How Variability in the Institutional Review Board Review Process Affects Minimal-Risk Multisite Health Services Research

Background: The Department of Health and Human Services recently called for public comment on human subjects research protections. Objective: To assess variability in reviews across institutional review boards (IRBs) for a multisite, minimal-risk trial of financial incentives for evidence-based hypertension care and to quantify the effect of review determinations on site participation, budget, and timeline. Design: A natural experiment occurring from multiple IRBs reviewing the same protocol for a multicenter trial (May 2005 to October 2007). Participants: 25 Veterans Affairs (VA) medical centers. Measurements: Number of submissions, time to approval, and costs were evaluated; patient complexity, academic affiliation, size, and location (urban or rural) between participating and nonparticipating VA medical centers were compared. Results: Of 25 eligible VA medical centers, 6 did not meet requirements for IRB review and 2 declined to participate. Of 17 applications, 14 were approved. The process required 115 submissions, lasted 27 months, and cost close to $170 000 in staff salaries. One IRB's concern about incentivizing a particular medication recommended by national guidelines prompted a change in our design to broaden our inclusion criteria beyond uncomplicated hypertension. The change required amending the protocol at 14 sites to preserve internal validity. The IRBs that approved the protocol classified it as minimal risk. The 12 sites that ultimately participated in the trial were more likely to be urban and academically affiliated and to care for more complex patients, which limits the external validity of the trial's findings. Limitation: Because data came from a single multisite trial in the VA system that uses a 2-stage review process, generalizability is limited. Conclusion: Complying with IRB requirements for a minimal-risk study required substantial resources and threatened the study's internal and external validity. The current review of regulatory requirements may address some of these problems.