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

Contemp Clin Trials Commun. 2023 Jun:33:101124. doi: 10.1016/j.conctc.2023.101124. Epub 2023 Mar 24.

Authors

Louise Marston^{1

2}, Marie Le Novere^{1

2}, Federico Ricciardi³, Irwin Nazareth^{1

2}, Alan Carson⁴, Mark Edwards⁵, Laura H Goldstein⁶, Jonathan Marsden⁷, Hayley Noble⁵, Markus Reuber⁸, Jon Stone⁴, Rachael M Hunter^{1

2}, Glenn Nielsen⁵

Affiliations

¹ Department of Primary Care and Population Health, UCL, London, UK.
² Priment Clinical Trials Unit, UCL, London, UK.
³ Department of Statistical Science, UCL, London, UK.
⁴ Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, Edinburgh, UK.
⁵ Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's, University of London, London, UK.
⁶ King's College London, Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, De Crespigny Park, London, UK.
⁷ School of Health Professions, University of Plymouth, Plymouth, UK.
⁸ Academic Neurology Unit, University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK.

Abstract

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.

Keywords: COVID-19; Clinical trial; Conversion disorder; Functional neurological disorder; Health economics; Physiotherapy; Randomised controlled trial; Statistics.