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

Introduction: 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 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. 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. Conclusion: 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.