How variability in the institutional review board review process affects minimal-risk multisite health services research

Abstract

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.

Figure 1

Site Identification to Submission of Applications VA = Veterans Affairs; PCPs = primary care physicians; IRB = Institutional Review Board; PI = principal investigator

Figure 2

Number of Days from Initial Submission to Approval by Date of Initial Submission* * For the 13 sites that approved the study before the modification was submitted. Sites 3, 4, and 13 did not approve the study, and the modification was incorporated into the application at Site 16 before their IRB had made an initial review decision. † Applications were submitted to Sites 10 and 11 on the same date, April 14, 2006. Site 10 approved the application in 230 days, and Site 11 approved it in 111 days.

Figure 3

Impact of IRB and R&D Approval Process on Study Timeline IRB = Institutional Review Board; R&D = VA Research & Development Committee; Jan = January; Feb = February; Mar = March; Apr = April; Jun = June; Jul = July; Aug = August; Sep = September; Oct = October; Nov = November; Dec = December