Kidney Health Initiative (KHI)

KHI Current Project

Overcoming Barriers to Drug Development in Children with CKD

Patient Care Issue:

Children with CKD are a vulnerable population in need of therapeutic innovation. The United States (US) and the European Union (EU) have permanent legislation in place mandating plans for pediatric development as part of an overall product development strategy.(1,2) EU and FDA requirement are not necessarily aligned. The overall number of children aged 0-19 on dialysis is about 2000 in the US with an equally small number estimated in the preceding stages of CKD.(3)

Challenge:
Only a fraction of children with CKD may be eligible for a particular study and there is active competition for different trials. There are marked clinical differences across age groups and the numbers dwindle with decreasing ages. This highlights the need to prioritize those programs that may be deemed most necessary and impactful by all stakeholders to facilitate successful study completion in this population of limited size. Furthermore, study design and execution must carefully consider specific technical and scientific issues related to diseases, treatments, age and ethics unique to children with CKD.(4) Safety concerns are often heightened due to greater uncertainties stemming from less directly applicable information on pharmacodynamics and toxicity for younger age groups.

KHI Solution:

This project aims to foster drug development in children with CKD by commissioning a workgroup to take inventory of current challenges, share insights and lessons learnt, and develop consensus based recommendations for overcoming barriers. The workgroup membership will take advantage of the diversity of constituent members within KHI and include representatives for patients, healthcare providers, researchers, professional organizations, industry partners, and regulators.

Deliverable:

A workgroup is being assembled to draft a white paper, over a 12 month timeframe, which is projected to take inventory of the current challenges and propose consensus based recommendations for improvements, including but not limited to:

The working group will seek to identify potential candidate surrogate outcome measures by:
  1. The current landscape of drug development in children with CKD
    • Disease burden in children with CKD
    • Unmet needs for drug development in children with CKD
    • Regulatory landscape for studies in children with CKD
    • Specific scientific and technical challenges for drug trials in children with CKD, including:
      • Pediatric formulation development and specific age group considerations
      • Infrastructure needs for trial conduct in children with CKD
  2. Opportunities for improving drug development in children with CKD
    • Coordination for needs assessment and prioritization
    • Reconciliation of regulatory requirements across different regions
    • Sharing and extrapolation of preclinical and clinical data to inform feasibility and safety
    • Considerations for successful trial design and execution in children with CKD that address unique scientific and technical issues
Timeline for Completion:

Fall 2017

Selected References:
  1. Covered by the Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA)
  2. Covered by Regulation (EC) No. 1901/2006 and Amending Regulation EC No 1902/2006
  3. 2014 USRDS ESRD Database http://www.usrds.org/2014/view/v2_07.aspx (accessed 12/13/2015)
  4. Clinical research in pediatric nephrology: challenges, and strategies to address them. Foster BJ, Warady BA. J Nephrol. 2009 Nov-Dec;22 (6):685-93.