Clinical Epidemiology (May 2024)
Hospitalization Endpoint in Clinical Trials of Outpatient Settings: using Anti-SARS-COV-2 Therapy as an Example
Abstract
Alhanouf Yousef Alnafisah,1 Ahmed Fawaz Alkhalidi,1 Hanin Aljohani,1 Manal Almutairi,1 Adel Alharf,2 Hadeel Alkofide3 1Efficacy and Safety Evaluation Department, Benefit and Risk Evaluation Directorate, Saudi Food and Drug Authority (SFDA), Riyadh, Saudi Arabia; 2Drug Sector, Saudi Food and Drug Authority (SFDA), Riyadh, Saudi Arabia; 3Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Ahmed Fawaz Alkhalidi, Efficacy and Safety Evaluation Department, Benefit and Risk Evaluation Directorate, SFDA, Riyadh, 5163, Saudi Arabia, Tel +966555546169, Email [email protected]: In response to the COVID-19 pandemic, the World Health Organization (WHO) developed a set of outcome measures for trials primarily aimed at hospitalised patients. However, a gap exists in defining outcome standards for non-hospitalised patients. Therefore, this study aims to discuss hospitalisation as a primary outcome in outpatient trials and its potential pitfalls, specifically focusing on trials related to anti-SARS-COV-2 therapy.Methods: In this narrative review, researchers thoroughly searched MEDLINE and ClinicalTrials.gov from January 2020 to December 2022, targeting Phase III randomized controlled trials involving outpatients with mild-to-moderate COVID-19. The trials were specifically related to anti-SARS-COV-2 monoclonal antibodies or antiviral agents. The study collected essential data, including the type of intervention, comparator, primary objective, primary endpoint, and the use of estimands in the trial.Results: The search identified 12 trials that evaluated the efficacy of anti-SARS COV-2 therapies in a predefined population. Three studies used hospitalisation and death as primary endpoints in high-risk patients receiving monoclonal antibodies. Nine studies assessed the efficacy of several antiviral agents: four trials used hospitalisation and death as the main endpoints, while others used different measures such as virologic measures using the Reverse Transcription-Polymerase Chain Reaction test (RT-PCR), the eight-point WHO ordinal scale, symptom alleviation by Day 7 and time to clinical response.Conclusion: Choosing hospitalization as an endpoint may provide meaningful data such as the cost-effectiveness ratio of a drug. However, different hospital utilisation patterns and investigator decisions could bias clinical outcomes if no specific criteria are considered. Therefore, investigators should have clear criteria for determining variables that influence this measure.Keywords: COVID-19, outcome measures, non-hospitalized patients, monoclonal antibodies, antiviral agents
