Facilitating NHLBI Clinical Trials Through Optimization of the IRB Process:
Are Central IRBs the Solution?

Executive Summary

The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group (WG) of invited external experts in heart, lung and blood research and clinical research oversight, bioethics, health economics, regulatory matters and information technology. The meeting was held at the Bethesda offices of the NHLBI on June 28-29, 2011. The purpose of this Working Group was to explore and discuss existing information and metrics on alternative Institutional Review Board (IRB) models and to discuss optimization of the IRB review process as one way to facilitate the conduct of NHLBI-funded human subjects research. The Working Group was responsive to NHLBI Strategic Plan Goal 2.

Discussion

Dr. Susan Shurin, Acting Director, NHLBI, began the meeting with an overview of the IRB process as one component of the protection of human subjects.  Dr. Jerry Menikoff, Director, Office of Human Research Protection, was officially supportive of efforts to reduce the number of duplicative IRB reviews that take place in many multicenter clinical trials.    

A variety of central IRB (CIRB) models was presented in panel format and a second panel discussed various aspects of CIRB impact from the perspective of investigators and ethicists.  Examples of regional IRBs and a local IRB that relies on CIRB for some studies were presented. It was emphasized that the key function of the IRB is protection of human subjects participating in research and that IRBs should not serve primarily as a risk management board to limit liability of the institution conducting the research. Outcome measures of quality could help ensure adherence to the goal of protection of human subjects.

The Working Group discussed issues of financial conflict of interest (COI) in the selection and management of IRB members.  They recognized that there is a need for balance between COI management and obtaining the best scientific expertise, but it was accepted that recusals must be complete. COI disclosures should be transparent and public.

The role of local IRBs in reviewing research from a local context was discussed in detail.  Many “local” issues were instead issues that were common to many geographic or social areas.  The Working Group discussed economic issues of IRB systems. It was noted that a certain volume of studies is needed to create economies of scale for CIRBs.  Information technology (IT) issues were discussed as potential critical roadblocks for quality improvement, risk management, research and user acceptance of alternative IRB models. WG members described the ongoing development of a system currently being planned under NCRR funding for a secure IT system to facilitate document sharing and shared review responsibilities among CTSA and/or other interested sites.

Consensus and Recommendations

Inefficiencies and variability in the time course of IRB review are only one part of a multi-step process that delays the start of clinical trials. These steps include local PI submission time, contract negotiations and others. However, the practice of multiple IRB reviews is inefficient and has not been shown to reliably enhance human subjects protection.

To raise awareness about the rate-limiting steps in clinical trials, NHLBI-issued FOAs should impose specific requirements for IRB review. Documentation of adherence to timeline metrics would be required of the investigators.

In addition, NIH or NHLBI should commit resources to study the process of IRB review, including the development of good metrics, which do not now exist, to assess the quality or substance of the review. Additionally, the institute should support research to develop a template for excellence in IRB review that could ensure that an IRB’s decisions hold merit with other IRBs and which would allow external review for content and quality, allowing such metrics to be collected.

NHLBI could mandate the use of alternative IRB models. These might include:

    • Use of an existing commercial IRB
    • Use of an existing system of regional or other multisite review
    • Use of a NCRR-funded (CTSA) model (not yet implemented) in which document sharing (including IRB decision-making processes) is key and the reliance on an external IRB for approval or disapproval is optional.
    • Piloting a partnership with the NCI-managed central IRB
    • Creation of an NHLBI-funded CIRB

However, use of the NCRR-funded CTSA proposed model would require development of an IT infrastructure which permits document sharing, including IRB decision-making processes. Creation of a separate NHLBI-funded CIRB would add burden to institutions by requiring different procedures for differently funded NIH research and would be costly.

Participating Divisions

Division of Cardiovascular Sciences
Division of Blood Diseases and Resources
Division of Lung Diseases
Office of Science and Technology

NHLBI Contacts

Alice Mascette, MD
Division of Cardiovascular Science
mascetta@nhlbi.nih.gov
301-435-0504

Donna DiMichele, MD
Division of Blood Diseases and Resources
donna.dimichele@nhlbi.nih.gov
301-435-0080

Gail Weinmann, MD
Division of Lung Diseases
weinmang@nhlbi.nih.gov
301-435-0233

Hilary S. Leeds, JD
Office of Science and Technology
leedsh@nhlbi.nih.gov
301-594-9869

Working Group Members

  • Gordon Bernard, MD, Vanderbilt University, Chair
  • C. Noel Bairey Merz, MD, Cedars-Sinai Heart Institute
  • Angela Bowen, MD, Angela J. Bowen & Associates, LLC
  • Nancy Neveloff Dubler, LL.B., Montefiore-Einstein Bioethics Center
  • Daniel E. Ford, MD, MPH, Johns Hopkins School of Medicine
  • Timothy J. Gardner, MD, Christiana Care Health Services
  • Christine Grady, RN, PhD, Clinical Center, NIH*
  • Jacquelyn Goldberg, JD, NCI, NIH
  • Jesse A. Goldner, JD, St. Louis University Schools of Law and Medicine
  • Robert A. Harrington, Duke Clinical Research Institute
  • Paul A. Harris, PhD, Vanderbilt University
  • Vita J. Land, MD, MBA, Children’s Memorial Hospital, Chicago*
  • Kerry L. Lee, PhD, Duke Clinical Research Institute
  • Fernando J. Martinez, MD, University of Michigan Health Systems
  • Karen J. Maschke, PhD, The Hastings Center, Garrison, NY
  • Jerry Menikoff, MD, JD, Office of Human Research protections
  • Diane Nugent, MD, Children’s Hospital of Orange County, CA
  • Thomas A Pearson, MD, MPH, PhD, Univ. or Rochester*
  • Bonnie Ramsey, MD, University of Washington*
  • Sherrill J. Slichter, MD, Puget Sound Blood Center, Seattle, WA
  • B. Taylor Thompson, MD, Massachusetts General Hospital/Harvard
  • David Tribble, MD, DrPH, Uniformed Services University of Health Sciences
  • Suresh Vedantham, MD, Washington University
  • Todd H. Wagner, PhD, VA Palo Alto Health Care System/Stanford

*denotes Planning Committee member

Last Updated: August 2011




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