Historical Initiatives

A major need exists to integrate clinical pharmacology and disease-specific therapeutic issues—identification of similarities and differences in the etiology, diagnosis, pathophysiology, prognosis, and natural response to therapy—of diseases or conditions affecting children and adults. NICHD and BPCA partly addressed this need through the IAPT.

The initiative focused on identifying similarities and differences in diseases or conditions expressed in children and adults by studying:

  • Etiology
  • Diagnosis
  • Diagnostic biomarkers
  • Pathophysiology
  • Outcome measures/endpoints
  • Manifestation (phenotypic expression)
  • Pharmacometrics
  • Natural history
  • Response to therapy
  • Extrapolation issues

Asthma, psychiatry, and diabetes were chosen as prototype therapeutic areas for the IAPT, and working groups were established for each area in 2012. Chairs of the working groups convened at the 2012 Workshop on Advancing Pediatric Therapeutics (PDF 126 KB) to formally launch the initiative. An additional group was added later to work toward advancing the ontogeny of drug transporters in children. Outcomes for the working groups included identifying knowledge gaps and research needs between clinical pharmacology and disease-specific therapeutic issues.

The asthma working group's goal was to develop a white paper for publication. It accomplished this goal in the Journal of Allergy and Clinical Immunology's (JACI) January 2014 theme issue external link (PMID: 24290281), which covered "asthma across the ages."

The diabetes working group had a similar goal and, in 2016, published "Expanding Treatment Options for Youth with Type 2 Diabetes: Current Problems and Proposed Solutions: A White Paper from the NICHD Diabetes Working Group" external link in Diabetes Care (PMID: 26908928).

​Working Group to Advance Ontogeny of Drug Transporters in Children

This working group included researchers dedicated to the study of drug transporters with the goal of promoting this area of research to determine their role in drug distribution and effects, including toxic effects. The specific objectives were to:

  • Promote knowledge creation
  • Develop a roadmap of research needs and priorities
  • Motivate other researchers from necessary disciplines

Initial activities included compiling feedback received from experts about what research was currently being conducted and problems encountered in studying ontogeny of transporters/receptors.

The group's literature review subgroup developed a literature search strategy for the ontogeny of transporters in certain organs, using transporters identified by the International Transporter Consortium. This subgroup, which was further divided into three groups that addressed the ontogeny of transporters in the liver, intestine, and kidneys, published a white paper in 2015 in Clinical Pharmacology and Therapeutics (PMID: 26088472).​

The mission of the Biomarkers in Pediatric Therapeutics Special Interest Group was to pursue opportunities for strengthening cross-disciplinary pediatric biomarker research at NIH while innovating beyond existing investments. Its goals were to provide leadership, vision, and support to promote a strong body of pediatric biomarker research funded by NIH; and to collect, evaluate, and disseminate scientific information and funding opportunities for biomarker research in pediatric therapeutics at NIH. The group promoted NIH-wide funding announcements, hosts speakers, and support panels and minisymposia, national and international webinars, and group discussions.

For more information, visit Pediatric Clinical Research and Outcomes Interest Group.

The PFI was designed to look at all the factors that affected the development of pediatric drugs. The goals were to create a roadmap for removing/mitigating barriers to pediatric drug development and to connect researchers and experts in pediatric formulation to discuss issues and challenges that may stimulate further research in the field.

The PFI had four groups:

  • Scientific, technical, and regulatory barriers for the development of pediatric formulations
  • Taste, smell, and flavor research in infants and children
  • Economic issues and partnerships
  • Use and application of new drug delivery systems in pediatrics

The following are links to the minutes from past PFI meetings:

The lack of a pediatric formulation was one consideration for prioritization because the lack of commercially available oral pediatric formulations is a continuing problem for children, parents, and pediatricians. Also, there is no coherent approach to the development of pediatric formulations.

​The ideal pediatric dosage form would:

  • Be orally dissolvable
  • Be tasteless
  • Have an appropriate dosage increment for the smallest infants
  • Contain minimal amounts of inactive substances like fillers or preservatives
  • Be stable in light, humidity, and heat
  • Have the necessary release characteristics, as applicable

​The Pediatric Formulations Platform used NIH BPCA funds to support U.S. Food and Drug Administration chemists' assessment of pediatric product formulations and produce an open-source, publicly available approach to pediatric oral formulations manufacturing. 

The work included five tasks:

  1. Perform an assessment of all commercially available products to determine which have pediatric formulations.
  2. Determine what technologies are publicly available, how these technologies have been used, and for what types of products.
  3. Use prototypical drug products and computational methods to distinguish their molecular structure through characteristics such as solubility, permeability, light sensitivity, pH instability, heat instability, hygroscopic properties, and bitterness.
  4. Determine the best formulations technology for specific drug categories based on information from tasks 1–3.
  5. Produce prototype batches of selected drug products.

The goal was to make these data publicly available as soon as possible.

As a first step, the Biopharmaceutics Classification System assessment of all commercially available products is archived as "Oral Formulations Platform—Reports 1 and 2." When further stages are completed, they will be posted.

BPCA formed a working group to discuss the current state of hypertension epidemiology, pathophysiology, diagnosis, and treatment in the pediatric population. Clinicians have grappled with the issue of treatment versus non-treatment for pediatric hypertension, and recent studies have shown that only a small percentage of children with hypertension are treated for the condition.

The working group published the following white paper summarizing issues and gaps identified in this area and determining key areas for future research:

  • Taylor-Zapata, P., Baker-Smith, C. M., Burckart, G., Daniels, S. R., Flynn, J. T., Giacoia, G., Green, D., Kelly, A. S., Khurana, M., Li, J. S., Pratt, C., Urbina, E. M., & Zajicek, A. (2019). Research gaps in primary pediatric hypertension. Pediatrics, 143(5), e20183517. PMID: 31023830

A working group meeting was held on September 25, 2017.

This collaboration was an interagency agreement between NICHD and the National Heart, Lung, and Blood Institute’s Prematurity and Respiratory Outcomes Program to investigate the molecular mechanisms that contribute to respiratory disease risk of premature neonates over the first year after birth.

Ryan, R. M., Keller, R. L., Poindexter, B. B., D'Angio, C. T., Shaw, P. A., Bellamy, S. L., Moore, P. E., McPherson, C., Greenberg, J. M., & PROP Investigators (2019). Respiratory medications in infants <29 weeks during the first Year Postdischarge: The Prematurity and Respiratory Outcomes Program (PROP) Consortium. The Journal of pediatrics, 208, 148–155.e3. PMID: 30857774

Pryhuber, G. S., Maitre, N. L., Ballard, R. A., Cifelli, D., Davis, S. D., Ellenberg, J. H., Greenberg, J. M., Kemp, J., Mariani, T. J., Panitch, H., Ren, C., Shaw, P., Taussig, L. M., Hamvas, A., & Prematurity and Respiratory Outcomes Program Investigators (2015). Prematurity and respiratory outcomes program (PROP): Study protocol of a prospective multicenter study of respiratory outcomes of preterm infants in the United States. BMC Pediatrics, 15, 37. PMID: 25886363

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