For decades the research community has hotly debated how best to conduct ethics review of multi-site studies. Over the din of this debate, one set of voices is clear: those of patients and study participants. These voices are passionate that review by a single IRB of record is more effective and brings life-saving medications to market more quickly. Today, we hear much lip service about the importance of developing patient-centric studies. If we are focusing on patient needs, why aren’t we listening to the patients and participants who demand more efficient IRB review?
The Origin of IRB Review
The debate over how to conduct IRB review of multi-site trials emerged years ago. Federal regulations require that each clinical study of a new medication or medical device subject to federal regulation must be reviewed by an ethics committee (an “institutional review board” or “IRB”) before the study can start. These review requirements and practices evolved in the 1970s, when most clinical trials were conducted at a single site or at a small number of sites. Traditionally these sites were university academic medical centers, each of which maintained its own ethics review committee to review research conducted on its premises, and these in-house or “local” IRBs would conduct the required review.
In the 1990s, as the life sciences industry grew, so did the number and complexity of multi-site trials. This growth placed considerable burdens on IRBs, sponsors, and clinical investigators seeking IRB review for multi-site trials. Often the local IRB at each university or hospital site of a multi-site trial would conduct a complete review of the protocol and informed consent, regardless of how many other local IRBs were conducting the same review. In the words of the FDA in 2006: “Such multiple reviews by multiple IRBs can result in unnecessary duplication of effort, delays, and increased expenses in the conduct of multi-site clinical trials.”
Understandably, calls for “centralized IRB review” by patient and participant advocates began by the early 2000s. With centralized review, one IRB is responsible for the oversight of multiple sites in a study. This IRB is considered a “central IRB,” and if there is only one IRB, it is the “single IRB of record” or “sIRB”. Patient advocates calling for centralized IRB review focused on the improved speed, efficiency, and safety that centralized review can achieve.
Voices for Change
An early advocate for centralized review was Suzanne Pattee, VP of Public Policy and Patient Affairs of the Cystic Fibrosis Foundation. At a 2006 conference, Ms. Pattee spoke from her perspective as a cystic fibrosis patient, as a lifelong research subject, and as a representative of the Cystic Fibrosis Foundation. Ms. Pattee raised several themes: the importance of speed in the research process, the delay introduced by duplicative IRB reviews, and the increased participant safety provided by centralized review. Ms. Pattee stressed that the knowledge required for expert review is relatively rare and can best be accessed through a central review mechanism, emphasizing that “such disease-specific expertise is important in protecting human subjects and in understanding their needs and concerns”. At the same time, she noted that central review can increase efficiencies by reducing delays, avoiding duplicative reviews, and reducing variation in consent forms.
Another patient advocate, Jane Perlmutter, Ph.D., has worked with the Clinical Trials Transformation Initiative (CTTI) to promote the use of a single IRB of record. Dr. Perlmutter is a member of several cancer research advisory panels and is the lead advocate advisor for NCI’s ISPY2 breast cancer clinical trial. Dr. Perlmutter helped develop the recommendations and guidelines for centralized IRB review published by CTTI, and co-authored the article “Using Central IRBs for Multicenter Clinical Trials in the United States.”
Dr. Perlmutter is concerned at the resistance of the research community to centralized IRB review, saying “as a patient advocate and long-term cancer survivor, I strongly believe that the efficiency and increased consistency facilitated by relying on a single IRB of record benefits both the study participants and those patients who can benefit from new medications being brought to market.”
sIRB Review Moves Research Forward
Diana Chingos points out that although many factors slow the successful completion of research, “we can address the challenges of IRB review through sIRB of multi-site studies”. Ms. Chingos is a cancer survivor who has represented patient interests as a member of the Secretary’s Advisory Committee on Human Research Protections (SACHRP), as an advisor on cancer research studies at multiple academic centers, and as an advisor to federal agencies including HHS and NCI. Ms. Chingos also serves as an IRB member for both a central IRB and the local IRB of an academic medical center. “Our modus operandi should be processes that speed up the approval process and answer important clinical questions for which we are in need of answers now, not tomorrow or next year”, says Ms. Chingos, “and the use of a single IRB of record is such a process.”
The ability of a central IRB to be more efficient while also better protecting study participants becomes especially clear to those of us who work within the walls of a central IRB. As an “independent” or “private” IRB that is not associated with a particular site, Quorum often is engaged to act as a central IRB in a multi-site study. At other times, we are engaged to act as a local IRB representing just one of many sites in the study.
Quorum’s ability to take action on behalf of subjects as a central IRB is telling. When we act as a central IRB with jurisdiction over numerous sites, we are able to work collaboratively with sponsors to ensure a protocol is amended to address participant safety concerns. In contrast, when we act as just one local IRB of many in a multisite study, our ability to drive study-wide changes is often slow and may be limited in the protocol or study design. Frequently, we must use site-specific restrictions, consent form changes and other work arounds that add cost and complexity to the research project.
It is perplexing that the research community is slow to heed the calls of patients and patient advocates. Policymakers are trying to promote the use of sIRB review through mandates such as Section 3021 of the 21st Century Cures Act, pending revisions to the Common Rule, and the NIH Policy on the Use of sIRB, but progress is limited. Of course, it is costly for institutions to undertake the necessary changes in process, and federal funding agencies may not yet be prepared to fund the costs of IRB review. Nevertheless, as patient advocates emphasize, the shift to centralized IRB review and the use of a single IRB of record can better protect study participants and speed the delivery of life-saving interventions to patients.
Quorum is poised to act as the single IRB of record for your research. We have spent over 25 years perfecting the systems and processes needed to track complex multi-site studies, and our systems are tested: we are frequently audited by clients, we are audited by the FDA every three to five years, and we are re-accredited by AAHRPP every five years. We are passionate about conducting quality ethics reviews, so contact us today and move your research forward!