The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative: methods of the EGAPP Working Group

Abstract

The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative, established by the National Office of Public Health Genomics at the Centers for Disease Control and Prevention, supports the development and implementation of a rigorous, evidence-based process for evaluating genetic tests and other genomic applications for clinical and public health practice in the United States. An independent, non-federal EGAPP Working Group (EWG), a multidisciplinary expert panel selects topics, oversees the systematic review of evidence, and makes recommendations based on that evidence. This article describes the EGAPP processes and details the specific methods and approaches used by the EWG.

Fig. 1

Analytic framework and key questions for evaluating one application of a genetic test in a specific clinical scenario: Testing for Cytochrome P450 Polymorphisms in Adults With Non-Psychotic Depression Treated With Selective Serotonin Reuptake Inhibitors (SSRIs); modified from reference 56. The numbers correspond to the following key questions: 1. Overarching question: Does testing for cytochrome P450 (CYP450) polymorphisms in adults entering selective serotonin reuptake inhibitor (SSRI) treatment for nonpsychotic depression lead to improvement in outcomes, or are testing results useful in medical, personal, or public health decision-making? 2. What is the analytic validity of tests that identify key CYP450 polymorphisms? 3. Clinical validity: A, How well do particular CYP450 genotypes predict metabolism of particular SSRIs? B, How well does CYP450 testing predict drug efficacy? C, Do factors such as race/ethnicity, diet, or other medications, affect these associations? 4. Clinical utility: A, Does CYP450 testing influence depression management decisions by patients and providers in ways that could improve or worsen outcomes? B, Does the identification of the CYP450 genotypes in adults entering SSRI treatment for nonpsychotic depression lead to improved clinical outcomes compared to not testing? C, Are the testing results useful in medical, personal, or public health decision-making? 5. What are the harms associated with testing for CYP450 polymorphisms and subsequent management options?