title: Bayesian monitoring of a phase 2 chemoprevention trial in high-risk cohorts for prostate cancer.
abstract: The objective of phase 2 cancer chemoprevention trials is to evaluate whether a chemopreventive agent will cause significant modulation of intermediate endpoint biomarkers (IEB) in patients at high risk for the disease. A phase 2 chemoprevention trial of 4-hydroxyphenyl retinamide (4-HPR) versus placebo was conducted in men with a histologic diagnosis of early prostate cancer and scheduled to have radical prostatectomy. A Bayesian monitoring method was used to sequentially monitor this trial for evidence of biological activity or ineffectiveness based on a single IEB variable. Different prior distributions were used and posterior distributions were obtained to calculate the probability that treatment differences are greater than or less than a predetermined clinically significant effect. The interim analysis of transforming growth factor-alpha expression indicated a high probability of insufficient biological activity of 4-HPR on this IEB. This study demonstrates the potential utility of Bayesian methods in the decision-making process in the conduct of phase 2 chemoprevention trials.
authors: Biostatistics Unit, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294-3300, USA. hlweiss@uab.edu
authors: H L
authors: HL
authors: Weiss
authors: D A
authors: DA
authors: Urban
authors: W E
authors: WE
authors: Grizzle
authors: K A
authors: KA
authors: Cronin
authors: L S
authors: LS
authors: Freedman
authors: G J
authors: GJ
authors: Kelloff
authors: R
authors: R
authors: Lieberman
mesh_terms: D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001499:Bayes Theorem; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D015331:Cohort Studies; D004311:Double-Blind Method; D017313:Fenretinide / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D015291:Transforming Growth Factors / Q000378:metabolism*
chemical_list: D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D017313:Fenretinide; D015291:Transforming Growth Factors