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Who is a ‘healthy subject’?—consensus results on pivotal eligibility criteria for clinical trials

INTRODUCTION/METHODS: A discussion forum was hosted by the German not-for-profit Association for Applied Human Pharmacology (AGAH e.V.) to critically review key eligibility criteria and stopping rules for clinical trials with healthy subjects, enrolling stakeholders from the pharmaceutical industry,...

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Autores principales: Breithaupt-Groegler, Kerstin, Coch, Christoph, Coenen, Martin, Donath, Frank, Erb-Zohar, Katharina, Francke, Klaus, Goehler, Karin, Iovino, Mario, Kammerer, Klaus Peter, Mikus, Gerd, Rengelshausen, Jens, Sourgens, Hildegard, Schinzel, Reinhard, Sudhop, Thomas, Wensing, Georg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350217/
https://www.ncbi.nlm.nih.gov/pubmed/28064353
http://dx.doi.org/10.1007/s00228-016-2189-8
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author Breithaupt-Groegler, Kerstin
Coch, Christoph
Coenen, Martin
Donath, Frank
Erb-Zohar, Katharina
Francke, Klaus
Goehler, Karin
Iovino, Mario
Kammerer, Klaus Peter
Mikus, Gerd
Rengelshausen, Jens
Sourgens, Hildegard
Schinzel, Reinhard
Sudhop, Thomas
Wensing, Georg
author_facet Breithaupt-Groegler, Kerstin
Coch, Christoph
Coenen, Martin
Donath, Frank
Erb-Zohar, Katharina
Francke, Klaus
Goehler, Karin
Iovino, Mario
Kammerer, Klaus Peter
Mikus, Gerd
Rengelshausen, Jens
Sourgens, Hildegard
Schinzel, Reinhard
Sudhop, Thomas
Wensing, Georg
author_sort Breithaupt-Groegler, Kerstin
collection PubMed
description INTRODUCTION/METHODS: A discussion forum was hosted by the German not-for-profit Association for Applied Human Pharmacology (AGAH e.V.) to critically review key eligibility criteria and stopping rules for clinical trials with healthy subjects, enrolling stakeholders from the pharmaceutical industry, contract research organisations, academia, ethics committees and competent authority. RESULTS: Pivotal eligibility criteria were defined for trials with new investigational medicinal products (IMPs) or with clinically established IMPs. In general, a pulse rate ranging between 50 and 90 beats/min is recommended for first-in-human (FIH) trials, while wider ranges seem acceptable for trials with clinically established IMPs, provided there are no indications of thyroid dysfunction. Hepatic laboratory parameters not to exceed the upper limit of normal (ULN) comprise ALT (alanine aminotransferase) and AST (aspartate aminotransferase) in FIH trials, whereas slight elevations (10% above ULN) seem acceptable in trials with clinically established IMPs without known hepatotoxicity. A normal renal function is required for any clinical trial in healthy subjects. A risk-adapted approach for stopping rules was adopted. Stopping rules for an individual subject are one adverse event of severe intensity or one serious adverse event. In case of a severe adverse event, some stakeholders demand a causal relationship with the IMP (i.e. an adverse reaction). Stopping rules for a cohort are one serious adverse reaction or ≥50% of subjects experiencing any adverse reaction of moderate or severe intensity. CONSEQUENCES: The application of this consensus resulted in a reduction in protocol deficiencies issued by the competent authority.
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spelling pubmed-53502172017-03-27 Who is a ‘healthy subject’?—consensus results on pivotal eligibility criteria for clinical trials Breithaupt-Groegler, Kerstin Coch, Christoph Coenen, Martin Donath, Frank Erb-Zohar, Katharina Francke, Klaus Goehler, Karin Iovino, Mario Kammerer, Klaus Peter Mikus, Gerd Rengelshausen, Jens Sourgens, Hildegard Schinzel, Reinhard Sudhop, Thomas Wensing, Georg Eur J Clin Pharmacol Review INTRODUCTION/METHODS: A discussion forum was hosted by the German not-for-profit Association for Applied Human Pharmacology (AGAH e.V.) to critically review key eligibility criteria and stopping rules for clinical trials with healthy subjects, enrolling stakeholders from the pharmaceutical industry, contract research organisations, academia, ethics committees and competent authority. RESULTS: Pivotal eligibility criteria were defined for trials with new investigational medicinal products (IMPs) or with clinically established IMPs. In general, a pulse rate ranging between 50 and 90 beats/min is recommended for first-in-human (FIH) trials, while wider ranges seem acceptable for trials with clinically established IMPs, provided there are no indications of thyroid dysfunction. Hepatic laboratory parameters not to exceed the upper limit of normal (ULN) comprise ALT (alanine aminotransferase) and AST (aspartate aminotransferase) in FIH trials, whereas slight elevations (10% above ULN) seem acceptable in trials with clinically established IMPs without known hepatotoxicity. A normal renal function is required for any clinical trial in healthy subjects. A risk-adapted approach for stopping rules was adopted. Stopping rules for an individual subject are one adverse event of severe intensity or one serious adverse event. In case of a severe adverse event, some stakeholders demand a causal relationship with the IMP (i.e. an adverse reaction). Stopping rules for a cohort are one serious adverse reaction or ≥50% of subjects experiencing any adverse reaction of moderate or severe intensity. CONSEQUENCES: The application of this consensus resulted in a reduction in protocol deficiencies issued by the competent authority. Springer Berlin Heidelberg 2017-01-07 2017 /pmc/articles/PMC5350217/ /pubmed/28064353 http://dx.doi.org/10.1007/s00228-016-2189-8 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review
Breithaupt-Groegler, Kerstin
Coch, Christoph
Coenen, Martin
Donath, Frank
Erb-Zohar, Katharina
Francke, Klaus
Goehler, Karin
Iovino, Mario
Kammerer, Klaus Peter
Mikus, Gerd
Rengelshausen, Jens
Sourgens, Hildegard
Schinzel, Reinhard
Sudhop, Thomas
Wensing, Georg
Who is a ‘healthy subject’?—consensus results on pivotal eligibility criteria for clinical trials
title Who is a ‘healthy subject’?—consensus results on pivotal eligibility criteria for clinical trials
title_full Who is a ‘healthy subject’?—consensus results on pivotal eligibility criteria for clinical trials
title_fullStr Who is a ‘healthy subject’?—consensus results on pivotal eligibility criteria for clinical trials
title_full_unstemmed Who is a ‘healthy subject’?—consensus results on pivotal eligibility criteria for clinical trials
title_short Who is a ‘healthy subject’?—consensus results on pivotal eligibility criteria for clinical trials
title_sort who is a ‘healthy subject’?—consensus results on pivotal eligibility criteria for clinical trials
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350217/
https://www.ncbi.nlm.nih.gov/pubmed/28064353
http://dx.doi.org/10.1007/s00228-016-2189-8
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