Inadequate Dissemination of Phase I Trials: A Retrospective Cohort Study

François Chapuis and colleagues examine a cohort of clinical trial protocols approved by French ethics committees, and show that Phase I trials are less frequently published than other types of trials

Impact of funding on biomedical research: a retrospective cohort study

BACKGROUND: Public funding is aimed at facilitating the initiation, completion and publication of research study protocols. However, no evaluation is made to investigate the impact of grant success on the conduct of biomedical research. It is therefore of great interest to compare the fate of funded protocols versus not funded: Are they initiated? Are they completed? Did the results confirm the hypothesis? Were they published? The objective was to investigate the fate of protocols submitted for funding, whether they were funded or not. METHODS: Retrospective cohort study of protocols submitted for funding to the Greater Lyon regional scientific committee in 1997. Initial characteristics of protocols (design, study size, investigator status) were abstracted from archives, and follow-up characteristics (initiation, completion and publication) from a mailed questionnaire to the principal investigators. RESULTS: Among the 142 submitted protocols, follow-up information was available for 114 (80%). As a whole, 38% of studies were funded by the Greater Lyon research committee. The rate of initiation varied from 62% for studies with no acknowledged funding to 100% for studies with both committee and other simultaneous funding. When initiated, the rate of completion was 62% for studies with at least one funding and 40% for studies without acknowledged funding. When completed, publication was reached for 77% of studies with either committee or external funding, for 58% of studies without acknowledged funding and for 37% of studies with both committee and external funding. CONCLUSION: Some protocols submitted for funding were initiated and completed without any funding declared. To our understanding this mean that not all protocols submitted really needed funding and also that health care facilities are unaware that they implicitly financially support and pay for biomedical research

The activity of French Research Ethics Committees and characteristics of biomedical research protocols involving humans: a retrospective cohort study

BACKGROUND: Clinical trials throughout the world must be evaluated by research ethics committees. No one has yet attempted to clearly quantify at the national level the activity of ethics committees and describe the characteristics of the protocols submitted. The objectives of this study were to describe 1) the workload and the activity of Research Ethics Committees in France, and 2) the characteristics of protocols approved on a nation-wide basis. METHODS: Retrospective cohort of 976 protocols approved by a representative sample of 25/48 of French Research Ethics Committees in 1994. Protocols characteristics (design, study size, investigator), number of revisions requested by the ethics committee before approval, time to approval and number of amendments after approval were collected for each protocol by trained research assistant using the committee's files and archives. RESULTS: Thirty-one percent of protocols were approved with no modifications requested in 16 days (95% CI: 14–17). The number of revisions requested by the committee, and amendments submitted by the investigator was on average respectively 39 (95% CI: 25–53) and 37 (95% CI: 27–46), per committee and per year. When revisions were requested, the main reasons were related to information to the patient (28%) and consent modalities (18%). Drugs were the object of research in 68% of the protocols examined. The majority of the research was national (80%) with a predominance of single-centre studies. Workload per protocol has been estimated at twelve and half hours on average for administrative support and at eleven and half hours for expertise. CONCLUSION: The estimated workload justifies specific and independent administrative and financial support for Research Ethics Committees

Systematic Review of the Empirical Evidence of Study Publication Bias and Outcome Reporting Bias

BACKGROUND: The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention. METHODOLOGY/PRINCIPAL FINDINGS: We review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40-62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies. CONCLUSIONS: Recent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials

Méconduites académiques : exploration d’une distinction potentielle de genres

Thème : Les nouvelles frontières de l’intégritéInternational audienceGender bias, widely investigated in science on positive aspects such as obtaining funding or publications, remains unexplored on the « negative » aspects of science such as bad academic practices: if women are less visible in science, are they less inclined to dishonest, reprehensible or condemnable behavior?Le biais de genre, largement investigué en sciences sur les aspects positifs tels que l’obtention de financements ou les publications, reste inexploré sur les aspects « négatifs » de la science comme les mauvaises pratiques académiques : si les femmes sont moins visibles dans les sciences, sont-elles pour autant moins enclines aux comportements malhonnêtes, répréhensibles ou condamnables

Oral presentation bias: a retrospective cohort study

The aim of this paper was to assess oral presentation bias at a national level. This was a retrospective cohort study with initial characteristics of the approved protocols extracted from the committee's archives, and follow‐up characteristics obtained from a questionnaire mailed to the principal investigators. A representative sample of French research ethics committees (25/48), the only committees legally endorsed for ethical authorisation in biomedical research, were studied. All completed research protocols, which had been approved in 1994 by these committees, were included. Initial characteristics (design, study size, investigator) of completed studies and follow‐up information (direction of results, rates of publication and rates of oral presentation) were collected. Complete information on results and their dissemination was available for 248 completed non‐confidential protocols. Half of these (49%) were declared as orally presented. The observed ranking for strategies to disseminate results was the following: orally presented and published, published only, neither orally presented nor published and orally presented only. Confirmatory results were more often orally presented, with an adjusted OR of 6.4 (95% CI 2.69 to 15.22). Other associated variables are the following: national/international scope of the study, protocol writer's university status, adverse events and interim analysis. There is a trend to submit or accept confirmatory results for oral presentations: meetings are a biased representation of research, and oral presentation bias could even be higher than publication bias

Fate of biomedical research protocols and publication bias in France: retrospective cohort study

Objectives To describe the fate of protocols approved by the French research ethics committees, a national system created by the French 1988 Huriet-Sérusclat Act; to assess publication bias at a national level. Design Retrospective cohort study. Setting Representative sample of 25/48 French research ethics committees in 1994. Protocols 649 research protocols approved by committees, with follow-up information. Main outcome measures Protocols' initial characteristics (design, study size, investigator) abstracted from committees' archives; follow-up information (rates of initiation, completion, and publication) obtained from mailed questionnaire to principal investigators. Results Completed questionnaires were available for 649/976 (69%) protocols. Of these, 581 (90%) studies were initiated, 501/581 (86%) were completed, and 190/501 (38%) were published. Studies with confirmatory results were more likely to be published as scientific papers than were studies with inconclusive results (adjusted odds ratio 4.59, 95% confidence interval 2.21 to 9.54). Moreover, studies with confirmatory results were published more quickly than studies with inconclusive results (hazard ratio 2.48, 1.36 to 4.55). Conclusion At a national level, too many research studies are not completed, and among those completed too many are not published. We suggest capitalising on research ethics committees to register and follow all authorised research on human participants on a systematic and prospective basis

Fate of protocols submitted to a French national funding scheme: a cohort study.

The fate of clinical research projects funded by a grant has been investigated, but there is no information on the projects which did not receive funding. The fate of these projects is not known: do they apply for and/or receive funding from other sources or are they carried out without specific funding?The aim of the study was to describe all clinical research projects submitted to a French national funding scheme (PHRC 2000) and to assess project initiation, completion and publication status taking into account whether or not they received funding.This study is a retrospective cohort. The initial project characteristics were retrieved from the submission files and follow-up information was collected from the primary investigator. The percentages of projects started, completed and published were studied.A total of 481 projects were studied. Follow-up information was obtained for 366. Overall, 185 projects were initiated (51%); 139 of them were funded by the PHRC 2000 or other sources. The most commonly cited reason for not initiating a project was a lack of funding. Subsequently, 121 of the projects initiated were completed (65%). Accrual difficulties were the main reason cited to explain why studies were stopped prematurely or were still ongoing. Finally, 88 of the completed projects were published (73%). Amongst the completed projects, the only factor explaining publication was the statistical significance of the results.Obtainment of funding was a determining factor for project initiation. However, once initiated, the funding did not influence completion or publication