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Research paper
Use of clinical staging in amyotrophic lateral sclerosis for phase 3 clinical trials
  1. Rubika Balendra1,
  2. Ashley Jones1,
  3. Naheed Jivraj2,
  4. I Nick Steen3,
  5. Carolyn A Young4,
  6. Pamela J Shaw5,
  7. Martin R Turner6,
  8. P Nigel Leigh7,
  9. Ammar Al-Chalabi1,
  10. UK-MND LiCALS Study Group, Mito Target ALS Study Group
  1. 1King's College London, Institute of Psychiatry, Department of Clinical Neuroscience, London, UK
  2. 2Health Service and Population Research, Institute of Psychiatry, King's College London, London, UK
  3. 3Institute of Health and Safety, Newcastle University, Newcastle Upon Tyne, UK
  4. 4Walton Centre for Neurology & Neurosurgery, Liverpool, UK
  5. 5Academic Neurology Unit, Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
  6. 6Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK
  7. 7Brighton and Sussex Medical School, Trafford Centre for Biomedical Research, University of Sussex, Falmer, East Sussex, UK
  1. Correspondence to Professor Ammar Al-Chalabi, Department of Clinical Neuroscience, King's College London, London SE5 8AF, UK; ammar.al-chalabi{at}kcl.ac.uk

Abstract

Objectives The use of clinical staging in the fatal neurodegenerative disease amyotrophic lateral sclerosis would have value in optimising future therapeutic trials. We aimed to use previous clinical trial data to determine the length of time patients spend in each of four proposed stages, its range and transition patterns to subsequent stages.

Methods Using databases from two multicentre clinical trials, patients were retrospectively staged through the trial course. At each stage we assessed whether patients then progressed to an earlier, consecutive or later stage or death. Duration spent in each stage before progression to a later stage was calculated.

Results There were 725 patients. No patients moved to an earlier stage. More patients at stages 1, 2 and 3 progressed to the consecutive stage rather than skipping a stage. 59.3% of patients at Stage 1 progressed to Stage 2, 54.0% of patients at Stage 2 progressed to Stage 3, 42.3% of patients at Stage 3 progressed to Stage 4 and 47.0% of Stage 4 patients progressed to death. Transition times between stages had a median duration of 3 to 7 months for stages 2 to 4.

Discussion We have shown using trial data that transition times between stages are short. Use of stage duration as an endpoint might allow a shorter trial duration. We have shown face validity in this system as most patients progress through consecutive stages, and none revert to earlier stages. Furthermore, we have shown the system is reliable across populations and therefore has content validity.

  • ALS
  • MOTOR NEURON DISEASE
  • RANDOMISED TRIALS
  • QUALITY OF LIFE
  • NEUROMUSCULAR

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