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Regional Variations Detected in Clinical Trial Outcomes in Oncology
Registration trials focused on oncology are expanding in number and are continually enrolling patients from many different countries and regions. According to findings from a recently published study, regional outcome variations occur in more than 20% of trials (J Natl Compr Canc Netw. 2022;20(8):879-886.e2. doi:10.6004/jnccn.2022.7029).
Brook E Wilson (Collaboration for Cancer Outcomes, Research and Evaluation, South West Clinical School, University of New South Wales, Liverpool, New South Wales, Australia and Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada) and colleagues examined FDA approvals for solid tumor malignancies based on multi-arm comparative studies, investigated regional differences in outcomes, and provided a question guide to aid clinicians in ascertaining whether regional differences are likely to be genuine.
Utilizing FDA archives, researchers identified registration studies in solid tumor malignancies from 2010 to 2020. The researchers extracted the baseline study characteristics in participating countries and determined whether the primary publication reported a regional subgroup analysis.
For studies presenting outcomes stratified by region, the stratified hazard ratios (HRs) were separated and extracted or calculated the test for heterogeneity. Researchers then conducted a random effects meta-analysis and a pairwise comparison to ascertain whether outcomes varied between high-income vs mixed-income regions.
A total of 147 studies were included in the final analysis and researchers discovered that studies that support FDA drug approval have become progressively more multinational over time (β = 0.5; P = 0.04).
In the cohort, the average percentage of countries from high-income groups was 81.2% (range, 44%-100%), with no participation from low-income countrie; regional subgroup analysis was presented for 78 studies (53%). Regional heterogeneity was discovered in 17.8% (8/45) and 18% (8/44) of studies presenting an overall survival (OS) and progression-free survival endpoint, respectively.
There was a difference in OS outcomes in high-income regions compared with mixed-income regions (n = 20; HR, 0.95; 95% confidence interval, 0.84-1.07).
The researchers noted that in order to establish whether regional variation is genuine, clinicians should assess the data according to the following five questions:
- Are the regional groupings logical?
- Is the regional difference on an absolute or relative scale?
- Is the regional difference consistent and plausible?
- Is the regional difference statistically significant?
- Is there a clinical explanation?
Researchers concluded, “As studies become more international, the oncology community needs to develop a strategy for reporting and interpreting regional variation. The question guide herein may help clinicians interpret regional variations in trials and determine whether they are likely to be clinically meaningful. Postregistration and real-world studies should be used to confirm benefit, particularly for regions where the primary registration study showed variability.”
