COVID-19 and the Physio4FMD trial: Impact, mitigating strategies and analysis plans

Louise Marston; Marie Le novere; Federico Ricciardi; Irwin Nazareth; Alan Carson; Mark Edwards; Laura H. Goldstein; Jonathan Marsden; Hayley Noble; Markus Reuber; Jon Stone; Rachael M. Hunter; Glenn Nielsen

doi:10.1016/j.conctc.2023.101124

COVID-19 and the Physio4FMD trial: Impact, mitigating strategies and analysis plans

Louise Marston, Marie Le novere, Federico Ricciardi, Irwin Nazareth, Alan Carson, Mark Edwards, Laura H. Goldstein, Jonathan Marsden, Hayley Noble, Markus Reuber, Jon Stone, Rachael M. Hunter, Glenn Nielsen

Research output: Contribution to journal › Article › peer-review

Original language	English
Pages (from-to)	101124
Journal	Contemporary clinical trials communications
Volume	33
DOIs	https://doi.org/10.1016/j.conctc.2023.101124
Publication status	Published - 24 Mar 2023

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Marston, L., Le novere, M., Ricciardi, F., Nazareth, I., Carson, A., Edwards, M., Goldstein, L. H., Marsden, J., Noble, H., Reuber, M., Stone, J., Hunter, R. M., & Nielsen, G. (2023). COVID-19 and the Physio4FMD trial: Impact, mitigating strategies and analysis plans. Contemporary clinical trials communications, 33, 101124. https://doi.org/10.1016/j.conctc.2023.101124

@article{c0a51d5c1dd1402eb5c1ba44cfaf627a,

title = "COVID-19 and the Physio4FMD trial: Impact, mitigating strategies and analysis plans",

author = "Louise Marston and {Le novere}, Marie and Federico Ricciardi and Irwin Nazareth and Alan Carson and Mark Edwards and Goldstein, {Laura H.} and Jonathan Marsden and Hayley Noble and Markus Reuber and Jon Stone and Hunter, {Rachael M.} and Glenn Nielsen",

note = "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: {\textcopyright} 2023 The Authors",

year = "2023",

month = mar,

day = "24",

doi = "10.1016/j.conctc.2023.101124",

language = "English",

volume = "33",

pages = "101124",

journal = "Contemporary clinical trials communications",

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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 H.

AU - Marsden, Jonathan

AU - Noble, Hayley

AU - Reuber, Markus

AU - Stone, Jon

AU - Hunter, Rachael M.

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 - 2023/3/24

Y1 - 2023/3/24

U2 - 10.1016/j.conctc.2023.101124

DO - 10.1016/j.conctc.2023.101124

M3 - Article

SN - 2451-8654

VL - 33

SP - 101124

JO - Contemporary clinical trials communications

JF - Contemporary clinical trials communications

ER -