How Generalizable Are Randomized Controlled Trials (RCTs) in Staphylococcus aureus Bacteremia? A Description of the Mortality Gap Between RCTs and Observational Studies.

In Staphylococcus aureus bacteremia, mortality rates in randomized controlled trials (RCTs) are consistently lower than observational studies. Stringent eligibility criteria and omission of early deaths in RCTs contribute to this mortality gap. Clinicians should acknowledge the possibility of a lower treatment effect when applying RCT results to bedside care.
Competing Interests: Potential conflicts of interest. M. P. C. reports grants from McGill Interdisciplinary Initiative in Infection and Immunity and grants from Canadian Institutes of Health Research during the conduct of the study; personal fees from GEn1E Lifesciences (as a member of the scientific advisory board) and personal fees from nplex biosciences (as a member of the scientific advisory board) and consulting fees from Astra Zaneca outside the submitted work. He is the co-founder of Kanvas Biosciences and owns equity in the company. In addition, M. P. C. has a patent Methods for detecting tissue damage, graft versus host disease, and infections using cell-free DNA profiling pending (Cornell Reference number 9401-01-US), and a patent Methods for assessing the severity and progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections using cell-free DNA pending (Cornell Reference number 9561-01-US) and rapid identification of antimicrobial resistance and other microbial phenotypes using highly multiplexed fluorescence in situ hybridization (Cooley Reference: BEEB-001/00US 342794-2002). T. C. L. and E. G. M. receive research salary support from the Fonds de recherche du Québec – Santé. M. L. reports having served on advisory boards for Sanofi, Pfizer, Medicago, Merck, Seqirus, Paladin Labs; Pan Data Safety, and Monitoring Committees for Medicago, CanSino biologics, National Institutes of Health (NIH), the World Health Organization (WHO) EML Antibiotic Working Group. E. G. M. reports being co-investigator on the SNAP staph aureus platform trial CIHR outside of the submitted work. T. C. L. reports operating funds for other studies from Canadian Institutes of Health Research and McGill Interdisciplinary Institute Infection and Immunity. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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