Clinical Researcher—December 2020 (Volume 34, Issue 10)

IRB INSIGHTS (PART 2)

Erica Heath, CIP, MBA; Dorothy Herbert, BSc, MAppSoc; Gary W. Cramer

 

Conditions never seem to stand still very long these days in the world of institutional review boards (IRBs) and other formats of ethics review bodies for clinical trials. For example, WCG announced in October the unification of its five IRBs—Western IRB (WIRB), Copernicus Group IRB (CGIRB), Midlands IRB (MLIRB), New England IRB (NEIRB), and Aspire IRB—into the single WCG IRB brand. Donald A. Deieso, PhD, WCG CEO, termed it an “example of our commitment to positively transform the clinical trial process while keeping patient safety as our highest priority.”

Meanwhile in November, Advarra, a supplier of IRB and institutional biosafety committee (IBC) review solutions and clinical site technologies, announced the acquisition of Longboat, a provider of clinical trial technologies focused on site training, protocol compliance, and patient engagement. According to Gadi Saarony, CEO of Advarra, the acquisition “creates a natural bridge from our IRB and IBC reviews and consulting services to our existing site-facing technology solutions” to “provide comprehensive offerings to facilitate the clinical research journey, with sites and trial participants in mind.”

With such moving and shaking in the IRB environment as a background, this second part of Clinical Researcher’s “IRB Insights” for this issue welcomes the following commentaries from experts in ethics review with perspectives from the United States and Canada.

Gary W. Cramer (gcramer@acrpnet.org) is Managing Editor for ACRP.

 

Predictions to Consider for the Future of IRBs

Making predictions is always a tricky business, but since the subject is near and dear to me, here are my best guesses about where IRBs are going in the near future.

Single IRB (sIRB) of Record

The U.S. Food and Drug Administration (FDA) regulations require investigators to have IRB approval for studies, but the source of that IRB approval is left to the investigator and sponsor. As of the early 1980s, most sponsors recognized that it was most efficient to have one central IRB review with that IRB incorporating review of all investigators/sites. This worked nicely for sites with no internal board, but when the investigators were in an academic medical center (AMC), they were usually required to use their own institution’s board. Eventually, like pulling teeth, one AMC after another started to accept the determinations of external boards.

Within the National Institutes of Health (NIH) there was a shift in 2017 that appeared to be sudden; multicenter grants would be required to name a single IRB to review for all the sites. This system is rapidly evolving, has now spread to grants from almost all federal agencies, and has proven to be anything but efficient. The minor problem is the actual IRB review. The major problem is the bureaucracy that surrounds institutions agreeing to rely on each other.

The Common Rule and institutional policies require a written reliance agreement between or among the institutions in order for one institution to rely upon the IRB in another institution. Academic institutions—most with “the very best IRB in the country”—were hesitant to defer to any other institution’s IRB. With the mandate to rely, there has emerged a bureaucracy covering reliance agreements, “local conditions,” and the creation of consent documents acceptable to both reviewing IRBs and relying institutions.

There are several groups (e.g., SMART IRB) dedicated to negotiation of reliance agreements. Once the reliance agreement is signed, one IRB becomes the lead and the others rely on it. The methods of communication, extent of review, individualization of consent and recruitment documents, and deference to “local” conditions are slowly becoming more mutually understood. Eventually, the single IRB of record (sIRB) system will be sorted out and may eventually become as efficient as the sponsor use of central IRBs, but it is likely that this will take several more years.

The sIRB movement is likely to cause a significant change to human subject protection in small hospitals. When review of clinical trials is outsourced, small hospital IRBs that used to meet monthly or quarterly often have no full board studies left. Even now, many small IRBs have no reason to meet although the size of their research portfolio remains as big as ever or even bigger. Management of this portfolio by a hospital research or compliance department will become more necessary than a functioning IRB. An IRB and IRB administrator may be retained for review of the remaining minimal risk studies, but their local expertise in IRB review of clinical studies will decline.

Growth of the External IRB Business

The first independent (or external) IRB is said to have been founded in 1968, although most were formed in the 1970s and new ones continue to emerge. As with internal IRBs, these external ones exist within a larger structure (the “institution”) that sets the tone and direction for the boards. The small-business, personal service nature of these companies continues in several remaining external IRBs, but as noted in the introduction, there are two very large companies owned by venture capital groups that also run a variety of clinical trial–related companies. The pros and cons of this can be debated, but these two companies certainly dominate the market.

In this environment, it is likely that external IRBs of all sizes will be increasingly selected as the reviewing sIRB of record for federally funded, multicenter clinical studies such that IRBs become even more centralized.

COVID-19 and IRB Review

The isolation requirements caused by COVID-19 have necessitated changes in the operations of both IRBs and sites. What might never have been considered possible a year ago has become commonplace. IRBs are meeting remotely; plans for consent following phone, video, and Zoom discussions are approvable; waivers of signature are more common; and studies are approved for remote visits, use of remote monitoring devices, and follow-up visits. These changes have been thoroughly covered in other articles. The question is whether we can ever return to the “old normal” or if the COVID-19 changes have been so disruptive and illustrative that we will find we like the “new normal” and will never go back.

Dual Regulatory Systems—Is Harmonization in Our Future?

The more things change, the more they stay the same. In clinical research there have been two regulatory structures—one from the FDA (21 CFR 50/56 in the Code of Federal Regulations) and the other from the Common Rule (45 CFR 46). They describe the operations and requirements for IRBs in almost the same way. Other than that, they derive from different sources, use different definitions, address different issues, cover different populations, have very different enforcement, penalties, and guidance, and, although similar, are distinct in ways that only a small percentage of regulators really appreciate. This duality affects investigators subject to both regulations and is particularly evident in minimal-risk studies.

Over the years this dual system grew, sometimes harmonizing and sometimes not. With the 2018 iteration of the Common Rule, that rule changed but the FDA requirements did not. Although we expect eventual harmonization, at least in the near future it appears these two systems will remain quite separate. I do not envision this changing.

Who knows what the future will bring? These are some best guesses, but if this year has taught us anything it’s that, well, anything is possible.

Erica Heath, CIP, worked at UCSF before founding an independent IRB, Independent Review Consulting (IRC), Inc., in 1984. In 2010, IRC and the Ethical Review Committee jointly formed Ethical and Independent Review Services (E&I Review). She has retired in the San Francisco Bay area.

 

A Canadian Perspective on the Mission of Research Ethics Boards

Here is some background and my opinion on the latest, greatest trends affecting how research ethics boards (REBs) that review clinical research in Canada function.

As I write this, our board, the REB for the Interior Health Authority in British Columbia, Canada, currently has 96 clinical studies active or under review (though a few have been suspended by the principal investigators due to COVID-19). That total includes 32 clinical trials, 10 biomedical research studies which are not clinical trials, and the remainder are other forms of clinical research (chart reviews, registries, etc.). Our REB also reviews social sciences research; clinical trials make up about 10% of all the research we review, so my perspective is from that somewhat limited basis.

For several years in British Columbia, REBs have been working together to create a platform for “harmonized” ethical review. This has substantially changed the landscape in the past two years or so, especially since we went live with the launch of a common electronic platform for REB applications involving two or more institutions in the province who entered into a partnership agreement (the partners are regional health authorities and academic institutions). Since the launch in January 2019, we have further refined the harmonized approach (a single REB application to gain ethical approval at all partner institutions) to achieve greater streamlining in special cases, including review of cancer research and review of COVID-19 research. For more information about the Provincial Research Ethics Platform (PREP) and harmonized ethical review in British Columbia, please visit https://researchethicsbc.ca/ or contact Terri Fleming, Director of Research Ethics BC, at tfleming@bcahsn.ca.

For cancer research, we have a single specialized board at BC Cancer, the institution that treats cancer patients throughout our province. If cancer research is happening locally, at a site where my REB would otherwise have geographical jurisdiction, it is still reviewed by the one expert board. We accept its review and approval.

There is a movement in Canada to do something similar (i.e., have a single expert board) for review of pediatric research. Information is available at https://cheerchildhealth.ca/.

The other latest, greatest trend is the “rapid ethical review” process for COVID-19 clinical studies adopted by the boards that participate in the harmonized ethical review process. To put this in context, ordinarily institutional REBs require (on average) two to three weeks of lead time for members to review a clinical study in advance of a full board meeting. This is primarily because our clinical reviewers are also busy clinicians.

When it came to the pandemic though, a province-wide commitment was made to review COVID-19 clinical studies within five days of receipt. This is an incredibly compressed time frame, especially as REB members were and are also dealing with extraordinary changes in their work environments and likely their home environments. It was a privilege to see them rise to the challenge.

Dorothy Herbert, BSc, MAppSoc, is Research Ethics Board Coordinator with the Interior Health Authority of British Columbia, Canada.