March 11, 2019: Applying “Translational Rigor” to Address the Opioid Crisis

The issues surrounding pain and addiction have created a tremendous urgency in this country for new and better treatments. This sense of urgency permeates all we do at NCATS, since patients with many types of diseases are waiting for the promise of science to reach them. In fact, we often paraphrase our Center’s mission as “getting more treatments to more patients more quickly.” But we are also aware that translational failure can be caused by information generated at one stage of translation not being accurate or reliable enough to support further development. So in our work to address the opioid crisis, we are taking care to be as rigorous as we are innovative and helping our collaborators do the same.

Observations made in particular laboratories, clinics or community settings are the seeds from which translation grows. But a great deal of published work over the last decade has shown that many of these observations cannot be reproduced by other researchers in different settings, sometimes for understandable reasons. Although such observations can be very valuable, they are not suitable for translation into interventions that improve health. Continuing my “seed” analogy, the translational “plants” that grow from such seeds can thrive in the specialized environment of a greenhouse but may not survive the rigors of the real world outside it.

I refer to the qualities required for an observation to be translatable as “translational rigor.” NCATS applies this level of rigor to every step of translating a scientific discovery into an intervention to improve health. Translational rigor results in more efficient translation and accelerates the development of therapies by decreasing the rate of failure.

NCATS’ Assay Guidance Manual (AGM), which I have highlighted before, serves as a guidebook for researchers to incorporate translational rigor into their drug discovery research. To promulgate this approach to NIH HEAL (Helping to End Addiction Long-termSM) Initiative researchers, NCATS AGM scientists recently co-hosted a two-day symposium on developing addiction and pain therapeutics with our colleagues at the National Institute on Drug Abuse and the National Institute of Neurological Disorders and Stroke.

The two days were filled with rich and candid discussions of what has and has not worked in the last 25 years. For example, current animal models for pain have serious limitations, particularly when applied to the complex issue of chronic pain. We need to develop new medicines using only approaches shown to be reliable and also consider entirely new approaches to more effectively address the addiction and pain epidemics facing our nation. You can read more in the HEAL symposium feature, but by the end of the event, the message was loud and clear: We all need to think about how to do our science differently if we are to achieve the goals of NIH HEAL.

On that note, I will highlight some of the unique ways we are working on approaches that address the challenges discussed at the symposium. NCATS is leveraging its existing resources and therapeutics development expertise and applying them to NIH HEAL work. Our HEAL initiatives provide researchers with funding and research collaborations with NCATS scientists to advance scientific discoveries across the translational spectrum. We are applying translational science approaches that have been developed in other challenging realms, such as rare disease research, with the goal of developing models and novel new treatments to address issues surrounding pain and opioid addiction. We are literally opening our doors so you can work with us to tackle this immediate need head on.

I encourage you to look into our collaboration proposal process, because it is designed with the goal of getting promising ideas through the translational “valley of death” with translational rigor and efficiency. In turn, NCATS will continue to think of new ways to speed translation and bring these solutions to bear on the opioid crisis.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences