Comparing drug effectiveness in children: A systematic review

Pharmacoepidemiol Drug Saf. 2018 Dec;27(12):1295-1301. doi: 10.1002/pds.4676. Epub 2018 Oct 31.


Purpose: The purpose of the study is to assess the current state of the art in pediatric comparative effectiveness research, potential gaps, and areas for improvement.

Methods: Relevant articles from inception to February 2015 were retrieved from Embase and Medline. We sequentially screened titles, abstracts, and full texts, with independent validation. Data regarding general information and study methods including statistical analysis were extracted. Study quality was assessed using Newcastle-Ottawa Scale (NOS). Investigated drugs were ranked and compared with data on the prevalence of pediatric drug use.

Results: Three thousand nine hundred twenty-six abstracts were screened for eligibility and inclusion, and 164 articles were included in the review. Most studies were from North America (46.7%). Only 78 studies (47.6%) reported the design: 90.8% were cohort studies. Neonates were least frequently investigated. The drugs that were most often studied included systemic antibacterials (11.4%), psycholeptics (7.9%), and antiepileptics (7.6%). Adjustment for confounding was made using propensity scores in 8.5% of the studies. Studies that did not report the design were of lower quality. Many effectiveness studies were done on antineoplastic agents, which are not frequently used and few studies on analgesics and drugs for obstructive airway diseases which are frequently prescribed.

Conclusions: There is ample opportunity to improve comparative effectiveness research for drugs used in pediatrics. Routinely prescribed drugs were seldom investigated. Modern methods for confounding adjustment, such as propensity scores, were rarely used.

Keywords: comparative effectiveness research; pediatrics; pharmacoepidemiology; review.

Publication types

  • Systematic Review

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Anticonvulsants / therapeutic use
  • Antipsychotic Agents / therapeutic use
  • Child
  • Comparative Effectiveness Research / methods*
  • Comparative Effectiveness Research / statistics & numerical data
  • Humans
  • Infant, Newborn
  • Observational Studies as Topic*
  • Propensity Score
  • Research Design*
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Anticonvulsants
  • Antipsychotic Agents