title: Prospective-retrospective biomarker analysis for regulatory consideration: white paper from the industry pharmacogenomics working group.
abstract: One approach to delivering cost-effective healthcare requires the identification of patients as individuals or subpopulations that are more likely to respond to an appropriate dose and/or schedule of a therapeutic agent, or as subpopulations that are less likely to develop an adverse event (i.e., personalized or stratified medicine). Biomarkers that identify therapeutically relevant variations in human biology are often only uncovered in the later stage of drug development. In this article, the Industry Pharmacogenomics Working Group provides, for regulatory consideration, its perspective on the rationale for the conduct of what is commonly referred to as the prospective-retrospective analysis (PRA) of biomarkers. Reflecting on published proposals and materials presented by the US FDA, a decision tree for generating robust scientific data from samples collected from an already conducted trial to allow PRA is presented. The primary utility of the PRA is to define a process that provides robust scientific evidence for decision-making in situations where it is not necessary, nor practical or ethical to conduct a new prospective clinical study.
authors.affiliation: Medical Sciences, Amgen Inc., 1 Amgen Center Drive MS 38-3-A, Thousand Oaks, CA 91320, USA. spatters@amgen.com
authors.forename: Scott D
authors.initials: SD
authors.lastname: Patterson
authors.forename: Nadine
authors.initials: N
authors.lastname: Cohen
authors.forename: Maha
authors.initials: M
authors.lastname: Karnoub
authors.forename: Sharada Louis
authors.initials: SL
authors.lastname: Truter
authors.forename: Eileen
authors.initials: E
authors.lastname: Emison
authors.forename: Shirin
authors.initials: S
authors.lastname: Khambata-Ford
authors.forename: Brian
authors.initials: B
authors.lastname: Spear
authors.forename: Ekopimo
authors.initials: E
authors.lastname: Ibia
authors.forename: Rizwana
authors.initials: R
authors.lastname: Sproule
authors.forename: Diane
authors.initials: D
authors.lastname: Barnes
authors.forename: Anahita
authors.initials: A
authors.lastname: Bhathena
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bristow
authors.forename: Chris
authors.initials: C
authors.lastname: Russell
authors.forename: Dai
authors.initials: D
authors.lastname: Wang
authors.forename: Amelia
authors.initials: A
authors.lastname: Warner
authors.forename: Agnes
authors.initials: A
authors.lastname: Westelinck
authors.forename: William
authors.initials: W
authors.lastname: Brian
authors.forename: Amir
authors.initials: A
authors.lastname: Snapir
authors.forename: Monique A
authors.initials: MA
authors.lastname: Franc
authors.forename: Peggy
authors.initials: P
authors.lastname: Wong
authors.forename: Peter M
authors.initials: PM
authors.lastname: Shaw
mesh_terms: D054316:Biomarkers, Pharmacological; D002986:Clinical Trials as Topic; D003657:Decision Making; D006801:Humans; D007221:Industry; D010597:Pharmacogenetics / Q000592:standards*; D057285:Precision Medicine; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration; D018631:ras Proteins / Q000235:genetics
chemical_list: D054316:Biomarkers, Pharmacological; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins