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Table 3 Examples of REC comments on protocols of drug trials

From: Shortcomings of protocols of drug trials in relation to sponsorship as identified by Research Ethics Committees: analysis of comments raised during ethical review

Review criteria Example
1. Proportionality “The committee has serious doubts regarding the proportionality of the study, because the trial is very burdensome for participants and a number of potentially risky interventions are being combined”.
“The committee would like to hear the expected benefit(s) of the study drug from the investigators; the clinical relevance of the trial is not clear”.
2. Minimisation of risks & burdens “The committee wonders why it is necessary to burden patients with completion of the proposed quality of life questionnaires; much is already known about the quality of life of this group of patients”.
“The investigators need to convince the committee of the usefulness of repeating skin biopsies and synovial biopsies”.
3. Privacy & confidentiality “The committee notes that questionnaires should be stored coded; there should be no personal data on the questionnaires, as is the case now for a number of questionnaires”.
“Trial medication is home delivered to participants by courier; the committee wants to know which provisions are made to prevent that participant addresses are known by the manufacturer”.
4. Patient safety “The committee wonders why no individual and group level stopping rules are defined and no DSMB is installed for this trial”.
“The committee wonders whether it is possible, in view of patient safety, to sequentially include participants in this trial”.
5. Recruitment process “The minimal time of 24 h to decide about participation is too short considering the chance of placebo treatment, and the potential risks and burdens of participating; it should be minimally 5 days”.
“The committee is concerned whether enough patients can be included; this type of cancer is particularly seen in patients with metastases, but these patients cannot participate in the trial”.
6. Information sheet & consent form “The written subject information is too long and too difficult (regarding both vocabulary and style); the committee would like to see a completely rewritten version, understandable to a layperson”.
“It should be more clearly explained to which extent the trial treatment deviates from the standard treatment and what subjects must undergo additionally by participating in the trial”.
7. Subject selection “The committee asks the investigators why they do not select subjects at inclusion based on pain complaints, while this is an objective of the trial”.
“The committee has the impression that the exclusion criteria are not complete, considering the SPC text; in particular, the committee believes that children with heart disease or kidney failure should be excluded”.
8. Protection vulnerable subjects “The committee would like to hear substantive arguments for the need to include minors; the investigators have not justified why this group should be involved in this trial”.
“The committee would like to hear how subjects and their relatives are informed on the procedures in case of resistance by subjects during the trial”.
9. Methodology & statistical analysis “The sample size calculation does not reflect the primary analysis described as a (mixed effect) repeated measures ANOVA; the current calculation does not reflect that there are 10 VAS pain measurements”.
“The trial is designed as cross-over; because of potential carry-over effects, the committee believes that a parallel comparison of 2 groups should be preferred”.
10. Product information “The committee needs more information on the endothelin receptor antagonists; information on product characteristics, pharmacological characteristics, efficacy and safety, and pharmacokinetics is missing”.
“The data in the IMPD are from 1997; the committee wants to know whether this batch is still being used or whether there has been a more recent production”.
11. Supporting documentation “The text in the Clinical Trial Agreement on (premature) termination of the trial and publication of results does not correspond to provisions in the Dutch regulation on assessment of Clinical Trial Agreements”.
“The committee wants to know whether the sponsor takes responsibility for the clinical trial liability insurance for all participating centres”.
12. Facilities & research staff “A student cannot be principal investigator for this trial, because a student lacks experience and cannot take final responsibility for the trial”.
“The committee believes that, considering the treatment during the trial, an oncologist should be involved in the design and conduct of the trial”.
13. Financial aspects “The committee would like to see an exact justification of the 100.000 euro that the department will receive for conducting the trial”.
“The committee does not agree with the independent physician appointed for 3 of the participating centres; this person also works as a physician for the pharmaceutical company sponsoring this trial”.