Analyzing multiple endpoints in clinical trials of pain treatments: IMMPACT recommendations

Abstract

The increasing complexity of randomized clinical trials and the practice of obtaining a wide variety of measurements from study participants have made the consideration of multiple endpoints a critically important issue in the design, analysis, and interpretation of clinical trials. Failure to consider important outcomes can limit the validity and utility of clinical trials; specifying multiple endpoints for the evaluation of treatment efficacy, however, can increase the rate of false positive conclusions about the efficacy of a treatment. We describe the use of multiple endpoints in the design, analysis, and interpretation of pain clinical trials, and review available strategies and methods for addressing multiplicity. To decrease the probability of a Type I error (i.e., the likelihood of obtaining statistically significant results by chance) in pain clinical trials, the use of gatekeeping procedures and other methods that correct for multiple analyses is recommended when a single primary endpoint does not adequately reflect the overall benefits of treatment. We emphasize the importance of specifying in advance the outcomes and clinical decision rule that will serve as the basis for determining that a treatment is efficacious and the methods that will be used to control the overall Type I error rate.

Deafferentation of the Affected Arm

“…Because our primary goal was to improve motor performance, we used performance of SSDT as the primary outcome criterion, whereas GOT and VFHT were secondary criteria. 42 We expected interactions between factors time and treatment because no differences were expected at t1 on either treatment, but significant differences were expected for the 2 types of treatment (placebo versus anesthetic cream) at t2. All statistical tests were performed with SPSS for Windows (version 15.0).…”

Efficacy of Biofeedback in Chronic back Pain: a Meta-Analysis

“…Following these recommendations, we included average pain intensity as a primary outcome [28] and as a measure of the core outcome domain Bpain.^Other outcome measures included the following: disability, as a measure of the suggested core outcome domain Bphysical functioning^; depression or another affective state (if depression was not assessed), as a measure of the core outcome domain Bemotional functioning^; self-efficacy or coping (subsequently referred to as cognitive coping), as a measure of the supplemental outcome domain Bcoping^; and reduction of muscle tension (EMG), as an additional outcome, since pain is often associated with muscle tenseness.…”

The Esophageal Multimodal Pain Model: Normal Values and Degree of Sensitization in Healthy Young Male Volunteers

“…Sensitization was tested between thresholds before and after acid perfusion using a paired t-test, or, if not normally distributed, a Wilcoxon signed-rank test. P values were not adjusted for multiple comparisons [26]. A one-way analysis of variance was used to compare the difference in sensitization between modalities.…”