Global variation in Opioid use in prostate cancer trials
Roydhouse, J and Suzman, DL and Menapace, LA and Mishra-Kalyani, PS and Sridhara, R and Blumenthal, GM and Beaver, JA and Pazdur, R and Kluetz, PG, Global variation in Opioid use in prostate cancer trials, JAMA Oncology, 5, (11) Article e192971. ISSN 2374-2445 (2019) [Refereed Article]
IMPORTANCE Regional variation in opioid use may be attenuated when pharmaceuticalsponsored trials include care that is often standardized by protocols. Understanding such
variation is important for global trials that sometimes include time to opioid use as an end
OBJECTIVE To identify whether regional and country-level variation in opioid use exists
among prostate cancer clinical trials across the world.
DESIGN, SETTING, AND PARTICIPANTS International phase 3 randomized clinical trials with
patients with metastatic prostate cancer and initiation from January 1, 2008, or later were
identified through internal databases of the US Food and Drug Administration. Data of
patients in the intention-to-treat population from each trial were pooled. Descriptive and
regression analyses of the collected data were conducted from September 2018 to
EXPOSURES Cancer therapy.
MAIN OUTCOMES AND MEASURES Opioid use data were from concomitant medications
reported in the database for each trial. Logistic regression models, descriptive statistics,
tests were used to compare opioid use across world regions while adjusting for patient
age, presence of visceral disease, bony disease, and baseline Eastern Cooperative Oncology
Group Performance Status score and pain score.
RESULTS In total, 9670 patients (mean [SD] age of 69.2 [8.3] years) from 8 prostate cancer
clinical trials in 46 countries were included. Patients in Eastern Europe (adjusted odds ratio
[AOR], 0.19; 95% CI, 0.16-0.22) and Asia (AOR, 0.31; 95% CI, 0.25-0.38) were less likely to
use opioids compared with patients in North America. These findings held even when the
analysis was restricted to patients who reported moderate to high pain levels at baseline
(Eastern Europe: AOR, 0.16 [95% CI, 0.12-0.22]; Asia: AOR, 0.47 [95% CI, 0.29-0.79]).
Within North America, rates of opioid use were similar between the United States and Canada
(AOR, 1.13; 95% CI, 0.93-1.37).
CONCLUSIONS AND RELEVANCE This study found that, despite the clinical trial setting, opioid
use appeared to vary by world regions, suggesting that this variability should be considered
in international clinical trials.