title: Can a treatment be licenced on the basis of post-treatment predictive biomarkers?
abstract: In recent years, there has been a great deal of literature published concerning the identification of predictive biomarkers and indeed, an increasing number of therapies have been licenced on this basis. However, this progress has been made almost exclusively on the basis of biomarkers measured prior to exposure to treatment. There are quite different challenges when the responding population can only be identified on the basis of outcomes observed following exposure to treatment, especially if it represents only a small proportion of patients. The purpose of this paper is to explore whether or when a treatment could be licenced on the basis of post-treatment predictive biomarkers (PTPB), the focus is on oncology but the concepts should apply to all therapeutic areas. We review the potential pitfalls in hypothesising the presence of a PTPB. We also present challenges in trial design required to confirm and licence on the basis of a PTPB: what's the control population?, could there be a detriment to non-responders by exposure to the new treatment?, can responders be identified rapidly?, could prior exposure to the new treatment adversely affect performance of the control in responders? Nevertheless, if the patients to be treated could be rapidly identified after prior exposure to treatment, and without harm to non-responders, in appropriately designed and analysed trials, may be more targeted therapies could be made available to patients.
authors.affiliation: AstraZeneca, Parklands, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Stone
authors.forename: Nicola
authors.initials: N
authors.lastname: Schmitt
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D017277:Drug Approval / Q000379:methods*; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods*
chemical_list: D015415:Biomarkers
keywords: biomarker; regulatory; trial design