Analgesic trials often fail to show a significant effect even when medications with known efficacy are tested. This could be attributed to insufficient assay sensitivity of analgesic trials, which may be due, in part, to the insensitivity of pain-related outcome measures. The aim of this methodological study was to assess the responsiveness of evoked pain generated by the staircase procedure compared with other commonly used pain outcomes in knee osteoarthritis.
This was a randomized, double-blind, placebo-controlled, cross-over trial of 1-week treatment of naproxen versus placebo. Participants were assigned to one of the 2 treatment sequences (naproxen-placebo or placebo-naproxen). Pain-at-rest, evoked pain using the Staircase-Evoked Pain Procedure (StEPP), pain diary, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) data were collected before and at the end of each treatment sequence.
A total of 55 osteoarthritis patients (30 M, 25 F) completed the study. Among all pain assessments, evoked pain was the most sensitive outcome to detect treatment effects, with Standardized Effect Size (SES) of 0.47 followed by the WOMAC and pain-at-rest with SES of 0.43 and 0.36, respectively. Sample size calculations demonstrated that compared with spontaneous pain, the evoked pain model reduces required number of subjects by 40%.
Study results support our hypothesis that evoked pain using the StEPP may demonstrate greater responsiveness to treatment effects compared with traditional pain-related outcome measures. Accordingly, these results may facilitate development and validation of other chronic pain-related evoked pain models, which could contribute to future research and development of new analgesics.
*Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel
†Analgesic Solutions, Natick
‡Tufts University School of Medicine, Boston, MA
R.T. and E.S.: contributed equally.
Support for this investigator-initiated study was provided by Astellas Pharma Inc. The funders had no role in data collection and analysis.
N.P.K. is the CEO of Analgesic Solutions, a clinical research and consulting firm with clients in the pharmaceutical industry. R.T. is a former employee of Analgesic Solutions and Lawal OD is a current employee of Analgesic Solutions. The remaining authors declare that they have nothing to disclose.
Reprints: Roi Treister, PhD, University of Haifa, 199 Aba Khoushy Avenue, Mount Carmel, Haifa 3498838, Israel (e-mail: firstname.lastname@example.org).
Received November 4, 2017
Received in revised form August 21, 2018
Accepted August 31, 2018