Evaluating causality may be difficult because of

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Evaluating causality may be difficult because of factors that influence associations (e.g., environmental exposures, behaviors, other genes). Principle 8: Understand Statistical Issues of Particular Relevance to Genetic Tests (3 of 4) Jonas DE, Wilt TJ, Taylor BC, et al. Challenges in and principles for conducting systematic reviews of genetic tests used as predictive indicators. In: Methods guide for medical test reviews. Available at .
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Overlapping Data Sets Publications may sometimes have overlapping data sets regarding prevalence of genetic variants. Genome-wide association studies or other large collaborative efforts may pool patients who were previously included in other published studies. To the extent possible, double-counting should be avoided by investigators. Assessing Tumor Genetics Tumor genomes may be in a dynamic state. Tumor specimens often contain normal patient cells. Specimen characteristics affect the operation and sensitivity of the test. Principle 8: Understand Statistical Issues of Particular Relevance to Genetic Tests (4 of 4) Jonas DE, Wilt TJ, Taylor BC, et al. Challenges in and principles for conducting systematic reviews of genetic tests used as predictive indicators. In: Methods guide for medical test reviews. Available at .
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Background on Genetic Tests Challenges in Reviews of Genetic Tests Principles for Addressing the Challenges Illustrative Examples General Overview: Section 4 Jonas DE, Wilt TJ, Taylor BC, et al. Challenges in and principles for conducting systematic reviews of genetic tests used as predictive indicators. In: Methods guide for medical test reviews. Available at .
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Adults with depression who are treated with selective serotonin reuptake inhibitors (SSRIs) undergo genetic testing for cytochrome P450 polymorphisms. This is an example of a well-defined predictive genetic testing scenario. The investigators developed an analytic framework and five key questions to explore the chain of evidence leading to intermediate outcomes. The investigators found no prospective studies of the use of genotyping to guide treatment that measured clinical outcomes The investigators evaluated the links between genotype and metabolism of SSRIs (phenotype), metabolism and SSRI efficacy, and metabolism and adverse drug reactions to SSRIs. Illustrative Example 1: Cytochrome P450 Testing (1 of 2) Jonas DE, Wilt TJ, Taylor BC, et al. Challenges in and principles for conducting systematic reviews of genetic tests used as predictive indicators. In: Methods guide for medical test reviews. Available at .
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