Central IRB

>> Project Summary

 

Project Category: Study Start-UpUse of Central IRBs for Multicenter Clinical Trials

CTTI Project Cateogy: Study Start-Up

Project Status: Complete

 

The willingness of institutions to defer full local institutional review board (IRB) review and approval to a central IRB in multicenter trials continues to vary, despite a 2006 U.S. Food and Drug Administration (FDA) guidance and a more recent endorsement by the U.S. Office for Human Research Protections1 recommending this approach.

CTTI's Definition of Central IRB:  A single IRB of record for all sites involved in a multi-center protocol. A range of entities may serve as a central IRB (e.g. another institution’s IRB, a federal IRB, an independent IRB).

1Menikoff J. The paradoxical problem with multiple-IRB review. N Engl J Med. 2010; 363:1591-1593.

 

What is the issue?

Before a clinical trial gets underway, the protocol (study plan) needs to be reviewed by someone not connected to the research to be sure it is ethical, provides potential benefits, and does not cause unnecessary harm to participants. This review is done by Institutional Review Boards (IRBs). In multicenter trials, where a study to answer a single research question is carried out at several different sites (locations), each site’s IRB usually reviews the protocol separately. This can take a long time, cause duplicate work, and can even result in the protocol being changed by individual sites so that it is no longer the same across all sites. One solution to this would be for all of the sites in a multicenter trial to use the same IRB (a central IRB). Use of a single, central IRB may save time and money and make sure the research is being done in the same way at each site. The U.S. Food and Drug Administration (FDA) and the U.S. Office of Human Research Protections (OHRP) have both encouraged the use of a single, central IRB for multicenter trials, rather than each site using its own. However, some research sites are hesitant to use a single, central IRB.

More about IRBs

IRBs do many other things in addition to making sure a study protocol is ethical and not unnecessarily risky. They may also:

  • Evaluate the scientific soundness of the protocol
  • Approve the informed-consent forms that participants must sign
  • Make sure investigators are qualified to do the research and comply with the approved study plans
  • Train staff and study coordinators
  • Credential staff
  • Register with the FDA and OHRP
  • Make sure studies comply with various federal and state regulations
  • Conduct a privacy review for the Health Insurance Portability and Accountability Act (HIPAA)
  • Seek to uncover any conflict of interest

 

What is the goal of this project?

Identify potential solutions to address barriers to the adoption of central IRBs for multicenter clinical trials

 

What are the objectives of this project?

  • Solicit current perceptions of barriers to the use of central IRBs in multicenter clinical trials
  • Develop strategies to address the identified barriers
  • Test reactions to such proposed solutions

 

What did the project accomplish?

  • We conducted a literature review: We identified journal articles about using central IRBs in multicenter trials in the United States; of the articles we found, most were commentary or editorials (as opposed to scientific studies). We concluded that more studies are needed to investigate the cost and time savings of using central IRBs and to compare the quality of work done by central vs. site-specific IRBs.
  • We interviewed experts to identify barriers to using central IRBs: We held group and individual discussions with 43 experts to identify barriers and generate ideas for solutions. Those interviewed included representatives from several different kinds of IRBs (e.g.  research institution, federal, and commercial), the pharmaceutical industry, and regulatory agencies (e.g. FDA).
  • We interviewed stakeholders at research sites to obtain feedback: The proposed solutions were presented to 25 people at sites that don’t typically use central IRBs.  The sites varied by how much research was done at each site, amount and type of research funding received (e.g. from government agencies and/or pharmaceutical industry), and geographic location.
  • We held an expert meeting to further refine solutions and recommendations: We held an expert meeting on April 25-26, 2012 to further refine solutions and recommendations. Meeting participants included representatives from government and pharmaceutical industry sponsors of clinical research, FDA, OHRP, academic and non-academic research institutions, commercial IRBs, and patient advocacy groups.

 

Highlighted Results of the Project

Considerations Document

We found that one of the main barriers to using central IRBs is that local sites use IRBs not only for approving protocols, but also for various site-specific tasks related to clinical trials, such as training staff, making sure investigators comply with research protocols, and making sure HIPAA privacy rules are being followed. There is confusion about how a central IRB could handle all the tasks that a typical site-specific IRB handles. To clarify this issue, we produced a “considerations document” that outlines how site-specific IRBs and a central IRB would interact in a multicenter trial using a central IRB. The document outlines which tasks—such as approving the protocol—would be taken care of by the central IRB and which tasks—such as conducting a conflict-of-interest review—would be taken care of by the site-specific IRBs. CLICK HERE to download a PDF version of the Considerations Document.

Other Recommendations

We discovered that sites that had used central IRBs were more comfortable with them than sites that had never used a central IRB. One way to give sites more experience with central IRBs would be for government and commercial sponsors to require the use of a central IRB as a condition for participating in a particular multicenter trial. The National Institute of Neurological Disorders and Stroke has done this. CLICK HERE to download the Official Recommendations resulting from this project.