Comparative evidence on harms in pediatric randomized clinical trials from less developed versus more developed countries is limited

Dario Tedesco; Mufiza Farid-Kapadia; Martin Offringa; Zulfiqar A Bhutta; Yvonne Maldonado; John P A Ioannidis; Despina G Contopoulos-Ioannidis

doi:10.1016/j.jclinepi.2017.11.016

Comparative evidence on harms in pediatric randomized clinical trials from less developed versus more developed countries is limited

J Clin Epidemiol. 2018 Mar:95:63-72. doi: 10.1016/j.jclinepi.2017.11.016. Epub 2017 Nov 28.

Authors

Dario Tedesco¹, Mufiza Farid-Kapadia², Martin Offringa², Zulfiqar A Bhutta³, Yvonne Maldonado⁴, John P A Ioannidis⁵, Despina G Contopoulos-Ioannidis⁶

Affiliations

¹ Department of Biomedical and Neuromotor Sciences, University of Bologna, Via San Giacomo, 12, 40126, Bologna, Italy.
² Department of Pediatrics, Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children University of Toronto, 555 University Avenue, Toronto, Ontario M5G-1X8, Canada.
³ Department of Pediatrics, Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children University of Toronto, 555 University Avenue, Toronto, Ontario M5G-1X8, Canada; Centre for Global Child Health, The Hospital for Sick Children, 686 Bay Street, Suite 11.9805, Toronto, ON, M5G-0A4, Canada; Center of Excellence in Women and Child Health, The Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan.
⁴ Division of Infectious Diseases, Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Room G312, Stanford, CA 94305, USA; Department of Health Research and Policy, Stanford University School of Medicine, 150 Governor's Lane, HRP Redwood Building, Stanford, CA 94305, USA; Senior Associate Dean for Faculty Development and Diversity, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁵ Department of Health Research and Policy, Stanford University School of Medicine, 150 Governor's Lane, HRP Redwood Building, Stanford, CA 94305, USA; Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, 1265 Welch Road, Stanford, CA 94305, USA; Meta Research Innovation Center at Stanford (METRICS), 1070 Arastradero Road, Palo Alto, CA 94304, USA.
⁶ Division of Infectious Diseases, Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Room G312, Stanford, CA 94305, USA; Meta Research Innovation Center at Stanford (METRICS), 1070 Arastradero Road, Palo Alto, CA 94304, USA. Electronic address: [email protected].

PMID: 29191447
DOI: 10.1016/j.jclinepi.2017.11.016

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: Cochrane Database of Systematic Reviews; Comparative; Harms; Meta-analyses; Mortality; Pediatrics; Randomized trials.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't
Review

MeSH terms

Child
Databases, Factual
Developed Countries
Developing Countries
Humans
Meta-Analysis as Topic
Odds Ratio
Patient Harm / statistics & numerical data*
Randomized Controlled Trials as Topic*