TY - JOUR
T1 - COVID-19 and the Physio4FMD trial: Impact, mitigating strategies and analysis plans
AU - Marston, Louise
AU - Le Novere, Marie
AU - Ricciardi, Federico
AU - Nazareth, Irwin
AU - Carson, Alan
AU - Edwards, Mark
AU - Goldstein, Laura
AU - Marsden, Jonathan
AU - Noble, Hayley
AU - Reuber, Markus
AU - Stone, Jon
AU - Hunter, Rachael
AU - Nielsen, Glenn
N1 - Funding Information:
This study is funded by the National Institute for Health and Care Research (NIHR) , Health Technology Assessment Programme (project reference 16/31/63 ) – A randomised controlled trial of specialist physiotherapy for functional motor disorder (Physio4FMD). Funding has been further granted by the NIHR HTA for a 22-month costed extension. This study also represents independent research (LHG) part-funded by the NIHR Maudsley Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King's College London . The views expressed are those of the authors and not necessarily those of the NIHR, NHS or the Department of Health and Social Care.
Funding Information:
The decisions regarding how to mitigate the impact of COVID-19 was given substantial consideration. We sought external advice from an expert group of statisticians, the Data Monitoring and Ethics Committee, the Trial Steering Committee, the funder (NIHR) and patient and public representatives to ensure that with our plans we produced meaningful results while maintaining the integrity of the trial. The need to augment the sample size with additional participants was clear. However, how to handle the data from the trial participants affected by the fall out of the pandemic was less obvious. An important point for consideration was the interpretation of the principles of ITT analysis. We initially considered the conservative approach, that is, including all randomised participants in the primary analysis, regardless of whether COVID-19 prevented them from receiving timely treatment or not. In this scenario, the effect of being randomised to the intervention group would be diluted. The variance in the data is likely to increase and the probability of showing a difference between randomised groups will be diminished. The study would most likely be under powered and the trial results, regardless of statistical significance, would not be meaningful.This study is funded by the National Institute for Health and Care Research (NIHR), Health Technology Assessment Programme (project reference 16/31/63) – A randomised controlled trial of specialist physiotherapy for functional motor disorder (Physio4FMD). Funding has been further granted by the NIHR HTA for a 22-month costed extension. This study also represents independent research (LHG) part-funded by the NIHR Maudsley Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NIHR, NHS or the Department of Health and Social Care.
Publisher Copyright:
© 2023 The Authors
PY - 2023/3
Y1 - 2023/3
N2 - Introduction: Functional motor disorder (FMD) is a common cause of disabling neurological symptoms such as weakness and tremor. Physio4FMD is a pragmatic, multicentre single blind randomised controlled trial to evaluate effectiveness and cost effectiveness of specialist physiotherapy for FMD. Like many other studies this trial was affected by the COVID-19 pandemic. Methods: The planned statistical and health economics analyses for this trial are described, as well as the sensitivity analyses designed to assess the disruption caused by COVID-19. The trial treatment of at least 89 participants (33%) was disrupted due to the pandemic. To account for this, we have extended the trial to increase the sample size. We have identified four groups based on how participants’ involvement in Physio4FMD was affected; A: 25 were unaffected; B: 134 received their trial treatment before the start of the COVID-19 pandemic and were followed up during the pandemic; C: 89 were recruited in early 2020 and had not received any randomised treatment before clinical services closed because of COVID-19; D: 88 participants were recruited after the trial was restarted in July 2021. The primary analysis will involve groups A, B and D. Regression analysis will be used to assess treatment effectiveness. We will conduct descriptive analyses for each of the groups identified and sensitivity regression analyses with participants from all groups, including group C, separately. Discussion: The COVID-19 mitigation strategy and analysis plans are designed to maintain the integrity of the trial while providing meaningful results. Trial registration: ISRCTN56136713.
AB - Introduction: Functional motor disorder (FMD) is a common cause of disabling neurological symptoms such as weakness and tremor. Physio4FMD is a pragmatic, multicentre single blind randomised controlled trial to evaluate effectiveness and cost effectiveness of specialist physiotherapy for FMD. Like many other studies this trial was affected by the COVID-19 pandemic. Methods: The planned statistical and health economics analyses for this trial are described, as well as the sensitivity analyses designed to assess the disruption caused by COVID-19. The trial treatment of at least 89 participants (33%) was disrupted due to the pandemic. To account for this, we have extended the trial to increase the sample size. We have identified four groups based on how participants’ involvement in Physio4FMD was affected; A: 25 were unaffected; B: 134 received their trial treatment before the start of the COVID-19 pandemic and were followed up during the pandemic; C: 89 were recruited in early 2020 and had not received any randomised treatment before clinical services closed because of COVID-19; D: 88 participants were recruited after the trial was restarted in July 2021. The primary analysis will involve groups A, B and D. Regression analysis will be used to assess treatment effectiveness. We will conduct descriptive analyses for each of the groups identified and sensitivity regression analyses with participants from all groups, including group C, separately. Discussion: The COVID-19 mitigation strategy and analysis plans are designed to maintain the integrity of the trial while providing meaningful results. Trial registration: ISRCTN56136713.
UR - http://www.scopus.com/inward/record.url?scp=85150798560&partnerID=8YFLogxK
U2 - 10.1016/j.conctc.2023.101124
DO - 10.1016/j.conctc.2023.101124
M3 - Article
SN - 2451-8654
VL - 33
JO - Contemporary Clinical Trials Communications
JF - Contemporary Clinical Trials Communications
M1 - 101124
ER -