issue.
One way to do that is to say, we want to minimize
obstacles to testing, counseling, access to clinical trials,
and appropriate treatment, and that all sectors must work
together to make this happen, or have an obligation to work
toward this end, private and public. Does that kind of
language seem to -- I mean, I am keenly alert to the idea
that I am mouthing extreme platitudes here, so I do not mind
dropping it if it does not seem to go anywhere. Good after
dinner speech rhetoric, but maybe not worth it -- paper.
PARTICIPANT: We are talking about public health
issues. Public health issue puts it in the public sector.
If we are serious about it, why don't we say that the public
sector needs to step forward and make sure this gets done?
If we are not going to be explicit about it, given
the anti-tax and all that stuff going on, it is going to be
shoved back into the private sector, and without throwing
stones, the private sector has to protect its own self(?) --
and there are going to be holes. So, if we are serious
about it, let's say it is public sector responsibility.
PARTICIPANT: I think it may be the public sector
responsibility to perhaps do the counseling and (inaudible)
the testing, but I think when you get into the treatment, I
think that has to certainly be a shared responsibility, I
think especially today, when it is very blurred out on the
playing field, in terms of what is public and what is
private, and the way that the systems of care have emerged.
So, I think the suggestion that you offered, Art, seems to
be a very reasonable one, to build into it, the opportunity
for therapy and clinical trials, as well.
MR. CAPLAN: Paul, can you just scribble that up
there under three, up there? The access to the clinical
trials and therapy (inaudible) -- it is just in penmanship.
And actually, you know what, Steve, that is actually just a
continuation of three, not even a new four there. Access to
clinical trials and appropriate treatment. You can put that
appropriate treatment thing in there, too.
What I am going to do is try and cast some
language that says the public and private sector must work
together. I do not know what to do with Paul's suggestion
about it, if it is a public health responsibility, move it
on the testing and counselling (inaudible), are we prepared
to endorse that?
PARTICIPANT: I think that is impractical. You
are not going to get a public health mechanism to do all
this. Most of it is going to fall on public -- on private
or general public insurance, etcetera.
PARTICIPANT: This is essentially the cost of
doing business.
PARTICIPANT: The other thing is, if this is going
to be -- the identified infected people are going to be out
of this broad catchment, and only a small proportion will
actually be transfused recipient infections. Some of them
may have mixed risk factors, including recipients. Others,
you know, basically, we will not be able to prove or
disprove whether who is found infected was transfused or
not. For the same reason as we cannot do effective look-backs.
MR. CAPLAN: Let me tell you one reason to keep
this statement in here, and then I will get off my hobby
horse about this. If I was trying to get coverage out of my
HMO for a test. Or if I was trying to get coverage for an
innovative form of therapy that might come down the road, I
might, if I was very lucky, know somebody who knew that this
group had said something like this, and use it. I mean, I
might bring it forward.
What happens from groups like ours is, they have
the function to some extent of a consensus panel. If we
say, well, this is very important, and this is a kind of
public health challenge, it is a standard of care. You can
sometimes wedge resources out of the private sector,
invoking that kind of thing. I have done that myself on
occasion.
It may have minimal power. I am not sure we could
probably command the public health budget, I think you are
right. It is just not going to happen. It probably is
overhead to somebody's business costs, but if you are
sitting there saying, are they going to put hep-C testing
into my HMO plan, that kind of statement sometimes works,
and say, well, this group said that they should, so, you
ought to. That happens.
Alright. Those who want to include -- let's do
this backwards. Recommendation three? In favor of that,
that we vote to include language that will minimize these
obstacles to these things? Opposed. That is a unanimous.
[Whereupon, the motion proposed by the Chairman
was passed unanimously by a vote of hands.]
MR. CAPLAN: Should we move votes on one or two?
We want to keep the language in at the end, as knowledge of
hep-C accumulates, we want to revisit, does that seem
reasonable to include? Favor? Okay. Opposed? That is a
unanimous.
[Whereupon, the motion proposed by the Chairman
was passed unanimously by a vote of hands.]
MR. CAPLAN: I cannot remember what the first one
was.
PARTICIPANT: Medical records (inaudible).
MR. CAPLAN: Oh, the medical records one. That
one we agreed we were going to hold over and revisit. Okay,
we do not have to vote that. I am getting the feeling that
we may have reached the end of the road of today's meeting.
We have not reached the end of the road of penmanship and
calligraphy, but what Steve and I and Paul will do is try to
reconstruct the language that we have been doing. This is
tough on overheads that can be wiped out. We will have to
put them in amber or something, as soon as we leave the
room.
We will send these out to you. For those in the
audience who are interested, we will keep copies available
through Paul's office, too, if you want to see what the
final language looks like. This is not to edit in any major
way, we are just getting it back to you so that you can make
sure that the commas and the periods and the textual
coherence is what you thought it should be, and at that
point, what I will do after that is, I will be back in touch
with you after Steve and Paul and I and maybe Eric, have
some further discussions about what we might do next.
I could be cruel and open that discussion up now,
but I am not going to, because I think we have come pretty
far today, that is a little mean to ask you to think about
other things, having gotten this far.
There are other topics we can revisit. I would
love to hear your ideas about what some of those might be,
whether it is plasma pool size. Availability of the blood
supply. Medical record-keeping. I do not much -- let me
know. E-mail me, fax me, phone me. Steve can be reached
through Eric's numbers and fax machine. You can let him
know if you have any ideas. That is going to become the
basis of our agenda.
We have not been asked formally to comment on the
CJD issue. It is there. We did not finish it, we just
heard about it. We could add in some of your infectious
agents. As somebody told me, I think it was Keith, this is
a committee that is supposed to look at availability, as
well as safety, so availability issues are out there.
Whether you think we ought to look at something like paid
donation or whether blood costs too much. That was bandied
about today a little bit.
We actually heard a speech which I never thought I
would hear in my life by someone in the blood system,
calling for a higher price. Charge me more. And all those
are fair game for us to move to.
We have no scheduled next meeting yet, but I will
probably see some dates and presume that there are things
that this group wants to talk about. So, I am not going to
wait until I get the topic, you are going to hear something
about next dates. Probably, some time in December, January,
which is when I think we will reassemble. And we can fill
in the agenda, if you will do that.
So, watch to make sure that you check the text as
it comes to you, by mail or fax. If you do not get it,
within, let's say, the next three weeks, call Steve and say,
I did not get what you said you were going to send. Just
call him or contact him. And send us your ideas about what
you would like to turn to next, and we will be getting back
to you with some dates for the next meeting, okay?
MR. CAPLAN: Art, I would like to get a sense of
the committee on recommendation number two, in the draft
submitted by Mike Busch. It is clear enough what is
recommended if there is a positive, supplemental test.
However, that leaves unstated and therefore unclear, what is
to be done if a supplemental test was not performed. And
there will be a significant percentage of generation II EIA-screened
positive, or repeat reactive, as we call it, for
which a screening test was not performed.
Is it the sense of the committee that the directed
look-back should be recommended, if supplemental testing was
not performed, or should it only be recommended if
supplemental testing was performed and was found positive?
MR. CAPLAN: I have a comment about this, but I
will open it up.
PARTICIPANT: I agree with Jay. There was a
period of time between March of 1992 and early 1993, before
FDA had licensed the original second gen REBA(?) test, which
was an appropriate, complementary, supplemental test to the
second gen screen.
Most blood banks gained access to second
generation REBA(?) at that period, ongoing, for online
confirmatory testing through a reference lab service that
FDA allowed to transpire. But there may be some modest
number of screen-reactive donations that the blood center
did not go through the hoops to get those things tested.
Now, to my mind, I do not think we can let those
off the hook. Those do need to trigger a look-back. You
either have the confirmatory data, or if you do not have it,
you get it now, if you have the sample, or you have to
notify, and that is part of FDA's language.
The same problem exists today, unfortunately,
because the third gen test was licensed now about a year
ago, and has been in place and regularly screening donors
without a third gen REBA(?) test to prove, and again, Red
Cross and a number of other blood centers have developed
mechanisms to gain access to that third gen, pre-licensure
test, and have those data coming on online, but other blood
centers have not done that. So there is again, now, a
period of time when there are people who are getting
screen-reactive results, without confirmation. And I think it
points to another issue that is dear to my heart, which is
the need for these companies and FDA to bring up
supplementals in concert with the screened, because
otherwise we are out of linkage and we have all these
problems.
I think, there again, if you do not have the
supplemental, I think you have to proceed with a look-back.
PARTICIPANT: That is what I would have said.
PARTICIPANT: Yes, I (inaudible). So that is the
spirit there, looking back, if you do not have it.
MR. CAPLAN: Yes. Mary.
PARTICIPANT: I guess I also wanted to hear(?) the
agencies, I guess, wanting the final clarification. CDC, as
you know from Marian and health presentations, has really
had the lead within the PHS right now for the educational
campaign. And I just wanted to make sure that it was clear
to me, the messages about education of providers and the
public, who include people at risk, among those, transfusion
recipients.
As I understand now, the structure of this
document, there is going to be something as a preamble that
kind of endorses the need for, and speedy implementation of,
a campaign, an education campaign, for providers and the
public about modes of acquisition, diagnosis, treatment,
prevention.
Then, within the specific recommendations, which
was up there on the transparency, number one. Aggressive
campaign to notify and test recipients transfused prior to
1992. And what is not clear to me is, is that the same? Is
it different?
MR. CAPLAN: That campaign -- the campaign
discussed up there is to tell people that they ought to go
out and get tested.
PARTICIPANT: Right. And I mean, if you review --
and (inaudible) passed out, I mean, admittedly, it is the
bones, it is the structure of, a working document, something
in progress. But, the messages that were originally crafted
were, transfusion before 1990, and this committee is
recommending that that message be changed to 1992.
Okay, fine, but you know, for each of these bodies
of -- for each of these target audiences, be it the public
or providers, you know, these are the messages, that
recipients are surely among those who are considered at risk
for infection.
What I am trying to distill out of this is, this
is the plan, the bones of the plan as you have it now. Is
this not, as best you can surmise, adequate to accomplish
one? Because -- it is confusing to me, because it is
mentioned in two places. It is in the preamble. We
endorse, there is this education campaign, dah, dah, dah,
dah. And that is going to happen, you know, as Hal and
Marian had spoken to earlier.
MR. CAPLAN: The way I would answer it is this,
and other committee members can pipe in if they want. I see
that one as a specific, get tested campaign, aimed mainly at
the public, with doctors being told that that is something
they should do.
I see the -- what you are calling the preamble and
set of recommendations there as, supplying doctors with the
information they need to answer questions, when people come
in and get results and say, can I have a baby? Can I
breastfeed? Can I have sexual relations? Should I ever
donate blood again? Can I -- am I safe forever from
hepatitis if I tested negative today? What about my
lifestyle, blah, blah, blah. How can I get in a clinical
trial if I am infected? Would you take interferon? That is
the list. I will send you my 20 failed questions of the
three physicians.
PARTICIPANT: No, we concur. We concur that there
is -- many providers are not informed to the level, anywhere
near we would hope for at this point. So there clearly is a
need to get information out to providers about all these
things.
MR. CAPLAN: That is the preamble part, it is that
(inaudible).
PARTICIPANT: Right. And because bear in mind,
the PHS campaign is directed towards providers, as well as
to the public-at-large, and the messages do, as I understand
it, include that if you were a transfusion recipient before,
now, 1992, yes, you are among the people then that need to
be tested.
PARTICIPANT: That is the concern I raised
earlier, that if the only public health campaign is what is
currently planned, and transfusion recipients are being
obviously targeted in this program, but it is a very small
piece of a much bigger risk pie, and what I envisioned was,
that this would transpire, but that this would be
supplemented by an additional notification campaign,
targeted at the recipient population. Practically, that is
probably saying a whole lot more money.
It is somehow enhancing the recipient piece to
what you already have planned, which may be more practical,
but --
PARTICIPANT: Again, I do not -- my understanding
is that the messages were going to be directed to an
audience, listing, these are the risks for HCV infection.
And even though we know that transfusion is a small part of
that pie, I do not think the message is going to be
minimized in any way. But I really cannot speak to that in
as much detail as the hepatitis (inaudible).
PARTICIPANT: You know, perhaps it is not the
patients that need the extra message related to transfusion
recipients, maybe it is the hospitals and the physicians.
It is the point you raised about the physicians need to be
educated to ask about transfusion histories. Perhaps
hospitals need to put messages up around, were you
transfused --
MR. CAPLAN: Signs.
PARTICIPANT: Enhancing(?) it through that method,
rather than necessarily changing the message to the public.
MR. CAPLAN: And Mary, I will talk to you if you
want, subsequent to the meeting, about those -- I have a
pretty good idea, just based upon the discussion of concrete
things that people had -- whether it is the PSA that says,
were you transfused, or making sure that the doctors do it.
Remember, we also said yesterday, putting it into
medical training so that when you are taught to take a
history, you begin to ask about this. So, I captured those
pretty well and I do not mind -- I will bring those back to
you. John?
DR. PENNER: A question to Mike. If I am
(inaudible), do you think that generation I reduced the
numbers of positive generation II tests?
DR. BUSCH: We are back to this. I think the
generation I test detected probably four-fifths of the
infected donors that the generation II detected -- would
have detected.
DR. PENNER: And therefore, excluded them from --
DR. BUSCH: That is correct.
DR. PENNER: From the donor pool?
DR. BUSCH: That is correct.
DR. PENNER: So that made the generation II 1992 a
much more manageable group.
DR. BUSCH: That is true.
DR. PENNER: Had generation II been available in
1990, had been implemented as the first set, then all of
those individuals, minus say, 50%, would have to be followed
up, as well as --
DR. BUSCH: I think -- if we had had an excellent
test like generation II with the supplemental, with the
knowledge we had today, and we were introducing that test, I
think I would recommend that we do look-backs routinely to
prior donations, period, across the board. It is the
context in all those issues, though, the supplemental being
online, which did not exist for the duration of 1.0
screening. The knowledge we have today. The time that has
elapsed, ten years, since that test.
DR. PENNER: And essentially, the difference would
be about 50% would have been excluded because they were
false positive -- [simultaneous discussion].
DR. BUSCH: I think that is (inaudible), I think
that is one of multiple reasons why that first gen look-back
is very problematic.
DR. PENNER: As the only one that has abstained, I
would just like to have my statement that I agree with what
we have done so far. I do not think it has gone far enough.
But I think our recommendations are inconsistent and not
really ethically justified in excluding generation I donor
look-backs. And hopefully, that might be revisited.
MR. CAPLAN: And what -- I think I went on record
as saying, I think we have to revisit, and I think we owe it
to the people who received blood, and for whom these tests
were done, to come back to this and see how we are doing.
So, at least I will try to get this back up on the agenda,
after some reasonable amount of time has passed, so we can
see what has been done and what is going on. Because I did
not vote on that one. I was trying not to influence this
group, and it made no difference to anybody, I lean in the
direction that John is articulating.
I do think that we have to go back there and take
a look, but if this does the job, or if it turns out to be
manageable in certain ways, it will give us certain
evidence, so I am willing to go with where we -- as far as
we have gone.
Okay. Thank you.
[Whereupon, at 3:00 p.m., the meeting was
concluded.]
|