New Congress, regulators could take up human subjects protection

Clinical trials registry issue may see action this year

From a renewed push for a mandatory clinical trials registry to a new secretary of Health and Human Services, the political landscape promises to keep IRBs and others involved in protecting human research subjects busy.

Those who watch federal activity surrounding research say the clinical trials issue — buoyed by concerns that problems with some drugs weren’t adequately disseminated to physicians and the public — is likely to be taken up seriously this year.

In October 2004, House and Senate versions of the Fair Access to Clinical Trials Act were introduced and sent to the committee in Congress. The bills would have required creation of a mandatory public electronic database (most likely building upon the existing www.clinicaltrials.gov web site) in which all privately and publicly funded clinical trials must be registered.

Rep. Edward Markey (D-MA), one of the co-sponsors of the House version of the bill, says he and Rep. Henry Waxman (D-CA) plan to reintroduce it during the 109th Congress.

Markey says he believes there is "significant momentum" this year to get the bill passed, spurred by reports of incidents in which important negative information about drugs was withheld from the public.

"Consumers are scared and outraged that drug companies have information about the risks of a drug that they don’t share with them or their doctor," he says. "Congress is a stimulus response institution, and it responds when thousands of constituents call and write their members of Congress."

David Korn, MD, senior vice president for biomedical and health sciences at the Association of American Medical Colleges (AAMC), agrees that congressional action is likely this year, despite efforts by the pharmaceutical companies to voluntarily post their trials on publicly accessible company web sites.

"Unfortunately, there’s been adverse publicity about suppressing clinical trial data and slanted reporting," he explains. "The companies have lost a fair amount of credibility over all of this well-publicized activity. For credibility’s sake, probably a public registry, meaning a federally funded and federally managed registry, is the only way out of this."

He hears there will be Republican co-sponsors to the bill this year, giving it needed political viability.

The difficulty will be in the details of exactly what would be posted on such a registry, and in what form.

Markey says his bill would require that all trials be posted except for those conducted solely to detect major toxicities in a drug or to investigate pharmacokinetics. Each trial registered would be assigned a unique identifying number, which would help keep duplicative studies from being republished in different journals.

IRBs would act as gatekeepers in this process, ensuring that trials don’t go forward without being registered. Markey says he doesn’t believe this would create a workload problem for IRBs, since their only task is to confirm that the trial has been registered.

The question remains what would happen with results of these trials. Markey’s bill would require that results be posted "in the form of a structured abstract and in such manner as the Secretary [of HHS] may require. The results consist of information determined by the Secretary to be important to clinicians or researchers, in a form that ensures that the information is accurate and not likely to mislead or distort the results of the trial."

But results may not be of much use unless they are digested into some understandable form, says Myron Genel, MD, professor emeritus of pediatrics at Yale University. Genel is chairman of the Public Policy Council, which consists of representatives from the American Pediatric Society, the Society for Pediatric Research, and the Association of Medical School Pediatric department chairs.

Genel says the public, and even general practice physicians, would have difficulty understanding much of the data that could find their way to a registry.

"Good evidence for that is to look at some of the data that is already posted on [trial registry] sites that have been opened by some of the pharmaceutical companies," he says. "One site I looked at for one of the antidepressant drugs had 28 pages of data. For the cognoscenti, I suppose that’s helpful, but it’s not very helpful for ordinary physicians and certainly not for the public."

Genel says it’s possible that working out the details of such a complicated issue could end up delaying action on a registry.

Also expected in Congress this year is the latest effort by Rep. Diana DeGette (D-CO) to pass a bill specifically aimed at improving protection for research participants.

The bill, which DeGette already has introduced twice before, would extend the protections of the Common Rule to all research participants, regardless of the source of funding for the research.

It would call for harmonization of HHS and FDA patient safety regulations, and give greater authority to OHRP to suspend research protocols regardless of funding source for reasons of noncompliance.

DeGette’s bill also would expand the nonscientific and nonaffiliated memberships of IRBs to at least two members or 20% of the total members for each board. At least two members or 25% of the total IRB members would be required to have scientific expertise.

All IRBs would be required to register with the secretary of HHS, and the bill would provide for a system of voluntary accreditation, facilitated by the secretary’s office.

DeGette’s press secretary, Josh Freed, says DeGette currently is looking for a Republican co-sponsor to reintroduce the bill in the 109th Congress; its former co-sponsor, Rep. Jim Greenwood (R-PA), retired last year.

Freed says the bill hasn’t faced particular opposition in its previous attempts.

"It’s a complex issue — on the one hand, the critical need to protect patients vs. what some may see as protecting the independence of research institutions," he says. "It’s going to be tricky maneuvering it through Congress, and oftentimes issues involving medical research and regulation may take a bit longer."

Marjorie Speers, PhD, executive director of the Association for Accreditation of Human Research Protection Programs (AAHRPP), says IRBs should keep an eye on the progress of DeGette’s bill, particularly if new problems erupt at individual research institutions.

"Congress has a lot of things on its mind right now, but as long as issues arise with respect to human research, then Congress could act at any time," she says.

Another issue that may receive attention from Congress this year is a 2004 report by the Institute of Medicine, "Ethical Conduct of Clinical Research Involving Children," that outlined ways to improve pediatric research. The report’s recommendations include increasing the number of pediatric specialists serving on IRBs that approve pediatric research, and having the government offer better guidance to researchers and IRBs regarding the more restrictive rules that apply to child research subjects.

Genel says that while the release of the report in March 2004 may have been overshadowed by the debate over a clinical trials registry, senators from both sides of the aisle have expressed interest in its findings.

"I think it’s generally bipartisan," he says. "I don’t think this is a partisan issue."

Genel adds that he expects to see the introduction of legislation this year that would address some of the IOM’s recommendations.

He says the upcoming reauthorization of the Children’s Health Act could provide a vehicle to enact some of the IOM’s recommendations. Genel says the Public Policy Council had recommended including demonstration grants that could show best practices involving children and research.

Leavitt statements encouraging’

In the area of federal regulation, Korn and Genel say they are encouraged by the early statements made by Mike Leavitt, who was sworn in in January as the new secretary of Health and Human Services. Testifying at his confirmation hearing before the Senate, Leavitt called the HHS a "trustee of our nation’s most treasured brands," particularly the FDA, the National Institutes of Health, and the Centers for Disease Control and Prevention.

"I can only go by his public pronouncements, which are very encouraging," Genel says. "There are issues relating to the operation of FDA that he says he will address. They’re going to have to be addressed. One of these is the issue of clinical trials registries, but another is post-approval surveillance."

The OHRP has a number of regulatory actions planned in the coming year (see the new OHRP proposed rules). Speers says IRBs should watch the actions of the Secretary’s Advisory Committee on Human Research Protection, which may suggest guidance or revisions to the Common Rule (45 CFR 46, Subpart A).

But IRBs can do more than simply be silent observers of the political debate, Genel says.

He says the research community can do a better job of communicating with legislators about issues of human subjects protection. By staying in contact, particularly with staff members, IRBs can help them navigate the nuances of research policy-making.

Genel suggests that IRBs work with professional organizations such as the AAMC. They also should keep in touch with their own representatives, even inviting them to an IRB meeting to help give them a better understanding of the review process.

Speers says that as more human subjects protection programs seek voluntary accreditation, it could assure Congress and regulators that the research community is behaving responsibly, potentially staving off new federal action.

"There will always be problems with individual protocols or individual investigators, but what accreditation should help is to prevent the systemic problems we were seeing a few years ago," she says. "I think accreditation will not only influence perhaps what Congress does, but I think it will perhaps influence what the regulators do and that there will be less need for more regulation or a more stringent interpretation of regulation if the institutions are conducting research according to high ethical standards."