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, 11. a173 1-12. ISSN 1745-6215

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Abstract

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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Sussex Health Outcomes Research & Education in Cancer (SHORE-C)
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 12 Feb 2021 08:33
Last Modified: 02 Mar 2021 14:30
URI: http://sro.sussex.ac.uk/id/eprint/97108

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