Thomas R. Fleming, Christine E. Garnett, Laurie S. Conklin, Solange Corriol‑Rohou, Sudharshan Hariharan, Daphne Hsu, Guenther Mueller‑Velten, Yeruk Mulugeta, Ronald Portman, Mark D. Rothmann, Norman L. Stockbridge, Simon Wandel, Jialu Zhang, Lynne Yao
University of Washington. U.S. Food and Drug Administration. Janssen Research and Development. AstraZeneca. Children’s Hospital at Montefiore and Albert Einstein College of Medicine. Novartis Pharma AG and Novartis Pharmaceuticals.
United States
Therapeutic Innovation and Regulatory Science
Ther Innov Regul Sci 2023; 57: 109-120
DOI: 10.1007/s43441-022-00445-6
Abstract
Even with recent substantive improvements in health care in pediatric populations, considerable need remains for additional safe and effective interventions for the prevention and treatment of diseases in children. The approval of prescription drugs and biological products for use in pediatric settings, as in adults, requires demonstration of substantial evidence of effectiveness and favorable benefit-to-risk. For diseases primarily affecting children, such evidence predominantly would be obtained in the pediatric setting. However, for conditions affecting both adults and children, pediatric extrapolation uses scientific evidence in adults to enable more efficiently obtaining a reliable evaluation of an intervention’s effects in pediatric populations. Bridging biomarkers potentially have an integral role in pediatric extrapolation. In a setting where an intervention reliably has been established to be safe and effective in adults, and where there is substantive evidence that disease processes in pediatric and adult settings are biologically similar, a ‘bridging biomarker’ should satisfy three additional criteria: effects on the bridging biomarker should capture effects on the principal causal pathway through which the disease process meaningfully influences ‘feels, functions, survives’ measures; secondly, the experimental intervention should not have important unintended effects on ‘feels, functions, survives’ measures not captured by the bridging biomarker; and thirdly, in statistical analyses in adults, the intervention’s net effect on ‘feels, functions, survives’ measures should be consistent with what would be predicted by its level of effect on the bridging biomarker. A validated bridging biomarker has considerable potential utility, since an intervention’s efficacy could be extrapolated from adult to pediatric populations if evidence in children establishes the intervention not only to be safe but also to have substantive effects on that bridging biomarker. Proper use of bridging biomarkers could increase availability of reliably evaluated therapies approved for use in pediatric settings, enabling children and their caregivers to make informed choices about health care.
Category
Review Articles Concerning Pulmonary Vascular Disease
Diagnostic Testing for Pulmonary Vascular Disease. Non-invasive Testing
Diagnostic Testing for Pulmonary Vascular Disease. Invasive Testing
Potential Biomarkers Associated with Pulmonary Vascular Disease
Medical Therapy. Efficacy or Lack of Efficacy
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes