Rationale and design of repeated cross-sectional studies to evaluate the reporting quality of trial protocols: the Adherence to SPIrit REcommendations (ASPIRE) study and associated projects
Dmitry Gryaznov,
Ayodele Odutayo,
Belinda von Niederhäusern,
Benjamin Speich,
Benjamin Kasenda,
Elena Ojeda-Ruiz,
Anette Blümle,
Stefan Schandelmaier,
Dominik Mertz,
Yuki Tomonaga,
Alain Amstutz,
Christiane Pauli-Magnus,
Viktoria Gloy,
Karin Bischoff,
Katharina Wollmann,
Laura Rehner,
Szimonetta Lohner,
Joerg J. Meerpohl,
Alain Nordmann,
Katharina Klatte,
Nilabh Ghosh,
Ala Taji Heravi,
Jacqueline Wong,
Ngai Chow,
Patrick Jiho Hong,
Kimberly Mc Cord,
Sirintip Sricharoenchai,
Jason W. Busse,
Arnav Agarwal,
Ramon Saccilotto,
Matthias Schwenkglenks,
Giusi Moffa,
Lars G. Hemkens,
Sally Hopewell,
Erik von Elm,
Matthias Briel
Affiliations
Dmitry Gryaznov
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Ayodele Odutayo
Applied Health Research Centre, Li Ka Shing Knowledge Instiute of St Michael’s Hospital
Belinda von Niederhäusern
Department of Clinical Research, Clinical Trial Unit, University Hospital Basel and University of Basel
Benjamin Speich
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Benjamin Kasenda
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Elena Ojeda-Ruiz
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Anette Blümle
Institute for Evidence in Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg
Stefan Schandelmaier
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Dominik Mertz
Department of Health Research Methods, Evidence, and Impact, McMaster University
Yuki Tomonaga
Epidemiology, Biostatistics and Prevention Institute, University of Zurich
Alain Amstutz
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Christiane Pauli-Magnus
Department of Clinical Research, Clinical Trial Unit, University Hospital Basel and University of Basel
Viktoria Gloy
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Karin Bischoff
Institute for Evidence in Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg
Katharina Wollmann
Institute for Evidence in Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg
Laura Rehner
Institute for Evidence in Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg
Szimonetta Lohner
Cochrane Hungary, Clinical Centre of the University of Pécs, Medical School, University of Pécs
Joerg J. Meerpohl
Institute for Evidence in Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg
Alain Nordmann
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Katharina Klatte
Department of Clinical Research, Clinical Trial Unit, University Hospital Basel and University of Basel
Nilabh Ghosh
Department of Neurosurgery and Department of Biomedicine, University Hospital Basel, University of Basel
Ala Taji Heravi
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Jacqueline Wong
Department of Health Research Methods, Evidence, and Impact, McMaster University
Ngai Chow
Department of Health Research Methods, Evidence, and Impact, McMaster University
Patrick Jiho Hong
Department of Health Research Methods, Evidence, and Impact, McMaster University
Kimberly Mc Cord
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Sirintip Sricharoenchai
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Jason W. Busse
Department of Health Research Methods, Evidence, and Impact, McMaster University
Arnav Agarwal
Department of Health Research Methods, Evidence, and Impact, McMaster University
Ramon Saccilotto
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Matthias Schwenkglenks
Epidemiology, Biostatistics and Prevention Institute, University of Zurich
Giusi Moffa
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Lars G. Hemkens
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Sally Hopewell
Oxford Clinical Trials Research Unit and Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford
Erik von Elm
Cochrane Switzerland, Centre for Primary Care and Public Health (Unisanté), University of Lausanne
Matthias Briel
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel and University of Basel
Abstract Background Clearly structured and comprehensive protocols are an essential component to ensure safety of participants, data validity, successful conduct, and credibility of results of randomized clinical trials (RCTs). Funding agencies, research ethics committees (RECs), regulatory agencies, medical journals, systematic reviewers, and other stakeholders rely on protocols to appraise the conduct and reporting of RCTs. In response to evidence of poor protocol quality, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline was published in 2013 to improve the accuracy and completeness of clinical trial protocols. The impact of these recommendations on protocol completeness and associations between protocol completeness and successful RCT conduct and publication remain uncertain. Objectives and methods Aims of the Adherence to SPIrit REcommendations (ASPIRE) study are to investigate adherence to SPIRIT checklist items of RCT protocols approved by RECs in the UK, Switzerland, Germany, and Canada before (2012) and after (2016) the publication of the SPIRIT guidelines; determine protocol features associated with non-adherence to SPIRIT checklist items; and assess potential differences in adherence across countries. We assembled an international cohort of RCTs based on 450 protocols approved in 2012 and 402 protocols approved in 2016 by RECs in Switzerland, the UK, Germany, and Canada. We will extract data on RCT characteristics and adherence to SPIRIT for all included protocols. We will use multivariable regression models to investigate temporal changes in SPIRIT adherence, differences across countries, and associations between SPIRIT adherence of protocols with RCT registration, completion, and publication of results. We plan substudies to examine the registration, premature discontinuation, and non-publication of RCTs; the use of patient-reported outcomes in RCT protocols; SPIRIT adherence of RCT protocols with non-regulated interventions; the planning of RCT subgroup analyses; and the use of routinely collected data for RCTs. Discussion The ASPIRE study and associated substudies will provide important information on the impact of measures to improve the reporting of RCT protocols and on multiple aspects of RCT design, trial registration, premature discontinuation, and non-publication of RCTs observing potential changes over time.
