What is the purpose of the Pediatric Research Equity Act of 2003 and the Best Pharmaceuticals for Children Act of 2002 regarding the safety and efficacy of medications in pediatric populations?

Purpose of the Pediatric Research Equity Act and Best Pharmaceuticals for Children Act

The Pediatric Research Equity Act of 2003 requires drug manufacturers to study pediatric medications for new drugs that would be used in diseases of childhood, while the Best Pharmaceuticals for Children Act of 2002 provides financial incentives (patent exclusivity extensions) for testing marketed pharmaceuticals in children. 1

Key Mechanisms of These Laws

Pediatric Research Equity Act (PREA) - 2003

• Mandates testing in children for new pharmaceuticals that would be used in diseases of childhood such as asthma and allergies 1
• Requires new drug applications to include pediatric assessments unless a waiver is granted 2
• Creates a regulatory mandate (not just incentives) for pharmaceutical companies to conduct pediatric studies 1

Best Pharmaceuticals for Children Act (BPCA) - 2002

• Provides an extension in patent exclusivity as a financial incentive for testing marketed pharmaceuticals in children 1
• Established processes for studying both off-patent and on-patent drugs used in pediatric populations 3
• Provides federal support to fund pediatric drug studies, particularly for older drugs that no longer qualify for pediatric exclusivity 1

Impact on Clinical Practice

Positive Outcomes

• These regulations have resulted in more than 500 labeling changes and improved rational prescribing for children 4
• Multiple drugs have gained FDA-approved labeling for younger children based on efficacy studies, including budesonide nebulizer suspension for 1-8 year olds, fluticasone propionate for 4-11 year olds, and montelukast for various pediatric age groups 1
• The FDA provided guidance allowing extrapolation of efficacy from studies in adults and older children when supplemented with safety and pharmacokinetic data in specific pediatric age groups 1

Persistent Limitations

• Despite these laws, 64% of new drug and biologic indications deemed relevant to pediatric patients still lack pediatric prescribing information at five years after FDA approval 5
• Only 21.7% of new drugs requiring pediatric assessments had been fully studied in children at the time of approval, with 68.5% having no pediatric data 2
• Among drugs approved without pediatric assessments, only 4.2% met FDA deferral deadlines, and the mean time between adult approval and availability of pediatric data was 6.5 years 2
• At a mean of 8.6 years post-approval, 57.6% of new drugs still had not been fully assessed in children 2

What These Laws Do NOT Do

Common Misconceptions

• These laws do NOT forbid providers from prescribing medications unless FDA-approved for use in children 4
• Off-label drug use remains legal and common in pediatrics, as the term "off-label" does not imply an improper, illegal, contraindicated, or investigational use 4
• Practitioners can use their professional judgment to determine off-label uses for the benefit of individual patients 4
• The lack of pediatric labeling information results in widespread off-label use in children, with greater than 50% of drugs lacking pediatric labeling 2

Clinical Implications

Why This Matters for Patient Safety

• The lack of safety data can result in inappropriate use in pediatric patients and expose them to potential risks related to age-specific adverse reactions that are unexpected from adult data 1
• Paediatric assessment is now an obligatory part of every Marketing Authorization Application in the EU and New Drug Application/Biologics License Application in the USA, unless a waiver has been granted 1
• Most drugs are empirically administered to newborns once efficacy is demonstrated in adults, which undermines the ability to perform appropriate studies to demonstrate short- and long-term safety and efficacy in neonates 3

Enforcement Challenges

• Concerns persist that delays and noncompliance with study requests contribute to high rates of off-label and potentially unsafe or ineffective medication use in children 5
• Fewer than one-third of pediatric study requests issued from 2002-2018 had been completed as of December 31,2018 5
• Enforcement of pediatric drug study policies should be strengthened to reduce non-evidence-based medication use in pediatric patients 5