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Human Genome Epidemiology (2nd ed.): Building the evidence for using genetic information to improve health and prevent disease
necessarily represent the views of the funding agency.”
Chapter 23 – The Evaluation of Genomic Applications in Practice and Prevention (EGAPP™) initiative: methods of the EGAPP™ Working Group
Steven M. Teutsch, Linda A. Bradley, Glenn E. Palomaki, James E. Haddow, Margaret Piper, Ned Calonge, W. David Dotson, Michael P. Douglas, and Alfred O. Berg
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 Nonpsychotic 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?
This is a flowchart reading from left to right. There is a big parenthesis encompassing the whole flowchart with a number 1.
Adults with non-psychotic depression entering therapy with SSRIs
arrow with a number 2 to
arrow with number 3a to
Metabolizer status (phenotype)
arrow with number 3b going to
Predicted drug efficacy
and arrow with number 3cgoing also to
Predicted risk for adverse drug reactions
parenthesis to one arrow with numbers 4a,b,c with Treatment decisions above arrow
arrow leading to
Symptoms of depression
Shorter time to response
Fewer drug reactions
another arrow leading off the 4a,b,c arrow to number 5 arrow leading to
Harms of subsequent management options
- Page last reviewed: January 6, 2010 (archived document)
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