Title |
Who is a ‘healthy subject’?—consensus results on pivotal eligibility criteria for clinical trials
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Published in |
European Journal of Clinical Pharmacology, January 2017
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DOI | 10.1007/s00228-016-2189-8 |
Pubmed ID | |
Authors |
Kerstin Breithaupt-Groegler, Christoph Coch, Martin Coenen, Frank Donath, Katharina Erb-Zohar, Klaus Francke, Karin Goehler, Mario Iovino, Klaus Peter Kammerer, Gerd Mikus, Jens Rengelshausen, Hildegard Sourgens, Reinhard Schinzel, Thomas Sudhop, Georg Wensing |
Abstract |
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. 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. The application of this consensus resulted in a reduction in protocol deficiencies issued by the competent authority. |
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Egypt | 1 | 100% |
Demographic breakdown
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Practitioners (doctors, other healthcare professionals) | 1 | 100% |
Mendeley readers
Geographical breakdown
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United States | 1 | 1% |
Unknown | 66 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 14 | 21% |
Researcher | 9 | 13% |
Other | 7 | 10% |
Student > Master | 7 | 10% |
Student > Bachelor | 5 | 7% |
Other | 12 | 18% |
Unknown | 13 | 19% |
Readers by discipline | Count | As % |
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Pharmacology, Toxicology and Pharmaceutical Science | 14 | 21% |
Medicine and Dentistry | 14 | 21% |
Nursing and Health Professions | 5 | 7% |
Biochemistry, Genetics and Molecular Biology | 4 | 6% |
Business, Management and Accounting | 3 | 4% |
Other | 13 | 19% |
Unknown | 14 | 21% |