Should IRB regulations be tweaked or revised?

Experts offer suggestions for best course

Human subjects research protection experts agree that IRBs are overburdened and that something should be done to improve the regulations and rules governing their work.

However, there is less agreement on how this could be accomplished. IRB Advisor asked IRB and research professionals to discuss how IRB regulations or the interpretation of them might be improved. Here’s what they had to say:

• Update prisoner research regulations. The U.S. Department of Health and Human Services (HHS) has not updated the regulations regarding research involving prisoners since the late 1970s, says Ernest Prentice, PhD, associate vice chancellor for academic affairs at the University of Nebraska Medical Center in Omaha. Prentice also is the chair of the Secretary’s Advisory Committee on Human Research Protection (SACHRP) for HHS.

"The penal system in the United States is distinctly different today than what it was in the 1970s," he explains. "We have a lot more incarcerated individuals; hepatitis C is endemic in the system, and a lot of prisoners are suffering from mental conditions and AIDS."

For these reasons, prison research also is different today, and members of SACHRP believe the regulations should be revised to reflect the current prison situation, Prentice says.

"We think research should be conducted in prisons to benefit prisoners," Prentice says. "The regulations are very restrictive, and you can’t do the research that needs to be done, so the subcommittee is looking at short-term fixes."

While the Office for Human Research Protections (OHRP) has been trying to provide guidance for the existing prison research regulations, the recent guidance perpetuated one of the problems, says Erica Heath, MBA, CIP, president of Independent Review Consulting Inc. of San Anselmo, CA.

"Recent guidance says that subpart C includes situations where a human subject becomes a prisoner after the research has commenced," she explains. "Because of one person who had already made a free, informed, and voluntary decision, subpart C kicks in, and the full board — with the prison representative — has to reconsider the study."

The IRB also has to notify OHRP of the change in the roster, make and document seven additional findings, and certify this to OHRP, Heath adds.

"What would you do with that one subject who is now incarcerated — re-review or drop the subject?" she asks. "There are certainly new risk issues, but this level of distance from the basic requirements is over the top."

One short-term solution might be to encourage IRBs to interpret the regulations in a way that does not inhibit the IRB review and the conduct of ethically appropriate research involving prisoners, Prentice suggests.

The long-term fix would be to rewrite a part of 45 CFR 46, subpart C, he adds.

Minimal risk, minimal review

• Change the way minimal risk research is handled. The human subjects research community needs to start a debate about how minimal risk research is handled, questioning whether there is too much effort spent on those kinds of activities, suggests Robert M. Nelson, MD, PhD, associate professor of anesthesia and pediatrics at the Children’s Hospital of Philadelphia.

Both IRBs and IRB staff spend considerable time on minimal risk research, he notes.

"For example, with chart reviews one could make an argument that the only risk of chart reviews is a loss of confidentiality — either through inappropriate data being extracted through the chart or an inappropriate storage of data in a way that breaches confidentiality," Nelson explains. "So why not move from a system where you have prior review of all applications to one where you do a spot audit of whether investigators are in compliance with all guidelines."

One could argue that random spot checks of minimum risk research would be more effective and efficient, he says.

"It’s more effective because you’d see what they were doing, and if the audit program is random it’d have the same effect as having radar on certain roads — people drive a little slower," Nelson says. "Investigators would like it because they wouldn’t have as much of a wait to get through the IRB approval process."

A chief drawback to this approach is that it would require regulatory change and that would take time, and it still would require someone to make an important decision about each minimal risk protocol, other experts say.

"Who makes the decisions on which protocols to review and which not to review?" asks Felix A. Khin-Maung-Gyi, PharmD, MBA, CIP, chief executive officer of Chesapeake Research Review Inc. in Columbia, MD. He also is the senior policy fellow with the Center for Drugs and Public Policy at the University of Maryland in Baltimore.

"We have a system where truly minimal risk studies under certain conditions can be expedited, and some can be exempt from IRB review," he says. "So there are two systems in place to expedite that."

Through the expedited review process, one member of the IRB is permitted to review and approve or modify the research, but to qualify a protocol must meet the criteria of minimum-risk research and fit into one of a number of specified categories, Prentice says.

"Could we expand and change the categories?" Prentice says. "Yes, it’s been done once in 1998, so you could expand them to allow IRBs more latitude to use the expedited review process."

The other issue is that expedited reviews aren’t used as often as the regulations allow because the concern over potential liability, he adds.

Perhaps IRBs should use expedited reviews more frequently, and the regulations should be changed to skip the continuing review of such research, since this also takes unnecessary time, Prentice says.

"When you add requirement after requirement, it’s no wonder IRBs are totally overloaded with work and documentation," he says. "Is it all necessary, and does it contribute to human subject protections?"

While the idea of random spot checks has some merit, a chief problem is figuring out how to do triage for the level of scrutiny, notes Dale Hammerschmidt, MD, FACP, associate professor of medicine at the University of Minnesota Medical School in Minneapolis.

Plus, the main reason IRBs spend a lot of time on minimal risk research now is because no one else has thought through the risks as well as necessary, he says.

"The investigator doing a transplant study will think a lot about risk, while someone doing a questionnaire study won’t think for a minute about how the questions are compromising for certain people," Hammerschmidt explains. "The fact is that if an investigator does not perceive a study as risky, then he does not spend much time on the IRB application, and he delegates that to a junior person, and you have a lousy application."

If an IRB wants to conduct a spot check, it can do so already, in addition to its current workload, but it’s another matter to substitute spot checks for IRB reviews, Heath says.

She also points out that many institutions — rather than IRBs — are instituting monitoring visits through quality assurance mechanisms, so the IRB remains the judge rather than both judge and police force.

Adding another category to the expedited review list could take care of many of these repetitive applications, Heath adds.

In the case of minimal risk, social-behavioral research, there might be some merit to the claim that the common rule is overly restrictive, and SACHRP will be looking at regulations to evaluate these concerns, Prentice says.

Child research has its own issues

• Work toward consistency in interpretation of subpart D. 45 CFR 45, subpart D, regarding research involving children as subjects, has been inconsistently interpreted by IRBs and institutions, leading to inconsistent protection of children, Prentice notes.

An example of this is the Dryvax smallpox vaccine study in which three IRBs reviewed the protocol, arriving at different conclusions. Two IRBs approved the protocol, and one did not, which meant that the protocol was sent to HHS for review at the Secretary’s level, a 407 review, he reports.

Ultimately, the federal government decided to pull the protocol and not conduct the research.

"I’m not suggesting that it was an unethical project, but I’m suggesting that IRBs inconsistently interpret these regulations, and we need more balanced protection across IRBs, and the only way we’re going to do this is through guidance," Prentice says.

Federal guidance should address what minimal risk means, what it means to have a minor increase over minimal risk, and other questions, he says.

"So the charge is to look at those terms under subpart D and meaningfully clarify them, so that we can make sure we’re protecting children consistently across the country," Prentice adds.