Regional variation in opioid use may be attenuated when pharmaceutical-sponsored 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 point.
To identify whether regional and country-level variation in opioid use exists among prostate cancer clinical trials across the world.
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 February 2019.
Cancer therapy.
Opioid use data were from concomitant medications reported in the database for each trial. Logistic regression models, descriptive statistics, and χ2 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.
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).
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.
JAMA oncology. 2019 Sep 12 [Epub ahead of print]
Jessica K Roydhouse, Daniel L Suzman, Laurel A Menapace, Pallavi S Mishra-Kalyani, Rajeshwari Sridhara, Gideon M Blumenthal, Julia A Beaver, Richard Pazdur, Paul G Kluetz
Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland., Office of Biostatistics, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland., Oncology Center of Excellence, Food and Drug Administration, Silver Spring, Maryland.