The Agency for Healthcare Research and Quality's (AHRQ) Technology Assessment (TA) Program supports and is committed to the transparency of its review process. Therefore, invited peer review comments and public review comments are publicly posted on the TA Program Web site at http://www.ahrq.gov/clinic/techix.htm within 3 months after the associated final report is posted on this Web site.
This document presents the peer review comments and public review comments sent in response to the draft report, Consideration of Evidence on Antiemetic Drugs for Nausea and Vomiting Associated with Chemotherapy or Radiation Therapy, posted on the AHRQ Web site. The final version of the report is available online.
Reviewer1 |
Section2 |
Reviewer Comments |
Author Response3 |
1 |
General |
We very much appreciate the opportunity to review this report, “Consideration of Evidence on Antiemetic Drugs for Nausea and Vomiting Associated with Chemotherapy or Radiation Therapy” prepared
by the Oregon Evidence-based Practice Center. |
Noted. |
2 |
General |
The Technology Assessment Report on antiemetic drugs
for nausea and vomiting associated with chemotherapy or radiation therapy
is comprehensive and well written. The three questions addressed are
clinically relevant and clearly impact on daily practice. I am in agreement
with most of the conclusions. I do not believe a compelling case has
been made for several conclusions, however, and I will cite additional
references which hopefully may illustrate my points |
Noted. |
3 |
General |
This is an important topic, as nausea and vomiting
is one of the most common side effects of chemotherapy and radiotherapy.
In addition, this is the side effect most likely to occur immediately
during or soon after receiving therapy and the one that patients and
the general public often associate with anti-cancer therapy. Fear
of nausea may lead patients to forego helpful therapies and severe
nausea and vomiting has an adverse effect on patients' quality of life
(QOL) and may lead them to abandon helpful therapies. |
Noted. |
3 |
General |
In addition, the categories of anti-nausea drugs that
have become available in the past two decades are generally felt to
be effective and are somewhat costly. Knowing how best to use
these medications will enhance the care of cancer patients, improve
QOL and should lead to cost-effective care. |
Noted |
3 |
General |
There was a specific need to address the use of antiemetics
in the elderly. However, the reviewers correctly concluded that
the currently available data cannot assure efficacy and safety in those
older than 65. There is no attempt in this report or study to
address the use of these medications in children or adolescents. Therefore,
I recommend that the words ‘in adults' be added to the end of
the title. Also, since the reviewers were unable to find enough
data regarding the use of these medications with radiation to evaluate
them in that setting, one wonders why the word ‘radiation' should
remain in the title. |
“in adults” added to title. Kept radiation
in title as a reflection of the objectives of the review. |
3 |
General |
Overall, the report is well-written and easy to read. The
data and conclusions are clearly presented throughout. The report
should achieve improved knowledge and care in adult patients who need
moderately or severely emetogenic chemotherapy. No conclusions
can be stated regarding radiation. |
Thank you. |
2 |
Introduction/Background |
The oral formulation of palonosetron, although approved
for use, is not currently available in the United States |
Footnote added to Table 1 |
3 |
Introduction/Background |
The introduction addresses the currently most commonly
used anti-emetic regimens that are FDA-approved. Very little
mention is made of medications that were commonly in used prior to
1991, when ondansetron was FDA approved and entered the marketplace. This
is appropriate, as older regimens were certainly less effective and
should not be used in the modern era. However, might it be better
to clearly state early in the report that only 5-HT3 antagonists, aprepitant
and steroids are being considered for this report. |
The introduction has been revised to indicate the history
of drug development in this area more clearly – including the
fact that older drugs were used but with inadequate response and intolerable
side effects.
The “Purpose of the Report” section states that the focus
of the report is on 5-HT3 antagonists, aprepitant and steroids. We
moved this section to earlier in the report, for more clarity. |
3 |
Introduction/Background |
The section entitled ‘Purpose and Limitations
of Systematic Reviews' is well written and important, as many practitioners
(medical and public health) may not be familiar with the reviews and
the technical terms that such reviews use. No changes are suggested. Under ‘Purpose
of the Report', there is no mention of whether children and adolescents
were included in the previous report. This information would
be helpful. The ‘Key Questions' section is fine. |
Added clarification about scope of previous DERP report |
1 |
Executive Summary |
The executive summary of the document is readable and
conveys the completion and findings of this systematic review succinctly. |
Thank you. |
3 |
Executive Summary |
The executive summary is well written and faithfully
represents the contents of the full report. Readers who need
quick information regarding the contents and conclusions of the study
will be able to glean the needed information from this summary. |
Thank you |
2 |
Methods |
Standard antiemetic outcomes were evaluated. A major
limitation of the analysis, however, is to include outcome data only
for the acute and delayed phases but not for the entire study period.
In nearly all the studies cited, complete response during the 120 hours
after chemotherapy administration was the primary endpoint. The separation
of response into discrete acute and delayed periods, while of interest
to antiemetic aficionados is of little interest to patients. They simply
wish to know whether they will experience nausea or vomiting during
the period of risk after chemotherapy (best encompassed by the 120
hour time period). I would recommend including this endpoint. |
Overall study period data added |
1 |
Methods |
Inclusion and exclusion criteria (pgs 16-17; 65): Further
explanation of these is required, particularly category 6 of wrong
study design. Insufficient information is provided for the list of
excluded trials. For example, the Abali et al., Cancer Investigation
2007, pg 65, trial should meet the pre-specified inclusion criteria
(the tropisetron arm could have been excluded and other analyses reported). |
Agree, Clarification added. Abali 2007 was excluded
due to being a comparison of all-IV vs all-IV |
1 |
Methods |
An additional criterion should consider drug doses
in a given trial. Studies which employ doses which are not consistent
with FDA-approved labels should be excluded, similar to the exclusion
of non-FDA approved therapies. Table 1 (pg 11) could be expanded to
include the range of doses approved by the FDA for each drug considered
in this systematic review. |
Dosage was considered within our interpretation of
the results, rather than as an eligibility criterion.
Added appendixes of FDA-recommended dosages |
1 |
Methods |
Search terms (pg 52): Suggest consider inclusion of
the drug categories, 5-HT3 serotonin receptor antagonists and Neurokinin-1
receptor antagonists, rather than the drug names alone. |
Our experience in conducting searches for the original
DERP review and for its update has not indicated that this approach
is necessary for this particular drug group. |
1 |
Methods |
Additional sources: Suggest consider additional sources
beyond the published medical literature including presentation and
posters from the following meetings: Multinational Association of Supportive
Care in Cancer (MASCC), American Society of Clinical Oncology (ASCO),
European CanCer Organisation, European Society for Medical Oncology
(ESMO), and American Society for Therapeutic Radiology and Oncology
(ASTRO). ASTRO would be particularly useful source for studies on radiation-induced
nausea and vomiting. |
Due to our concerns about potential for outcome reporting
bias and insufficient methodological reporting detail, our current
policy is to exclude conference proceedings. |
1 |
Methods |
Emetic risk (pg 16): Verification of emetic risk in
future reports is suggested. Inconsistencies between author designation
and current risk stratifications schemas were noted.
Notably, the emetic risk classification schema was revised (http://www.mascc.org/mc/page.do?sitePageId=88041,
accessed 04/30/2010) at the MASCC 2009 meeting. As well, the draft
update of the ASCO evidence-based guideline for antiemetic therapy
for cancer patients also includes a revised emetic risk classification
schema. |
No inconsistencies identified between emetic risk in
included trials and MASCC 2009 revision. Added MASCC 2009 revision
as source for emetic risk classification |
1 |
Methods |
Collation of findings for the different questions (two
or three therapy treatment arms) is described without separating trials
based on emetic risk; either high or moderate. Studies may be combined
or compared inappropriately by failing to consider such. Results may
then be extrapolated to cover an array of emetic risk categories rather
than considering direct evidence for a given risk category. |
Comparisons of all-oral regimens were restricted to
trials of moderate emetic risk. Whereas, comparisons of mixed regimens
were restricted to trials of high emetic risk, with one exception.
In Chiou 2000, emetic risk was high for 57% and moderate for 43%. Added
clarification to Executive Summary and Summary Table to better emphasize
this. |
1 |
Methods |
Outcome Measures (pg 17): The most meaningful outcome
measure included is total control, which includes effects on nausea.
The importance of this endpoint, which represents a true antiemetic
effect, is paramount in making, determinations about strength of evidence.
This is equally important when making coverage determinations. A failure
to effectively control nausea, in addition to emesis, considering the
antiemetic therapies available represents strides lost in the battle
to control this symptom with significant impact on quality-of-life. |
We agree and have emphasized its importance in this
review |
1 |
Methods |
Intention to Treat (ITT) Analyses: Suggest utilization
of the ITT definition published within the report (pg 45), which includes
all patients randomized. For those non-ITT analyses, would suggest
specification that an analysis is actually a modified ITT (mITT) to
increase transparency. |
As there exist multiple and variable definitions for
modified ITT, to avoid ambiguity, we have hesitated to adopt use of
this terminology. |
1 |
Methods |
Additionally, a “very small number” is
not defined.
The language in the data abstraction section (pages 17, 18) does not
indicate when ITT was calculated by the authors. This section is difficult
to interpret; it is not clear when ITT was calculated or when a “very
small number of patients” were not included. In those cases when
it could not be calculated because data was lacking, indicating that
results are per-protocol can also increase transparency. This information
is particularly critical for readers considering results for the numerous
meta-analyses. |
We define “very small” as ≤ 5% and added
this clarification. Also added clarification that we would note
cases where we calculated intention-to-treat results when only per-protocol
results were available. There were no occasions for such calculations
in this review. |
1 |
Methods |
Data Synthesis (pg 20): Suggest that meta-analysis
is first conducted with fixed-effects model to determine whether a
random-effects model is necessary. |
We adhere to the guidance issued by the EPC program
which recommends against choosing a statistical model based on the
significance level of a heterogeneity test and, instead, recommends
routine use of random effects models. |
1 |
Methods |
An increased I2 does not necessarily indicate that
a random-effects model is required, particularly in trials with homogeneity.
It may, alternatively, suggest that factors not accounted for in stratification
mediate outcomes. |
See above response. |
3 |
Methods |
The methods used for this review are clearly presented
in this section. However, I find it interesting that the reviewers
state that they went back to 1966 (perhaps this is just because it
is the lower limit of the MEDLINE® database), when the review really
is limited to relatively new (< 2 decades) medications (with the
exception of steroids). |
Yes, the start date of our search reflects the lower
limit of the MEDLINE® database |
3 |
Methods |
The definitions used for emetogenic potential of chemotherapy
regimens are clearly presented, and the effectiveness and harms outcomes
are also clearly presented. |
Thank you. |
2 |
Results |
Key Question 1: All-oral regimens -Comparison of regimens
with and without aprepitant
- Two studies are cited, Warr et al and Yeo et al. Both are described
as “fair-quality” studies. To rate the quality of these
studies as equivalent makes little sense to me. The Warr study
with 866 patients is properly sized to address the question of
interest. The other trial is woefully underpowered to address the
primary endpoint.
|
The impact of sample size is considered to be distinct
of risk of bias and is evaluated in the form of “precision” in
our grades of the strength of the evidence. |
2 |
Results |
Key Question 1: All-oral regimens -Comparison of regimens
with and without aprepitant
- Recently, another large (848 patients) phase III trial (Rapoport
et al) has been published in a MEC population with an identical
study design to the Warr trial. Unlike the Warr trial in which
the aprepitant regimen was better than the control regimen in the
acute and overall periods only, in the Rapoport trial the addition
of aprepitant improved outcome across all the phases(acute, delayed,
overall). The combined weight of both the Rapoport and Warr trials
should improve the level of evidence to a high level of confidence
that an all oral three-drug regimen with aprepitant is superior
to an oral two-drug regimen without aprepitant in achieving complete
response in the overall study period.
|
This recently published study was added. |
2 |
Results |
Key Question 1: All-oral regimens – comparisons
of regiments of a 5-HT3 antagonist plus a corticosteroid, without aprepitant
- Essentially no data. One very small randomized trial.
|
We agree. |
2 |
Results |
Key Question 1: All-oral regimens compared to all-injectable
regimens
|
We agree. |
2 |
Results |
Key Question 1: Comparison of mixed oral and injectable
regimens with and without aprepitant
- I again do not understand the quality rating for the trials in
that only one trial was rated of good quality. I agree with the
conclusions. The strength of evidence is very high that mixed oral
and injectable regimens with aprepitant are superior to those without
aprepitant.
|
None of the 7 trials of mixed oral and injectable regimens
that compared the addition of aprepitant to dual therapy provided sufficient
detail to determine adequacy of allocation concealment. According
to our quality assessment methods, unless allocation methods can be
verified as adequate, the highest rating that can be given is “Fair”.
Schmoll 2006 changed to Fair for this reason. Added explanation of
rating. |
2 |
Results |
On p 27 the statement is made that no trials reported
on the ability to tolerate sequential chemotherapy sessions. This is
not true. Both the Hesketh33 and Poli-Bigelli35 trials allowed patients
to remain on assigned treatment arms during subsequent cycles of cisplatin-based
chemotherapy. The multi-cycle data was reported by de Wit et al in
the EJC in 2004. I will forward the reference. In addition, multi-cycle
data is also available from the Warr27 trial as well (Herrstedt et
al Cancer 2005). I will forward this reference as well. |
Added. |
2 |
Results |
Key Question 1: Comparison of mixed oral and injectable
regimens of a 5-HT3 antagonist plus a corticosteroid
- Very little data. Agree with conclusions.
|
No changed needed |
2 |
Results |
Key Question 1: How do regimens given immediately prior
to and/or for 48 hours after initiation of chemotherapy compare to
those regimens given for longer periods of time?
- Definitive evidence demonstrating that a single day aprepitant
regimen has comparable effectiveness to a multi-day regimen has
not yet been published. Neither the small pilot trial of Herrington32
nor the randomized phase II trial of Navari34 was powered to answer
this question. Further support for the concept that single day
NK1 receptor antagonist dosing can achieve comparable efficacy
to multi-day NK1 receptor antagonist is provided by the report
of Grunberg et al in Lancet Oncology 2009 detailing a large phase
III trial with the NK1 receptor antagonist casopitant. The manufacturer
of caospitant, GlaxoSmithKline has decided not to pursue a regulatory
filing with this agent. I will forward this reference.
|
Agree. We rated the strength of this evidence as moderate,
due to the imprecision of effect estimates caused by the small sample
sizes in these trials. No change needed. |
3 |
Results |
Key Question 1:
- In section A, there is a discussion of 2 studies that compare
a 2 drug regimen with ondansetron and dexamethasone to a 3 drug
regimen that adds aprepitant. The reader must look at several
tables and the references to confirm that both are randomized clinical
trials. Clarification that these were randomized clinical
trials with the simple insertion of the word ‘randomized'
in the first sentence would be helpful and allow the reader to
focus on the data and results, rather than chasing down this information. Also,
similar to my comments regarding table 4 (see below), in the QOL
paragraph on p 23, one must infer that the order of outcomes is
3-drug vs. 2-drug. It seems that this is likely standard
throughout the manuscript. If so, it should be more clear. The
last paragraph in section A is clear.
|
Both changes made. |
3 |
Results |
Key Question 1:
- In section C, please point out that the Evidence tables can be
found in which appendix (G).
|
Added |
3 |
Results |
Key Question 1:
- On page 25, there is a typo: in the last line before table
6, the word should be ‘significant'.
|
Corrected |
3 |
Results |
Key Question 1:
- The quality of life paragraph on page 27 is important and may
warrant a subheader.
|
No change made; While quality of life is very important
to patients and clinicians alike, this was only a brief report
on quality of life and we felt it did not warrant adding an additional
level of subheading. |
2 |
Results |
Key Question 2: Safety
|
Noted. |
1 |
Results |
Key Question 2C, pg 29
- Review of the question indicates that relevant trials should
compare therapies given 48 hours following chemotherapy delivery
versus those given for over less than 48 hours. Antiemetic agents
are delivered prior chemotherapy (generally ranging from 60 to
30 minutes before administration). Therefore, agents delivered
before chemotherapy administration for three consecutive days period
would fall within this 48 hour limit. Alternatively, agents delivered
following chemotherapy over three days would fall into the beyond
48 hour category.
|
Agree |
1 |
Results |
Key Question 2C, pg 29
- The Herrington 2008 publication in Cancer does not compare these
two sorts of regimens. The study design evaluates one day of aprepitant
compared to three consecutive days; study therapies are all delivered
before administration of chemotherapy. As such, both regimens are
within the 48 hour time limit.
|
Agree. Removed Herrington 2008. |
3 |
Results |
Key Question 2:
- The relatively short section on ‘harms' is clear and concise. The
message is that these medications are relatively well tolerated
and that the evidence for significantly different side effects
from differing regimens is currently lacking.
|
Thank you |
2 |
Results |
Key Question 3: Applicability of the evidence to patients
age 65 and older?
- Retrospective analyses assessing predictive factors for emesis
have suggested that patient age may be relevant with younger patients
experiencing more emesis than older patients. One of the earliest
reports in this regard was by Pollera and colleagues in 1989. (see
ref 6 from the NEJM 2008 review by Hesketh).
- Although definitive information on the impact of age is not available
as age has never been a stratification factor in antiemetic trials,
a recent analysis of predictive factors for emesis published by
Hesketh et al (J Support Care Cancer 2009) strongly supports the
conclusion that patients over age 65 also benefit from the addition
of aprepitant. In this analysis of the combined data set from the
two pivotal phase III trials of aprepitant with highly emetogenic
chemotherapy, 285 (28%) of the total 1023 patients were over age
65. The complete response rate was significantly greater for the
aprepitant-containing arm than the active-control arm, regardless
of age.
|
We have cited the Pollera paper to indicate that it
is known that older patients have lower rates of nausea and vomiting. The
publication in J Support Care Cancer did not come up in our Medline
searches, we appreciate this being brought to our attention and have
added it, along with additional unpublished data submitted by Merck
regarding the 2 trial from which data were pooled in this analysis,
as well as others. Our conclusions have changed based on the
new evidence. |
2 |
Results |
Key Question 3: Is there evidence of disparate effects
on gender?
- I do not agree with the conclusion that there is a low level
of evidence that gender is a relevant factor in defining antiemetic
outcomes. Early on, there was widespread recognition that female
gender was an important predictive factor for antiemetic outcome,
with women consistently having more nausea and vomiting than men
with the same emetic stimulus. See references 6-9 from the Hesketh
2008 NEJM review. An analysis of the combined database from
the two pivotal phase III trials of aprepitant with highly emetogenic
chemotherapy by Hesketh et al43 again demonstrated significantly
worse outcome in the control arms in women compared to men. Of
note, for the first time the significant difference by gender was
negated with the addition of aprepitant in the investigational
arms, suggesting an even greater benefit with the addition of aprepitant
in women compared to men. In my opinion the reports conclusions
on p 32 that “further studies are highly likely to change
these findings” are misleading and incorrect.
|
To introduce the discussion of comparative effectiveness
differences in women versus men, we have added reference to the known
difference between genders in nausea and vomiting. The publication
in J Support Care Cancer did not come up in our Medline searches, we
appreciate this being brought to our attention and have added it, Our
conclusions have changed her also, but both are focused solely on the
comparisons between treatment groups, such that analyses that do not
take treatment group into account are not as relevant. |
2 |
Results |
Key Question 3: Is there evidence of disparate effects
on race?
|
Noted. |
2 |
Results |
Key Question 3: Are certain groups more likely to receive
one treatment over another , due to prescription trends in a geographic
region, socioeconomic status, health insurance coverage, etc.?
|
Noted. |
3 |
Results |
Key Question 3:
The relative lack of data on the effectiveness and side effects of these
regimens in those older than 65 is unfortunate and clearly comes
across in section A on page 31. I think that the concluding
sentence, that presumes that adding aprepitant in all age groups
is superior but may be overturned as evidence is accumulated, is
correctly stated. Similarly, the concluding statement about
differences across gender differences on page 32 is also correctly
stated. It is unfortunate that studies have enrolled insufficient
minorities for there to be data sufficient to analyze differences
across races and ethnic groups. |
Noted |
1 |
Results |
The Navari trial, alternatively, does compare regimens
as described in key question 2C. Arm A includes five days of aprepitant,
Arm B includes one day of aprepitant, and the third arm is a placebo
comparator. However, The Navari trial includes a non-approved dose
of aprepitant (original, FDA-approved label for Emend®; http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory,
accessed 4/26/2010). The dose included in this trial is over three
times the FDA-approved dose (125mg day one, 80mg days two and three).
Moreover, this study was one of a number of dose-finding efforts completed
by the manufacturer prior to approval of this agent.
Recommend exclusion of this trial from consideration throughout the entire
report. It was also included in the analysis of aprepitant use (two vs.
three drug regimens); this study is not appropriate for pooling in that
meta-analysis because of the difference in aprepitant dosing. This study
does not meet the predefined requirement for homogeneity (pg 20). |
Agree. Removed Navari 1999 from meta-analyses. Added
clarification about difference in formulation and dosage used in this
trial. |
1 |
Results |
Further discussion of Herrington, though irrelevant
to this question: Similarly, the reported findings of the Herrington
paper suggest potential biases. This pilot study did not stratify
patients by known risk factors for chemotherapy-induced nausea and
vomiting (CINV) nor were any of the differences noted statistically
significant:
- More patients in the three day aprepitant arm received cisplatin,
an agent with high emetogenic potential. The other agents included
are all moderate or low risk chemotherapeutics. As well, the combined
sample size for the two aprepitant arms was 57 patients.
- Two of the three arms received the same therapy on day one and
yet findings during the acute period are not the same (outcomes:
proportion of patients without emesis, severity of nausea using
mean VAS, and percentage with no rescue medications).
- The difference in outcomes during the acute phase is most likely
attributed to small sample sizes and the lack of stratification
for known risk factors. This pilot study did not include the comprehensive
outcome of total control, which is important when considering the
implications of the findings.
|
Removed Herrington 2008 from Key Question 1d |
1 |
Results |
These points, together, suggest that the moderate strength
of evidence support for the conclusion that one day of Aprepitant is
equivalent to three days is an overstatement. |
The above changes resulted in tour rating of the strength
of evidence to become Low |
1 |
Results |
The 2006 evidence-based guideline from ASCO on use
of antiemetic for CINV (Kris, JCO 2006) cited a number of studies to
justify the recommendation that patients undergoing highly emetogenic
chemotherapy receive three days three days of aprepitant. Chawla, Cancer
2003 was a phase II trial to evaluate dosing for this therapy prior
to FDA approval. Findings from this trial are reported on pages 102
and 111 of this report and support use of multi-day aprepitant. Two
of the phase III trials examined aprepitant therapy for patients undergoing
cisplatin-based therapy (Heskth, JCO 2003; Poli-Bigelli, Cancer 2003).
The final trial (Warr, JCO 2005) considered treatment in women undergoing
combined anthracycline and cyclophosphamide regimens for breast cancer.
Other studies that should be considered are the pivotal trial completed
to obtain FDA approval for aprepitant, which was the basis for the
dose label of three days of treatment (125 mg on day one followed by
80 mg on days two and three). However, those studies may not include
different delivery methods and thus, not appropriate for inclusion
in this systematic review. Nevertheless, these are critical trials
to consider if recommendations about dosing regimens for aprepitant
are proposed. |
Our review of the FDA's Medical Review indicated that
Hesketh 2003 and Poli-Bigelli 2003 are the pivotal trials and are already
included. However, we realized we had previously omitted Campos 2001
(study 012) and added this trial. |
1 |
Discussions/Conclusions |
Additional Trials for Consideration
- Radiation-Induced Nausea and Vomiting (RINV): One relevant study
is from Wong 2006, which was an intergroup study. All patients
received ondansetron and were randomized to treatment with dexamethasone
or placebo.
|
We excluded Wong 2006 because it compared dual therapy
to monotherapy with a 5-HT3 antagonist alone, and therefore does not
meet the inclusion criteria. |
1 |
Discussions/Conclusions |
Conclusions outside the scope of this systematic review
- The methodology crafted by the CMS team in cooperation with the
report authors was designed to answer questions about route of
delivery, comparing oral and intravenous delivery of antiemetic
therapies. Relevant trials were excluded because drugs approved
outside the U.S. were included, specifically tropisetron.
- For example, the Abali paper published in Cancer Investigation,
2007 compared ondansetron, granisetron, and tropisetron. This study
could have been included without assessment of the tropisetron
study but was deemed outside the scope.
|
Abali 2007 was excluded because all drugs were given
by intravenous delivery, and therefore does not meet the inclusion
criteria. |
1 |
Discussions/Conclusions |
The narrow request from CMS limited the authors' ability
to consider the broader antiemetic literature. This review does not
reflect the entire body of antiemetic literature evaluating therapies
for patients undergoing moderate and high risk chemotherapy. As such,
commentary beyond the differences and similarities between oral and
intravenous delivery methods is without sufficient evidentiary basis.
Assessment of such questions requires completion of a systematic review
with a broader set of inclusion and exclusion criteria. |
Agree |
3 |
Discussions/Conclusions |
The Summary and Conclusions section is concise and
summarizes the data well. Tables 8, 9 and 10 are much longer
than the narrative. This reviewer is mildly bothered by the presence
of these tables here, rather than in the sections above specifically
related to the key questions. |
Moved tables to ends of related sections. |
1 |
Tables |
Headers for tables should be include across all pages,
including evidence tables and Appendix D |
Agree. Added headers where applicable. |
2 |
Tables |
Table formatting in some cases diminishes readability.
- Results are not presented in a consistent manner, diminishing
the ability to easily compare data from tables between trials.
- Organization of studies within tables is not immediately clear;
alphabetizing would assist readers.
- Doses for all therapies should be included, whether it was part
of the study regimen or control. Particularly important for dexamethasone,
where different doses are indicated when aprepitant is used versus
when only used with a 5HT3 antagonist.
- Include sample sizes in each treatment group on the results tables
as well as an abbreviated description of the treatment arm (see
pages 108, Warr and 112, Hesketh)
|
Thank you. We always welcome suggestions for ways to
improve the readability of our Evidence Tables and have made the suggested
changes. |
3 |
Tables |
Table 1 is good. No suggested changes.
Table 2 is clear and important to readers not familiar with these reviews. No
suggested changes.
Table 3 is well done and clear. No suggested changes.
Table 4: No suggested changes
Table 5: No suggested changes
Table 6: No suggested changes
Table 7: No suggested changes |
Noted |
3 |
Tables |
Table 8: One formatting change is suggested. The
subquestions 1.A., 1.C., and 1.D., all get a separate subheading with
the outcomes each getting a line below. Even though subquestion
1.B. did not have any studies and thus no data, you might split this
into 2 lines, so that formatting is consistent throughout the table. The
content is fine. |
Formatting change made. |
3 |
Tables |
Table 9: If you accept the formatting suggestion
made for Table 8, carry this into Table 9 as well. Given the
paucity of information addressing key question 2, I found the formatting
in Table 9 less objectionable than when I noted it in Table 8. The
content is fine. |
Formatting change made. |
3 |
Tables |
Table 10: No suggested changes. |
Noted |
3 |
Figures |
Figure 1 is very clear and important. No suggested
changes.
Figures 2, 3 are clear and show the data from the studies in an easily
understood fashion. |
Thank you |
1 |
Appendices |
Please see previously stated comments. |
Noted |
3 |
Appendices |
Appendix A: The glossary is a welcome addition
to a work such as this and appears to be complete.
Appendix B: Important to include but not interesting to most readers. Those
skilled at literature searches will be able to discern whether any strategies
were flawed. To my eye, the search strategies seemed appropriate.
Appendix C: This methods appendix is important and clearly shows
how the reviewers categorized the studies reviewed.
Appendix D: No suggested changes.
Appendices E, F & G: The three appendices that explain the
strength of evidence of the various studies used to address the key questions
are extremely important. They are clear and no changes are suggested. |
Noted |
3 |
References |
The 48 references cited are appropriate and span the
timeframe of these modern medicine (‘90s and ‘00s). |
Noted |