Data driven evaluation of healthy volunteer characteristics at screening for phase I clinical trials to inform on study design and optimize screening processes
| Autor: | Freya Rasschaert, Annemie Deiteren, Sabine Lenders, Erwin Coenen, Peter Verwilst, Erik Mannaert |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Population Vital signs RM1-950 QT interval Article General Biochemistry Genetics and Molecular Biology Young Adult Internal medicine medicine Humans Mass Screening General Pharmacology Toxicology and Pharmaceutics education Aged Retrospective Studies Prothrombin time education.field_of_study medicine.diagnostic_test business.industry Patient Selection Research General Neuroscience Articles General Medicine Middle Aged Healthy Volunteers Clinical trial Blood pressure Research Design Inclusion and exclusion criteria Female Therapeutics. Pharmacology Public aspects of medicine RA1-1270 Liver function tests business |
| Zdroj: | Clinical and Translational Science Clinical and Translational Science, Vol 14, Iss 6, Pp 2450-2460 (2021) |
| ISSN: | 1752-8062 1752-8054 |
| Popis: | Protocols for clinical trials describe inclusion and exclusion criteria based on general and compound‐specific considerations to ensure subject safety and data quality. In phase I clinical trials, healthy volunteers (HVs) are screened against these criteria that often specify predefined eligibility ranges for vital signs, electrocardiogram, and laboratory tests. HVs are excluded if baseline parameters deviate from these ranges even though this may not indicate underlying pathology, which could delay trial execution. Data from 3365 HVs participating in 9670 screening visits for 94 phase I HV trials, conducted between December 2008 and May 2019 at the Janssen Clinical Pharmacology Unit, were retrospectively analyzed. Commonly predefined protocol ranges were overlaid with HV data to estimate predicted screen failure rates (SFRs). Of the overall population, 91% was White and 64% were men with mean age of 42.8 ± 12.5 years. High predicted SFRs are related to cardiovascular/metabolic (body mass index, heart rate [HR], blood pressure [BP], and corrected QT Fridericia’s formula [QTcF]), renal (estimated glomerular filtration rate [eGFR]), liver (alanine aminotransferase [ALT], and total bilirubin), and coagulation (prothrombin time [PT]) parameters. Predicted SFRs increased with age for high systolic and diastolic BP, QTcF interval, and eGFR. In contrast, lower SFRs in the older age groups were seen for low diastolic BP, liver function test, ALT, PT, and total bilirubin. This analysis can be used to inform on study design, protocol inclusion and exclusion criteria, and to optimize the screening process. Data‐driven critical appraisal of proposed inclusion and exclusion criteria using a risk‐based approach may significantly reduce screen failure rates without compromising subjects’ safety. |
| Databáze: | OpenAIRE |
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