Stakeholder Perspectives on Adaptive Clinical Trials: a Scoping Review

Background: Adaptive clinical trials (ACTs) represent an emerging approach to trial design where accumulating data are used to make decisions about future conduct. Adaptations can include comparisons of multiple dose tiers, response-adaptive randomization, sample size re-estimation, and efficacy/futility stopping rules. The objective of this scoping review is to assess stakeholder attitudes, perspectives, and understanding of adaptive trials.

Methods: We conducted a review of articles examining stakeholders encompassing the broad medical trial community's perspectives of adaptive designs (ADs). A computerized search was conducted of four electronic databases with relevant search terms. Following screening of articles, the primary findings of each included article were coded for study design, population studied, purpose, and primary implications.

Results: Our team retrieved 167 peer-reviewed titles in total from the database search and 5 additional titles through searching web-based search engines for gray literature. Of those 172 titles, 152 were non-duplicate citations. Of these, 119 were not given full-text reviews, as their titles and abstracts indicated that they did not meet the inclusion criteria. Thirty-three articles were carefully examined for relevance, and of those, 18 were chosen to be part of the analysis; the other 15 were excluded, as they were not relevant upon closer inspection. Perceived advantages to ADs included limiting ineffective treatments and efficiency in answering the research question; -perceived barriers included insufficient sample size for secondary outcomes, challenges of consent, potential for bias, risk of type 1 error, cost and time to adaptively design trials, unclear rationales for using Ads, and, most importantly, a lack of education regarding ADs among stakeholders within the clinical trial community. Perceptions among different types of stakeholders varied from sector to sector, with patient perspectives being noticeably absent from the literature.

Conclusion: There are diverse perceptions regarding ADs among stakeholders. Further training, guidelines, and toolkits on the proper use of ADs are needed at all levels to overcome many of these perceived barriers. While education for principal investigators is important, it is also crucial to educate other groups in the community, such as patients, as well as clinicians and staff involved in their daily implementation.