When COVID Hit, Research Speed Was Key

Harvard Catalyst has spent more than a decade building the solution: a system that enables research institutions conducting multisite studies to agree in advance to rely on a single IRB to review the study, known as a “reliance agreement,” in order to eliminate multiple reviews.

This effort began with a multi-institutional reliance agreement among Harvard affiliates in 2009 and culminated in 2016 with a national SMART IRB agreement and, a year later, an online reliance system (ORS), the software platform developed by Harvard Catalyst’s informatics team that supports SMART IRB.

When the pandemic arrived, these efforts paid off, as academic health care centers, universities, and hospitals that had adopted SMART IRB already had a rapid and streamlined IRB process in place to conduct multisite studies on COVID-19.

Hitting logistical walls

Promising study protocols can often hit a logistical wall when it comes time for IRB review, especially when multiple institutions are involved.

The NIH recognized this with its single IRB rule, which mandated, with some exceptions, consolidated IRB review for any NIH-funded study conducted at more than one site, as of 2018.

Federal regulations governing research in human participants extended the NIH requirement in 2020, via the Common Rule, to include research funded by any federal agency.

Taken together, those moves constituted an acknowledgment by federal regulators that duplicative IRB review is inefficient and had no apparent benefit to human research participants.

The system conceived at Harvard Catalyst for 11 Harvard schools and 19 academic health care centers preceded the single IRB mandate by nearly a decade.

The solution was a back-end fix to achieve a vital mission: to accelerate scientific discovery across institutions while ensuring a high level of protection for research participants.

Barbara Bierer, HMS professor of medicine and faculty lead for Harvard Catalyst’s Regulatory Foundations, Ethics, and Law program, is one of the system’s primary architects and its director of regulatory policy.

Bierer said it’s the kind of science infrastructure that no one notices unless something goes wrong.

“The better it works, the more invisible it becomes,” she said.

With NCATS funding, Harvard Catalyst and the University of Wisconsin-Madison jointly launched the system as SMART IRB in 2016. The online reliance system was introduced a year later, extending it far beyond Harvard’s campus and regional networks.

In August 2022, the number of institutions signed onto SMART IRB surpassed 1,000, a milestone experts in the IRB world have called unprecedented.

By the end of 2022, the system had received 7,505 requests for reliance (to cede the review process to another institution), a number that speaks to the demand for a platform that is optional for investigators and institutions to use, Bierer said.

Nearly a third of requests are completed in less than a week; 60 percent take less than a month, which Bierer called an “extraordinary pace” for multisite studies.

Modeling advance readiness

Metrics on multisite studies related to COVID-19 offer a glimpse of the initiative’s impact. To date, reliance agreements have been finalized for 377 studies using the ORS, and many more were facilitated through the SMART IRB agreement without use of the ORS.

The median time to get institutions to agree on an IRB to review a study has been under 10 days. A reliance agreement for one study was approved in 16 minutes, representing an extreme, not the norm.

Other factors contribute to how quickly the process moves, of course, and many studies were moving fast during the prime years of the pandemic. But SMART IRB removed one roadblock to moving clinical research forward rapidly during a public health emergency.

“Thank goodness we had this in place,” said Susan Kornetsky, director of clinical research compliance at Boston Children's Hospital. “Every institution was geared up to prioritize COVID-19, and this was a mechanism that allowed us to get our research off and running very, very quickly. You absolutely needed that during the pandemic.”

Kornetsky was an early adopter of the Harvard cede review process a decade before the surge of COVID-19 science tested its real-world relevance in a public health emergency.

Advance readiness was key, and will remain key in future health emergencies. An October 2022 request from the White House Office of Science and Technology Policy for information on clinical research infrastructure highlighted single IRB review as one critical element for emergency clinical trial preparedness.

“The SMART IRB agreement and resources we developed to support reliance helped people make the transition to adopting single IRB,” said Nichelle Cobb, senior advisor for strategic initiatives at the Association for the Accreditation of Human Research Protection Programs (AAHRPP) and a core member of the team that developed and launched SMART IRB.

New norm?

Martha Jones, now vice president of human research affairs at Mass General Brigham, has used single IRB models for over 20 years and was an early proponent of the SMART IRB system.

She said not having SMART IRB in place during the pandemic turned out to be a liability for some institutions.

“Our experience during the pandemic of wanting to do research at sites that had not yet signed on really showed us how valuable it is to already have that agreement in place,” Jones said.

“Because the studies were moving so quickly, we couldn't involve many of those sites. We didn’t have the time to go through a long, drawn-out negotiating process over a reliance agreement that wasn't already set up. So unfortunately, those sites were left out, whereas if they had already been part of the SMART IRB process and were signed up, we could have easily brought them into studies.”

The SMART IRB platform was purposely designed to be one-size-fits-all, to meet the needs of institutions that have their own IRBs as well as those that don't, from small clinics and nonprofits to large hospital systems and universities, and from minimal risk to high-risk research. The vast majority of the current 1,100 signatories are academic medical centers.

“In my 20-plus years working in human subjects protection, I've never seen any sort of effort agreed upon to this level across this many institutions. That, to me, speaks to how robust it is,” Cobb said.

Jones of Mass General Brigham agreed.

“IRBs and leading institutions are not very good about agreeing on the same language on anything that's contractual, so the fact that we've all not only accepted the concept of a single IRB but have signed on to the same agreement is in and of itself a superb achievement,” Jones said.

SMART IRB has become “a voice of authority,” Cobb said, and is setting the bar for newly enacted single IRB accreditation standards. “The SMART IRB agreement and standard operating procedures meet the AAHRPP standard for single IRB.”

Moving the field forward

Influencing the standards of the only accreditation agency for human research protections is one way SMART IRB is helping define and hone best practices in the new world of single IRB. It has also helped the IRB field get clear on where an IRB’s role begins and ends.

Kornetsky credits SMART IRB developers for not being afraid to take on “the gnarly issues” about where responsibility lies under reliance agreements.

The reliance process engenders collaboration, Jones said, which is helping drive refinements as it evolves.

“When you're working with a collaborator, and they're asking questions about how you do things and you're asking questions about how they do things, that helps to educate us all to a level that I think helps protect human subjects,” Jones said. “It helps us all improve our game.”

SMART IRB has also fostered a sense of community as problems are addressed together.

“A national virtual community has been created,” Bierer said, one she hopes will continue to harmonize common processes and policies.

“We're not quite there yet, but we're working on ways to make everything a lot easier for IRB professionals and researchers.”

Over the years, a number of tools and resources have been added to the SMART IRB website to help research teams and IRBs access the system and smoothly transition to a single IRB.

Top downloads include a reliance checklist, SMART IRB standard operating procedures, and a popular communication plan for SMART IRB review.

A team of SMART IRB “ambassadors” works directly with institutions to help them understand how to engage in single IRB review and answer any questions.

An online learning center, topical webinars and monthly SMART Talks encourage connection, collaboration, and feedback for continuous improvement.

“Our goal is to make this as easy as possible and ensure that it does what it needs to do for research teams as well as IRBs and their institutions,” said Cobb.