Why have thousands of researchers asked NIH to delay revising clinical trials policy?
Why have thousands of biomedical researchers, traditionally strong supporters of National Institutes of Health (NIH) leadership, signed an open letter asking NIH to delay implementing policies revising the definition of a clinical trial? The answer is surprising, given their agreement with NIH’s laudable goal of enhancing transparency and reporting of clinical research results. Quite simply, the researchers find that these policies are fraught with dangerous unintended consequences.
Although in October of 2014, NIH said that its new definition of clinical trials “is not intended to expand the scope of the category of clinical trials,” it appears that the new policies, scheduled to go into effect in January of 2018, actually do just that; they dramatically expand the scope of the category of clinical trials, sweeping up much of what, historically, has been regarded as basic research.
Many researchers think that the review and administrative burdens associated with this new classification will harm science and public health. They don’t believe assurances that “all you have to do is register” (with clinicaltrials.gov), because there is onerous oversight of true clinical trials, and because NIH has stated that one of the goals of the new policy is to exert more control and hold investigators to plan.
The point of a clinical trial is to conduct a study that can be done and that is important for health. So, feasibility and statistical power are key, while innovation is deemphasized. This is very different from basic research, which often puts a premium on innovation and agility. The concern, then, is that proposals for basic research, suddenly classified as clinical trials, will suffer in review, and will not be administered properly. (NIH staff are smart and capable. They can deal with unintended consequences one at a time. But when the whole portfolio is changed at once, it is a recipe for chaos.)
Thousands signed an open letter outlining concerns that these new policies will harm American science and public health. Tens of thousands more are represented by the university associations that sent a joint letter expressing similar concerns. Those letters describe harm to science and health that the new policies will cause. This focus on science, however, makes it easy to overlook a different kind of harm: The uncertainty arising from the divergence of interpretation, and the ultimate impact on trust.
The misalignment between the new policies and the previously stated purpose has caused confusion, which is raising questions of trust. In discussions with researchers, this issue comes up over and over again — and it is painful to hear colleagues raise fears related to the reliance they placed on the intentions that NIH expressed in 2014, in light of the unintended consequences of the expanded definition. A recent article in Neuron describes the new policies as “… dangerously chilling to basic science if implemented as literally written.”
To be sure, the new policies have already been revised. In particular, an early assertion by NIH that all functional MRI studies in humans should be classified as clinical trials was withdrawn, after it was pointed out that the rationale for that approach was problematic. Of course, that progress is gratifying. The point, however, is that such nit-picking arguments about language should be unnecessary, given the clear divide between basic research and clinical trials.
In biology, the idea of a “manipulation” is fundamental to the definition of experimental (vs. observational) science. Experimental science is about seeing how manipulations affect measurements, while clinical trials are about seeing how interventions affect health or biomedical-related outcomes. Historically, there has been little confusion regarding these distinctions, but NIH’s published “Cases” appear to avoid this historical understanding and instead manifest expansive readings of “intervention” and “health outcomes” so as to create a vast enlargement of the category of clinical trials, in a manner that diverges from NIH’s original statement of purpose. That inconsistency, and the harm that will be done by the resulting unintended consequences, has caused what feels like concerns regarding trust.
What then is the solution to these concerns? The open letter asks NIH to “invite … representatives from affected basic research communities, listen to the concerns raised, and work with us to shape a policy for this important segment of NIH grantees.” The joint association letter offers “to assist the NIH in reaching the laudable goals of transparency and accountability, consistent with… principles…” along the lines outlined above.
I believe that a good solution is likely to include these elements:
- Keeping the clinical trials definition narrow enough to include only true clinical trials focused on improvement in or prevention of disease;
- Keeping the current application form for everything else, to heighten that distinction;
- Building an alternative public website that is not ClinicalTrials.gov (something more like PubMedCentral) where synopses of all NIH-funded human subjects research, and links to datasets, will be posted.
Basic research and clinical trials both serve public health, and respecting the distinction between the two is valuable. The NIH should slow down and take time to to fulfill the good intentions and laudable goal of increasing transparency and reporting in clinical research, without the harm to science, health, and trust that the unintended consequences of the new policies will bring.