An article published in Circulation by a group of authors from the Duke Clinical Institute, some of whom are investigators and leaders in ADAPTABLE describes tensions between pragmatic clinical trial design and Good Clinical Practice (GCP) guidelines, which were established in 1996 to help ensure the safety of participants in clinical trials and the validity of trial findings. Pragmatic clinical trials (PCTs) such as ADAPTABLE are designed to test interventions in real-world settings and populations rather than under highly controlled conditions, and thus rely on simplified procedures, such as those used for screening, informed consent, and participant follow-up.
The authors concede that many PCT features appear to be at odds with GCP guidance, which has arguably led to improvements in the consistency and quality of trial conduct. However, they also note data suggesting that the intensive approach to monitoring and documentation fostered by GCP may ultimately increase trial cost and complexity by emphasizing minutia that “may direct focus away from critical aspects of trial conduct.”
The authors go on to suggest that GCP guidance should be updated to account for a growing proportion of research that incorporates aspects of pragmatic trial design and is conducted with data gathered from electronic health records and registries. They also offer a path forward for pragmatic research under current GCP guidelines by outlining strategies for areas that include participant enrollment, monitoring, study visits, participant follow-up, and documentation.
The authors conclude that collaborative efforts from trial sponsors, regulators, clinical trialists, and patients will be necessary to realign the guidance with contemporary trial conduct while preserving its central goal of protecting trial participants.
ADAPTABLE is PCORnet’s first pragmatic demonstration study. ADAPTABLE will leverage electronic health records and web-based technologies to identify, consent, randomize, and engage study participants. Throughout the 30-month study, participants will complete surveys and report outcomes using an interactive web portal.