Determining the return on investment of a global adaptive platform trial for critically ill patients during COVID-19: A value of implementation analysis in low- and middle-income countries and globally

Background: Adaptive platform trials rapidly generate robust evidence, essential for resource-limited health systems like those in low- and middle-income countries (LMICs). We analyzed the return on investment (ROI) of an adaptive platform trial using Value of Implementation analysis. Methods: This was a retrospective observational cohort study comparing the uptake and benefits of corticosteroid therapy in COVID-19 patients admitted to intensive care units (ICUs) participating in the Randomized, Embedded Multifactorial Adaptive Platform trial for Community-Acquired Pneumonia (REMAP-CAP) versus patients admitted to ICUs that did not participate in REMAP-CAP. Value of Implementation analysis enabled us to determine the maximum investment in the REMAP-CAP corticosteroid therapy domain to achieve a positive net monetary benefit in terms of reducing the incidence of mortality. In other words, even if the REMAP-CAP corticosteroid therapy domain had cost up to the maximum investment, the number of lives saved would have led to net savings. We accessed individual patient data from the ISARIC COVID-19 Data Platform and the Collaboration for Research, Implementation and Training in Critical Care in Asia-Africa (CCAA) Data Platform. Results: Of the 89,147 ICU patients with COVID-19 receiving oxygen therapy between June 2020 and February 2022, 55% (n=49,376) received corticosteroids. Globally, patients at REMAP-CAP sites had a higher rate of corticosteroid use (80.9% vs 49.2%, p<0.001) and a 3.8% lower mortality risk than patients at sites not participating in REMAP-CAP. LMIC sites participating in REMAP-CAP, compared to LMIC sites not participating in REMAP-CAP, also had a higher rate of corticosteroid use (78.2% vs 31.5%, p<0.001) and an 8.8% lower mortality risk. Results show that even if the REMAP-CAP corticosteroid domain had cost up to $118.5 million (2024 United States Dollars [USD]) and $33.8 million (2024 USD) in LMICs, it would have still led to net savings due to lives saved. Conclusions: The corticosteroid therapy domain of the REMAP-CAP trial represented good value for money during the COVID-19 pandemic both globally and in LMICs, given the mortality benefits of corticosteroid therapy and the implementation of high-quality care among REMAP-CAP sites. Participation in high-quality global RCTs leads to the implementation of high-quality care.