TY - JOUR
T1 - Assessing clinically meaningful treatment effects in controlled trials
T2 - Chronic migraine as an example
AU - Dodick, David W.
AU - Turkel, Catherine C.
AU - Degryse, Ronald E.
AU - Diener, Hans Christoph
AU - Lipton, Richard B.
AU - Aurora, Sheena K.
AU - Nolan, Marissa E.
AU - Silberstein, Stephen D.
N1 - Funding Information:
The authors thank Allergan, Inc, for funding Imprint Publication Science, New York, NY, for providing support in formatting and editing of this manuscript.
Funding Information:
S.K.A. has received research support from Advanced Bionics , Allergan, Inc , Boston Scientific , eNeura , GlaxoSmithKline , MAP Pharmaceuticals, Inc , Merck , NuPathe, Inc , and the NIH ; has served as a consultant for Allergan, Arteaus Therapeutics, Merck, and eNeura; and has received honoraria from Merck, GlaxoSmithKline, Allergan, Inc, Nautilus, and Zogenix, Inc.
Funding Information:
H.C.D. received honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from Addex Pharma, Allergan, Almirall, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Boehringer Ingelheim, Bristol-Myers Squibb, Coherex, CoLucid, GlaxoSmithKline, Grünenthal, Janssen-Cilag, Lilly, La Roche, 3M Medica, Medtronic, Menerini, Minster, MSD, Neuroscore, Novartis, Johnson & Johnson, Pierre Fabre, Pfizer, Schaper and Brümmer, Sanofi, St. Jude, and Weber & Weber. He has received financial support for research projects from Allergan , Almirall , AstraZeneca , Bayer , GSK , Janssen-Cilag, MSD , and Pfizer . Headache research at the Department of Neurology in Essen is supported by the German Research Council (DFG), the German Ministry of Education and Research (BMBF), and the European Union. H.C.D. has no ownership interest and does not own stocks of any pharmaceutical company.
Funding Information:
R.B.L. receives research support from the NIH [ PO1 AG03949 (Program Director), RO1AG025119 (Investigator), RO1AG022374-06A2 (Investigator), RO1AG034119 (Investigator), RO1AG12101 (Investigator), K23AG030857 (Mentor), K23NS05140901A1 (Mentor), and K23NS47256 (Mentor), the National Headache Foundation , and the Migraine Research Fund ; serves on the editorial boards of Neurology and Cephalalgia and as senior advisor to Headache ; has reviewed for the NIA and NINDS; holds stock options in eNeura Therapeutics (a company without commercial products); and serves as consultant, advisory board member, or has received honoraria from Allergan, American Headache Society, Autonomic Technologies, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cognimed, Colucid, Eli Lilly, Endo, eNeura Therapeutics, GlaxoSmithKline, MAP, Merck, Nautilus Neuroscience, Novartis, NuPathe, Pfizer, and Vedanta.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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. Perspective 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.
AB - 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. Perspective 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.
KW - Chronic migraine
KW - clinical meaningfulness
KW - onabotulinumtoxinA
KW - prophylactic treatment
KW - topiramate
UR - http://www.scopus.com/inward/record.url?scp=84922779487&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922779487&partnerID=8YFLogxK
U2 - 10.1016/j.jpain.2014.11.004
DO - 10.1016/j.jpain.2014.11.004
M3 - Article
C2 - 25464159
AN - SCOPUS:84922779487
VL - 16
SP - 164
EP - 175
JO - Journal of Pain
JF - Journal of Pain
SN - 1526-5900
IS - 2
ER -