Real-World Evidence to Assess Medication Safety or Effectiveness in Children: Systematic Review

Tamar Lasky^{1

2}, Bruce Carleton³, Daniel B Horton^{4

5

6}, Lauren E Kelly^{7

8}, Dimitri Bennett^{9

10}, Angela S Czaja¹¹, Dina Gifkins¹², Osemeke U Osokogu¹³, Ann W McMahon¹⁴

Affiliations

¹ Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Biostatistics and Epidemiology, 10903 New Hampshire Avenue, White Oak-71, Room 1253, Silver Spring, MD, 20993, USA. Tamar.lasky@fda.hhs.gov.
² MIE Resources, Baltimore, MD, USA. Tamar.lasky@fda.hhs.gov.
³ Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
⁴ Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
⁵ Rutgers Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, New Brunswick, NJ, USA.
⁶ Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA.
⁷ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
⁸ Children's Hospital Research Institute of Manitoba, and Geroge and Fay Yee Centre for Healthcare Innovation, Winnipeg, Canada.
⁹ Department of Epidemiology, Takeda Pharmaceutical Company Limited, Boston, MA, USA.
¹⁰ Perelman School of Medicine, Adjunct, University of Pennsylvania, Philadelphia, PA, USA.
¹¹ Department of Pediatrics, Critical Care University of Colorado, School of Medicine, Denver, USA.
¹² Janssen Research and Development, Raritan, NJ, USA.
¹³ Department of Content and Innovation, Elsevier (Information Analytics), New York, USA.
¹⁴ Office of Pediatric Therapeutics, Food and Drug Administration, Silver Spring, USA.

PMID: 32112359
PMCID: PMC7221095
DOI: 10.1007/s40801-020-00182-y

Review

Real-World Evidence to Assess Medication Safety or Effectiveness in Children: Systematic Review

Tamar Lasky et al. Drugs Real World Outcomes. 2020 Jun.

. 2020 Jun;7(2):97-107.

doi: 10.1007/s40801-020-00182-y.

Authors

Tamar Lasky^{1

2}, Bruce Carleton³, Daniel B Horton^{4

5

6}, Lauren E Kelly^{7

8}, Dimitri Bennett^{9

10}, Angela S Czaja¹¹, Dina Gifkins¹², Osemeke U Osokogu¹³, Ann W McMahon¹⁴

Affiliations

¹ Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Biostatistics and Epidemiology, 10903 New Hampshire Avenue, White Oak-71, Room 1253, Silver Spring, MD, 20993, USA. Tamar.lasky@fda.hhs.gov.
² MIE Resources, Baltimore, MD, USA. Tamar.lasky@fda.hhs.gov.
³ Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
⁴ Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
⁵ Rutgers Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, New Brunswick, NJ, USA.
⁶ Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA.
⁷ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
⁸ Children's Hospital Research Institute of Manitoba, and Geroge and Fay Yee Centre for Healthcare Innovation, Winnipeg, Canada.
⁹ Department of Epidemiology, Takeda Pharmaceutical Company Limited, Boston, MA, USA.
¹⁰ Perelman School of Medicine, Adjunct, University of Pennsylvania, Philadelphia, PA, USA.
¹¹ Department of Pediatrics, Critical Care University of Colorado, School of Medicine, Denver, USA.
¹² Janssen Research and Development, Raritan, NJ, USA.
¹³ Department of Content and Innovation, Elsevier (Information Analytics), New York, USA.
¹⁴ Office of Pediatric Therapeutics, Food and Drug Administration, Silver Spring, USA.

PMID: 32112359
PMCID: PMC7221095
DOI: 10.1007/s40801-020-00182-y

Abstract

Background: The promise of real-world evidence (RWE) is especially relevant to pediatrics, where medicines prescribed for children are often used without evidence derived from randomized clinical trials.

Objectives: The aim of this systematic review was to describe the state of RWE in pediatrics by identifying observational studies published during 2016 that used RWE to assess medication safety or effectiveness in children.

Methods: An electronic search of PubMed was combined with an extended search of references within systematic reviews and expert suggestions. Studies were included if they reported on an infant or child under 18 years with exposure to medications; assessed safety or effectiveness; specified a comparison or control group, and were published in English in 2016. Data extraction was conducted by one team member using a standardized form and reviewed by a second team member. Study quality was assessed using the GRACE checklist for rating the quality of observational studies.

Results: After removing duplicates, 915 citations were screened and 29 studies met the eligibility criteria. Most of the eligible studies relied on primary data collection or chart review at a single institution and did not use the growing number of administrative or electronic health record databases available. One-quarter of the studies did not use well-established statistical methods to control for confounders. No single disease group or medication predominated, and age groups ranged from infants to adolescents.

Conclusions: A small body of observational studies published in 2016 were categorized by the study team as using real-world data to assess medication safety or effectiveness in children. Studies varied in age groups, diseases or conditions, and methods, and may not have fully met the FDA definition of RWE. Our review indicates that the use of RWE is not fully developed in pediatrics, and suggests an opportunity to further develop capabilities and more fully leverage administrative and electronic health record databases to study medication safety and effectiveness in children. Our systematic review appears generalizable to pediatrics broadly, and documents that the high level of activity in RWE in general has had less of an impact on pediatrics.

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Conflict of interest statement

Tamar Lasky, Angela S. Czaja, Dina Gifkins, Lauren E. Kelly, Ann W. McMahon, Osemeke U. Osokogu, and Bruce Carleton have no conflicts of interest directly relevant to the content of this article. Dimitri Bennett is an employee of Takeda. Daniel B. Horton has received travel support and grant funding on unrelated matters from the Childhood Arthritis and Rheumatology Research Alliance and the Arthritis Foundation, grant funding on unrelated matters from Bristol–Myers Squibb, and an honorarium from the American College of Rheumatology on unrelated matters.

Figures

**Fig. 1**
Age ranges in 20 studies with participants under 18

See this image and copyright information in PMC

References

1. US Congress. 21st Century Cures Act. HR 34, 114th Congress, enacted on Dec 13, 2016.
1. Sherman RE, Anderson SA, Dal Pan GJ, Gray GW, Gross T, Hunter NL, et al. Real-world evidence—what is it and what can it tell us? N Engl J Med. 2016;375(23):2293–2297. doi: 10.1056/NEJMsb1609216. - DOI - PubMed
1. Committee on Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act, Pediatric Research Equity Act, Board on Health Sciences Policy, Institute of Medicine. In: Field MJ, Boat TF, editors. Safe and effective medicines for children: pediatric studies conducted under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: National Academies Press; 2012. - PubMed
1. Frattarelli DA, Galinkin JL, Green TP, Johnson TD, Neville KA, Paul IM, et al. Off-label use of drugs in children. Pediatrics. 2014;133(3):563–567. doi: 10.1542/peds.2013-4060. - DOI - PubMed
1. Joseph PD, Craig JC, Caldwell PHY. Clinical trials in children. Br J Clin Pharmacol. 2015;79(3):357–369. doi: 10.1111/bcp.12305. - DOI - PMC - PubMed

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Real-World Evidence to Assess Medication Safety or Effectiveness in Children: Systematic Review

Affiliations

Real-World Evidence to Assess Medication Safety or Effectiveness in Children: Systematic Review

Authors

Affiliations

Abstract

Conflict of interest statement

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References

Publication types

Grants and funding

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Full Text Sources

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