title: Twin Peaks? No Evidence of Bimodal Distribution of Outcomes in Clinical Trials of Nonsurgical Interventions for Spinal Pain: An Exploratory Analysis.
abstract: The presence of bimodal outcome distributions has been used as a justification for conducting responder analyses, in addition to, or in place of analyses of the mean between-group difference, in clinical trials and systematic reviews of interventions for pain. The aim of this study was to investigate the distribution of participants' pain outcomes for evidence of bimodal distribution. We sourced data on participant outcomes from a convenience sample of 10 trials of nonsurgical interventions (exercise, manual therapy, medication) for spinal pain. We assessed normality using the Shapiro-Wilk test. When the Shapiro-Wilk test suggested non-normality we inspected distribution plots visually and attempted to classify them. To test whether responder analyses detected a meaningful number of additional patients experiencing substantial improvements we also calculated the risk difference and number needed to treat to benefit. We found no compelling evidence suggesting that outcomes were bimodally distributed for any of the intervention groups. Responder analysis would not meaningfully alter our interpretation of these data compared with the mean between group difference. Our findings suggest that bimodal distribution of outcomes should not be assumed in interventions for spinal pain and do not support the automatic prioritization of responder analysis over the between group difference in the evaluation of treatment effectiveness for pain.
  
  
  
  Secondary analysis of clinical trials of nonsurgical interventions for spinal pain found no evidence for bimodally distributed outcomes. The findings do not support the automatic prioritization of responder analyses over the average between group difference in the evaluation of treatment effectiveness for spinal pain.
authors.affiliation: Health Economics Research Group, Institute of Environment, Health and Societies, Department of Clinical Sciences, Brunel University London, Uxbridge, United Kingdom. Electronic address: neil.oconnell@brunel.ac.uk.
authors.forename: Neil E
authors.initials: NE
authors.lastname: O'Connell
authors.affiliation: The George Institute for Global Health, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kamper
authors.affiliation: The George Institute for Global Health, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Stevens
authors.affiliation: The George Institute for Global Health, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D005081:Exercise Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D017116:Low Back Pain / Q000628:therapy*; D008297:Male; D026201:Musculoskeletal Manipulations / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D020069:Shoulder Pain / Q000628:therapy*
chemical_list: D000700:Analgesics
keywords: Pain; clinical trials; effectiveness; systematic reviews