New strategies for the conduct of clinical trials in paediatric Pulmonary Arterial Hypertension (PAH): Outcome of a multi-stakeholder meeting with patients, academia, industry and regulators held at EMA on Monday 12th June 2017

Forskningsoutput: TidskriftsbidragÖversiktsartikel


Aims: Drug development for paediatric pulmonary arterial hypertension (PAH) is
pressingly needed. Experts from the US Food and Drug Administration, EuropeanMedicines Agency, Health Canada, key opinion leaders, academia, patients, and industry representatives held a workshop on 12th June 2017 dedicated to addressing challenges and unmet needs. This report summarises the approaches proposed during the meeting to address key issues in extrapolation, trial design, and study endpoints in pediatric drug development.
Methods and Results: A pre-workshop stakeholder survey was conducted and showed that most respondents believe the pathophysiology of heritable PAH and some forms of idiopathic PAH is thought to be sufficiently similar in adult and paediatric patients, although the clinical manifestations may differ. In this situation, placebo-controlled trials might not be required to confirm clinical benefit in paediatrics. The study endpoints used to support drug approvals in adults were reviewed to determine if these existing study endpoints can be applied in paediatric PAH efficacy trials. It showed that non-invasive study endpoints, such as the time to clinical worsening, WHO functional
class, and 6-Minute-Walk-Test could be applicable in paediatric PAH trials, although each presents some limitations in paediatrics.
Conclusion: Extrapolation of efficacy from informative adult studies may be appropriate in some forms of PAH. Initial dose-finding studies and exposure-response modelling are warranted in paediatric PAH, followed by an efficacy and safety study to explore the response to treatment and exposure-response relationship. A novel, non-invasive, developmentally-appropriate, and reliable study endpoint needs to be developed.


  • Cecille Olivier
  • Haihao Sun
  • Wayne Amchin
  • Maurice Beghetti
  • Rolf Berger
  • Stefanie Breitenstein
  • Christine Garnett
  • Ninna Gullberg
  • Patrik Hassel
  • Dumbar Ivy
  • Steven Kawut
  • Agnes Klein
  • Catherine Lesage
  • Marek Migdal
  • Barbara Nije
  • Michal Odermarsky
  • James Strait
  • Pieter de Graeff
  • Norman Stockbridge
Enheter & grupper
Externa organisationer
  • European Medicines Agency (EMA)
  • United States Food and Drug Administration
  • Geneva University Hospital
  • University of Groningen
  • Bayer Pharma AG
  • PH Sweden
  • University of Colorado School of Medicine
  • University of Pennsylvania
  • Public Health Agency of Canada
  • Actelion Pharmaceuticals Ltd.
  • Children’s Memorial Health Institute
  • Merck Sharp & Dohme, Switzerland
  • Medicines Evaluation Board, Utrecht
  • Skåne University Hospital

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Kardiologi
  • Farmaceutisk vetenskap
Sidor (från-till)1-10
TidskriftJournal of the American Heart Association
StatusPublished - 2019
Peer review utfördJa