title: The challenge of comorbidity in clinical trials for multiple sclerosis.
abstract: OBJECTIVE
  We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS).
  
  
  METHODS
  We held an international workshop, informed by a systematic review of the incidence and prevalence of comorbidity in MS and an international survey about research priorities for studying comorbidity including their relation to clinical trials in MS.
  
  
  RESULTS
  We recommend establishing age- and sex-specific incidence estimates for comorbidities in the MS population, including those that commonly raise concern in clinical trials of immunomodulatory agents; shifting phase III clinical trials of new therapies from explanatory to more pragmatic trials; describing comorbidity status of the enrolled population in publications reporting clinical trials; evaluating treatment response, tolerability, and safety in clinical trials according to comorbidity status; and considering comorbidity status in the design of pharmacovigilance strategies.
  
  
  CONCLUSIONS
  Our recommendations will help address knowledge gaps regarding comorbidity that interfere with the ability to interpret safety in monitored trials and will enhance the generalizability of findings from clinical trials to "real world" settings where the MS population commonly has comorbid conditions.
authors.affiliation: From the Departments of Internal Medicine (R.A.M.) and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; Icahn School of Medicine at Mount Sinai (A.M.), New York, NY; Biostatistic Unit (M.P.S.), Department of Health Sciences, University of Genova, Italy; Faculty of Brain Sciences (A.T.), University College London, UK; University of California San Francisco (E.W.); Department of Basic Medical Sciences, Neurosciences and Sense Organs (M.T.), University of Bari, Italy; St. Michael's Hospital (P.O.), Toronto, Canada; Scientific and Clinical Review Associates, LLC (S.R.), Salisbury, CT; and Mellen Center for MS Treatment and Research (J.A.C.), Cleveland Clinic, OH. rmarrie@hsc.mb.ca.
authors.forename: Ruth Ann
authors.initials: RA
authors.lastname: Marrie
authors.affiliation: From the Departments of Internal Medicine (R.A.M.) and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; Icahn School of Medicine at Mount Sinai (A.M.), New York, NY; Biostatistic Unit (M.P.S.), Department of Health Sciences, University of Genova, Italy; Faculty of Brain Sciences (A.T.), University College London, UK; University of California San Francisco (E.W.); Department of Basic Medical Sciences, Neurosciences and Sense Organs (M.T.), University of Bari, Italy; St. Michael's Hospital (P.O.), Toronto, Canada; Scientific and Clinical Review Associates, LLC (S.R.), Salisbury, CT; and Mellen Center for MS Treatment and Research (J.A.C.), Cleveland Clinic, OH.
authors.forename: Aaron
authors.initials: A
authors.lastname: Miller
authors.affiliation: From the Departments of Internal Medicine (R.A.M.) and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; Icahn School of Medicine at Mount Sinai (A.M.), New York, NY; Biostatistic Unit (M.P.S.), Department of Health Sciences, University of Genova, Italy; Faculty of Brain Sciences (A.T.), University College London, UK; University of California San Francisco (E.W.); Department of Basic Medical Sciences, Neurosciences and Sense Organs (M.T.), University of Bari, Italy; St. Michael's Hospital (P.O.), Toronto, Canada; Scientific and Clinical Review Associates, LLC (S.R.), Salisbury, CT; and Mellen Center for MS Treatment and Research (J.A.C.), Cleveland Clinic, OH.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.affiliation: From the Departments of Internal Medicine (R.A.M.) and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; Icahn School of Medicine at Mount Sinai (A.M.), New York, NY; Biostatistic Unit (M.P.S.), Department of Health Sciences, University of Genova, Italy; Faculty of Brain Sciences (A.T.), University College London, UK; University of California San Francisco (E.W.); Department of Basic Medical Sciences, Neurosciences and Sense Organs (M.T.), University of Bari, Italy; St. Michael's Hospital (P.O.), Toronto, Canada; Scientific and Clinical Review Associates, LLC (S.R.), Salisbury, CT; and Mellen Center for MS Treatment and Research (J.A.C.), Cleveland Clinic, OH.
authors.forename: Alan
authors.initials: A
authors.lastname: Thompson
authors.affiliation: From the Departments of Internal Medicine (R.A.M.) and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; Icahn School of Medicine at Mount Sinai (A.M.), New York, NY; Biostatistic Unit (M.P.S.), Department of Health Sciences, University of Genova, Italy; Faculty of Brain Sciences (A.T.), University College London, UK; University of California San Francisco (E.W.); Department of Basic Medical Sciences, Neurosciences and Sense Organs (M.T.), University of Bari, Italy; St. Michael's Hospital (P.O.), Toronto, Canada; Scientific and Clinical Review Associates, LLC (S.R.), Salisbury, CT; and Mellen Center for MS Treatment and Research (J.A.C.), Cleveland Clinic, OH.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Waubant
authors.affiliation: From the Departments of Internal Medicine (R.A.M.) and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; Icahn School of Medicine at Mount Sinai (A.M.), New York, NY; Biostatistic Unit (M.P.S.), Department of Health Sciences, University of Genova, Italy; Faculty of Brain Sciences (A.T.), University College London, UK; University of California San Francisco (E.W.); Department of Basic Medical Sciences, Neurosciences and Sense Organs (M.T.), University of Bari, Italy; St. Michael's Hospital (P.O.), Toronto, Canada; Scientific and Clinical Review Associates, LLC (S.R.), Salisbury, CT; and Mellen Center for MS Treatment and Research (J.A.C.), Cleveland Clinic, OH.
authors.forename: Maria
authors.initials: M
authors.lastname: Trojano
authors.affiliation: From the Departments of Internal Medicine (R.A.M.) and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; Icahn School of Medicine at Mount Sinai (A.M.), New York, NY; Biostatistic Unit (M.P.S.), Department of Health Sciences, University of Genova, Italy; Faculty of Brain Sciences (A.T.), University College London, UK; University of California San Francisco (E.W.); Department of Basic Medical Sciences, Neurosciences and Sense Organs (M.T.), University of Bari, Italy; St. Michael's Hospital (P.O.), Toronto, Canada; Scientific and Clinical Review Associates, LLC (S.R.), Salisbury, CT; and Mellen Center for MS Treatment and Research (J.A.C.), Cleveland Clinic, OH.
authors.forename: Paul
authors.initials: P
authors.lastname: O'Connor
authors.affiliation: From the Departments of Internal Medicine (R.A.M.) and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; Icahn School of Medicine at Mount Sinai (A.M.), New York, NY; Biostatistic Unit (M.P.S.), Department of Health Sciences, University of Genova, Italy; Faculty of Brain Sciences (A.T.), University College London, UK; University of California San Francisco (E.W.); Department of Basic Medical Sciences, Neurosciences and Sense Organs (M.T.), University of Bari, Italy; St. Michael's Hospital (P.O.), Toronto, Canada; Scientific and Clinical Review Associates, LLC (S.R.), Salisbury, CT; and Mellen Center for MS Treatment and Research (J.A.C.), Cleveland Clinic, OH.
authors.forename: Stephen
authors.initials: S
authors.lastname: Reingold
authors.affiliation: From the Departments of Internal Medicine (R.A.M.) and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; Icahn School of Medicine at Mount Sinai (A.M.), New York, NY; Biostatistic Unit (M.P.S.), Department of Health Sciences, University of Genova, Italy; Faculty of Brain Sciences (A.T.), University College London, UK; University of California San Francisco (E.W.); Department of Basic Medical Sciences, Neurosciences and Sense Organs (M.T.), University of Bari, Italy; St. Michael's Hospital (P.O.), Toronto, Canada; Scientific and Clinical Review Associates, LLC (S.R.), Salisbury, CT; and Mellen Center for MS Treatment and Research (J.A.C.), Cleveland Clinic, OH.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Cohen
mesh_terms: D002986:Clinical Trials as Topic / Q000941:ethics / Q000379:methods; D015897:Comorbidity; D006801:Humans; D009103:Multiple Sclerosis / Q000150:complications / Q000453:epidemiology* / Q000628:therapy*