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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

Olivier, Cecille ; Sun, Haihao ; Amchin, Wayne ; Beghetti, Maurice ; Berger, Rolf ; Breitenstein, Stefanie ; Garnett, Christine ; Gullberg, Ninna ; Hassel, Patrik and Ivy, Dumbar , et al. (2019) In Journal of the American Heart Association 8(10). p.1-10
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the American Heart Association
volume
8
issue
10
pages
1 - 10
publisher
Wiley-Blackwell
external identifiers
  • pmid:31088189
  • scopus:85066243720
  • pmid:31088189
ISSN
2047-9980
DOI
10.1161/JAHA.118.011306
language
English
LU publication?
yes
id
485334f5-1241-4527-9e46-71c7d9ef4940
date added to LUP
2018-09-15 14:55:42
date last changed
2022-04-25 08:55:53
@article{485334f5-1241-4527-9e46-71c7d9ef4940,
  abstract     = {{Aims: Drug development for paediatric pulmonary arterial hypertension (PAH) is<br/>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.<br/>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<br/>class, and 6-Minute-Walk-Test could be applicable in paediatric PAH trials, although each presents some limitations in paediatrics.<br/>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.}},
  author       = {{Olivier, Cecille and Sun, Haihao and Amchin, Wayne and Beghetti, Maurice and Berger, Rolf and Breitenstein, Stefanie and Garnett, Christine and Gullberg, Ninna and Hassel, Patrik and Ivy, Dumbar and Kawut, Steven and Klein, Agnes and Lesage, Catherine and Migdal, Marek and Nije, Barbara and Odermarsky, Michal and Strait, James and de Graeff, Pieter and Stockbridge, Norman}},
  issn         = {{2047-9980}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{1--10}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of the American Heart Association}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1161/JAHA.118.011306}},
  doi          = {{10.1161/JAHA.118.011306}},
  volume       = {{8}},
  year         = {{2019}},
}