Abstract
Objectives
Evaluate comparative harm rates from medical interventions in pediatric randomized
clinical trials (RCTs) from more developed (MDCs) and less developed countries (LDCs).
Study Design and Setting
Meta-epidemiologic empirical evaluation of Cochrane Database of Systematic Reviews
(June 2014) meta-analyses reporting clinically important harm-outcomes (severe adverse
events [AEs], discontinuations due to AEs, any AE, and mortality) that included at
least one pediatric RCT from MDCs and at least one from LDCs. We estimated relative
odds ratios (RORs) for each harm, within each meta-analysis, between RCTs from MDCs
and LDCs and calculated random-effects-summary-RORs (sRORs) for each harm across multiple
meta-analyses.
Results
Only 1% (26/2,363) of meta-analyses with clinically important harm-outcomes in the
entire Cochrane Database of Systematic Reviews included pediatric RCTs both from MDCs
and LDCs. We analyzed 26 meta-analyses with 244 data sets from pediatric RCTs, 116
from MDCs and 128 from LDCs (64 and 66 unique RCTs respectively). The summary ROR
was 0.92 (95% confidence intervals: 0.78–1.08) for severe AEs; 1.13 (0.54–2.34) for
discontinuations due to AEs; 1.10 (0.77–1.59) for any AE; and 0.99 (0.61–1.61) for
mortality and for the all-harms-combined-end point 0.96 (0.83–1.10). Differences of
ROR-point-estimates ≥2-fold between MDCs and LDCs were identified in 35% of meta-analyses.
Conclusion
We found no major systematic differences in harm rates in pediatric trials between
MDCs and LDCs, but data on harms in children were overall very limited.
Keywords
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Article info
Publication history
Published online: November 27, 2017
Accepted:
November 22,
2017
Footnotes
Conflict of interest statement: The authors have stated that they have no conflicts of interest.
Funding: This study was supported in part by a grant from the Meta-Research Innovation Center at Stanford (METRICS).
Ethical approval: Not applicable.
Transparency declaration: Dr. Contopoulos-Ioannidis (the manuscript's guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.
Identification
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