Interpreting the clinical importance of group differences in chronic pain clinical trials: IMMPACT recommendations.
An essential component of the interpretation of results of randomized clinical trials of treatments for chronic pain involves the determination of their clinical importance or meaningfulness. This involves two distinct processes--interpreting the clinical importance of individual patient improvements and the clinical importance of group differences--which are frequently misunderstood. In this article, we first describe the essential differences between the interpretation of the clinical importance of patient improvements and of group differences. We then discuss the factors to consider when evaluating the clinical importance of group differences, which include the results of responder analyses of the primary outcome measure, the treatment effect size compared to available therapies, analyses of secondary efficacy endpoints, the safety and tolerability of treatment, the rapidity of onset and durability of the treatment benefit, convenience, cost, limitations of existing treatments, and other factors. The clinical importance of individual patient improvements can be determined by assessing what patients themselves consider meaningful improvement using well-described methods. In contrast, the clinical meaningfulness of group differences must be determined by a multi-factorial evaluation of the benefits and risks of the treatment and of other available treatments for the condition in light of the primary goals of therapy. Such determinations must be conducted on a case-by-case basis, and are ideally informed by patients and their significant others, clinicians, researchers, statisticians, and representatives of society at large.
Dworkin
Robert H
RH
Departments of Anesthesiology and Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA Department of Anesthesiology, University of Washington, Seattle, WA, USA Departments of Biostatistics and Computational Biology and Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA United States Food and Drug Administration, Bethesda, MD, USA American Chronic Pain Association, Rocklin, CA, USA Department of Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA Johnson & Johnson Pharmaceutical Research & Development LLC, Raritan, NJ, USA Faculdade de Medicina de Lisboa, Portugal.
Turk
Dennis C
DC
McDermott
Michael P
MP
Peirce-Sandner
Sarah
S
Burke
Laurie B
LB
Cowan
Penney
P
Farrar
John T
JT
Hertz
Sharon
S
Raja
Srinivasa N
SN
Rappaport
Bob A
BA
Rauschkolb
Christine
C
Sampaio
Cristina
C
D000700:Analgesics / Q000009:adverse effects / Q000627:therapeutic use; D002908:Chronic Disease; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D017408:Guidelines as Topic; D006801:Humans; D010146:Pain / Q000188:drug therapy; D059408:Pain Management; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012107:Research Design; D016896:Treatment Outcome
D000700:Analgesics