Article Text

Original research
A composite clinical motor score as a comprehensive and sensitive outcome measure for Parkinson’s disease
  1. Christine Lo1,2,
  2. Siddharth Arora3,4,
  3. Michael Lawton5,
  4. Thomas Barber1,
  5. Timothy Quinnell6,
  6. Gary J Dennis7,
  7. Yoav Ben-Shlomo5,
  8. Michele Tao-Ming Hu8
  1. 1 Department of Clinical Neurosciences, University of Oxford Nuffield, Oxford, UK
  2. 2 Department of Clinical Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
  3. 3 University of Oxford Somerville College, Oxford, UK
  4. 4 University of Oxford Said Business School, Oxford, UK
  5. 5 Population Health Sciences, University of Bristol, Bristol, UK
  6. 6 Papworth Hospital NHS Foundation Trust, Cambridge, UK
  7. 7 Department of Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
  8. 8 Division of Neurology, Nuffield Department of Clinical Neurosciences, Oxford, UK
  1. Correspondence to Dr Christine Lo, Department of Clinical Neurosciences, University of Oxford Nuffield, Oxford OX1 1NF, Oxfordshire, UK; christine.lo{at}nhs.net

Abstract

Background An unmet need remains for sensitive outcome measures in neuroprotective trials. The study aims to determine whether a composite clinical motor score, combining the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III motor examination score, Purdue Pegboard Test, and Timed Up and Go, provides greater sensitivity in detecting motor change in early disease than the MDS-UPDRS III alone.

Methods The Oxford Discovery longitudinal cohort study involves individuals with isolated rapid eye movement sleep behaviour disorder (iRBD) (n=272, confirmed polysomnographically, median follow-up: 1.6 years), idiopathic Parkinson’s disease (PD) (n=909, median follow-up: 3.5 years, baseline: <3.5 years disease duration) and controls (n=316, age-matched and sex-matched, without a first-degree family history of PD). Motor and non-motor assessments were performed at each in-person visit.

Results Compared with the MDS-UPDRS III, the composite clinical motor score demonstrated a wider score distribution in iRBD and controls, lower coefficient of variation (37% vs 67%), and higher correlation coefficients with self-reported measures of motor severity (0.65 vs 0.61) and overall health status (−0.40 vs −0.33). Greater score range in mild to moderate PD, higher magnitude of longitudinal change in iRBD and longitudinal score linearity suggest better sensitivity in detecting subtle motor change. The composite clinical motor score was more accurate than the MDS-UPDRS III in predicting clinical outcomes, requiring 64% fewer participants with PD and 51% fewer participants with iRBD in sample size estimations for a hypothetical 18-month placebo-controlled clinical trial.

Conclusion The composite clinical motor score may offer greater consistency and sensitivity in detecting change than the MDS-UPDRS III.

  • Parkinson's disease
  • sleep disorders

Data availability statement

Data are available upon reasonable request. Qualified investigators seeking access to de-identified participant data relating to the Oxford Discovery cohort may submit their request by means of a formal application to the OPDC Data Access Committee. The application form, protocol, and terms and conditions may be found at opdc.medsci.ox.ac.uk/external-collaborations.

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Data availability statement

Data are available upon reasonable request. Qualified investigators seeking access to de-identified participant data relating to the Oxford Discovery cohort may submit their request by means of a formal application to the OPDC Data Access Committee. The application form, protocol, and terms and conditions may be found at opdc.medsci.ox.ac.uk/external-collaborations.

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Footnotes

  • Contributors All authors have been involved in revising this manuscript critically for intellectual content and have read and approved the final version of the manuscript. The paper has not been previously published and is not under simultaneous consideration by another journal. MH accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.

  • Funding This study was funded by the Monument Trust Discovery Award from Parkinson’s UK (J-1403) and supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC).

  • Disclaimer The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The study sponsor had no role in the study design; in the collection, analysis and interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication.

  • Competing interests CL was funded by the NIHR Oxford BRC. TB was funded by the Wellcome Trust Doctoral Training Fellowship. TQ is currently a short term Consultant for Jazz Pharmaceuticals and a CI for an NIHR grant for a therapeutic trial in OSA.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.