Under new rules, basic studies of how the brain processes images could be redefined as clinical trials.

© Vassar College/Karl Rabe

Some scientists hate NIH’s new definition of a clinical trial. Here's why

Nancy Kanwisher, a cognitive neuroscientist, has spent her career pinning down how the human brain responds to visual inputs such as faces. As part of that work, Kanwisher asks volunteers—usually college students at the Massachusetts Institute of Technology (MIT) in Cambridge, where she works—to lie in an MRI machine that records their brain activity while they do a task, such as viewing a photo. Although such studies reveal information that can be relevant to diseases, and disorders such as autism, they do not test treatments.

But a few weeks ago, Kanwisher and colleagues in related behavioral research fields—from cognitive psychology to vision science—were dismayed to learn that the U.S. National Institutes of Health (NIH) in Bethesda, Maryland, could soon deem their studies to be clinical trials. That designation would impose a raft of new requirements on studies that have already passed ethics review, such as following different standards for funding applications, and reporting results on clinicaltrials.gov, a public database.

NIH officials say they simply want to ensure that all clinical trials—including those testing drugs, medical devices, and behavioral interventions—meet recently bolstered standards for rigor and transparency. But Kanwisher and others say that the agency’s widening definition of clinical trials could sweep up a broad array of basic science studies, resulting in wasted resources and public confusion. “The massive amount of dysfunction and paperwork that will result from this decision boggles the mind” and will hobble basic research, Kanwisher says. To prevent that outcome, she and dozens of other researchers, along with several scientific societies, have flooded NIH with letters and emails expressing concern about the policy, which the agency announced last September but is only now implementing.

NIH says it is too soon to know whether the agency will ultimately define Kanwisher’s study and others like it as clinical trials. Still, “it’s fair to say there are probably going to be more [studies] under the clinical trial definition than we have seen previously,” says NIH Acting Chief of Staff Carrie Wolinetz. But, she adds, “it is going to be less than some in the community are anticipating.”

The policy change began to emerge in 2014, when NIH revised its definition of clinical trials to include studies that evaluate the effects of “interventions” such as “manipulation … of the subject’s environment” on “health-related biomedical or behavioral outcomes.” Then, last September, NIH announced more extensive requirements for all trials the agency funds. For example, it mandated new training for trial staff as well as registration and results reporting on clinicaltrials.gov. The agency also said research projects that fit the definition could only receive NIH backing in response to a formal funding opportunity announcement (FOA) for trials, and that all such applications would be sent to a clinical trial review group, which would assess the study’s rationale and statistical design.

The massive amount of dysfunction and paperwork that will result from this decision boggles the mind.

Nancy Kanwisher, Massachusetts Institute of Technology

Few basic behavioral and brain researchers who study humans took notice of the change, because they didn’t think of their studies as clinical trials. But that changed early last month, after William Riley, director of the NIH Office of Behavioral and Social Sciences Research, gave a talk to the behavioral sciences board at the National Academy of Sciences in Washington, D.C. Riley warned that many studies in disciplines under his office’s purview could fall under the new policy, which kicks in with applications submitted in January 2018.

The remarks sparked fierce pushback. In a 6 June letter to NIH, the Association for Psychological Science (APS) in Washington, D.C., argued that the agency’s definition of an intervention “is exceptionally broad and appears to encompass any manipulation of a variable hypothesized to have an impact on a measured behavioral outcome.” APS also worries that many researchers may not be aware of the new FOA requirement, leading NIH to reject their applications and forcing them to miss a funding cycle. And it fears that applications that do reach a review may suffer, because the criteria traditionally used to evaluate a clinical trial might not apply to the proposed research.

Similar “serious concerns” were voiced by the Federation of Associations in Behavioral & Brain Sciences (FABBS) in Washington, D.C., which represents 20 scientific societies, in a 12 July letter asking NIH to pause the policy and gather more feedback. Among other fears, FABBS members worry that researchers will be required to report any added experiment as a new protocol on clinicaltrials.gov—something not usually required in basic research. “It would bureaucratize the science in a way that would cripple exploratory research,” says Harvard University cognitive psychologist Jeremy Wolfe, FABBS president.

The FABBS letter also predicts that including a wider range of studies on clinicaltrials.gov, which many patients use to find trials that are seeking participants, will confuse the public by clogging the database with irrelevant studies. Although the policy might help address the “file drawer problem” in psychology and neuroscience—the failure to report negative results—using clinicaltrials.gov as a solution may do more harm than good, Wolfe says.

Wolinetz says NIH has “heard the concerns,” which are also being voiced by leaders at some NIH institutes, and is working to clarify the scope of the definition. “We’re not out to harm our grantee community in any way here,” she says, adding that “our interpretation is evolving as we recognize areas that are ambiguous.” The agency expects to offer guidance within a few months on which behavioral studies will now be called clinical trials.

*Clarification, 31 July, 6:53 p.m.: This story originally characterized autism as a disease, although it is generally classified as a neurodevelopmental disorder.