Are we enrolling the right patients? A scoping review of external validity and generalizability of clinical trials in bloodstream infections.

Bloodstream infections Clinical trials External validity Generalizability Health equity

Journal

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
ISSN: 1469-0691
Titre abrégé: Clin Microbiol Infect
Pays: England
ID NLM: 9516420

Informations de publication

Date de publication:
24 Aug 2023
Historique:
received: 19 06 2023
revised: 15 08 2023
accepted: 20 08 2023
pubmed: 27 8 2023
medline: 27 8 2023
entrez: 26 8 2023
Statut: aheadofprint

Résumé

Having a representative population in randomized clinical trials (RCTs) improves external validity and generalizability of trial results. There are limited data examining differences between RCT-enrolled and real-world populations in bloodstream infections (BSI). We conducted a scoping review aiming to review studies assessing generalizability of BSI RCT populations, to identify sub-groups that have been systematically under-represented and to explore approaches to improve external validity of future RCTs. MEDLINE, Embase, and Cochrane Library databases were searched for terms related to external validity or generalizability, BSI, and clinical trials in papers published up to 1 August 2023. Studies comparing enrolled versus nonenrolled patients, or papers discussing external validity or generalizability in the context of BSI RCTs were included. Sixteen papers were included in the final review. Five compared RCT-enrolled and nonenrolled participants from the same source population. There were significant differences between the two groups in all studies, with nonenrolled patients having a greater comorbidity burden and consistently worse outcomes including mortality. We identified several barriers to improving generalizability of RCT populations and outlined potential approaches to reduce these barriers, such as alternative/simplified consent processes, streamlining eligibility criteria and follow-up procedures, quota-based sampling techniques, and ensuring diversity in site and study team selection. Study cohorts in BSI RCTs are not representative of the general BSI patient population. As we increasingly adopt large pragmatic trials in infectious diseases, it is important to recognize the importance of maximizing generalizability to ensure that our research findings are of direct relevance to our patients.

Sections du résumé

BACKGROUND BACKGROUND
Having a representative population in randomized clinical trials (RCTs) improves external validity and generalizability of trial results. There are limited data examining differences between RCT-enrolled and real-world populations in bloodstream infections (BSI).
OBJECTIVES OBJECTIVE
We conducted a scoping review aiming to review studies assessing generalizability of BSI RCT populations, to identify sub-groups that have been systematically under-represented and to explore approaches to improve external validity of future RCTs.
SOURCES METHODS
MEDLINE, Embase, and Cochrane Library databases were searched for terms related to external validity or generalizability, BSI, and clinical trials in papers published up to 1 August 2023. Studies comparing enrolled versus nonenrolled patients, or papers discussing external validity or generalizability in the context of BSI RCTs were included.
CONTENT BACKGROUND
Sixteen papers were included in the final review. Five compared RCT-enrolled and nonenrolled participants from the same source population. There were significant differences between the two groups in all studies, with nonenrolled patients having a greater comorbidity burden and consistently worse outcomes including mortality. We identified several barriers to improving generalizability of RCT populations and outlined potential approaches to reduce these barriers, such as alternative/simplified consent processes, streamlining eligibility criteria and follow-up procedures, quota-based sampling techniques, and ensuring diversity in site and study team selection.
IMPLICATIONS CONCLUSIONS
Study cohorts in BSI RCTs are not representative of the general BSI patient population. As we increasingly adopt large pragmatic trials in infectious diseases, it is important to recognize the importance of maximizing generalizability to ensure that our research findings are of direct relevance to our patients.

Identifiants

pubmed: 37633330
pii: S1198-743X(23)00402-0
doi: 10.1016/j.cmi.2023.08.019
pii:
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Auteurs

Sean W X Ong (SWX)

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia; Sunnybrook Health Sciences Centre, Toronto, Canada. Electronic address: s.ong@mail.utoronto.ca.

Steven Y C Tong (SYC)

Department of Infectious Diseases, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.

Nick Daneman (N)

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada; Sunnybrook Health Sciences Centre, Toronto, Canada.

Classifications MeSH