dissemination of trial results
A research activity involving human subjects is complete when its results are released into the public domain. There are a number of inter-related imperatives for the public dissemination of the results of clinical trials:
A judgment that the nature of the proposed research meets the requirement of scientific and social value presupposes that the research results will be publicly disseminated. This is analogous to the notion that the requirement of scientific and social value cannot be fulfilled if the research design is not scientifically (internally) valid. (1).
Research on human subjects typically includes interventions that offer the prospect of health-related benefits, and interventions performed solely to answer the research question. This is invariably the case in clinical trials. While the risks associated with therapeutic interventions may be justified on the basis of anticipated health-related benefits, the risks (demarcated research risk) associated with non-therapeutic interventions are justified solely by the prospect of acquiring valuable and relevant knowledge (2). This distinction is elaborated upon more fully in a separate section of this statement. Failure to publish the acquired knowledge renders the exposure of research participants to demarcated research risks ethically unjustifiable.
Failure to disseminate research results, positive or negative, adversely affects the relevance of published results of other trials and the utility of Systematic Reviews and Meta-analyses of trials (publication bias). Failure to publish negative results may expose future patient-subjects in trials to interventions known to be inferior to other currently utilized treatments (3).
Empirical research (4) evaluating reasons why patients agree to participate in clinical research, including trials, has revealed that patients are primarily motivated by two factors: the anticipation of health-related benefits, and an expression of trust in the physician proposing research participation. A third motivation is an altruistic one -- the hope that future patients will benefit from the knowledge gained -- and the failure to publish the research results dishonors such principled volunteerism.
The research participants, whose enrollment made the clinical trial possible, are entitled to know the results of the trial, and the implications for their health.
The duty to share new knowledge with colleagues is a longstanding norm in the medical profession, commonly enunciated in professional codes of conduct. This imperative applies also to the acquisition of knowledge by a physician engaged as an investigator in clinical trials. These notions are summarized in the table below.
In recognition of these imperatives, research ethics committees should ascertain the nature of plans to disseminate research results in a timely manner after completion of the trial. Full publication of results in peer-reviewed print and online journals should be the primary means of results dissemination. Results of clinical trials are often presented initially in the form of abstracts or short reports at medical conferences. Scherer (5) has reported an analysis of 46 studies describing subsequent full reporting of studies initially presented in abstract or short-form, showing an average rate of full publication of 44.8%. The utility of such reports is limited, particularly with respect to an assessment of the trial's internal and external validity, and the inability to incorporate the results of these trials in Systematic Reviews or Meta-analyses of the pertinent clinical literature. Thus, only full reports of trials should be considered an acceptable form of results dissemination. Investigators should be made aware of the CONSORT statement (6) regarding the appropriate reporting of trial results. Alternative forms of results dissemination may be the submission of results to established Trial Banks(7), or publication on a Web page which is linked to an established trial register. The last is least desirable, but the advent of the Internet makes dissemination of all results feasible. Investigators should also be encouraged to make the patient-level (raw) data accumulated during the trial publicly available at an appropriate time. This is a notion worthy of more debate.
Research ethics committees typically have oversight obligations during the ongoing conduct of research- related activities. For example, in the U.S., federal regulations specify the need for continuing review and re-approval of research at intervals not exceeding one year (8). In general, trial completion is considered to be the point at which all trial-related interventions have been completed in all participants. However, a more meaningful concept is that trial completion coincides with the public availability of the research results, which may then be integrated into the corpus of existent knowledge.
To assure the dissemination of research results, particularly the reporting of the pre-specified primary and secondary outcome measures, committees should conduct continuing review until these results are reported as described above. To this end, the application for research should provide the name of the investigator, with contact information, assuming responsibility for the public dissemination of the research results. In the case of multicenter trials, the names and affiliations of members of the trial's Publication Committee should be provided. These investigators should be encouraged to provide updated information concerning the publication of trial results on a trial-related Web site as described elsewhere in this statement. This will enable the committee to determine the progress towards results dissemination with minimal effort.
Failure to report research results should be considered a form of research misconduct (9). Research ethics committees should ascertain whether the investigators who assumed responsibility for results dissemination are culpable. Committees need to ascertain whether investigators proposing to conduct human subjects research are qualified to do so, and failure to disseminate research results bears directly on this issue. Such failure is a proper consideration when the investigators submit new research proposals for review. Unfortunately, such considerations are necessary in the current research environment wherein financial conflicts of interest and questionable industry-investigator alliances not uncommonly culminate in attempts to suppress the dissemination of unfavorable research results (10-13).
References available online are hyperlinked
1. Freedman B. Scientific value and validity as ethical requirements for research: A proposed explication. IRB 1987; 9:7-10.
2. Weijer C. The ethical analysis of risk. J Law Med Ethics 2000; 28(4):344-61.
3. Chalmers I. Using systematic reviews and registers of ongoing trials for scientific and ethical trial design, monitoring, and reporting. In, Egger M, Smith DG, Altman DG (editors) Systematic Reviews in Health Care: Meta-analysis in Context. London. BMJ Books. 2001, pp 429-443
4. Sugarman J, Kass NE, Goodman SN, et al. What patients say about medical research IRB 1998; 20:1-7
5. Scherer RW, Langenberg P. Full publication of results initially presented in abstracts:Revisited. Fourth International Congress on Peer Review in Biomedical Publication 2001, Barcelona, Spain.
7 Sim I, Owens DK, Lavori PW, Rennels GD. Electronic trial banks: A complementary method for reporting randomized trials. Medical Decision Making.2000; 20:440-450.
9. Chalmers I. Underreporting research is scientific misconduct. JAMA 1990; 263:1405-8.
10. Bodenheimer T. Uneasy Alliance - Clinical Investigators and the Pharmaceutical Industry. NEJM 2000; 342:1539-1542.
11. Wise J. Research suppressed for seven years by drug company. BMJ 1997; 314:1145.
13. Gottlieb S. Firm tried to block report on failure of AIDS vaccine. BMJ 2000; 321:1173.