Design, analysis and reporting of multi-arm trials and strategies to address multiple testing.

Clinical Trials as Topic / methods Cohort Studies Humans Multilevel Analysis Research Design
Multi-arm trials multiple testing type I error type II error

Journal

International journal of epidemiology
ISSN: 1464-3685
Titre abrégé: Int J Epidemiol
Pays: England
ID NLM: 7802871

Informations de publication

Date de publication:
01 06 2020
Historique:
accepted: 31 01 2020
pubmed: 17 3 2020
medline: 30 3 2021
entrez: 17 3 2020
Statut: ppublish

Résumé

It is unclear how multiple treatment comparisons are managed in the analysis of multi-arm trials, particularly related to reducing type I (false positive) and type II errors (false negative). We conducted a cohort study of clinical-trial protocols that were approved by research ethics committees in the UK, Switzerland, Germany and Canada in 2012. We examined the use of multiple-testing procedures to control the overall type I error rate. We created a decision tool to determine the need for multiple-testing procedures. We compared the result of the decision tool to the analysis plan in the protocol. We also compared the pre-specified analysis plans in trial protocols to their publications. Sixty-four protocols for multi-arm trials were identified, of which 50 involved multiple testing. Nine of 50 trials (18%) used a single-step multiple-testing procedures such as a Bonferroni correction and 17 (38%) used an ordered sequence of primary comparisons to control the overall type I error. Based on our decision tool, 45 of 50 protocols (90%) required use of a multiple-testing procedure but only 28 of the 45 (62%) accounted for multiplicity in their analysis or provided a rationale if no multiple-testing procedure was used. We identified 32 protocol-publication pairs, of which 8 planned a global-comparison test and 20 planned a multiple-testing procedure in their trial protocol. However, four of these eight trials (50%) did not use the global-comparison test. Likewise, 3 of the 20 trials (15%) did not perform the multiple-testing procedure in the publication. The sample size of our study was small and we did not have access to statistical-analysis plans for the included trials in our study. Strategies to reduce type I and type II errors are inconsistently employed in multi-arm trials. Important analytical differences exist between planned analyses in clinical-trial protocols and subsequent publications, which may suggest selective reporting of analyses.

Sections du résumé

BACKGROUND
It is unclear how multiple treatment comparisons are managed in the analysis of multi-arm trials, particularly related to reducing type I (false positive) and type II errors (false negative).
METHODS
We conducted a cohort study of clinical-trial protocols that were approved by research ethics committees in the UK, Switzerland, Germany and Canada in 2012. We examined the use of multiple-testing procedures to control the overall type I error rate. We created a decision tool to determine the need for multiple-testing procedures. We compared the result of the decision tool to the analysis plan in the protocol. We also compared the pre-specified analysis plans in trial protocols to their publications.
RESULTS
Sixty-four protocols for multi-arm trials were identified, of which 50 involved multiple testing. Nine of 50 trials (18%) used a single-step multiple-testing procedures such as a Bonferroni correction and 17 (38%) used an ordered sequence of primary comparisons to control the overall type I error. Based on our decision tool, 45 of 50 protocols (90%) required use of a multiple-testing procedure but only 28 of the 45 (62%) accounted for multiplicity in their analysis or provided a rationale if no multiple-testing procedure was used. We identified 32 protocol-publication pairs, of which 8 planned a global-comparison test and 20 planned a multiple-testing procedure in their trial protocol. However, four of these eight trials (50%) did not use the global-comparison test. Likewise, 3 of the 20 trials (15%) did not perform the multiple-testing procedure in the publication. The sample size of our study was small and we did not have access to statistical-analysis plans for the included trials in our study.
CONCLUSIONS
Strategies to reduce type I and type II errors are inconsistently employed in multi-arm trials. Important analytical differences exist between planned analyses in clinical-trial protocols and subsequent publications, which may suggest selective reporting of analyses.

Identifiants

DOI: 10.1093/ije/dyaa026 PMID: 32176282
pubmed: 32176282
pii: 5807639
doi: 10.1093/ije/dyaa026
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

968-978

Informations de copyright

© The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Auteurs

Ayodele Odutayo (A)

Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada.

Dmitry Gryaznov (D)

Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland.

Bethan Copsey (B)

Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Paul Monk (P)

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Benjamin Speich (B)

Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland.

Corran Roberts (C)

Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Karan Vadher (K)

Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Peter Dutton (P)

Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Matthias Briel (M)

Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland.
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

Sally Hopewell (S)

Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Douglas G Altman (DG)

Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

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Classifications MeSH

questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études cliniques comme sujet › Essais cliniques comme sujet › Design, analysis and reporting of multi-arm...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Design, analysis and reporting of multi-arm...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Design, analysis and reporting of multi-arm...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse multiniveaux › Design, analysis and reporting of multi-arm...
questionsmedicales.fr › Disciplines des sciences naturelles › Science › Recherche › Plan de recherche › Design, analysis and reporting of multi-arm...