title: Assessing clinically meaningful treatment effects in controlled trials: chronic migraine as an example.
abstract: In addition to headache, persons with chronic migraine (CM) experience multiple symptoms, both ictal and interictal, that may contribute to their suffering. Translating clinical trial results into practice requires assessment of the results' clinical meaningfulness. When examining treatment benefit in this disabled patient population, multiple headache-symptom measures should be considered to fully reflect clinical relevance. Currently, only onabotulinumtoxinA is approved specifically for headache prophylaxis in adults with CM. Topiramate is the only other therapeutic agent with double-blind, placebo-controlled evidence in this population. Herein we evaluate the clinical meaningfulness of onabotulinumtoxinA and topiramate as headache prophylaxis in CM by comparing primary endpoints from the placebo-controlled, double-blind phase of the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program and the topiramate clinical trial (frequency of headache days [primary endpoint in PREEMPT; secondary in topiramate trial] and migraine/migrainous days [primary in topiramate trial, or "migraine/probable-migraine days"; secondary in PREEMPT]). Additionally, outcome measures such as responder rates, health-related quality of life, discontinuation rates, safety, and tolerability profiles are important clinical considerations. The clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate. These data support these treatments as meaningful headache prophylaxis in adults with CM.
  
  
  CONCLUSIONS
  CM is a chronic pain condition. We sought to determine the clinical relevance of recent trials in this disabled population. Clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate, and support use of these treatments as meaningful headache prophylaxis in CM.
authors.affiliation: Department of Neurology, Mayo Clinic Arizona, Phoenix, Arizona. Electronic address: dodick.david@mayo.edu.
authors.forename: David W
authors.initials: DW
authors.lastname: Dodick
authors.affiliation: Allergan, Inc, Irvine, California.
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Turkel
authors.affiliation: Allergan, Inc, Irvine, California.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: DeGryse
authors.affiliation: Department of Neurology and Stroke Center, University of Essen, Essen, Germany.
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Diener
authors.affiliation: Department of Neurology and the Montefiore Headache Center, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Lipton
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, California.
authors.forename: Sheena K
authors.initials: SK
authors.lastname: Aurora
authors.affiliation: Formerly of the Department of Medical Affairs, Imprint Publication Science, New York, New York.
authors.forename: Marissa E
authors.initials: ME
authors.lastname: Nolan
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Silberstein
mesh_terms: D000328:Adult; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D002908:Chronic Disease; D002986:Clinical Trials as Topic / Q000379:methods*; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000175:diagnosis / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D017063:Outcome Assessment, Health Care; D011788:Quality of Life; D013997:Time Factors; D000077236:Topiramate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018696:Neuroprotective Agents; D000077236:Topiramate; D005632:Fructose; D019274:Botulinum Toxins, Type A
keywords: Chronic migraine; clinical meaningfulness; onabotulinumtoxinA; prophylactic treatment; topiramate