Estimands for factorial trials

Advanced search
Browse by:

Department | Year

UCL Theses | Latest

Deposit your research

Estimands for factorial trials

Kahan, Brennan C; Morris, Tim P; Goulão, Beatriz; Carpenter, James; (2022) Estimands for factorial trials. Statistics in Medicine 10.1002/sim.9510. (In press). Green open access

Preview

Text
Statistics in Medicine - 2022 - Kahan - Estimands for factorial trials.pdf - Published Version
Download (1MB) | Preview

Abstract

Factorial trials offer an efficient method to evaluate multiple interventions in a single trial, however the use of additional treatments can obscure research objectives, leading to inappropriate analytical methods and interpretation of results. We define a set of estimands for factorial trials, and describe a framework for applying these estimands, with the aim of clarifying trial objectives and ensuring appropriate primary and sensitivity analyses are chosen. This framework is intended for use in factorial trials where the intent is to conduct "two-trials-in-one" (ie, to separately evaluate the effects of treatments A and B), and is comprised of four steps: (i) specifying how additional treatment(s) (eg, treatment B) will be handled in the estimand, and how intercurrent events affecting the additional treatment(s) will be handled; (ii) designating the appropriate factorial estimator as the primary analysis strategy; (iii) evaluating the interaction to assess the plausibility of the assumptions underpinning the factorial estimator; and (iv) performing a sensitivity analysis using an appropriate multiarm estimator to evaluate to what extent departures from the underlying assumption of no interaction may affect results. We show that adjustment for other factors is necessary for noncollapsible effect measures (such as odds ratio), and through a trial re-analysis we find that failure to consider the estimand could lead to inappropriate interpretation of results. We conclude that careful use of the estimands framework clarifies research objectives and reduces the risk of misinterpretation of trial results, and should become a standard part of both the protocol and reporting of factorial trials.

Type:	Article
Title:	Estimands for factorial trials
Location:	England
Open access status:	An open access version is available from UCL Discovery
DOI:	10.1002/sim.9510
Publisher version:	https://doi.org/10.1002/sim.9510
Language:	English
Additional information:	© 2022 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/)
Keywords:	2 × 2, ICH-E9 addendum, estimand, factorial trial, randomized controlled trial
UCL classification:	UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI:	https://discovery.ucl.ac.uk/id/eprint/10150985