Evidence map›Paper›PMID 33648562›Full record

ArticleTrials2021

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

Matthew Burnell, Aleksandra Gentry-Maharaj, Steven J Skates, Andy Ryan, Chloe Karpinskyj, Jatinderpal Kalsi, Sophia Apostolidou, Naveena Singh, Anne Dawnay, Robert Woolas and 6 more

Abstract readLetter
PubMed Full text at PMC Publisher
In one paragraph

Article in Trials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Trial
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Matthew BurnellMRC CTU at UCL, Institute of Clinical Trials and Methodology, University College London, 90 High Holborn, 2nd Floor, London, WC1V 6LJ, UK.
Aleksandra Gentry-MaharajMRC CTU at UCL, Institute of Clinical Trials and Methodology, University College London, 90 High Holborn, 2nd Floor, London, WC1V 6LJ, UK.
Steven J SkatesMGH Biostatistics, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
Andy RyanMRC CTU at UCL, Institute of Clinical Trials and Methodology, University College London, 90 High Holborn, 2nd Floor, London, WC1V 6LJ, UK.
Chloe KarpinskyjMRC CTU at UCL, Institute of Clinical Trials and Methodology, University College London, 90 High Holborn, 2nd Floor, London, WC1V 6LJ, UK.
Jatinderpal KalsiDepartment of Women's Cancer, Institute for Women's Health, University College London, 84-86 Chenies Mews, London, WC1E 6HU, UK.
Sophia ApostolidouMRC CTU at UCL, Institute of Clinical Trials and Methodology, University College London, 90 High Holborn, 2nd Floor, London, WC1V 6LJ, UK.
Naveena SinghDepartment of Pathology, Barts Health National Health Service Trust, The Royal Hospital, Whitechapel Rd, London, E1 1BB, UK.
Anne DawnayDepartment of Clinical Biochemistry, Barts Health National Health Service Trust, Barts Health, 4th floor, Pathology and Pharmacy, 80 Newark St, London, E1 2ES, UK.
Robert WoolasDepartment of Gynaecological Oncology, Queen Alexandra Hospital, Cosham, Portsmouth, Hampshire, PO6 3LY, UK.
Lesley FallowfieldSussex Health Outcomes Research and Education in Cancer, Brighton and Sussex Medical School, University of Sussex, Science Park Road, Falmer, Brighton, BN1 9RX, UK.
Stuart CampbellCreate Health, 150 Cheapside, London, EC2V 6ET, UK.
Alistair McGuireDepartment of Social Policy, London School of Economics, Houghton Street, London, WC2A 2AE, UK.
Ian J JacobsDepartment of Women's Cancer, Institute for Women's Health, University College London, 84-86 Chenies Mews, London, WC1E 6HU, UK.
Mahesh ParmarMRC CTU at UCL, Institute of Clinical Trials and Methodology, University College London, 90 High Holborn, 2nd Floor, London, WC1V 6LJ, UK.
Usha MenonMRC CTU at UCL, Institute of Clinical Trials and Methodology, University College London, 90 High Holborn, 2nd Floor, London, WC1V 6LJ, UK. u.menon@ucl.ac.uk.ORCID http://orcid.org/0000-0003-3708-1732

Funding

Cancer Research UK C1479/A2884Department of Health 16/46/01Medical Research Council G0801228Medical Research Council G9901012Medical Research Council G9901012 and G0801228Medical Research Council MC_UU_12023/29
6 · The paper itself

Abstract

backgroundDuring 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.

methodsWe 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.

resultsOf 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.

conclusionsThe 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 registrationISRCTN22488978 . Registered on 6 April 2000.

Indexed as

Early Detection of CancerOvarian NeoplasmsFemaleFollow-Up StudiesHumansProportional Hazards ModelsUnited KingdomCancer screeningDelayed effectFollow-upMortality analysisOvarian cancerUKCTOCS

Identifiers

PMID33648562
PMCPMC7919310

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.