March 23, 2017: Achieving the Impossible Through Translational Teamwork

The workings of living things are replete with teamwork. Strands of DNA pair in complementary symmetry, proteins work with each other to turn on genes in exquisitely specific patterns, enzymes modify their molecular partners in a myriad of ways critical to life, and diverse cell types work together to function as an organ. Given nature’s example, it is perhaps curious that scientists frequently feel reluctant to work with others. Traditional scientific incentive and reward structures can reinforce this reticence. Translation absolutely requires teamwork for success, and many opportunities for translational success are missed because the right people, disciplines or organizations are not working together.

Via its unique science, organization and culture, NCATS is creating a collaborative ecosystem in which teamwork among diverse contributors is the norm. Two recent advances epitomize the enormous potential of this approach, each cracking a longstanding problem that had been previously intractable.

In the realm of clinical translation, patients and researchers often endure waits of months or even years for a clinical trial to begin, due to multiplicative ethics reviews by participating institutions’ Institutional Review Boards (IRBs). These delays are costly in financial and human terms: Patients may progress in their disease (making them ineligible for the trial) or even die while waiting for the trial to start. To overcome this roadblock, NCATS developed a platform for multisite trials for which all sites agree to rely on the review of a single IRB, greatly simplifying the process and time required.

What was once thought impossible — convincing institutions to sublimate their own processes to a united one — has now happened, thanks to the teamwork of literally hundreds of devoted physicians, ethicists and legal experts from around the country who worked to create the NCATS Streamlined, Multisite, Accelerated Resources for Trials (SMART) IRB Reliance Platform. Today, NIH announced that all Clinical and Translational Science Awards (CTSA) Program sites have now signed the SMART IRB authorization agreement. This achievement makes single-IRB review possible for any clinical study that uses the NCATS CTSA Program network. CTSA Program awardees Harvard Catalyst, the University of Wisconsin-Madison Institute for Clinical and Translational Research, and Dartmouth SYNERGY led the team effort, which involved the close collaboration of all the CTSA Program sites as well as NCATS and other NIH staff. In total, more than 150 institutions have signed on to the agreement, with more to come. This collaboration promises to dramatically reduce waiting times for patients and translational researchers, with no loss of human subjects protections, and thus get new interventions to improve health tested for safety and effectiveness much more quickly.

On the pre-clinical front, scientists at NCATS and the University of Tokyo have come together to address another problem previously thought to be intractable, in this case finding a potential drug to treat parasitic roundworm infections that cause river blindness and lymphatic filariasis (elephantiasis) in more than 150 million people worldwide. A particular enzyme target offered an “Achilles’ heel” to kill these parasites, but previous approaches to finding a drug had repeatedly failed, leading to the conclusion that the target was “undruggable.”

The NCATS-Tokyo team developed a new approach to the problem that emerged from the diversity of the team members’ backgrounds: They created both a library of more than 1 trillion special peptides that they predicted would better fit the target’s unusual shape and a way to screen the peptides for activity against the critical enzyme. NIH will announce the team’s results when they are published in the coming weeks.

NCATS is following nature’s example, bringing together disparate minds and scientific disciplines and organizations to achieve what was previously impossible. This is, as we like to say, improving health through smarter science.

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