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

  • Author Footnotes
    1 Both authors contributed equally to this work.
    Dario Tedesco
    Footnotes
    1 Both authors contributed equally to this work.
    Affiliations
    Department of Biomedical and Neuromotor Sciences, University of Bologna, Via San Giacomo, 12, 40126, Bologna, Italy
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  • Author Footnotes
    1 Both authors contributed equally to this work.
    Mufiza Farid-Kapadia
    Footnotes
    1 Both authors contributed equally to this work.
    Affiliations
    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
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  • Martin Offringa
    Affiliations
    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
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  • Zulfiqar A. Bhutta
    Affiliations
    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
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  • Yvonne Maldonado
    Affiliations
    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
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  • John P.A. Ioannidis
    Affiliations
    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
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  • Despina G. Contopoulos-Ioannidis
    Correspondence
    Corresponding author. Tel.: +1-650-723-5682; fax: +1-650-725-8040.
    Affiliations
    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
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  • Author Footnotes
    1 Both authors contributed equally to this work.
Published:November 27, 2017DOI:https://doi.org/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

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