On behalf of the Association of American Medical
Colleges, Darrell G. Kirch, M.D., President,
sent the following comments to CMS Adminstrator
Mark McClellan, M.D., Ph.D., by letter:

The Association of American Medical Colleges
represents approximately 400 major teaching
hospitals and health systems, 126 U.S.
allopathic medical schools, 96 academic
societies, and the faculty, residents, and
students. We appreciate CMS’s willingness to
address a number of issues that have surfaced
since the issuance of the national coverage
decision (NCD) on clinical trials. The
importance of these rules extends beyond the
Medicare program, as many payers look to
Medicare when establishing their own payment
criteria, particularly for items and services
that may not be included as part of traditional
insurance coverage. The AAMC comments have been
submitted via the CMS website. This letter is
being sent to ensure that you are aware of them.

The AAMC supports the three overarching goals
identified by CMS and hopes that, in addition,
the revisions to the Clinical Research Policy
will provide consistency, clarity, and
flexibility that minimize the risk that
researchers and their institutions will be
subjected to investigations and second-guessing
when bills are submitted to Medicare for items
and services provided to beneficiaries enrolled
in clinical trials. Below are comments on a
number of issues that were identified by the CMS
Tracking Sheet as well as suggestions for
additional issues to be included when the
revised NCD is published.

1. Develop a strategy to ensure that
Medicare covered clinical studies are enrolled
in the NIH clinical trials registry website

The AAMC supports the development of such a
strategy and urges CMS to work with NIH to
ensure a reasonable process for enrolling
studies in the existing clinical trials registry
website. The AAMC encourages CMS to determine
whether it also is appropriate to recognize
trial registration in other sites. The
registration requirement should apply only for
Phase II and III and later trials. While
registration of Phase I trials should not be
required, it is appropriate that, at a minimum,
Phase I trials with therapeutic intent should be
included under the Medicare coverage policy.
Studies that are “exploratory” or “hypothesis
generating” should be excluded.

Implementation of this strategy will require CMS
to define “clinical studies.” One possibility is:

In addition to clinical trials, studies that
collect data by various means (e.g., patient
registries) in order to evaluate the efficacy
and cost effectiveness of items and services to
determine whether they should be covered by
Medicare.


2. Develop criteria to assure that any
Medicare covered clinical research study
includes a representative sample of Medicare
beneficiaries, by demographic and clinical
characteristics

Having a “representative sample of Medicare
beneficiaries” should not be a requirement of
the NCD as it is a criterion that will be
virtually impossible to meet in all instances.

Federal regulations already impose numerous
requirements for human subjects research,
including that the institutional review board
(IRB) must ensure that the selection of subjects
is equitable:

In making this assessment the IRB should take
into account the purposes of the research and
the setting in which the research will be
conducted and should be particularly cognizant
of the special problems of research involving
vulnerable populations, such as children,
prisoners, pregnant women, mentally disabled
persons, or economically or educationally
disadvantaged persons. (45 CFR section 46.111(a)
(3))

CMS should not impose any additional and
possibly conflicting requirements that could
affect the design of studies and the ability to
recruit participants.

As CMS is well aware, the older population
already is underrepresented in research
studies. Imposing this requirement will likely
hinder CMS’s overarching goal of “allowing
Medicare beneficiaries to participate in
research studies” since it will mean that even
fewer studies will qualify for Medicare
coverage, and thus even fewer Medicare
beneficiaries will have access to them.
Additionally, the requirement for a
representative sample could be very problematic
for multi-site studies since any individual site
may not meet this standard even if it is met (or
there has been a good faith effort to meet it)
when all sites are considered in aggregate.

An alternative to requiring a representative
sample would be for CMS to require that—as
appropriate for the particular condition or
disease being studied—there must be a reasonable
process for making good faith attempts to
recruit diverse Medicare beneficiaries. However,
no study should be excluded from Medicare
coverage because of the inability to recruit
these individuals.

Further, it is extremely important to ensure
that researchers not be placed in the untenable
position of learning that CMS has performed a
retrospective evaluation of the study population
and determined that because a representative
sample of Medicare beneficiaries was not
recruited, all payments made for services to
beneficiaries in the study will be recouped. To
encourage studies to enroll Medicare
beneficiaries, there must be ample assurance
that once a study has been deemed to qualify for
Medicare coverage, that decision will not be
reversed. Otherwise, this requirement will be
seen as an insurmountable barrier to encouraging
Medicare beneficiaries to enroll in clinical
trials.

3. Clarify the definitions of routine
clinical care costs and investigational costs in
clinical research studies including clinical
trials

Defining what is encompassed by the
term “routine costs” has been a challenge since
the issuance of the NCD. Most clinical
researchers assume that “routine costs” means
payment for what often is called the “standard
of care.” The AAMC urges CMS to adopt a policy
that allows for flexibility in deciding which
items and services qualify for Medicare
payment. Eligibility for payment should be
determined by asking the question: absent the
clinical trial, would this physician treat this
patient using this item or service? If yes, and
if the item or service is not paid for by the
sponsor as per the clinical trial agreement,
then it should be paid for by Medicare.

Before a study begins, determinations should be
made as to which costs are routine and which are
not. However, CMS policy should allow for some
deviation from these determinations when
supported by a judgment that the particular item
or service is medically necessary based on the
condition of a specific patient. To adopt a more
restrictive policy may have the unintended
consequence of discouraging researchers from
recruiting Medicare beneficiaries.

While CMS should not be in the position of
determining what does and does not constitute
routine costs, the agency should provide
guidance about what is considered to be an
acceptable process for making these decisions.

Finally, we request assurance that Medicare will
not deny payment for all services to a patient
if it is determined that some portion of the
services do not meet the definition of “routine
costs.”

4. Remove the self-certification process
that was never implemented

The AAMC supports the removal of the self-
certification process, but urges CMS to adopt a
process that allows for institutional
certification so that Medicare coverage can
extend to trials other than those that that
are “deemed.” In 2000 AHRQ held two public
hearings to gather comments about which trials
other than those that are “deemed” should
qualify for Medicare coverage, yet the agency
never issued any guidance. It may be
appropriate for the agency to do so now.

5. Clarify the scientific and technical
roles of federal agencies in overseeing IND
Exempt trials

This area has traditionally been under the aegis
of the Food and Drug Administration (FDA) and
should remain there. CMS’s role should continue
to be that of payer and not overseer of any
trials.

6. Determine if coverage of routine
clinical care costs is warranted for studies
beyond those covered by the current policy

As was discussed in #4 above, the AAMC supports
Medicare coverage for studies beyond those
currently covered. Generally, Phase I studies
are paid for by manufacturers, so in many cases
the items and services would not be eligible for
Medicare coverage. However, in some Phase I
studies—particularly cancer studies—this may not
be true. As long as the study has a therapeutic
intent, then it should be eligible for Medicare
coverage, regardless of whether it is Phase I,
II, or III. CMS should recognize that in some
cases even studies that establish baseline
levels or monitor toxicity absent signs or
symptoms may have “therapeutic intent” and
therefore should be eligible for Medicare
coverage.

It has become clear to the research community
that determining whether a study has therapeutic
intent is key to deciding if enrollees in that
study will be covered by Medicare. We are aware
that CMS stated in an FAQ that “’[t]he
phrase ‘therapeutic intent’ is open to
interpretation.” (AHLA Audioconference: February
22, 2006; “Legal Issues in Medicare
Reimbursement of Clinical Trials”, CMS Response
2). As is often true, the need for certainty
must be balanced with the need for flexibility.
Therefore, AAMC suggests that to fulfill
the “therapeutic intent” criteria, a reasonable
requirement would be that institutions must have
in place a consistent, articulated method for
determining whether a study has therapeutic
intent. Once an institution demonstrates that it
has implemented and adhered to such a method to
make a determination, CMS should accept its
judgment that a particular study has therapeutic
intent.

The AAMC also supports coverage of research
studies that enroll patients who have not yet
been diagnosed with a disease, but are at high
risk of acquiring it because of family history
and/or genetics. If CMS concludes that it does
not have the statutory authority to cover such
studies because they are considered to be
preventive care, then we urge the agency to ask
Congress for the necessary authority.

7. Clarify whether and under what
conditions an item/service non-covered
nationally may be covered in the context of
clinical research to elucidate the impact of the
item or service on health outcomes in Medicare
beneficiaries

Any rules adopted to implement this policy
should not be so rigid that they become a
barrier to the rapid dissemination of new
treatments and technologies. CMS already has
begun to deal with this matter by approving
coverage for specified new technologies that are
conditioned upon clinical studies to evaluate
efficacy and cost effectiveness. We applaud
this effort and urge CMS to expand it.

8. Discuss Medicare policy for payment of
humanitarian use device (HUD) costs

The AAMC supports Medicare payment for HUDs.
Medicare payment policy should be consistent
with rules and guidance issued by the FDA. For
example, the recently issued Humanitarian Device
Exemption (HDE) Regulations: Questions and
Answers (July 18, 2006) state that:

• HUDS are for a condition or disease
affecting fewer than 4000 individuals in the US
per year;
• IRB approval must be obtained before a
HUD is used, except in emergencies where the
physician determines that approval cannot be
obtained in time to prevent serious harm or
death to the patient;
• The IRB should be responsible for
initial as well as continuing review of the HUD;
• Off-label use of a HUD allowed in an
emergency situation; and
• A HUD can be used for compassionate use

For Medicare payment purposes, the patient’s
medical record should contain documentation that
the use of the HUD is medically necessary and
that no alternative exists.

9. Other Issues

The AAMC requests that CMS also address the
issues below when the final revision of the
Clinical Research Policy is published.

a. Clarify application of the phrase “items and
services customarily provided by the research
sponsor free of charge to any enrollee in the
trial”

The current NCD excludes coverage for “items and
services customarily provided by the research
sponsors free of charge for any enrollee in the
trial”. In the FAQ published following the
February 22 AHLA Teleconference, CMS stated
that “[t]he intent is to not have Medicare pay
for services that are provided free to non-
Medicare participants.” (CMS Response 6). The
AAMC agrees with this clarification and asks
that it be incorporated into the revised NCD.

b. Clarify policy for Medicare Advantage
beneficiaries enrolled in research studies

Some AAMC members have reported that the policy
in the current NCD regarding Medicare
beneficiaries enrolled in HMOs is a disincentive
for these individuals to enroll in clinical
studies. The 2000 NCD says that for M+C (now
Medicare Advantage) enrollees, contractors are
to “pay providers directly on a fee for service
basis for covered clinical trial services.” The
AAMC has learned that some contractors interpret
this to mean that Medicare Advantage enrollees
are responsible for co-pays at the same rate of
20% of charges that is paid by Medicare fee for
service beneficiaries. However, many fee for
service beneficiaries have insurance that covers
these out-of-pocket costs, whereas most Medicare
Advantage enrollees do not. Additionally, if
Medicare Advantage enrollees have co-pays, the
amount usually is substantially less than the
fee for service co-pay.

Once a Medicare Advantage enrollee understands
that he/she will be responsible for certain
charges when enrolled in the research study, yet
will not incur out-of-pocket costs for standard
treatment, the enrollee often opts not to
participate in the study. Not only does this
limit access to these studies, but it imposes
yet another barrier to recruiting Medicare
beneficiaries. The AAMC requests that CMS adopt
a policy that pays providers for “routine costs”
of Medicare Advantage enrollees participating in
research studies on a fee for service basis and
does not allow contractors to impose co-pays or
deductibles (other than amounts that must be
paid by the beneficiary for any in plan service)
on those individuals for those services.

c. Clarify relationship between “diagnostic
intervention” and “therapeutic intent”
requirement

Under 2000 NCD, a clinical trial must meet three
initial requirements. The second requirement is
that the trial must have “therapeutic intent.”
The third requirement states, in part, that “[t]
rials of diagnostic intervention may enroll
healthy patients in order to have a proper
control group.” Requiring a diagnostic
intervention to have therapeutic intent appears
to be contradictory. If CMS retains these
criteria, the agency should clarify that a trial
of a diagnostic intervention that often may not
have therapeutic intent would be covered by the
Medicare policy.

d. Screening tests/exams to determine
eligibility for study participation

The AAMC suggests that the Medicare Clinical
Research Policy should cover screening tests to
determine eligibility for enrollment in a trial
provided that these tests would be covered as
part of the standard of care for a specific
patient. All other screening tests should be
charged to the study.

e. Allow Medicare payment for “compassionate use”

The AAMC requests that CMS allow coverage for
enrollees enrolled in research studies when a
physician has determined that there is no
alternative treatment available and that the
patient is likely to die without treatment
(“compassionate use”). It seems unreasonable to
deny Medicare payment for these treatments when
no other options exist and the provision of the
treatment may give researchers valuable
information about treating future patients with
the same disease or condition.

f. Application of the Medicare Secondary Payer
rules

On July 19 the AAMC sent a letter to Steve
Phurrough asking that CMS not adopt a narrow
interpretation of the Medicare secondary payer
(MSP) rules that would act as a barrier to
Medicare payment for clinical trials. Should CMS
not publish a policy on this issue prior to the
issuance of the revised NCD, then the revisions
to the NCD should include a clear statement of
CMS policy about the impact of the MPS rules on
Medicare payment for clinical trials.