US Government Mulls Changes to Rules for Research in Humans

Two perspectives published online this week in the New England Journal of Medicine make the case for proposed revisions to how human research subjects are treated in the United States.

This September, the US Department of Health and Human Services—along with no fewer than 15 other governmental departments and agencies—announced a 131-page proposal to amend the Common Rule, the informal name for regulations that have existed since 1991. The process is ongoing, with the period for public comment recently extended to January 6, 2016. It is unclear when, if formalized, the new rules would be put into place.

Motivating the effort is the fact that the “research landscape has changed radically,” since the rules were first introduced more than 2 decades ago, write Kathy L. Hudson, PhD, and Francis S. Collins, MD, PhD, of the NIH (Bethesda, MD). Studies have become larger and involve more sites, subjects expect to take on more active roles, data are ever more readily shared, and increasingly more sophisticated information can be obtained from biospecimens.

The revisions aim “to enhance respect and safeguards for research participants and to increase research efficiency by reducing unnecessary burdens and calibrating oversight to the level of risk,” they explain.

Most notably, informed consent paperwork would be streamlined, individuals would need to give explicit permission for all use of their biospecimens, multisite studies could more easily be overseen by a single institutional review board, and ongoing monitoring of studies would become less onerous for those deemed less risky to their participants. The standards would apply to all clinical trials being done at institutions receiving federal funding, with the exception of studies regulated by the FDA, which has its own set of regulations.

Few Immediate Changes to Research

But what would these changes mean to cardiologists and to their patients?

According to Ori Ben-Yehuda, MD, executive director of the Cardiovascular Research Foundation’s Clinical Trials Center (New York, NY), the answer is not much—at least for now. He told TCTMD in an interview that while reform is welcome, “there are some worrisome signs. Will it just make [research] more complicated?”

Importantly, “it really just applies to government-sponsored research,” such as basic and observational studies as well as therapies that have not yet reached the FDA, he explained. “Most research is actually by the private sector, and particularly the research that actually impacts patients,” such as new medications and devices. Ben-Yehuda did, however, predict there will be a ripple effect, because “usually people do follow the government’s lead.”

Ezekiel J. Emanuel, MD, PhD, University of Pennsylvania (Philadelphia, PA), meanwhile, also observes in his NEJM piece that these reforms, which he started advocating for back in 2009 while working at the White House Office of Management and Budget, are worthy but far from perfect.

Detractors of the effort may point to its “near obsession” with oversight of biospecimens, Emanuel says. Similarly, Ben-Yehuda expressed worries that those rules in particular might dampen future studies. Imagine a 10,000-patient study, in which “we have enormous data on heart failure in this group,” he related. “Then I discover 12 years later that there is a new biomarker, that if we could test it in the stored biobank specimens, we would be able to discover some very important things. Even today it’s difficult; with this new arrangement it sounds like it might not be possible.”

But What About the Patient?

Patients deserve to have their rights and privacy protected, Ben-Yehuda stressed, but that must be “counterbalanced” with the benefits of research. Egregious violations like the Tuskegee experiment are no longer seen, he asserted, and data are de-identified to the point of being less invasive that the details attached to credit cards and floating around on the Internet.

Asked whether patients become more comfortable with enrolling in trials when these issues are aired publicly and covered on the news, Ben-Yehuda said that the result is quite the opposite. “It seems overly complex. It seems overly frightening. It again raises demons from the past that have long since been overcome,” he commented.

The best path toward more efficient and helpful research is to integrate it into the clinical setting through anonymized electronic medical records, Ben-Yehuda suggested. “The only way that will happen is if it’s easy and without bureaucratic hurdles. What I’m reading [in these NEJM papers] suggests to me that we are very far from it.”

According to Emanuel, a “proposed centralized database for adverse events that would have streamlined reporting and provided a comprehensive picture of research risks was unfortunately dropped.” Other skeptics, he added, may doubt that the rules will achieve their goals or that the government will follow through on logistical support for its proposals.

“Inherently, this reform is a compromise. But we cannot let our ideal undermine the only substantive effort since 1991 to reform human-subjects protections,” Emanuel emphasizes. “If reforms are spurned because people are holding out for a better deal, the status quo will be maintained. And who knows when the requisite ingredients will come together to generate change?”

Sources: 
1. Hudson KL, Collins FS. Bringing the common rule into the 21st century. N Engl J Med. 373;2293-2296.
2. Emanuel EJ. Reform of clinical research regulations, finally. N Engl J Med. 313;2296-2299.

Disclosures:

• Ben-Yehuda, Collins, and Hudson report no relevant conflicts of interest.
• Emanuel reports receiving personal fees from a variety of companies and organizations for unrelated work. He takes part in paid speaking engagements across the healthcare spectrum.

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