In September 2012, when neurologist Chris Austin at the National Institutes of Health (NIH) in Bethesda, Maryland, took charge of a new translational science center, he faced a host of skeptics. In launching the new center, NIH Director Francis Collins said he wanted to re-engineer drug development to speed new treatments to the clinic. But some accused NIH of wanting to become a drug company or solve the pharmaceutical industry's challenges—a notion one former CEO likened to believing in fairies. It fell to Austin to prove that the National Center for Advancing Translational Sciences (NCATS) wasn't going to compete with industry, but could give it powerful new tools. After 7 years, the jury is still out.
Austin is proud of his record. In a recent conversation with Science, he pointed to a long list of programs he says will make drug development and clinical trials run more smoothly. "We've taken a quite different approach than everyone else," says Austin, who spent 7 years at Merck before joining NIH in 2002. Whereas other NIH institutes and companies study specific diseases, "Our disease is the system: the translational science process," Austin says.
Some who have tracked NCATS, however, say it has yet to help improve the failure rate of at least 95% in drug development and is barely on the radar of major drug company executives. Even Austin admits, "I don't know how much the bigwigs have kept up" with the center's accomplishments. For one thing, his supporters say, NCATS's resources never matched its ambitions. Given that NCATS's resources were "a rounding error" compared with those of multinational companies, Collins's "grandiose vision" was unlikely to be realized, says cardiologist and pharmacologist Garret FitzGerald of the University of Pennsylvania.
Most of the center's current budget of $806 million is taken up by Clinical and Translational Science Awards (CTSAs), large grants that fund training, staff, and other resources for bench-to-bedside research at about 60 academic medical centers. The CTSA program predated NCATS; Austin wanted to reduce CTSA core funding so he could support new programs. But the program's leaders worked with Congress to thwart some of his efforts. That and other preexisting programs absorbed by NCATS have left at most a few tens of millions of dollars each year for new initiatives.
Austin has pushed the CTSAs to ramp up their therapeutics development efforts, from beefing up bioinformatics to forming a trials network across the centers. To streamline multisite trials, CTSAs now use a central ethical review board, to replace reviews done by each separate institution. This single review board pilot tested by the CTSAs became a model for an NIH-wide policy, Austin says.
FitzGerald, who heads his university's CTSA, says he has noticed an uptick in the number of new treatments coming out of academic medical centers. "If [NCATS's] objective was to realize the untapped potential of the academic sector to play as partners in the process of drug development, then I think that has been remarkably successful," FitzGerald says.
But he says it's hard to trace the uptick to specific CTSA changes. And U.S. academic centers remain a small player in drug development. Companies still outsource most clinical trials to cheaper and more efficient offshore sites, Austin admits.
A bright spot has been NCATS work on rare or neglected diseases that don't initially interest drug companies. Academic scientists have partnered with NCATS's intramural drug screening center in Rockville, Maryland, where four giant yellow robots screen hundreds of thousands of chemicals in search of potential drugs. NCATS has launched more than 40 drug development efforts, mostly for rare diseases, producing many candidates that have been picked up by companies and reached clinical trials. These include potential treatments for sickle cell anemia and Niemann-Pick disease, a lethal metabolic disorder. After NCATS-funded researchers showed that a drug already used to prevent organ transplant rejection could also help patients with a rare lung disease, the NCATS rare disease effort had its first (and so far, only) U.S. Food and Drug Administration (FDA) approval, in 2015.
Austin also points to its efforts to remove roadblocks to drug development. These include developing tools for testing potential drugs' toxicity and efficacy, including tissue chips, 3D bioprinted organs, and induced pluripotent stem cells. But he and others acknowledge that these tools haven't been widely adopted by drug companies as alternatives to animal tests. "This is a conservative industry that is slow to embrace new technology," explains Bernard Munos, a former Eli Lilly scientist based in Indianapolis who has served on NCATS's advisory board. Some also blame FDA for failing to lay out a pathway for accepting such data in lieu of animal tests.
Austin remains optimistic that NCATS programs will pay off. The center is working on a "biomedical data translator" that will create a resource for drug developers by merging a range of data types—from genetic information to cell studies, animal models, and patients' symptoms. Another project aims to develop freely available gene-therapy vectors—modified viruses for delivering therapeutic genes to cells—that would allow developers to swap in genes for different diseases without requiring new FDA approval each time.
Such efforts "are really important," says a former NIH official now in industry, who asked not to be identified. But this scientist says NCATS "hasn't had the money to move the needle." Austin acknowledges NCATS is still a long way from transforming the industry: "It is still a heavy lift," he says.