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UKCTOCS update: applying insights of delayed effects in cancer screening trials to the long-term follow-up mortality analysis
Version 2 2023-06-12, 09:44
Version 1 2023-06-09, 23:03
journal contribution
posted on 2023-06-12, 09:44 authored by Matthew Burnell, Aleksandra Gentry-Maharaj, Steven J Skates, Andy Ryan, Chloe Karpinskyj, Jatinderpal Kalsi, Sophia Apostolidou, Naveena Singh, Anne Dawnay, Robert Woolas, Lesley FallowfieldLesley Fallowfield, Stuart Campbell, Alistair McGuire, Ian J Jacobs, Mahesh Parmar, Usha MenonBackground 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.
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Publication status
- Published
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- Published version
Journal
TrialsISSN
1745-6215Publisher
BMCExternal DOI
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11Page range
1-12Article number
a173Department affiliated with
- Sussex Health Outcomes Research & Education in Cancer (SHORE-C) Publications
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- Yes
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- Yes
Legacy Posted Date
2021-02-12First Open Access (FOA) Date
2021-03-02First Compliant Deposit (FCD) Date
2021-02-11Usage metrics
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