Patients participate in clinical trials for a variety of reasons, giving weight to considerations such as gaining possible access to treatment options, receiving visit stipends, and making a contribution to science. Regardless of individual motivation, there is arguably a general sense among participants that all trials have scientific merit, but this is not always the case. These uninformative clinical trials rob the resources desperately needed for valid, scientifically relevant research efforts. But there is something research Sites can do to help.
5 qualifications for informative clinical trials.
Recent research by Zarin, Goodman, and Kimmelman (2019) demonstrates the harms from "uninformative" clinical trials that do not meet the following qualifications for informativeness:
- Importance: the trial hypothesis is likely to inform and important medical or policy decision
- Design: the trial design can provide meaningful evidence related to the important hypothesis
- Feasibility: participants can be recruited and are able to complete the trial to meet the required sample size
- Integrity: the study design is valid and the trial is registered completely and in a timely manner
- Reporting: Sponsor allows for timely dissemination of results
A persistent problem.
Despite a call for change, research reviews show evidence of a high percentage of trials that fail to meet at least one of these qualifiers (Zarin, et al., 2019) and identifies dozens of trials that have not been registered on www.ClinicalTrials.gov, representing more than 85,000 patients (Tatsioni et al., 2019)
Zarin et al. (2019) argue negative consequences of this persistent problem of uninformative trials, including:
- Violation of the principle of social value that has long contributed to justifying the call for research volunteers
- Disconnection with the spirit of informed consent when the trial cannot fully contribute to scientific progress
- Diversion of energy from informative trials, both in terms of patient participation and the limited attention of the clinical audiences that may not be aware of deficiencies in the trials
How can we help?
The Institutional Review Board's role in trial review is focused on risk/benefit and the protection of patient safety, and falls short of scientific merit, so Sites must look elsewhere for support in identifying uninformative clinical trials. Sponsors have incentives to design valid trials in support of further approval, yet uninformative studies are still making their way to Sites.
Larger institutions might include scientific merit in their internal feasibility or scientific review committees for purposes of integrity as well as resource allocation. For smaller Sites and Site networks, a thorough internal review process that goes beyond recruitment feasibility to include scientific merit and requirements for informativeness will benefit its patient population and its role as a responsible citizen in the clinical research community.
What does your site, site network, or Institution do to combat uninformative clinical trials?
Does your review include these same five requirements for informativeness: Importance, Design, Feasibility, Integrity, and Reporting?
References
Tatsioni A, Karassa FB, Goodman SN, Zarin DA, Fanelli D, Ioannidis JPA. Lost evidence from registered large long-unpublished randomized controlled trials: a survey [published online May 7, 2019]. Ann Intern Med. doi:10.7326/M19-0440
Zarin DA, Goodman SN, Kimmelman J. Harms From Uninformative Clinical Trials. JAMA. Published online July 25, 2019. doi:10.1001/jama.2019.9892