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OHRP move might increase trend of research sites using centralized IRBs
'Many organizations are reluctant to go outside their four walls'
Research institutions increasingly are turning to central IRBs for multisite clinical trials, and this trend probably will accelerate due to recent news that federal regulators are encouraging the change, experts say.
The Office for Human Research Protections (OHRP) in Washington, DC, recently posted a letter that clarifies this philosophical shift by the agency. Essentially, the letter states that OHRP fully agrees with the Food and Drug Administration's position on the benefits of using a single central IRB for multisite research. IRBs and others can post comments on the change
The letter was written April 30, 2010, to Carolinas Medical Center of Charlotte, NC, in response to a letter asking whether research institutions using an external IRB would be held liable for non-compliance on the part of the independent IRB.
"As the letter noted, for a while we've been trying to send a message on changing accountability rules," says Jerry A. Menikoff, MD, JD, director of OHRP. Menikoff signed the OHRP letter to Carolinas Medical Center.
"OHRP has in a sense been trying to send the message that there are benefits from having a more centralized IRB review," Menikoff says.
"We recognize there can be inappropriate administrative burdens by having multiple reviews, and that can slow down research," he explains. "You can get appropriate protections for subjects through the use of a central IRB, so it really could be a win-win situation."
Even before OHRP published its letter, there had been a growing trend toward the use of central IRBs, experts say.
"Somewhere around half of academic medical centers are outsourcing IRB review almost exclusively on industry-sponsored trials," says John Isidor, JD, chief executive officer of Schulman Associates IRB of Cincinnati, OH.
And more than half of community hospitals outsource their IRB reviews, he adds.
"We've been around for 22 years and are among the oldest central IRBs, and we are seeing more and more interest on the part of organizations to use an external IRB," says Jim Saunders, MBA, vice president of the New England Institutional Review Board (NEIRB) of Newton, MA.
Does trend threaten internal IRBs?
Some research institutions that have their own internal IRB might opt to use an external, central IRB for industry-sponsored studies. Another model is that some research sites might decide to disband their own IRB and rely on an external IRB for all study reviews, Saunders explains.
"We are seeing a lot of activity along those lines, and I think institutions are realizing that it's very expensive to have one's own internal IRB," he adds. "It's very resource consuming and challenging to keep track of all of the regulatory changes and to have good systems in place that meet the requirements one has to meet."
The OHRP letter could shift more research sites to using a central IRB, although there remains the regulatory roadblock, he adds.
Most people would interpret current regulations to mean that an organization that uses an external IRB is responsible for any noncompliance issues that IRB has, Saunders says.
"Many organizations are reluctant to go outside their four walls and seek external IRB review because they feel they can't always guarantee that everything will be done completely appropriately by an external IRB," he says.
"So they're worried they'll end up being in trouble with OHRP for reasons not of their own doing," he adds.
The regulations date back to the days when most human subjects research was done by a single institution and reviewed by a single IRB. Now research investigators and sponsors have to coordinate a trial across a number of different institutions, juggling many IRB reviews of the same protocol, Saunders notes.
"People weren't thinking about multisite studies when the regulations were written, so there's a huge emphasis on local context," Menikoff says. "That has changed over time, and today there are large numbers of multisite studies."
However, as the research industry has evolved to increasing numbers of multisite studies, the regulations remained the same.
Still, OHRP sees flexibility in the regulations, Menikoff says.
"It's a very different research world today versus 30 to 40 years ago, and we believe the regulations are flexible enough to recognize it," he adds.
Menikoff's letter to Carolinas Medical Center acknowledges the regulatory roadblock, but refers the research institution to a letter written last year as an example of how OHRP interprets the regulations in a way that's favorable to the institution.
"Obviously, the best action of all would be to change the regulation," Saunders says. "I could see that within institutions there are folks who would say, 'We don't care what this letter says, if the regulations say something different then we still don't feel comfortable utilizing an external IRB, and we won't until the regulations are formally changed.'"
There's interest in the research community to improve the system, Menikoff acknowledges.
"I can't comment on whatever people will be looking at internally in the government," he adds. "We certainly want to improve the system, and nothing is off the table, in general."
From a research institution's perspective, even a regulatory change might not alleviate all liability fears.
"They could still be sued by a subject," Isidor says.
"Any lawsuit about a personal injury case will be governed under state law," he adds. "And in most instances, the lawyers for the plaintiff will prefer to sue in state court because they assume they'll get a more sympathetic jury and judge."
Still, OHRP's public move toward encouraging the use of central IRBs is likely to have a positive impact on the trend. At the very least, research institutions that are already using external IRBs will view this as affirmation that they've made the right decision, Isidor says.
"For those who have not chosen to use them, it will create more pressure in the institution to start using them," he adds. "Investigators will want to speed up their IRB review process, and institutions will have a more reasoned basis for making outsourcing decisions."
Accreditation driving trend
Also, the trend toward IRB accreditation is helping move more institutions toward central or external IRBs, he notes.
"All the major IRBs are accredited now," Isidor says.
Institutions can use the Association for the Accreditation of Human Research Protection Programs (AAHRPP) as a due diligence standard, he notes.
'They might feel comfortable outsourcing to accredited IRBs because that provides a reliable third-party oversight mechanism," Isidor adds. "Accreditation shows that an IRB is functioning appropriately and that it will provide the same level of protection as your own institution's IRB."
Research institutions can rely on accreditation information, OHRP compliance data, and the status of an independent IRB serving as a central IRB for a multisite study as standards for their decision to outsource the IRB review, he says.
"In addition, some institutions will independently visit the IRB to have a higher level of due diligence, and some will do their own audits," Isidor says.
Eventually, the IRB world likely will include more central IRBs, although many larger institutions will maintain their local human subjects review boards, Saunders predicts.
"You won't see a day where everyone decides they'll go with one centralized approach," Saunders adds. "I think the regulations will be modified, and there will be more interest on the part of institutions to look at models of centralized review."