Stakeholder Reflections on Implementing the National Institutes of Health's Policy on Single Institutional Review Boards.

The National Institutes of Health (NIH) requires use of a single institutional review board (sIRB) for multisite, nonexempt, NIH-funded research with human participants. The Clinical Trials Transformation Initiative (CTTI) conducted in-depth interviews with 34 stakeholders at two universities and in research administration leadership positions at multiple institutions about their experiences implementing the sIRB model, focusing on the NIH policy's goals soon after the policy was enacted. While some stakeholders suggested that using an sIRB has streamlined and reduced inefficiencies associated with the local IRB model, more stakeholders indicated that the sIRB model has not simplified the ethics review process and instead created new inefficiencies due to unclear roles and responsibilities for staff and institutions; a lack of systems and processes for implementing the sIRB model, including communication systems; and increased workloads. CTTI used these findings to propose a new framework for evaluating the NIH sIRB policy.

Factors Associated with IRB Review Time in a Non-Federally Funded Study Using an sIRB of Record.

From 2018 to 2020, U.S. federal mandates began requiring the use of a single institutional review board (sIRB) of record for federally funded, multisite studies. With an interest in the efficiency of site activation, we compared the frequency with which local review and approval and three different reliance options (ways to establish a reliance agreement between the sIRB and the relying institution) were used during this period in a multisite, non-federally funded study (ClinicalTrials.gov identifier: NCT03928548). Using general linear models, we analyzed the relationships between local reliance or approval and sIRB of record approval times and (a) the regulatory option selected and (b) relying-site and process characteristics. Eighty-five sites received sIRB approval through 72 submissions (40% using local review, 46% using the SMART IRB agreement, 10% using an IRB authorization agreement, and 4% using a letter of support). Median time to establish a local reliance or study approval and sIRB approval were longest for sites using a SMART IRB agreement. Study-site region and the time of submission were significantly associated with local reliance or approval time, which averaged 129 and 107 days faster for Midwestern (p = 0.03) or Western (p = 0.02) sites, respectively, and 70 days slower for Northeastern sites (p = 0.42) compared with sites in the South, and 91 days slower when regulatory communication was initiated during or after February 2019 compared with before (p = 0.02). Similar relationships between sIRB approval time and region and time frame were observed; in addition, approval time was 103 days slower for sites affiliated with a research 1 (R1) university versus not (p = 0.02). Region of the country, time frame, and R1 university affiliation were associated with variations in study-site activation in a non-federally funded, multisite study.

Demonstration Project: Transitioning a Research Network to New Single IRB Platforms.

Since the 2016 National Institutes of Health (NIH) mandate to use a single IRB (sIRB) in multicenter research, institutions have struggled to operationalize the process. In this demonstration project, the University of Utah Trial Innovation Center assisted the Collaborative Pediatric Critical Care Research Network to transition from using individually negotiated reliance agreements and paper-based documentation to a new sIRB master agreement and an informatics platform to capture reliance documentation. Lessons learned that can guide other academic institutions and IRBs as they operationalize sIRBs included the need for sites to understand what type of engagement or reliance is required and their need to understand the difference between reliance and activation. Requirements around local review remain poorly understood. Further research is needed to determine approaches that can achieve the NIH vision of reviews becoming more efficient and improving study start-up times, relieving administrative burden while advancing human research protections.

Economic analysis of a single institutional review board data exchange standard in multisite clinical studies.

BACKGROUND: Single Institutional Review Boards (sIRB) are not achieving the benefits envisioned by the National Institutes of Health. The recently published Health Level Seven (HL7®) Fast Healthcare Interoperability Resources (FHIR®) data exchange standard seeks to improve sIRB operational efficiency. METHODS AND RESULTS: We conducted a study to determine whether the use of this standard would be economically attractive for sIRB workflows collectively and for Reviewing and Relying institutions. We examined four sIRB-associated workflows at a single institution: (1) Initial Study Protocol Application, (2) Site Addition for an Approved sIRB study, (3) Continuing Review, and (4) Medical and Non-Medical Event Reporting. Task-level information identified personnel roles and their associated hour requirements for completion. Tasks that would be eliminated by the data exchange standard were identified. Personnel costs were estimated using annual salaries by role. No tasks would be eliminated in the Initial Study Protocol Application or Medical and Non-Medical Event Reporting workflows through use of the proposed data exchange standard. Site Addition workflow hours would be reduced by 2.50 h per site (from 15.50 to 13.00 h) and Continuing Review hours would be reduced by 9.00 h per site per study year (from 36.50 to 27.50 h). Associated costs savings were $251 for the Site Addition workflow (from $1609 to $1358) and $1033 for the Continuing Review workflow (from $4110 to $3076). CONCLUSION: Use of the proposed HL7 FHIR® data exchange standard would be economically attractive for sIRB workflows collectively and for each entity participating in the new workflows.

An Approach to Reviewing Local Context for Exception from Informed Consent Trials Using a Single IRB.

In the context of emergency research, researchers can ask the institutional review board (IRB) to waive the regulatory requirement that individuals provide informed consent when enrolling in research studies. A requirement of the waiver of informed consent is that the reviewing IRB must review and approve a community consultation and public disclosure plan. It is critical that an IRB serving as the single IRB (sIRB) for multisite research be thoroughly versed in the local context concerns for each participating site to determine whether the site's community is being adequately consulted about the research in which individuals will be enrolled under an exception to the informed consent requirement. We designed an sIRB review model for evaluating site-specific community consultation plans that included a local evaluation and feedback step, and we piloted the model with a four-site, pediatric exception from informed consent (EFIC) clinical trial. We identified three key roles for the model: the sIRB, the investigators, and the representative of the institution's human research protection program (HRPP). We successfully collected the information and local input needed to evaluate each site's community consultation plan and applied the information to a thorough IRB review, despite the geographic distance between the study site and the sIRB.

Transitioning to the National Institutes of Health single institutional review board model: Piloting the use of the Streamlined, Multi-site, Accelerated Resources for Trials IRB Reliance.

BACKGROUND/AIMS: Obtaining ethical approval from multiple institutional review boards is a long-standing challenge to multi-site clinical trials and often leads to significant delays in study activation and enrollment. As of 25 January 2018, the National Institutes of Health began requiring use of a single institutional review board for US multi-site trials. To learn more and further inform the research and regulatory communities around aspects of transitioning to single institutional review board review, this study evaluated the efficiency, resource use, and user perceptions of a nascent institutional review board reliance model (Streamlined, Multi-site, Accelerated Resources for Trials IRB Reliance). METHODS: This research was embedded within the Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure trial-a multi-site trial of two influenza vaccine formulations. In the first year of the trial, a sample of sites agreed to use the developing Streamlined, Multi-site, Accelerated Resources for Trials IRB Reliance model and participated in its evaluation. In keeping with a least burdensome approach, short surveys were developed and obtained from each reporting entity (relying sites, non-relying site, lead site, and reviewing institutional review board). Data regarding time to institutional review board approval and site activation, costs, and user perceptions of reliant review were self-reported and collected via the survey form. Quantitative and qualitative analyses were performed, with costs analyzed as actual versus estimated due to the lack of established baseline cost data. RESULTS: A total of 13 sites ceded review and received institutional review board approval. Mean time to approval was substantially faster in sites that ceded review using the Streamlined, Multi-site, Accelerated Resources for Trials IRB Reliance model versus the site that did not cede review (81 vs 121 days). The mean time to approval was also faster than published averages for academic medical centers (81 vs 103 days). Time to first enrollment was faster for ceding sites versus the non-ceding site, and also faster than published averages (126 vs 149 and 169 days, respectively). Costs were higher than estimates for local institutional review board review and approval. Nearly half (47%) the stakeholders reported being very satisfied or satisfied with the reliance experience, although many noted the challenge related to institutional culture change. CONCLUSION: Implementation of a single institutional review board represents a shift in practice and culture for many institutions. Evaluation of the reliance arrangements for this study highlights both the potential of, and challenges for, institutions as they transition to single institutional review board review. Although efficiencies were observed for study start-up, we anticipate a learning curve as institutions and research teams implement necessary process and resource changes to adapt to single institutional review board oversight. Findings may inform research teams but are, however, limited by the relatively small number of sites and lack of a control group.

The efficiency of single institutional review board review in National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network-initiated clinical trials.

BACKGROUND/AIMS: Timely review of research protocols by institutional review boards leads to more rapid initiation of clinical trials, which is critical to expeditious translation from bench to bedside. This observational study examined the impact of a single institutional review board on time and efforts required to initiate clinical trials by the National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network. METHODS: Collection of data from the same six main clinical sites for three current clinical trials and two past clinical trials, including time from institutional review board submission to approval, pages submitted, consent form length, number of required attachments, other regulatory requirements, order of review at central or local sites, and language in documents at individual participating sites. Results from two past clinical trials were also included. RESULTS: While time required for actual institutional review board submission's review and initial approval was reduced with use of a single institutional review board for multicenter trials (from a mean of 66.7-24.0 days), total time was increased (to a mean of 111.2 or 123.3 days). In addition to single institutional review board approval, all institutions required local approval of some components (commonly consent language and use of local language), which varied considerably. The single institutional review board relied on local institutions for adding or removing personnel, conflict of interest review, and auditing of activities. CONCLUSION: A single institutional review board reduced time for initial review and approval of protocols and informed consents, although time for the entire process was increased, as individual institutions retained oversight of components of required regulatory review. In order to best achieve the National Institute of Health's goals for improved efficiency in initiation and conduct of multisite clinical research, greater coordination with local institutional review boards is key to streamlining and accelerating initiation of multisite clinical research.