As healthcare systems across the world, continue to grapple with the pressures of COVID-19, Cytel advances yet another strategic role for adaptive platform trials to play in alleviating the pressures on healthcare systems in Low and Middle-Income countries. These innovative designs enable several therapies to be tested against a single placebo, ensuring that a smaller percentage of patients are enrolled into the placebo arm. They also create efficiencies by making early stopping an option for low performing therapies, creating opportunities to redistribute resources to more promising medicines. The TOGETHER Trial, designed and implemented by Cytel along with colleagues in Brazil, published its results last month in the Journal of the American Medical Association (JAMA).
The clinical study encompassed a three arm trial for hydroxychloroquine and lopinavir-ritonavir against placebo, aimed at patients with early stages of COVID-19. The advanced stages of COVID-19 are the deadliest and require hospitalization, but over 95% of cases never advance to that degree. The TOGETHER Trial was based on the premise that an effective intervention in the earlier stages would reduce patients who advance to the deadlier stages, and thereby relieve hospital burden.
The other benefit of battling COVID-19 at earlier stages is that therapies like hydroxychloroquine and lopinavir-ritonavir might have proven more effective before the disease had progressed. Had this been the case, cheaper medicines would have been available in low resource settings to address the rising number of hospitalizations.
Adaptive platform designs form an efficient way to test for therapies which have been shown to not be effective for advanced stages of COVID-19, but which might prove beneficial in earlier phases. The adaptive element of the design ensured that the clinical trial could stop for futility before 50% of patients had enrolled, ensuring that sick patients were not unduly subjected to therapies that were not effective.
Meanwhile the platform design enabled multiple therapies to be tested against placebo simultaneously, so that a smaller percentage of patients were enrolled into the placebo arm than would have been in a series of 2-arm clinical trials.
The TOGETHER Trial was the result of the combined efforts of Cytel biostatisticians who designed the unique three-arm study, and project managers with the experience to implement these highly innovative designs.
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About the Author of Blog:
Dr. Esha Senchaudhuri is a research and communications specialist, committed to helping scholars and scientists translate their research findings to public and private sector executives. At Cytel Esha leads content strategy and content production across the company's five business units. She received a doctorate from the London School of Economics in philosophy, and is a former early-career policy fellow of the American Academy of Arts and Sciences. She has taught medical ethics at the Harvard School of Public Health (TH Chan School), and sits on the Steering Committee of the Society for Women in Philosophy's Eastern Division, which is responsible for awarding the Distinguished Woman in Philosophy Award.