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 has been 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:

  1. Recognize the legal remit and regulatory framework for pediatric study plans in US and Europe. Outline the current avenues of collaboration and communication between the regulatory agencies in US and Europe regarding pediatric plans
  2. Explore avenues for harmonization of study designs (including endpoints) and timelines for pediatric plans across US and European regulatory agencies.
  3. Develop a mechanism to prioritize drugs and drug classes for trials in children with CKD through multi-stakeholder guidance and input, considering the following prioritization factors:
    • Unmet patient needs (e.g., new drug class, new mechanism of action)
    • Finite research resources in terms of number of patients affected and sites, in context of numerous pediatric commitments
    • Regulatory landscape for studies in children with CKD
    • Timelines and priority metrics
  4. Optimize planning of pediatric drug trials by
    • Enabling feasibility assessment in terms of the available patient populations through data sharing and access to CKD pediatric registries
    • Consultation on design and protocols by a panel of pediatric nephrologists, trialists, patient representatives early in the design process
    • Enhance the likelihood of successful trial execution through assessment of the capacity of various pediatric renal clinical trial organizations
  5. Identify key considerations for a balanced assessment of perceived benefits and risks (including toxicity), through a collaboration with experts (including toxicologists, clinical trialists from other pediatric disciplines that deal with toxicology risk vs. benefit, patients and caregivers). The prioritization process in Goal 3 should be informed by the patient/caregiver perspective in terms of this balance.
Timeline for Completion:

Winter 2017.

Workgroup:
Co-Chairs:

Stuart Goldstein, MD
Cincinnati Children's Hospital Medical Cener
KHI Board of Director's Liaison

Katrin Uhlig, MD, MS
Keryx Biopharmaceuticals, Inc.


Members:

Ann Danderand, MD
Otsuka America Pharmaceuticals, Inc.

Pamela Duquette
Johns Hopkins University
KHI Patient and Family Partnership Counicl

Elizabeth Fox, MD, MS
Children’s Hospital of Philadelphia

Debbie Gipson, MD
University of Michigan

Egger Gunter, DVM
European Medicines Agency

Jan Iles, MD, MPH
Amgen, Inc.

Mona Khurana, MD
Division of Pediatric and Maternal Health, FDA

Teresa Vu Lewis, PharmD, BCPS
The University of Oklahoma Health Sciences Center, College of Pharmacy

Amy Mason, MD, MS
Bayer AG

Alicia Neu, MD
Johns Hopkins University
Liaison for North American Pediatric Renal Trials and Collaborative Studies

Ron Portman, MD, FAAP, FASN
Novartis Pharmaceutical Corporation

Marco Prunotto, PhD
Roche Pharmaceuticals

Jesse Roach, MD
Center for Medicare and Medicaid Services

Michelle Rheault, MD
University of Minnesota

H. William Schnaper, MD
Northwestern University

Sandi See Tai, MD
Pfizer, Inc.

Aliza Thompson, MD
Center for Drug Evaluation and Research


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.