September 30, 2020: Clinical trial innovations — COVID and chips
Clinical trials — the systematic testing of an intervention in people for safety and effectiveness — are the lynchpin of the translational process. All the work in the preclinical laboratory is aimed at making an eventual clinical trial successful, and all the work to implement a new intervention in the community is predicated on controlled clinical trials showing benefit. Clinical trials also are the most complex and expensive part of the translational process. They are fraught with scientific uncertainties and operational inefficiencies that limit our ability to test new treatments in humans and thus deliver interventions to patients more quickly. They need scientific and operational innovation perhaps more than any other part of the translational process.
NCATS is developing, demonstrating and disseminating more efficient, innovative and collaborative clinical research models, study designs, patient recruitment methods, institutional review board and contracting harmonization, and other advances in clinical trials. This month, I highlight an important demonstration of the NCATS approach in trials of convalescent plasma for COVID-19 and the development of a technology with the potential to revolutionize how clinical trials are performed in the future.
Observational studies suggest that convalescent plasma — blood plasma taken from people who have recovered from COVID-19 — may improve outcomes among severely ill patients with COVID-19. Randomized controlled clinical trials now are urgently needed to determine whether convalescent plasma is, in fact, effective and safe for the treatment of COVID-19 and, if so, in which patient populations. To answer this question, NCATS is directing two randomized, placebo-controlled clinical trials to evaluate convalescent plasma as a treatment for patients hospitalized with COVID-19. Both trials leverage the innovative national network of the Clinical and Translational Science Awards (CTSA) Program and demonstrate how nimbly the CTSA Program hubs and the Trial Innovation Network can respond to the nation’s research needs and shorten the path from discovery to treatment. Through the network, a trial based at Vanderbilt University is rapidly adding up to 50 new clinical sites to maximize enrollment, and a trial based at NYU Langone Health has added multiple sites in Texas and Florida and is adding sites in other states as the pandemic evolves.
While one part of NCATS is innovating on clinical trial design and operations to meet an immediate public health need, another part is testing an entirely new approach to clinical trials that is aimed at improving the success rates of new drugs tested in trials. Currently, 85% of candidate drugs fail in clinical trials because of safety problems or ineffectiveness, despite promising preclinical test results. Much of this is due to the poor ability of preclinical research models to predict responses in humans. To inform the design and implementation of clinical trials, NCATS has launched a new program, “Clinical Trials on a Chip.” Funded researchers will use tissue chips — tiny, bioengineered models of living human tissues and organ systems — to better predict which patients with common and rare diseases are most likely to benefit from investigational therapies, and which are likely to be at risk for harmful side effects, prior to initiating clinical trials. This tissue chip data could improve clinical trial success rates and get treatments to patients more quickly and safely.
Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences