Whether institutions are the IRB of record or the relying IRB, setting up a seamless process involves many time-consuming processes — and it can take years.
“We’ve been serving as a single IRB, and we did our first big study in 2010,” says Hallie Kassan, MS, CIP, director of the human research protection program at Northwell Health in Manhasset, NY. “It’s very complicated, and there are many systems out there. [For instance], we use the SMART IRB agreement, but we don’t use the SMART IRB Reliance platform when we’re the IRB of record.” Instead, the Northwell Health IRB uses its own protocol management system.
The reliance process is efficient, but it takes time to develop. “The goal of the single IRB process was to make research start up more efficiently and to get clinical trials up and running,” says Janelle A. Maddox-Regis, MS, associate director of the IRB Reliance Program at Johns Hopkins University School of Medicine. “I think we’re seeing the efficiency now. At first, it was challenging because there wasn’t any broad guidance for sites to follow on how to start up a single IRB at your institution.”
IRB directors had to learn much of this on their own, with the help of conferences, peers, and collaboration with other institutions. “We created documents and templates to make things more efficient,” Maddox-Regis says. “Other IRBs have asked for these tools, and we have them on our website.”
As IRB staff learn about the forms, the process becomes more efficient, Maddox-Regis notes. (See story on maintaining consistency with reliance agreements in this issue.)
One of the obstacles to an efficient IRB reliance effort is handling the technological details. “One obstacle is that people put in a request to have an account set up, and they have a hard time getting in touch with someone in IT to have the password to their account, so it can be delayed for days,” Kassan explains. “Also, we have these accounts set up and researchers have a Northwell email, which they need to get their password reset. They’re not checking their Northwell email because they’re not Northwell employees.”
The passwords are reset after 90 days. Kassan receives calls from people who cannot access their information, and solving these technological issues is resource-intensive.
“It pulls in a lot of people who are trying to fix the problem, and I feel badly because the whole idea is to make things easier for study teams,” Kassan says.
Kassan and Maddox-Regis describe other challenges and solutions in making a reliance program work:
• Use the SMART IRB agreement. This agreement helps create a consistent reliance process. (For more information, visit: https://smartirb.org.)
“One way to document the reliance is through an online platform,” Kassan says.
IRBs do not select sites for studies, but the IRB of record can ensure sites are using SMART IRB and have signed a letter of indemnification. “If they signed both documents, we would assume the process would be more expedited,” Maddox-Regis says.
In rare cases where a site did not sign onto the SMART IRB agreement, they received an exception to receive local IRB review. “Sites need to get an exception from the National Institutes of Health to obtain local review, or we have a standard reliance agreement we use where the site is not signatory to the SMART IRB agreement,” Maddox-Regis says. “We didn’t have many cases where we had to use it.”
• Use time efficiently. Part of the process is for the IRB to approve the study before obtaining local information from the site.
“My job is to work with lead sites to execute all of the reliance agreements either before or concurrently of IRB review,” Maddox-Regis says. “Reliance agreements, historically, have taken longer periods.”
The goal is to execute all the necessary reliance agreements before the study is approved. This means the study and site have the context review as soon as possible after the IRB approves the study.
“We work with the lead sites at Hopkins and we work closely with them to make sure that by the time the study is approved, they have appropriate instructions to ensure context review at the site,” she says.
• Solve technology interface issues. “One issue is figuring out access to our electronic submissions system, an issue across the board,” Kassan says. “How should teams outside of Northwell have access to it? How do we get them access?”
Some institutions decide they want relying IRBs to access the reliance IRB’s management system. This might not go smoothly. “We have a process set up to get [other IRBs] access to our system, with a Northwell login,” Kassan explains. “But that’s one of the struggles.”
Another struggle is differing processes between teams. Some teams that rely on the Northwell IRB want the IRB of record to manage all submissions and paperwork for all relying sites, and others want their own IRB to perform some of this work. “The biggest challenge is figuring out how to streamline processes to accommodate all the needs of sites and researchers,” Kassan says. “Different researchers want different things, and we’re trying to develop processes that are acceptable to everyone.”
“Our rule here is that all investigators, like the principal investigator of an external site, need to set up an account to have access to our electronic system,” Kassan says. “I thought it was important for the principal investigator of a site to go in and get their own documents if they have to and not to rely on someone at Northwell.”
• Look at local context. Managing local context issues also can be difficult. One way to handle this is for local sites to complete a form that includes study-specific information, Kassan says. Sites can be blocked from participating if they do not complete a local context process.
“If a site is unmotivated to complete the paperwork, not doing what they need to do to participate, then they can’t be approved to be in the study,” Kassan says. “If they’re relying on us for three studies, they’re filling out the form three times. I’d like them to move to a bank of information where they don’t have to do it every time because this is another obstacle.”
• Create modification form. “One thing we recently did was create a modification form,” Kassan says.
If the main site makes modifications to the protocol and the consent template, on behalf of the whole study, they submit a form to the IRB of record. The approval is automatically sent to all the sites.
The main site doesn’t have to remember to give materials to other sites,” Kassan says. “We’ve been using the modification form for several months, and the study team is very happy about it because it takes a little burden off our local team.”
Before the automatic notification system, word of the modification might be delayed if a study team was out of the office. “Because of the modification notification [process], when the main site is notified, the other sites are notified at the same time,” Kassan says.
• Find efficiencies. “There are many institutions we work with many times,” Maddox-Regis says. “Because we have collaborative relationships with them, and they rely on us for other studies, the reliance process has been much more efficient.”
The IRB has reviewed many COVID-19-related studies. To make these reviews faster and more efficient, the IRB developed an emergency IRB that reviews only COVID-19 cases. “Our institution’s COVID-related IRB, the emergency IRB, is comprised of board members from our other IRBs,” Maddox-Regis explains. “In the peak of the pandemic, they were meeting every day because there were so many COVID-related projects.”
To facilitate a more efficient review process with multiple relying IRBs, the institution requires all relying IRBs to be signatories to the agreement. “More than 850 institutions have signed onto the SMART IRB agreement, a master reliance agreement that we use in all reliance studies,” Maddox-Regis says. “There’s also an addendum to the SMART agreement, called indemnification, which requires sites to execute that.”
These are the basis of reliance. “We have over 200 domestic institutions that have met those basic requirements through SMART, and it does expedite the process because they don’t have to sign any new agreements or go through the legal teams to wait for any potential revisions or modifications,” she explains.
Turnaround time for IRB reviews of projects with relying IRBs is the same as it was for single IRB reviews.
“IRB review, which is the lengthiest part of the process, is already done for [relying IRBs], and we can turn around site approval in a couple of weeks,” Maddox-Regis adds.
The reliance process is much faster than multiple IRBs reviewing the same project, especially with some that meet less frequently.
For example, institution A submitted a multisite study in the pre-reliance world. That IRB experienced issues and tabled the application because they wanted to ask the investigator more questions. If the investigator responded after the IRB’s cutoff for the next agenda, the IRB would have to wait another month to gather responses to issues.
Now, sites just need to complete two documents and send their local language, local context, and any other information relevant to the study.
“That passage is much quicker because we’ve already done the IRB review, and they gave us all the information we need to approve the research at their site, and the time savings is an asset,” she adds.