From the Deputy Director for Intramural Research

IRBs at NIH Revisited

Serving the Interests of Patients and Clinical Investigators

BY MICHAEL GOTTESMAN, DDIR, AND RICHARD WYATT, DEPUTY DIRECTOR, OIR

The NIH Clinical Center (CC) pioneered institutional review boards (IRBs) more than 60 years ago in recognition of the need for analyzing the risks versus the benefits of clinical protocols. IRBs are fundamental to the scientific integrity of the protocols and the protection of the human subjects involved in the research. As IRBs evolved at NIH and elsewhere, so did the federal policies and regulations that govern federally funded research today.

Academic, pharmaceutical, and government institutions have developed a range of IRBs—from community-based and hospital-based IRBs to for-profit, commercial IRBs. The need for consistency and uniformity in procedures led to the formation of a national accrediting body 16 years ago: The Association for Accreditation of Human Research Protection Programs (AAHRPP). NIH sought and achieved AAHRPP accreditation in 2014 and received full re-accreditation in 2017.

At NIH, the IRB evolved from a central entity with subpanels to 12 individual IRBs, based in institutes and centers (ICs) today. Some 20 years ago, then–NIH Director Harold Varmus and other leaders questioned why there were so many IRBs at NIH and recommended consolidating them. But nothing happened. During AAHRPP’s rigorous accreditation process, that theme re-emerged: Why does NIH have so many IRBs that function largely as IC-based entities rather than having the kind of centralized IRB system that exists in many major medical centers?

NIH’s decentralized system has created an unwieldly process with three different information technology (IT) systems; some inconsistencies in review processes across multiple IRBs; lack of standardized application forms, consent templates, and protocol templates; duplication of effort between scientific reviews and IRB reviews; and inefficiencies in the conduct and operation of individual IRBs.

Although the NIH human-subjects research program has achieved well-earned, continuing full accreditation from the AAHRPP, we need a well-functioning, centrally managed IRB system to improve efficiency and ensure consistency. The system must allow NIH investigators to move forward expeditiously and efficiently with their clinical-trial protocols in the interest of patients for whom effective treatments are lacking. The urgency of these compelling clinical-research efforts at the NIH CC is portrayed well in an exciting three-part Discovery Channel series, “First in Human,” scheduled to air beginning on August 10, 2017 (9:00–11:00 p.m.).

So, with the best interests of our patients and clinical investigators in mind and based on thoughtful recommendations made by many professionals, NIH has set out to revise and centralize our IRB system. The following action steps were proposed and are being implemented by a group of IRB and NIH leaders, clinical investigators, protocol navigators, and others who understand the needs of the NIH:

1. Implementation of one NIH-wide Integrated Risk Information System (iRIS) to manage all protocols. This IT system will replace the three current computer systems including two iRIS systems and the Protocol Tracking and Management System (PTMS).

2. Use of standard protocol templates for scientific and IRB reviews. The proposal clarifies that the ICs, not IRBs, are responsible for the scientific and conflict of interest reviews. A future goal is to integrate a protocol-authoring tool, data management, and protocol resource requirements into a relational database using Biomedical Translational Research Information System (BTRIS) resources.

3. Creation of a centralized IRB Operations Office and six NIH IRB panels, each with seven to 13 members. The central office will assign protocols and track progress for reviews by the panels, which will meet weekly. (Note: The first of the new IRBs is being established as a pilot under the leadership of NHLBI senior investigator Richard Cannon. The new IRB will review all protocols from NHLBI, NCI, and NIAID institute leaders as well as from NHGRI and NHLBI staff.)

4. The other five proposed IRB panels will be generic (medicine and pediatrics) or thematic with possible special panels as needed (for example, epidemiology or oncology). New protocols will be assigned to the next available panel with attention to subject-matter expertise as needed.

5. Expedited reviews will be evaluated and approved by the IRB Operations Office staff, IRB chairs and vice-chairs, and/or the chairs’ designees. Panel review, however, remains an option.

6. A centralized Office of Research Support within the CC will assure that all NIH clinical investigators will have access to protocol navigators.

There are many other fine details in the proposed centralization plan, but it is important to point out that we can’t fully implement it until the actions steps are achieved. At the conclusion of this process, a more efficient IRB system will serve both research patients and clinical investigators in ways that will enhance the research environment in the NIH Intramural Research Program.