Editor’s note: IRB Advisor was first published in 2001, a couple of years after research participant Jesse Gelsinger died during a gene therapy clinical trial. Shortly after Gelsinger’s death, the federal government began to increase oversight of human research studies. To commemorate the past 20 years of human research protection, as well as two decades of IRB Advisor, we asked editorial advisory board members to comment on how things have changed since 2001.
Kay Ball, PhD, RN, CNOR, CMLSO, FAAN, adjunct professor, nursing, Otterbein University, Westerville, OH, has been on the newsletter’s editorial advisory board since 2001.
James Riddle, MCSE, CIP, CPIA, CRQM, vice president, research services and strategic consulting, Advarra, Columbia, MD, is a current editorial advisory board member.
Below are the questions and answers, which have been edited for length and clarity.
IRB Advisor: What do you believe are the biggest changes IRBs have experienced over the past two decades, and how well has the industry handled this change?
Ball: One of the biggest changes is the increase in research — the number of research projects assigned to nursing students working on advanced degrees and the ability of IRBs to handle this increased workload. For some, wait times for IRB approvals have decreased when more professionals have been added to handle this extra workload.
IRBs exist to protect human rights, but sometimes bureaucratic procedures for this protection have slowed the progress of research. IRBs are continually working to solve this problem.
IRBs also have worked diligently to maintain ethical, regulatory, and scientific goals for protecting human subjects over the years. In addition, IRBs review more potential research that involves multiple sites and even include international sites within the same research project. If an IRB has enough members who represent diverse backgrounds (ethics, science, research), then the IRB is able to handle the increase in workload properly.
Riddle: I’m not fond of the term “industry” when we describe IRBs. I prefer the word “community,” and view IRBs and organizations that administer them as part of the research community facilitating and advancing research in collaboration with researchers.
The biggest change over the last two decades is consolidation of the independent IRB community. Twenty years ago, there were lots of smaller independent IRBs. Now, there are two large IRBs and several other smaller independent IRBs. We can be better partners with the community and with researchers when we have more resources available to us. We can offer more support and services and help facilitate the research more.
New private research sites and institutions do not have to use as many different IRBs as they used in the past.
Over the last 20 years, there has been a recognition that a centralized IRB is OK and is good for the overall community. Many people have accepted that having more ethics committees review the same protocol does not necessarily produce a better protocol. That idea has manifested in guidance and regulation. You see the National Institutes of Health mandating a single IRB in multicenter studies, and the new Common Rule requires single IRBs. Those regulatory changes have been building up for the last 20 years.
IRB Advisor: When IRB Advisor was first published, research programs were still dealing with the fallout from Jesse Gelsinger’s death (1999) during a gene therapy clinical trial. Then, in 2001, Ellen Roche, a young lab technician died after participating in a clinical trial for treating asthma. IRB Advisor provided analysis of the implications of these tragedies in its first year of covering human research protection. Now, looking back at these incidents, how do you believe the IRB and human research protection world has evolved and changed in response to those deaths?
Riddle: Even the terminology of research protection has changed. In the late 1990s and early 2000s, the primary focus was on compliance of the IRB — the oversight committee. Reviewing the facts of the Gelsinger and Roche tragedies reveals multiple failures, throughout the institutions, that led to their deaths. Yes, there were IRB issues, but there also were other issues related to what was going on at the institutions that were beyond the IRB’s scope.
The biggest thing that has happened in response to the deaths has been this transformation from focusing just on compliance of IRBs to creation of overall human research protection programs at universities or institutions conducting the research. The Roche and Gelsinger deaths were tragic, and out of that tragedy came a betterment of the overall human research protection program.
Ball: The IRB and human research protection continue to advance, but very slowly. A lot more can be done with IRB oversight of human subjects and determining if the risk to the human is warranted in the study.
IRB Advisor: What do you see as the biggest challenge IRBs will face over the next two decades, and why?
Ball: One of the challenges is protection of human subjects, which should be comprehensive but not obstructive to the advancement of the research. Just overseeing studies is a challenge.
Also, it is a challenge to have timely approvals of the exempt studies if the IRB is backlogged with applications for research approvals.
Riddle: There will always be challenges. This past year has shown us that sometimes we do not even see the challenges coming.
If I had to pick the two biggest challenges, they would be, first, determining as a community how to operationalize the logistics of doing a single IRB. The Common Rule mandate to do a single IRB is only a [couple of years] old. The NIH policy for mandating single IRBs has only been around for a few years. Institutionally based IRBs — academic or health system — have not yet figured out how to efficiently operate a single or central IRB. Independent IRBs have been operating as single IRBs for 30-plus years and have perfected intricate and expensive computer systems and work flows to facilitate the logistics of handling many research protocols with hundreds of performance sites.
I still hear from my academic friends that institutional-based IRBs continue to struggle with the logistics of five- or 10-site studies. Over the next decade, we’ll see a continued shift and recognize that companies that administer IRBs have the resources to be able to do the single IRB more efficiently, handling the logistics of recordkeeping and document distribution as well as other logistical issues that go into a single IRB.
I am not talking about the ethics portion of the single IRB. By and large, we all do a good job of reviewing the ethics of the studies. Instead, I am referring to the logistics of managing multiple sites. The biggest challenge for academic IRBs is to handle the logistics of managing a single IRB. At some point, they’ll just get tired of doing it, or they’ll come to the realization that there are private companies that have already figured out how to do it.
The second and equally challenging issue for the IRB community is the transition from a traditional protocol to more virtual protocol technologies. We see this with COVID-19 and teleconferences instead of onsite visits, and remote monitoring. Researchers can use Google glasses to see what is going on in participants’ homes. For example, a participant cannot go to see the researcher. A home health nurse can go to the home and wear Google glasses to observe the participant do their walk test or determine if they are having a drug reaction. This is super cool technology.
My point is that in relation to the IRB community, that will change the way IRBs think about design of protocols and change the IRB’s approach and evaluation of risk in protocols. We have to be ready as a community for that shift.
Over the next two decades, virtual trial technologies and logistical challenges of the single IRB will be the biggest challenges we’ll see.
IRB Advisor: As someone who has worked in healthcare, research, and/or human research protection and been an editorial advisory board member for IRB Advisor since its first issue, what do you know about the human research enterprise now that you wish you had known in 2001?
Ball: I wish I would have known more about how closely human subjects are monitored in research studies. Are the risks to the humans in line with the goals of the research or usefulness of the data collected? Also, I would have liked to know more about the details of the definition and/or requirements of an exempt study when involved with nursing student applications.