eprintid: 10205884
rev_number: 14
eprint_status: archive
userid: 699
dir: disk0/10/20/58/84
datestamp: 2025-03-11 10:29:55
lastmod: 2025-03-11 10:29:55
status_changed: 2025-03-11 10:29:55
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Marston, Louise
creators_name: Moncrieff, Joanna
creators_name: Priebe, Stefan
creators_name: Cro, Suzie
creators_name: Cornelius, Victoria R
title: Exploring the effect of COVID-19 restrictions on the Social Functioning Scale in a clinical trial of Antipsychotic Reduction: using multiple imputation to target a hypothetical estimand
ispublished: inpress
divisions: UCL
divisions: B02
divisions: D12
divisions: G20
keywords: COVID-19, estimands, missing data, multiple imputation, randomised controlled trial, social functioning
note: © The Author(s), 2025. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/
abstract: Objective:
Many trials are affected by unforeseen events after recruitment has commenced. The aim of this study is to explore a hypothetical strategy for dealing with an intercurrent event that occurred during trial follow-up; COVID-19 restrictions.//

Study Design and Setting:
Secondary analysis of a randomised controlled trial in schizophrenia, comparing antipsychotic reduction versus maintenance medication on the Social Functioning Scale (SFS) score at 12 months’ follow-up. A hypothetical analysis strategy was used to estimate the treatment effect in a COVID-19 restriction-free world. Outcome data were set to missing and multiple imputation was used to replace values affected by COVID-19.//
Results:
The trial randomised 253 participants, 187 participants had an SFS score at 12 months, 75 of those were collected during COVID-19 restrictions. In the original complete case regression analysis, targeting a treatment policy estimand, the treatment effect was estimated to be 0.51 (95%CI -1.33, 2.35) points higher in the reduction group. After multiple imputation, targeting the hypothetical estimand, the mean SFS score was -3.01 (95%CI -7.22, 1.20) points lower in the reduction group, but varied with different assumptions about the timing of events and in sensitivity analyses to increase the size of difference between randomised groups.//
Conclusion:
We demonstrated how the intervention effect can change when estimating the intervention effect in a pandemic world (treatment policy estimand) versus a pandemic restriction-free world (hypothetical estimand) and that estimates are sensitive to imputation and input assumptions. Trialists should be aware of potential intercurrent events and plan the analysis to take them into account.
date: 2025-03-06
date_type: published
publisher: Elsevier BV
official_url: https://doi.org/10.1016/j.jclinepi.2025.111753
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2368528
doi: 10.1016/j.jclinepi.2025.111753
pii: S0895-4356(25)00086-1
lyricists_name: Marston, Louise
lyricists_id: LMARS51
actors_name: Marston, Louise
actors_id: LMARS51
actors_role: owner
full_text_status: public
publication: Journal of Clinical Epidemiology
article_number: 111753
pagerange: 111753
event_location: United States
issn: 0895-4356
citation:        Marston, Louise;    Moncrieff, Joanna;    Priebe, Stefan;    Cro, Suzie;    Cornelius, Victoria R;      (2025)    Exploring the effect of COVID-19 restrictions on the Social Functioning Scale in a clinical trial of Antipsychotic Reduction: using multiple imputation to target a hypothetical estimand.                   Journal of Clinical Epidemiology      , Article 111753.  10.1016/j.jclinepi.2025.111753 <https://doi.org/10.1016/j.jclinepi.2025.111753>.    (In press).    Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10205884/7/Marston_1-s2.0-S0895435625000861-main.pdf
document_url: https://discovery.ucl.ac.uk/id/eprint/10205884/2/RADAR%20covid%20Appendices_17012025_clean.docx
document_url: https://discovery.ucl.ac.uk/id/eprint/10205884/3/Figure%201.docx