Clinical Validity and Utility of Genomic-targeted Chemoprevention of PCa: Aim 4a
Condition: Prostate Cancer; Prostate Cancer, Familial; Hereditary Prostate Cancer
MeSH terms: Prostatic Neoplasms
Study type: Interventional

Summary: 
      This study was designed to compare the efficacy, perception, decision making, and
      cost-effectiveness of genomic and non-genomic approaches for risk assessment of prostate
      cancer and for chemoprevention of prostate cancer.
    

Detailed description: 
      ABSTRACT: This clinical trial registration is focused on Aim 4 within the overall project
      described in the following.

      Prostate cancer (PCa) is the most common cancer among men in the U.S. One important strategy
      to address this public health concern is to prevent the disease. Two large randomized
      clinical trials, The Prostate Cancer Prevention Trial (PCPT) and The Reduction by Dutasteride
      of Prostate Cancer Events (REDUCE), have demonstrated a 23-25% reduction in PCa risk with the
      use of 5 alpha reductase inhibitors (5ARIs: finasteride and dutasteride). However, 5ARIs have
      not been widely adopted due, in part, to poor cost-effectiveness. We hypothesize that
      targeted chemoprevention, based on 1) overall genetic risk [family history (FH) and PCa
      risk-associated genetic variants], and 2) polymorphisms that interact with 5ARIs, may be more
      efficacious and cost-effective, and thus more likely to be employed by physicians and their
      patients. The effectiveness of this genomic-targeted approach needs to be systematically
      evaluated and compared to non-genomic approaches using evidence-based methods such as those
      recommended by the EGAPP (Evaluation of Genomic Applications in Practice and Prevention)
      working group. We have assembled a multidisciplinary research team to address an overarching
      question of whether a genomic-targeted approach improves outcomes related to chemoprevention
      of PCa using 5ARIs compared to a non-targeted approach. We will evaluate and compare the
      efficacy, perception, decision making, and cost-effectiveness of genomic and non-genomic
      approaches in two existing large randomized clinical trials (Reduction by Dutasteride of
      Prostate Cancer Events (REDUCE) and Prostate Cancer Prevention Trial (PCPT)), two new study
      populations of men at risk for PCa, and in a survey of physicians. The unique study design of
      REDUCE and PCPT, with end-of-study prostate biopsies, allows us to address two critical
      questions in this study: Prostate Specific Antigen (PSA) detection-bias of PCa
      risk-associated Single Nucleotide Polymorphisms (SNPs) and efficacy of genomic-targeted
      chemoprevention of PCa using 5ARIs. We have the following specific aims: 1) assess the
      clinical validity of PCa risk prediction models using a panel of non PSA detection biased PCa
      risk-associated SNPs. 2) identify and assess the clinical validity of novel polymorphisms
      that interact with 5ARIs in reducing PCa diagnosis using both genome-wide and candidate gene
      approaches, 3) assess the clinical utility of a genomic-targeted approach by comparing its
      reduction in rates of PCa with non-targeted chemoprevention, 4) compare perception and
      decision making of physicians and patients for genomic and non-genomic-targeted
      chemoprevention of PCa, and 5) Compare the cost-effectiveness of genomic and
      non-genomic-targeted chemoprevention of PCa. Results from this study will provide
      comprehensive data for evidence-based evaluation by the Center for Disease Control's
      Evaluation of Genomic Applications in Practice and Prevention (EGAPP) working group, provide
      a proof of principle study of Comparative Effectiveness Research (CER), and will help build a
      road map for future Genomic and Personalized Medicine (GPM) in the 21st century.
    

Intervention name(s): Genetic Risk Score: Number Format; Genetic Risk Score: Number + Pictograph; Family History: Number Format; Family History: Number + Pictograph
Intervention type(s): Genetic; Genetic; Behavioral; Behavioral
Intervention description(s): Genetic Risk Score: Number + Pictograph Genetic risk score based on validated panel of 46 single nucleotide polymorphisms previously identified to be associated with Prostate Cancer risk by Genome Wide Association Studies, presented to subjects as a number.; Genetic Risk Score: Number + Pictograph Risk information conveyed as either a number or a number + pictograph, depending on randomization group.; Family History: Number Format Risk information conveyed as either a number or a number + pictograph, depending on randomization group.; Family History: Number + Pictograph Risk information conveyed as either a number or a number + pictograph, depending on randomization group.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: Genetic testing; Genomic testing; Chemoprevention; Prostate Specific Antigen; Prostate Cancer; Predictive Genetic Testing; Genetic Counseling; Prostate-Specific Antigen