An Analysis of Contemporary Oncology Randomized Clinical Trials From Low/Middle-Income vs High-Income Countries

Abstract

IMPORTANCEThe burden of cancer falls disproportionally on low-middle-income countries (LMICs). It is not well known how novel therapies are tested in current clinical trials and the extent to which they match global disease burden.OBJECTIVES To describe the design, results, and publication of oncology randomized clinical trials (RCTs) and examine the extent to which trials match global disease burden and how trial methods and results differ across economic settings. DESIGN, SETTING, AND PARTICIPANTSIn this retrospective cohort study, a literature search identified all phase 3 RCTs evaluating anticancer therapies published from 2014 to 2017. Randomized clinical trials were classified based on World Bank economic classification. Descriptive statistics were used to compare RCT design and results from high-income countries (HICs) and low/middle-income countries (LMICs). Statistical analysis was conducted in January 2020.MAIN OUTCOMES AND MEASURES Differences in the design, results, and output of RCTs between HICs and LMICs. RESULTSThe study cohort included 694 RCTs: 636 (92%) led by HICs and 58 (8%) led by LMICs. A total of 601 RCTs (87%) tested systemic therapy and 88 RCTs (13%) tested radiotherapy or surgery. The proportion of RCTs relative to global deaths was higher for breast cancer (121 RCTs [17%] and 7% of deaths) but lower for gastroesophageal cancer (38 RCTs [6%] and 14% of deaths), liver cancer (14 RCTs [2%] and 8% of deaths), pancreas cancer (14 RCTs [2%] and 5% of deaths), and cervical cancer (9 RCTs [1%] and 3% of deaths). Randomized clinical trials in HICs were more likely than those in LMICs to be funded by industry (464 [73%] vs 24 [41%]; P < .001). Studies in LMICs were smaller than those in HICs (median, 219 [interquartile range, 137-363] vs 474 [interquartile range, 262-743] participants; P < .001) and more likely to meet their primary end points (39 of 58 [67%] vs 286 of 636 [45%]; P = .001). The observed median effect size among superiority trials was larger in LMICs compared with HICs (hazard ratio, 0.62 [interquartile range, 0.54-0.76] vs 0.84 [interquartile range, 0.67-0.97]; P < .001). Studies from LMICs were published in journals with lower median impact factors than studies from HICs (7 [interquartile range, 4-21] vs 21 [interquartile range, 7-34]; P < .001). Publication bias persisted when adjusted for whether a trial was positive or negative (median impact factor: LMIC negative trial, 5 [interquartile range, 4-6] vs HIC negative trial, 18 [interquartile range, 6-26]; LMIC positive trial, 9 [interquartile range, 5-25] vs HIC positive trial, 25 [interquartile range, 10-48]; P < .001). CONCLUSIONS AND RELEVANCEThis study suggests that oncology RCTs are conducted predominantly by HICs and do not match the global burden of cancer. Randomized clinical trials from LMICs are more likely to identify effective therapies and have a larger effect size than RCTs from HICs. This study suggests that there is a funding and publication bias against RCTs led by LMICs. Policy makers, research funders, and ...

Text Messaging in Cancer-Supportive Care: A Systematic Review

“…Comparable trends also exist in the broader cancer literature. A retrospective analysis of all phase 3 treatment studies published from 2014–2017 ( n = 694 RCTs) found that just 8% were led by LMIC investigators [ 50 ]. LMICs experience high cancer incidence as well as disproportionately high mortality [ 51 ].…”

Cancer, Clinical Trials, and Canada: Our Contribution to Worldwide Randomized Controlled Trials

“…The present report is a secondary analysis to understand Canada’s contribution to the global research ecosystem using other HICs as a comparator. The primary report of the global population including the electronic search strategy has been reported elsewhere [ 14 ]. A structured literature search was designed using PUBMED to identify phase III RCTs evaluating cancer-targeted therapies published during 2014–2017.…”

Equity of medical research representation on the global stage: A need for change

“…Another recent systematic review published on JAMA Oncology reflects the fact that irrespective of the quality of the research performed, pervasive inequity in publication still exists. A study by Wells et al assessed 694 Phase 3 randomized control trials (RCTs) in oncology published from 2014to 2017 and found, unsurprisingly, that Medicina Universitaria most RCTs were led by HICs (92%) and were more likely to be funded by the pharmaceutical industry in comparison to LMICs (73% vs. 41%) 4 . Although studies from LMICs were smaller, they were more likely to meet their primary endpoints, remarkably, studies from LMICs were published in journals with lower impact factors, with a median of 7 versus 21 4 .…”

“…A study by Wells et al assessed 694 Phase 3 randomized control trials (RCTs) in oncology published from 2014to 2017 and found, unsurprisingly, that Medicina Universitaria most RCTs were led by HICs (92%) and were more likely to be funded by the pharmaceutical industry in comparison to LMICs (73% vs. 41%) 4 . Although studies from LMICs were smaller, they were more likely to meet their primary endpoints, remarkably, studies from LMICs were published in journals with lower impact factors, with a median of 7 versus 21 4 . This study highlights the fact that current research in oncology does not match the global cancer burden and that there is a stark pervasive funding and publication bias against LMICs.…”