Presidential commission promotes reforms

Panel takes up human subjects protections

Add another voice to the national conversation on improving protection of research participants: The Presidential Commission for the Study of Bioethical Issues, which recently released its recommendations for reforming federal oversight of human subjects research.

The commission was charged more than a year ago by President Barack Obama with investigating allegations of unethical research in Guatemala in the 1940s and determining whether current regulations adequately protect participants.

In its first report, the commission concluded that the Guatemala experiments, in which vulnerable populations were deliberately exposed to sexually transmitted diseases (STDs), represented "unconscionable basic violations of ethics."

In this new report, "Moral Science: Protecting Participants in Human Subjects Research," the commission concludes that while modern regulations would not permit similar abuses to occur today, there is still more the federal government can do to protect current research subjects.

Included were 14 recommendations for action, including steps to improve accountability, ensuring that communities in which research occurs are protected and compensating those who are injured by research (see accompanying description of recommendations).

"The commission's report is thoughtful and thorough," says Heather Pierce, JD, MPH, senior director for science policy and regulatory counsel for the Association of American Medical Colleges (AAMC) in Washington, DC. "It took pains to assess the current state [of research protections] and incorporate that into the recommendations."

Pierce says the recommendations also recognize the resource constraints faced by institutions and regulators.

"They seem to have an awareness that the protection of human subjects is of utmost importance, and therefore we need to use our resources wisely, strategically and effectively, as opposed to a recommendation that would represent some ideal scenario that could absolutely not be implemented," she says. "I think that gives it some additional potential for implementation."

At several points in the commission's report, it notes that previous similar reviews and recommendations have gone unanswered, and the group calls on regulators to enact these reforms or explain why they won't do so.

"The public should know whether the federal government intends to move forward, and if so in what way, with any or all of these recommendations," the commission wrote in its report.

The Department of Health and Human Services (HHS) released a statement thanking the commission for its work and pledging to "review its recommendation for strengthening these safeguards."

Accountability, ANPRM

Pierce notes that a recent HHS announcement may point to a response to one of the commission's concerns.

The department announced in January that it would commit $775,000 to health initiatives combating STDs in Guatemala and $1 million to evaluate whether proposed revisions to the human subjects protection regulations actually improve protections for research participants.

While the commission's recommendations were not referenced in this announcement, one recommendation involved research into the effectiveness of human subjects regulations as a way of improving accountability.

"It seems like it is certainly an issue that is being taken seriously and it doesn't seem like a commission that is going to be entirely ignored," Pierce says.

The recommendations come as HHS is considering responses to its 2011 advance notice of proposed rule-making (ANPRM), a proposed revision of the Common Rule.

In its report, the commission generally praises the ANPRM proposals, particularly those that would better calibrate the level of oversight to the level of risk involved in a study and steps that would reduce unnecessary duplicated IRB reviews of multisite studies. The commission also supports a plan to create standardized consent forms with more understandable language, and proposed harmonization of regulatory requirements across federal agencies.

"It will be interesting to see how the commission's recommendations are taken up while the agency is going through the comments to the ANPRM, and how that comes out in the next iteration of either proposed rules or some additional questions," Pierce says.

Compensating for injury

Two of the recommendations concern subjects who are harmed by research. The commission calls for the federal government to move "expeditiously" to study the scope of research-related injuries and to determine whether there needs to be a national compensation program. If there is found to be a need, it calls on HHS to work on a pilot study to determine the proper mechanism for doing that.

Larry D. Scott, MD, MA, a professor of medicine at The University of Texas Medical School at Houston who has written on the topic of research-related injury, notes that other panels have made similar recommendations over the past several decades.

"It's never gotten off the ground, and I don't know that it's any more likely to happen this time around," Scott says. "What has changed is the complexity of research over the past 20 years. We're getting into some pretty high-profile kinds of interventions with added risks," pointing to gene transfer trials as an example.

The commission notes these previous efforts and asks either HHS or the Office of Science and Technology Policy to issue an official reply to this point, explaining why the current system should be either changed or maintained.

The commission outlines a number of different approaches to compensation currently in use, including policies of the National Institutes of Health, the Medicare program and the University of Washington, which has a long-standing self-insured compensation policy.

Standard of care

The commission also delved into a thorny issue in international research: Is it ethical to provide either placebo or a treatment that is not considered the best proven intervention for the control arm of a clinical trial, particularly in developing countries where the standard of care may not be as high as it is in the West?

The commission proposes a set of requirements for when these types of interventions are appropriate — when the intervention is known not to be the best for the study population (for genetic reasons or because of lack of infrastructure, for example); when the scientific and ethical justifications have been properly reviewed; and when safeguards have been enacted, including monitoring subjects and providing rescue measures when necessary.

Pierce says the issue is a tricky one, requiring that reviewers look not just at the type of trial proposed, but the circumstances.

"In some cases, a very well-designed placebo-controlled trial may in fact be the right answer," she says.

"It's certainly an issue that we'll need to continue to address and both educate on a national scale and an international scale — teaching IRBs and other ethics boards how to evaluate not simply the type of trial that it is, but how does that relate to the situation, to assess whether it's the right approach."

To read the report "Moral Science: Protecting Participants in Human Subjects Research," visit the website of the Presidential Commission for the Study of Bioethical Issues at http://bioethics.gov/.