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Unpublished trials affected evidence synthesis substantially when estimating medication harms in children

Zuhaer Yisha1, Zhaohu Fan2, Luis Furuya-Kanamori3

  • 1Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China.

Journal of Clinical Epidemiology
|April 20, 2026
PubMed
Abstract

Insights

Unpublished trials significantly impact medication harm estimates. Even a few unpublished studies can alter results, especially in smaller drug safety reviews. Comprehensive searches for all trial data are crucial.

Area of Science:

  • Pharmacovigilance
  • Clinical Trial Methodology
  • Biostatistics

Background:

  • The completeness of evidence in systematic reviews is critical for accurate medication safety assessments.
  • Unpublished studies may introduce bias into pooled estimates of drug harms.

Purpose of the Study:

  • To investigate the influence of unpublished trials on pooled estimates of medication harms in pediatric drug safety research.
  • To quantify the impact of excluding unpublished trials on meta-analytic results.

Main Methods:

  • Systematic search and data extraction from Cochrane reviews (up to Feb 2023) on pediatric drug interventions and adverse events.
  • Replication of meta-analytic effects by excluding unpublished trials and examining associations with their prevalence.
  • Logistic regression analysis using odds ratios (OR) and 95% confidence intervals (CI) to assess impact.

Main Results:

  • 14.9% of 740 eligible meta-analyses included unpublished trials.
  • Exclusion of unpublished trials altered effect direction (26.4%), statistical significance (28.2%), and magnitude (>50% in 8.2%).
  • Impact was greater in smaller meta-analyses and increased with a higher percentage of unpublished trials (OR=11.5 for significance).

Conclusions:

  • A small number of unpublished trials can substantially change pooled effect estimates for medication harms.
  • Findings underscore the importance of including unpublished data in systematic reviews for robust drug safety evaluations.
  • Systematic reviews must prioritize comprehensive searches for unpublished harms data.
Keywords:
ChildrenEvidence synthesisMedication harmsMeta-analysisSystematic reviewUnpublished study

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