Philippe Amiel

Informed consent in clinical research in France: assessment and factors associated with therapeutic misconception

Background: Informed consent in clinical research is mandated throughout the world. Both patient subjects and investigators are required to understand and accept the distinction between research and treatment. Aim: To document the extent and to identify factors associated with therapeutic misconception in a population of patient subjects or parent proxies recruited from a variety of multicentre trials (parent studies). Patients and methods: The study comprised two phases: the development of a questionnaire to assess the quality of informed consent and a survey of patient subjects based on this questionnaire. Results: A total of 303 patient subjects or parent proxies were contacted and 279 questionnaires were analysed. The median age was 49.5 years, sex ratio was 1 and 61% of respondents were professionally active. Overall memorisation of the oral or written communication of informed consent was good (69–97%), and satisfaction with the process was around 70%. Therapeutic misconception was present in 70% of respondents, who expected to receive better care and ignored the consequence of randomisation and treatment comparisons. This was positively associated with the acuteness and severity of the disease. Conclusion: The authors suggest that the risk of therapeutic misconception be specifically addressed in consent forms as an educational tool for both patients and investigators.

Peer Review of Grant Applications: Criteria Used and Qualitative Study of Reviewer Practices

Background Peer review of grant applications has been criticized as lacking reliability. Studies showing poor agreement among reviewers supported this possibility but usually focused on reviewers’ scores and failed to investigate reasons for disagreement. Here, our goal was to determine how reviewers rate applications, by investigating reviewer practices and grant assessment criteria. Methods and Findings We first collected and analyzed a convenience sample of French and international calls for proposals and assessment guidelines, from which we created an overall typology of assessment criteria comprising nine domains relevance to the call for proposals, usefulness, originality, innovativeness, methodology, feasibility, funding, ethical aspects, and writing of the grant application. We then performed a qualitative study of reviewer practices, particularly regarding the use of assessment criteria, among reviewers of the French Academic Hospital Research Grant Agencies (Programmes Hospitaliers de Recherche Clinique, PHRCs). Semi-structured interviews and observation sessions were conducted. Both the time spent assessing each grant application and the assessment methods varied across reviewers. The assessment criteria recommended by the PHRCs were listed by all reviewers as frequently evaluated and useful. However, use of the PHRC criteria was subjective and varied across reviewers. Some reviewers gave the same weight to each assessment criterion, whereas others considered originality to be the most important criterion (12/34), followed by methodology (10/34) and feasibility (4/34). Conceivably, this variability might adversely affect the reliability of the review process, and studies evaluating this hypothesis would be of interest. Conclusions Variability across reviewers may result in mistrust among grant applicants about the review process. Consequently, ensuring transparency is of the utmost importance. Consistency in the review process could also be improved by providing common definitions for each assessment criterion and uniform requirements for grant application submissions. Further research is needed to assess the feasibility and acceptability of these measures.

Non-financial conflicts of interest in academic grant evaluation: a qualitative study of multiple stakeholders in France.

Background Peer review is the most widely used method for evaluating grant applications in clinical research. Criticisms of peer review include lack of equity, suspicion of biases, and conflicts of interest (CoI). CoIs raise questions of fairness, transparency, and trust in grant allocation. Few observational studies have assessed these issues. We report the results of a qualitative study on reviewers’ and applicants’ perceptions and experiences of CoIs in reviews of French academic grant applications. Methodology and Principal Findings We designed a qualitative study using semi-structured interviews and direct observation. We asked members of assessment panels, external reviewers, and applicants to participate in semi-structured interviews. Two independent researchers conducted in-depth reviews and line-by-line coding of all transcribed interviews, which were also subjected to Tropes® software text analysis, to detect and qualify themes associated with CoIs. Most participants (73/98) spontaneously reported that non-financial CoIs predominated over financial CoIs. Non-financial CoIs mainly involved rivalry among disciplines, cronyism, and geographic and academic biases. However, none of the participants challenged the validity of peer review. Reviewers who felt they might be affected by CoIs said they reacted in a variety of ways: routine refusal to review, routine attempt to conduct an impartial review, or decision on a case-by-case basis. Multiple means of managing non-financial CoIs were suggested, including increased transparency throughout the review process, with public disclosure of non-financial CoIs, and careful selection of independent reviewers, including foreign experts and methodologists. Conclusions Our study underscores the importance of considering non-financial CoIs when reviewing research grant applications, in addition to financial CoIs. Specific measures are needed to prevent a negative impact of non-financial CoIs on the fairness of resource allocation. Whether and how public disclosure of non-financial CoIs should be accomplished remains debatable.

Improving recruitment in pediatric clinical research: a strategy to consider

We thank Benkouiten et al. [1] for their recent correspondence to the Editor on our multicenter survey that quantified refusal rates in pediatric clinical research and identified factors pertaining to studies and investigators that influenced the decision to participate [2]. We do agree that the presence of a dedicated clinical research assistant (CRA) to assist investigators in the recruitment of patients would be of great help in the context of research conducted by most experienced and motivated investigators such as, according to our results, recruiting pediatricians with teaching responsibilities. However, as shown by a previous qualitative study from our team [3], reluctance of investigators to enroll their patients in clinical research was, for a part of them, related to pediatricians’ personal concerns about the interest/burden ratio of the study or about anticipated refusals. In that case, the presence of a CRA will probably make no significant difference in recruitment rates. Also, participation of a CRA in the recruitment process raises legal and ethical questions. The Declaration of Helsinki [4] and the ICH Guidelines for Good Clinical Practice [5] state that a specifically trained person designated by the investigator can provide study information and obtain subject’s written informed consent. Nevertheless, it is a legal requirement in France and in other countries that these tasks be performed by a medical doctor (L. 1121-1, French Public Health Code). The mission of a CRA dedicated to recruitment should be clearly delineated with respect to the law. Training of CRAs should enable them to be familiar with not only the study protocol but also the specifics of the disease or the drug under evaluation, if applicable. This is essential to ensure that families will obtain complete and correct information before consenting. Benkouiten et al. suggest a very interesting and practical way to improve the participation rate in pediatric clinical research. We believe that such a way should be specifically evaluated in terms of effectiveness and in terms of ethics.