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UKCTOCS update: applying insights of delayed effects in cancer screening trials to the long-term follow-up mortality analysis

Burnell, Matthew, Gentry-Maharaj, Aleksandra, Skates, Steven J., Ryan, Andy, Karpinskyj, Chloe, Kalsi, Jatinderpal, Apostolidou, Sophia, Singh, Naveena, Dawnay, Anne, Woolas, Robert, Fallowfield, Lesley, Campbell, Stuart, McGuire, Alistair, Jacobs, Ian J., Parmar, Mahesh and Menon, Usha (2021) UKCTOCS update: applying insights of delayed effects in cancer screening trials to the long-term follow-up mortality analysis. Trials, 22 (1). p. 173. ISSN 1745-6215

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Identification Number: 10.1186/s13063-021-05125-8


Background: During trials that span decades, new evidence including progress in statistical methodology, may require revision of original assumptions. An example is the continued use of a constant-effect approach to analyse the mortality reduction which is often delayed in cancer-screening trials. The latter led us to re-examine our approach for the upcoming primary mortality analysis (2020) of long-term follow-up of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (LTFU UKCTOCS), having initially (2014) used the proportional hazards (PH) Cox model. Methods: We wrote to 12 experts in statistics/epidemiology/screening trials, setting out current evidence, the importance of pre-specification, our previous mortality analysis (2014) and three possible choices for the follow-up analysis (2020) of the mortality outcome: (A) all data (2001–2020) using the Cox model (2014), (B) new data (2015–2020) only and (C) all data (2001–2020) using a test that allows for delayed effects. Results: Of 11 respondents, eight supported changing the 2014 approach to allow for a potential delayed effect (option C), suggesting various tests while three favoured retaining the Cox model (option A). Consequently, we opted for the Versatile test introduced in 2016 which maintains good power for early, constant or delayed effects. We retained the Royston-Parmar model to estimate absolute differences in disease-specific mortality at 5, 10, 15 and 18 years. Conclusions: The decision to alter the follow-up analysis for the primary outcome on the basis of new evidence and using new statistical methodology for long-term follow-up is novel and has implications beyond UKCTOCS. There is an urgent need for consensus building on how best to design, test, estimate and report mortality outcomes from long-term randomised cancer screening trials. Trial registration: ISRCTN22488978. Registered on 6 April 2000.

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Additional Information: Funding Information: The LTFU UKCTOCS is supported by National Institute for Health Research (NIHR HTA grant 16/46/01), Cancer Research UK (CRUK) and The Eve Appeal. UKCTOCS was funded by Medical Research Council (G9901012 and G0801228), CRUK (C1479/A2884), and the Department of Health, with additional support from The Eve Appeal. Researchers at UCL are supported by the NIHR University College London Hospitals (UCLH) Biomedical Research Centre and MRC CTU at UCL core funding (MR_UU_12023). Publisher Copyright: © 2021, The Author(s).
Divisions: Health Policy
Social Policy
Subjects: R Medicine > RA Public aspects of medicine
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Date Deposited: 18 Mar 2021 06:15
Last Modified: 21 Jun 2024 03:21

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