A meta-research study of randomized controlled trials found infrequent and delayed availability of protocols

Christof Manuel Schönenberger; Alexandra Griessbach; Ala Taji Heravi; Dmitry Gryaznov; Viktoria L Gloy; Szimonetta Lohner; Katharina Klatte; Nilabh Ghosh; Hopin Lee; Anita Mansouri; Ioana R Marian; Ramon Saccilotto; Edris Nury; Jason W Busse; Belinda von Niederhäusern; Dominik Mertz; Anette Blümle; Ayodele Odutayo; Sally Hopewell; Benjamin Speich; Matthias Briel

doi:10.1016/j.jclinepi.2022.05.014

A meta-research study of randomized controlled trials found infrequent and delayed availability of protocols

J Clin Epidemiol. 2022 Sep:149:45-52. doi: 10.1016/j.jclinepi.2022.05.014. Epub 2022 May 30.

Authors

Christof Manuel Schönenberger¹, Alexandra Griessbach², Ala Taji Heravi², Dmitry Gryaznov², Viktoria L Gloy², Szimonetta Lohner³, Katharina Klatte², Nilabh Ghosh², Hopin Lee⁴, Anita Mansouri⁴, Ioana R Marian⁴, Ramon Saccilotto⁵, Edris Nury⁶, Jason W Busse⁷, Belinda von Niederhäusern⁸, Dominik Mertz⁹, Anette Blümle¹⁰, Ayodele Odutayo¹¹, Sally Hopewell⁴, Benjamin Speich¹², Matthias Briel¹³

Affiliations

¹ Meta-Research Centre, Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland. Electronic address: [email protected].
² Meta-Research Centre, Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland.
³ Cochrane Hungary, Clinical Centre of the University of Pécs, Medical School, University of Pécs, Pécs, Hungary; Department of Public Health Medicine, Medical School, University of Pécs, Pécs, Hungary.
⁴ Oxford Clinical Trials Research Unit/Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
⁵ Clinical Trial Unit, Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland.
⁶ Institute for Evidence in Medicine (for Cochrane Germany Foundation), Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany; Department of General Practice and Primary Care, Medical Center Hamburg-Eppendorf - UKE, Hamburg, Germany.
⁷ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada; Department of Anesthesia, McMaster University, Hamilton, Canada.
⁸ Roche Pharma AG, Grenzach-Wyhlen, Germany.
⁹ Department of Medicine, McMaster University, Hamilton, Canada.
¹⁰ Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
¹¹ Oxford Clinical Trials Research Unit/Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; Department of Anesthesia, McMaster University, Hamilton, Canada.
¹² Meta-Research Centre, Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland; Oxford Clinical Trials Research Unit/Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
¹³ Meta-Research Centre, Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.

PMID: 35654268
DOI: 10.1016/j.jclinepi.2022.05.014

Abstract

Objectives: Availability of randomized controlled trial (RCT) protocols is essential for the interpretation of trial results and research transparency.

Study design and setting: In this study, we determined the availability of RCT protocols approved in Switzerland, Canada, Germany, and the United Kingdom in 2012. For these RCTs, we searched PubMed, Google Scholar, Scopus, and trial registries for publicly available protocols and corresponding full-text publications of results. We determined the proportion of RCTs with (1) publicly available protocols, (2) publications citing the protocol, and (3) registries providing a link to the protocol. A multivariable logistic regression model explored factors associated with protocol availability.

Results: Three hundred twenty-six RCTs were included, of which 118 (36.2%) made their protocol publicly available; 56 (47.6% 56 of 118) provided as a peer-reviewed publication and 48 (40.7%, 48 of 118) provided as supplementary material. A total of 90.9% (100 of 110) of the protocols were cited in the main publication, and 55.9% (66 of 118) were linked in the clinical trial registry. Larger sample size (>500; odds ratio [OR] = 5.90, 95% confidence interval [CI], 2.75-13.31) and investigator sponsorship (OR = 1.99, 95% CI, 1.11-3.59) were associated with increased protocol availability. Most protocols were made available shortly before the publication of the main results.

Conclusion: RCT protocols should be made available at an early stage of the trial.

Keywords: Meta-research; Protocol publication; Randomized controlled trials; Transparency; Trial protocols; Trial registration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Germany
Humans
Odds Ratio
Randomized Controlled Trials as Topic
Registries
Research Personnel*
Sample Size