Unintended consequences: What is a "clinical trial"?

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More than 2,400 researchers have now signed an "Open Letter to NIH Director Francis Collins" that starts like this:

We are writing to request that NIH delay implementation of its policy that sweeps basic science into a clinical trials framework until adequate feedback about its impact is obtained from the affected scientific community. We wholeheartedly agree with NIH’s goals of increasing scientific transparency and rigor, but we ask that you consider alternative mechanisms to accomplish those goals that would have fewer adverse effects on basic research.

The background is a new definition of what counts as a "clinical trial", to be enforced starting 1/1/2018 ("NIH's Definition of a Clinical Trial"):

A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

Interpreted literally, this means that a study of priming effects on speech perception in healthy undergraduate students might count as a "clinical trial", since "human subjects are prospectively assigned to one or more interventions" (the priming part), and speech perception is a "health-related biomedical or behavioral outcome". Or maybe not. NIH has given some bizarrely irregular examples of how to interpret this rather general definition — thus vision and memory in adults are apparently "health-related outcomes" but learning in children is not.

Does this matter? The open letter cites these negative impacts on research:

  • Basic scientists whose research is now deemed a “clinical trial” may only submit applications for funding through a funding opportunity announcement designated specifically for clinical trials, even though other funding vehicles are more appropriate;
  • The basic research studies now classified as “clinical trials” will be reviewed by study sections constituted for clinical trial review and would need to be significantly reconstituted to handle discovery science;
  • Training grants cannot be used to fund “clinical trials,” so basic research involving humans will be ineligible for T-awards;
  • Exploratory research, which is the lifeblood of discovery, would be hampered. If exploratory research could be registered at all, such registration is likely to slow the pace of research, impeding innovation and discovery;
  • The new policies unnecessarily increase the administrative burden on investigators, and this burden will fall disproportionately on researchers at less well-funded universities and colleges, which have fewer administrative resources to help; and,
  • Members of the public who seek information in clinicaltrials.gov will find a potentially confusing array of basic science experiments that are not in the clinical trial stage.

The letter goes on to explain that this absurd new policy is apparently an unintended consequence of good intentions:

We understand that a motivation for this change is to increase transparency and replicability in NIH funded research. We strongly applaud this motivation. Indeed, many of the undersigned are actively involved in scientist-led efforts to increase replicability and transparency. Examples include the Open Science Framework (OSF), and OpenfMRI. And other efforts to increase transparency are underway, both inside and outside government. NIH has also helped to increase data sharing in the NIMH data archive. And scientists are currently developing mechanisms for more sharing of code as well. We encourage (and applaud the NIH for encouraging) pre-registration, data sharing, protocol sharing, and code sharing.

We support the goals of transparency and replicability. Unfortunately, the current effort to improve transparency and replicability in basic science does so by mislabeling basic research as a clinical trial.

Jocelyn Kaiser has a year-long series of articles in Science News on this topic: "NIH aims to beef up clinical trial design as part of new data sharing rules", 9/16/2016; "Some scientists hate NIH’s new definition of a clinical trial. Here's why", 7/19/2017; "Basic studies of how our brains work are now clinical trials, NIH says", 8/25/2017.  But I haven't seen anything in the mainstream media.

See also Mike Lauer, "4 Questions For Researchers and Institutions Involved In Human Subjects Research", NIH 8/11/2017.

Lawyers and legislators are not the only ones who have issues with non-obvious interpretation of contracts, statutes, and regulations.


  1. Linda Seebach said,

    September 1, 2017 @ 2:35 pm

    Scott Alexander at slatestarcodex has a post about dealing with overzealous institutional review boards, and a followup post excepting comments, including one discussing this proposed rule change.

  2. Kasey Chang said,

    September 5, 2017 @ 8:13 pm

    Wonder if this has anything to do with the "right to try" law that passed the Senate? But this is WELL beyond the scope of language log. OTOH, there doesn't seem to be any impetus to redefine "clinical trial"… until now. Why?

  3. Yosemite Semite said,

    September 6, 2017 @ 9:43 pm

    Lawyers and legislators are not the only ones who have issues with non-obvious interpretation of contracts, statutes, and regulations.

    It's a thorny subject. In 2016, the Prize in Economic Sciences (aka the Nobel Prize in Economics) was awarded to Holt and Holmström for their research into contracts. The press release: https://www.nobelprize.org/nobel_prizes/economic-sciences/laureates/2016/press.html

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