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
Authors: Gryaznov Dmitry , Odutayo Ayodele , von Niederhäusern Belinda , Speich Benjamin , Kasenda Benjamin , Ojeda-Ruiz Elena , Blümle Anette , Schandelmaier Stefan , Mertz Dominik , Tomonaga Yuki , Amstutz Alain , Pauli-Magnus Christiane , Gloy Viktoria , Bischoff Karin , Wollmann Katharina , Rehner Laura , Lohner Szimonetta , Meerpohl Joerg J. , Nordmann Alain , Klatte Katharina , Ghosh Nilabh , Heravi Ala Taji , Wong Jacqueline , Chow Ngai , Hong Patrick Jiho , Cord Kimberly Mc , Sricharoenchai Sirintip , Busse Jason W. , Agarwal Arnav , Saccilotto Ramon , Schwenkglenks Matthias , Moffa Giusi , Hemkens Lars G. , Hopewell Sally , von Elm Erik , Briel Matthias 
Published: October 2020

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.