The US should consider establishing a national registry for healthy volunteers participating in Phase I clinical trials, to guard against the risks of overlapping enrolment and protect data integrity, a commentary in the Journal of the American Medical Association (JAMA) suggests.
As David Resnik from the US National Institute of Environmental Health Sciences (National Institutes of Health) and Greg Koski from the James Mongan Institute for Health Policy point out in JAMA, some people in the US have enrolled in as many as 80 phase 1 studies, to the extent of pursuing research participation as a full-time job.
“Professional research participants have developed their own social networks, web pages, associations, and publications, which they use to learn about new studies, share information and experiences, and understand the ethical, regulatory, and scientific aspects of clinical research,” they comment.
This intense commitment heightens the risk of potentially dangerous drug interactions between investigational agents and medication taken by the study participant either currently or recently, Resnik and Koski note. The risk is especially pronounced in Phase I trials “designed to induce toxicity to determine the maximum tolerable dose”.
Recent participation in another clinical; study can also skew safety data, Resnik and Koski add. While there is a standard exclusion interval of 30 days for Phase I trials in the US, and protocols should ideally specify an appropriate waiting period based on the half-life of the investigational drug, professional volunteers “have a strong financial incentive to conceal recent or even current enrolment in phase 1 studies”, the commentators write.
Although the incidence of adverse drug reactions from overlapping trial enrolment “is presumed to be rare, it may be under-reported because participants who experience adverse drug reactions might not inform investigators making adverse event reports, to avoid jeopardising their current or future enrolments”, they suggest.
A number of other countries, such as France and the UK, already have national registries for healthy volunteers participating in clinical research, Resnik and Koski point out. Registries also have been implemented in parts of the US, although geographical limitations mean these can be circumvented.
“To adequately deal with the problem of overlapping enrolment, a national registry is needed,” Resnik and Koski argue. This should be linked to databases providing investigators with key information about studies volunteers have participated in, such as interventions, drugs taken, estimated duration of the research and contact information. Costs “would be modest and could be financed by fees from study sponsors”.
According to the commentators, federal agencies that regulate or sponsor research involving human participants, such as the US Food and Drug Administration (FDA) and the National Institutes of Health (NIH), could make participation in the national registry a requirement for conducting Phase 1 trials with healthy volunteers. The registry could also be administered by the FDA or the NIH.
Some might argue, Resnik and Koski note, that overlapping enrollment could be reduced substantially by removing financial incentives “to cheat the system” and not paying individuals for study participation.
“However,”, they say, “it is unlikely that Phase 1 studies enrolling healthy volunteers could achieve enrolment goals without offering participants a financial reward, because that is the main reason most individuals participate in such research.”