title: Recommendations for the assessment of progression in randomised cancer treatment trials.
abstract: Progression-free survival (PFS) is an increasingly important end-point in cancer drug development. However, several concerns exist regarding the use of PFS as a basis to compare treatments. Unlike survival, the exact time of progression is unknown, so progression times might be over-estimated (or under-estimated) and, consequently, bias may be introduced when comparing treatments. In addition, the assessment of progression is subject to measurement variability which may introduce error or bias. Ideally trials with PFS as the primary end-point should be randomised and, when feasible, double-blinded. All patients eligible for study should be evaluable for the primary end-point and thus, in general, have measurable disease at baseline. Appropriate definitions should be provided in the protocol and data collected on the case-report forms, if patients with only non-measurable disease are eligible and/or clinical, or symptomatic progression are to be considered progression events for analysis. Protocol defined assessments of disease burden should be obtained at intervals that are symmetrical between arms. Independent review of imaging may be of value in randomised phase II trials and phase III trials as an auditing tool to detect possible bias.
authors.affiliation: National Cancer Institute of Canada-Clinical Trials Group, 10 Stuart Street, Queen's University, Kingston, Ontario, Canada. jdancey@ctg.queensu.ca
authors.forename: J E
authors.initials: JE
authors.lastname: Dancey
authors.forename: L E
authors.initials: LE
authors.lastname: Dodd
authors.forename: R
authors.initials: R
authors.lastname: Ford
authors.forename: R
authors.initials: R
authors.lastname: Kaplan
authors.forename: M
authors.initials: M
authors.lastname: Mooney
authors.forename: L
authors.initials: L
authors.lastname: Rubinstein
authors.forename: L H
authors.initials: LH
authors.lastname: Schwartz
authors.forename: L
authors.initials: L
authors.lastname: Shankar
authors.forename: P
authors.initials: P
authors.lastname: Therasse
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015982:Bias; D018450:Disease Progression; D018572:Disease-Free Survival; D023381:Endpoint Determination; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents