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Feasibility of Comparative Health Research Outcome of Novel Surgery in prostate cancer (IP4-CHRONOS): statistical analysis plan for the randomised feasibility phase of the CHRONOS study

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Emily Day, A. Toby Prevost, Matthew R. Sydes, Deepika Reddy, Taimur T. Shah, Mathias Winkler, Tim Dudderidge, John Staffurth, Stuart McCracken, Vincent Khoo, Puja Jadav, Natalia Klimowska-Nassar, Thiagarajah Sasikaran, Hashim U. Ahmed, Francesca Fiorentino

Original languageEnglish
Article number547
JournalTrials
Volume22
Issue number1
DOIs
PublishedDec 2021

Bibliographical note

Funding Information: TTS receives funding from Prostate Cancer UK and the St Peters Trust for clinical research and has received funding for conference attendance from Astellas, Ferring and Galil Medical. Funding Information: HA’s research is supported by core funding from the United Kingdom’s National Institute of Health Research (NIHR) Imperial Biomedical Research Centre. HA currently receives funding from the Wellcome Trust, Medical Research Council (UK), Cancer Research UK, Prostate Cancer UK, The Urology Foundation, BMA Foundation, Imperial Health Charity, NIHR Imperial BRC, Sonacare Inc., Trod Medical and Sophiris Biocorp for trials in prostate cancer. HA is a paid medical consultant for Sophiris Biocorp and Sonacare Inc. HA is a proctor for cryotherapy and HIFU and paid for training other surgeons in these procedures. HA is paid proctor for Rezum for the treatment of benign prostate hyperplasia. Funding Information: MRS reports grants and non-financial support outside the submitted work from Astellas, grants from Clovis Oncology, grants and non-financial support from Janssen, grants and non-financial support from Novartis, grants and non-financial support from Pfizer, grants and non-financial support from Sanofi and personal fees from Lilly Oncology and personal fees from Janssen all outside the submitted work. Funding Information: IP4-CHRONOS pilot is funded by Prostate Cancer UK (Award number RIA17-ST2-012). Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Background: Randomised controlled trials (RCTs) for surgical interventions have often proven difficult with calls for innovative approaches. The Imperial Prostate (IP4) Comparative Health Research Outcomes of Novel Surgery in prostate cancer (IP4-CHRONOS) study aims to deliver level 1 evidence on outcomes following focal therapy which involves treating just the tumour rather than whole-gland surgery or radiotherapy. Our aim is to test the feasibility of two parallel RCTs within an overarching strategy that fits with existing patient and physician equipoise and maximises the chances of success and potential benefit to patients and healthcare services. Methods and design: IP4-CHRONOS is a randomised, unblinded multi-centre study, including two parallel randomised controlled trials targeting the same patient population: IP4-CHRONOS-A and IP4-CHRONOS-B. IP4-CHRONOS-A is a 1:1 RCT and the other is a multi-arm, multi-stage (MAMS) RCT starting with three arms and a 1:1:1 randomisation. The two linked RCTs are discussed with patients at the time of consent and the choice of A or B is dependent on physician and patient equipoise. The primary outcome is the feasibility of recruitment, acceptance of randomisation and compliance to allocated arm. Results: This paper describes the statistical analysis plan (SAP) for the feasibility study within IP4-CHRONOS given its innovative approach. Version 1.0 of the SAP has been reviewed by the Trial Steering Committee (TSC), Chief Investigator (CI), Senior Statistician and Trial Statistician and signed off. The study is ongoing and recruiting. Recruitment is scheduled to finish later in 2021. The SAP documents approved methods and analyses that will be conducted. Since this is written in advance of the analysis, we avoid bias arising from prior knowledge of the study data and findings. Discussion: Our feasibility analysis will demonstrate if IP4-CHRONOS is feasible in terms of recruitment, randomisation and compliance, and whether to continue both A and B or just one to the main stage. Trial registration: ISRCTN ISRCTN17796995. Registered on 08 October 2019

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