Comparison of weekly and daily recall of pain as an endpoint in a randomized phase 3 trial of cabozantinib for metastatic castration-resistant prostate cancer

Clin Trials. 2021 Aug;18(4):408-416. doi: 10.1177/17407745211009547. Epub 2021 Apr 22.

Abstract

Introduction: Scant evidence reveals whether the use of weekly versus daily pain ratings leads to meaningful differences when measuring pain as a clinical trial outcome. We compared the ability of weekly ratings and descriptors of daily ratings to evaluate pain as an endpoint in a randomized phase 3 drug trial.

Methods: Participants (n = 119) with metastatic castration-resistant prostate cancer were randomized to treatment arms and rated their pain on the average and at its worst during a baseline week and at weeks 3, 6, and 12 of study treatment. For each reporting period, participants rated their pain daily for 7 days. On day 7, participants rated their pain over the prior 7 days. We estimated mean differences and intraclass correlation coefficients of the weekly ratings and the mean and the maximum daily ratings. We compared the ability of the weekly ratings and the daily rating descriptors to detect change in pain and evaluated the agreement of the weekly rating and the mean daily rating of pain at its worst to detect treatment response.

Results: For both pain constructs, the weekly rating was consistently higher than the mean daily rating and lower than the maximum daily rating yet was moderately to highly correlated with both daily rating descriptors (intraclass correlation coefficient range = 0.55-0.94). The weekly rating and the daily rating descriptors consistently detected change in pain for the study sample and participant subgroups. Substantial agreement existed between the weekly rating and the mean daily rating of pain at its worst when used with trial protocol opioid criteria to detect treatment response (Cohen's κ = 0.71).

Conclusion: Use of daily over weekly ratings delivered no added benefit in evaluating pain in this clinical trial. This study is the first to compare weekly and daily recall to measure pain as an endpoint in a randomized phase 3 drug trial, and the pattern of differences in ratings that we observed is consistent with other recent evaluations of weekly and daily symptom reporting.

Keywords: Mental recall; cancer pain; patient-reported outcome; randomized phase 3 drug trial.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anilides / therapeutic use*
  • Humans
  • Male
  • Pain Measurement / methods*
  • Pain* / drug therapy
  • Pain* / etiology
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Pyridines / therapeutic use*
  • Treatment Outcome

Substances

  • Anilides
  • Pyridines
  • cabozantinib