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. 2021 Jan 25;22(1):90.
doi: 10.1186/s13063-021-05026-w.

Streamlining the institutional review board process in pragmatic randomized clinical trials: challenges and lessons learned from the Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness (ADAPTABLE) trial

Guillaume Marquis-Gravel  1 , Holly Robertson  1 , W Schuyler Jones  1   2 , Danielle Riley  3 , Daniel E Ford  4 , David Crenshaw  5 , Yvonne A Joosten  5 , Lindsey Rudov  6 , Adrian F Hernandez  1   2 , Rachel Hess  7
Affiliations

Streamlining the institutional review board process in pragmatic randomized clinical trials: challenges and lessons learned from the Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness (ADAPTABLE) trial

Guillaume Marquis-Gravel et al. Trials. .

Abstract

Background: New considerations during the ethical review processes may emerge from innovative, yet unfamiliar operational methods enabled in pragmatic randomized controlled trials (RCT), potentially making institutional review board (IRB) evaluation more complex. In this manuscript, key components of the pragmatic "Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE)" randomized trial that required a reappraisal of the IRB submission, review, and approval processes are discussed.

Main text: ADAPTABLE is a pragmatic, multicenter, open-label RCT evaluating the comparative effectiveness of two doses of aspirin widely used for secondary prevention (81 mg and 325 mg) in 15,000 patients with an established history of atherosclerotic cardiovascular disease. The electronic informed consent form is completed online by the participants at the time of enrollment, and endpoint ascertainment is conducted through queries of electronic health records. IRB challenges encountered regarding centralized IRB evaluation, electronic informed consent, patient engagement, and risk determination in ADAPTABLE are described in this manuscript. The experience of ADAPTABLE encapsulates how pragmatic protocol components intended to facilitate the study conduct have been tempered by unexpected, yet justified concerns raised by local IRBs. How the lessons learned can be applied to future similar pragmatic trials is delineated.

Conclusion: Development of engaging communication channels between IRB and study personnel in pragmatic randomized trials as early as at the time of protocol design allows to reduce issues with IRB approval. Integrations of the lessons learned in ADAPTABLE regarding the IRB process for centralized IRBs, informed consent, patient engagement, and risk determination can be emulated and will be instrumental in future pragmatic studies.

Keywords: Aspirin; Cardiology; Ethics; Informed consent; Institutional review boards; Pragmatic trials.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Distribution of time from shipment of regulatory package and primary IRB approval in ADAPTABLE study sites. Arrows indicate multi-site approvals in three Clinical Data Networks
Fig. 2
Fig. 2
Informed consent study comprehension tool integrated to the e-consent online portal, developed by Duke’s program for empirical bioethics through iterative cognitive interviews with patients. After watching a video summarizing the trial, participants answer 6 questions to verify their comprehension of the study before signing the e-consent form
See this image and copyright information in PMC

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