Implications for Practice and Policy to Address Barriers and Inequities

Key IssuesRecommendations or Suggested Research and Policy Priorities (Examples and Initiatives Underway)
Advocate for trials in children• Campaign for children’s participation in trials, using both ethical and economic justification strategies
• Analyze health, epidemiologic, and registries data to inform clinical research needs in children
• Align the academic, pharmaceutical sponsor, and policy maker’s agendas to prioritize research in response to child health needs through a multinational consortium
• Invest and direct prioritization of trials in children from government
• Incentivize trials of off-patent medicines (eg, priority list of off-patent medicines developed by the US Pediatric Trials Network32)
• Improve initiatives to study rare diseases (eg, FDA priority review voucher,33 International Rare Diseases Research Consortium34)
• Encourage philanthropic approaches to conduct high-quality research that changes pediatric labeling
• Provide better incentives to encourage clinicians’ participation and enthusiasm
Strengthen and develop pediatric trial capacity• Invest in sustainable centralized trial infrastructure, including dedicated management team of a statistician, research nurse, data manager, and pharmacist to support investigators
• Establish networks with sustainable funding to collaborate and support trials in children, especially nonindustry-sponsored trials (eg, Medicines for Children Research Network31)
• Develop standards and guidance on trial design, conduct, and reporting (eg, valid child health outcomes including child-reported outcomes), explicit definitions (eg, minimal risk, adequate sample size), selection of appropriate comparators, reduction of risk of bias (eg, StaR Child Health,35 Toronto Outcomes Research in Child Health,36 Enhancing Research Impact in Child Health,37 Standard Protocol Items for Randomized Trials–Children,38 Consolidated Standards of Reporting Trials–Children39)
• Invest in training and standards for consistency and high-quality review of ethics applications
• Develop guidelines for data safety monitoring committees
• Implement programs to audit the conduct of trials at sites
Mitigate disparities in LMICs• Increase research and development investment to encourage trials in LMICs
• Build expertise in LMICs by encouraging research collaborations with investigators from high-income countries
• Share trial resources of high-income countries for adaptation to local contexts
• Advocate for philanthropic investment to build local trial and health care capacity
• Encourage operational research (advanced analytical techniques) on improving practices in these difficult contexts
• Invest in prevention and curative health services and research to address some of the neglected health burdens
• Promote health and health education of the community
• Encourage sponsor provision of ongoing supportive medical care posttrial and ancillary care to siblings and other family members
Enhance regulatory frameworks• Adopt pediatric regulations and incentives globally to encourage pharmaceutical industry to trial medicines in children (eg, the US and European Union regulations)
• Improve pediatric regulations and incentives to encourage trials in child-specific diseases, including trials of off-patent medicines (eg, Pediatric Trials Network initiatives)32
• Establish a global-level pediatric medicines regulatory framework under the leadership of the World Health Organization to regulate and harmonize country of trials conduct, transferability of results, availability of medicines, and improve medicine access and reimbursement strategies (eg, TransCelerate40 initiative)
• Create an international network of regulators to manage the regulatory requirements and provide support for less-experienced regulators
• Develop a log of trials to prevent duplication and identify gaps (eg, enprEMA,41 Medicines for Children Research Network, Global Research in Pediatrics42 initiatives)
Improve evidence-base practice• Encourage multicenter collaborative trials to reduce research waste
• Develop good referral network among pediatric clinicians to enhance recruitment
• Conduct trials of more economically feasible treatment modalities for LMICs, where appropriate
• Promote ongoing supplies of successful interventions to participants, while expediting regulatory approvals of pediatric labeling
• Invest in developing formulation of medicines appropriate for children in all income regions (eg, suspensions)
• Review medicine reimbursement strategies to improve access of medicines addressing pediatric needs
• Embed clinical research as part of routine clinical care and in disease-specific registries (eg, Key Performance Indicator of organization to involve children in trials)
• Invest in a governance framework of registries to address the evidence gaps in children and monitor expedient availability of trial results
• Invest in funding for translation and implementation of effective interventions
Embrace child-appropriate approaches• Design protocols around pediatric needs with consultation and partnering with the academic, practicing community, and families (eg, United Kingdom, Young Peoples Advisory Group,43 International Children’s Advisory Network)44
• Develop guidelines to engage children and parents in setting priorities, designing and conducting trials (eg, feasibility and selection of patient-reported outcomes, review of consent forms, scheduling appointments)
• Adopt child-appropriate strategies such as reducing pain and discomfort of painful invasive procedures (eg, distraction techniques such as DVDs)
• Develop alternative robust strategies to monitor compliance in children (eg, devices that can monitor use)
• Further research to develop guidelines on adequate pediatric decision-making (assent)
• Further research regarding payment to children for participating in optional research that does not offer direct benefit for the child
• Provide patient-specific results sheet to families and children who participated
Streamline ethical review• Develop clear ethical review regulations to reduce the ambiguity of current guidelines
• Standardize and simplify ethics processes and templates (eg, consent forms)
• Clarify definition of key terms such as minimal risk and minor increase over minimal risk in the pediatric context
• Recommend education and adherence to Data Monitoring Committees standards in pediatric trials (eg, Star Child Health group Data Monitoring Committee Standard)45
• Harmonize and expedite authorization of pediatric protocols (eg, Maternal Infant Youth and Child Research Network,46 Global Research in Pediatrics initiative)
• Develop guidelines to manage incidental findings of whole-genome sequencing that may have lifelong relevance
• Develop explicit and shared guidelines for the retention of biospecimens and how to engage children in consent for the ongoing use of stored specimens once children become adults
Equity in trial participation• Develop explicit and shared guidelines on when it is appropriate to conduct Phase I clinical trials in children
• Support the design and conduct of appropriate trials in pregnancy, obese children, premature infants, and newborns47
• Develop explicit and shared policies regarding appropriate incentives for child participation
• Investigate payment to children for participating in optional research not offering the possibility of treatment
  • The suggested research and policy priorities were formulated by respondents and discussion among the research team. FDA, US Food and Drug Administration.