title: The use of biomarkers in human pharmacology (Phase I) studies.
abstract: The development of a new medicine is a risky and costly undertaking that requires careful planning. This planning is largely applied to the operational aspects of the development and less so to the scientific objectives and methodology. The drugs that will be developed in the future will increasingly affect pathophysiological pathways that have been largely unexplored. Such drug prototypes cannot be immediately introduced in large clinical trials. The effects of the drug on normal physiology, pathophysiology, and eventually the desired clinical effects will need to be evaluated in a structured approach, based on the definition of drug development as providing answers to important questions by appropriate clinical studies. This review describes the selection process for biomarkers that are fit-for-purpose for the stage of drug development in which they are used. This structured and practical approach is widely applicable and particularly useful for the early stages of innovative drug development.
authors.affiliation: Centre for Human Drug Research, 2333 CL Leiden, The Netherlands; email: ac@chdr.nl.
authors.forename: A F
authors.initials: AF
authors.lastname: Cohen
authors.forename: J
authors.initials: J
authors.lastname: Burggraaf
authors.forename: J M A
authors.initials: JM
authors.lastname: van Gerven
authors.forename: M
authors.initials: M
authors.lastname: Moerland
authors.forename: G J
authors.initials: GJ
authors.lastname: Groeneveld
mesh_terms: D000818:Animals; D054316:Biomarkers, Pharmacological / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery / Q000379:methods*; D054796:Drug Dosage Calculations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000517:prevention & control; D023381:Endpoint Determination; D006801:Humans; D061214:Patient Safety; D010599:Pharmacokinetics; D010600:Pharmacology / Q000379:methods*; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D054316:Biomarkers, Pharmacological
keywords: clinical trials; precision medicine; prediction in pharmacology; question-based drug development; surrogate endpoints