Outcomes Evaluated in Controlled Clinical Trials on the Management of COVID-19: A Methodological Systematic Review
Alexander G. Mathioudakis,
Markus Fally,
Rola Hashad,
Ahmed Kouta,
Ali Sina Hadi,
Sean Blandin Knight,
Nawar Diar Bakerly,
Dave Singh,
Paula R. Williamson,
Tim Felton,
Jørgen Vestbo
Affiliations
Alexander G. Mathioudakis
Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester M23 9LT, UK
Markus Fally
Department of Internal Medicine, Section for Pulmonary Diseases, Herlev Gentofte Hospital, 2900 Hellerup, Denmark
Rola Hashad
Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester M23 9LT, UK
Ahmed Kouta
Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester M23 9LT, UK
Ali Sina Hadi
Department of Respiratory Medicine, Salford Royal Infirmary NHS Foundation Trust, Manchester M6 8HD, UK
Sean Blandin Knight
Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester M23 9LT, UK
Nawar Diar Bakerly
Department of Respiratory Medicine, Salford Royal Infirmary NHS Foundation Trust, Manchester M6 8HD, UK
Dave Singh
Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester M23 9LT, UK
Paula R. Williamson
MRC/NIHR Trials Methodology Research Partnership, Department of Health Data Science, University of Liverpool, Liverpool L69 3BX, UK
Tim Felton
Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester M23 9LT, UK
Jørgen Vestbo
Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester M23 9LT, UK
It is crucial that randomized controlled trials (RCTs) on the management of coronavirus disease 2019 (COVID-19) evaluate the outcomes that are critical to patients and clinicians, to facilitate relevance, interpretability, and comparability. This methodological systematic review describes the outcomes evaluated in 415 RCTs on the management of COVID-19, that were registered with ClinicalTrials.gov, by 5 May 2020, and the instruments used to measure these outcomes. Significant heterogeneity was observed in the selection of outcomes and instruments. Mortality, adverse events and treatment success or failure are only evaluated in 64.4%, 48.4% and 43% of the included studies, respectively, while other outcomes are selected less often. Studies focusing on more severe presentations (hospitalized patients or requiring intensive care) most frequently evaluate mortality (72.5%) and adverse events (55.6%), while hospital admission (50.8%) and viral detection/load (55.6%) are most frequently assessed in the community setting. Outcome measurement instruments are poorly reported and heterogeneous. Follow-up does not exceed one month in 64.3% of these earlier trials, and long-term COVID-19 burden is rarely assessed. The methodological issues identified could delay the introduction of potentially life-saving treatments in clinical practice. Our findings demonstrate the need for greater consistency, to enable decision makers to compare and contrast studies.
