"Broken" Institutional Review Board System Charge Sparks HHS Committee Debate

HHS Secretary's Advisory Committee on Human Research Protections Chairman Prentice argues that the nation's network of IRBs may be inconsistent in their protection of human research subjects, but it is not as broken as many would portray it. "It's never going to be a perfect system," Prentice says.

Although there are inconsistent levels of protection for human subjects across the nation's institutional review boards, the system clearly is not broken, HHS Secretary's Advisory Committee on Human Research Protections Chairman Ernest Prentice, PhD, said April 18.

The debate about inconsistent IRB oversight and how it sometimes results in the deaths of human subjects was sparked during the public comment period of a SACHRP meeting in Alexandria, Va.

Members of the Alliance for Human Research Protections took the opportunity to lambaste SACHRP for failing to react to a "steady stream of scandals" in clinical research. The IRB system is "broken," AHRP President Vera Sharav charged.

Inconsistencies in the IRB system can be attributed to a dearth of resources and a lack of education among board members and investigators, but it is not a system that completely is in disrepair, said Prentice, associate vice chancellor for academic affairs and regulatory compliance at the University of Nebraska Medical Center.

The death of 24-year-old Ellen Roche has been held up as an example of inadequate protections for human subjects. Roche died during a non-therapeutic asthma study at Johns Hopkins Bayview Medical Center in June 2001.

Another high-profile case was the Phase I gene therapy study that resulted in the death of Arizona teenager Jesse Gelsinger in 1999. The Justice Department recently ruled that the investigators and institutions involved in the study will be subject to research restrictions for the next three to five years.

"Could there be another Ellen Roche?" Prentice asked. "Yes. Could there be another Gelsinger? Yes. These are tragedies that we hope we can avoid, but we may not be able to."

"It's never going to be a perfect system," Prentice said. "We can't make a perfect system because we're only human beings and we deal with human errors."

He added, "I really believe we're making progress and I think I echo the sentiments of all my IRB colleagues here that we've seen some remarkable changes since 1998. Could one say the system was broken prior to 1998? Maybe. But I don't think its broken anymore. Does it need to be fixed further? Yeah."

SACHRP may want to identify a way to evaluate claims that the IRB system is deficient in order to better understand what is being done to prevent future research deaths, HHS Office for Human Research Protections Director Bernard Schwetz, PhD, said.

The question should be approached empirically, perhaps by issuing a request for application, SACHRP member Susan Weiner, PhD, said. "The burden of answering that question should be on the research community," the president of The Children's Cause, Inc. commented.

Schwetz cited a recent report from the National Academy of Engineering that discusses private sector mechanisms in place to protect workers who report "near-misses" from being fired in retribution. "Within the research community we're not there at all, because there is considerable fear that if I report a near-miss, then I won't be around to see the next one," he said.

The Department of Veterans Affairs has a similar system in place, Schwetz said. OHRP intends to arrange for VA representatives to speak to the committee about its policies that "allow upgrading of the system based on near-misses," Schwetz stated.

Other SACHRP members advocated penalizing researchers for non-compliance. "The only way that investigators are going to modify their behavior, when we're talking about investigators who don't take their roles seriously, who don't think the record-keeping requirements apply to them, who think they can use devices off-label in a study without getting an [investigational device exemption], the only way those people are going to correct their action is through enforcement," said Mark Barnes, partner at the N.Y. law firm Ropes and Gray.

"There should be a hammer. There should be an appropriate response to non-compliance," Prentice remarked. "When investigators can violate the regulations with impunity that simply precipitates more violations."

SACHRP has charged a subcommittee to review Subpart A of 45 CFR 46, or the Common Rule, to identify possible modifications to the federal regulation that lays out protections for human subjects in research. The intent is to lift regulatory burdens on IRBs and investigators.

- Andrew J. Hawkins