Dataset Information

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

ABSTRACT:

Importance

The 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 participants

In 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.

Results

The 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 relevance

This 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 journals need to address this issue with a range of measures including building capacity and capability in RCTs.

SUBMITTER: Wells JC

PROVIDER: S-EPMC7844695 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceMany randomized clinical trials (RCTs) led by high-income countries (HICs) now enroll patients from lower middle-income countries (LMICs) and upper middle-income countries (UMICs). Although enrolling diverse populations promotes research collaborations, there are issues regarding which countries participate in RCTs and how this participation may contribute to global research.ObjectiveTo describe which UMICs and LMICs participate in RCTs led by HICs.Design, setting, and participantsA cross-sectional study of all oncology RCTs published globally during January 1, 2014, to December 31, 2017, was conducted. The study cohort was restricted to RCTs led by HICs that enrolled participants from LMICs and UMICs. Study analyses were conducted in November 1, 2021, to May 31, 2022.Main outcomes and measuresA bibliometric approach (Web of Science 2007-2017) was used to explore whether RCT participation was proportional to other measures of cancer research activity. Participation in RCTs (ie, percentage of RCTs in the cohort in which each LMIC and UMIC participated) was compared with country-level cancer research bibliometric output (ie, percentage of total cancer research bibliometric output from the same group of countries that came from a specific LMIC and UMIC).ResultsAmong the 636 HIC-led RCTs, 186 trials (29%) enrolled patients in LMICs (n = 84 trials involving 11 LMICs) and/or UMICs (n = 181 trials involving 26 UMICs). The most common participating LMICs were India (42 [50%]), Ukraine (39 [46%]), Philippines (23 [27%]), and Egypt (12 [14%]). The most common participating UMICs were Russia (115 [64%]), Brazil (94 [52%]), Romania (62 [34%]), China (56 [31%]), Mexico (56 [31%]), and South Africa (54 [30%]). Several LMICs are overrepresented in the cohort of RCTs based on proportional cancer research bibliometric output: Ukraine (46% of RCTs but 2% of cancer research bibliometric output), Philippines (27% RCTs, 1% output), and Georgia (8% RCTs, 0.2% output). Overrepresented UMICs include Russia (64% RCTs, 2% output), Romania (34% RCTs, 2% output), Mexico (31% RCTs, 2% output), and South Africa (30% RCTs, 1% output).Conclusions and relevanceIn this cross-sectional study, a substantial proportion of RCTs led by HICs enrolled patients in LMICs and UMICs. The LMICs and UMICs that participated in these trials did not match overall cancer bibliometric output as a surrogate for research ecosystem maturity. Reasons for this apparent discordance and how these data may inform future capacity-strengthening activities require further study.