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Am Fam Physician. 2009;80(11):1218-1220

Author disclosure: Nothing to disclose.

Family physicians cannot have missed the rapid increase in the number of available genetic tests, which have potential application to screening, disease risk assessment, diagnosis, management, and prognosis. Although most genetic tests are promoted for use in the context of physician-counseled clinical care, some are promoted directly to consumers and are publicly available through Web-based companies.

As with all new technologies, physicians and patients want authoritative advice on potential benefits and harms of new genetic tests. There is also increasing interest in comparative effectiveness (do new tests do a better job than currently available tests?) and cost-effectiveness (is the incremental benefit worth the cost?). An international consensus about how to evaluate new technologies, led by the Agency for Healthcare Research and Quality in the United States and by the National Institute for Health and Clinical Excellence in the United Kingdom, is emerging. In recent years, these agencies and affiliated groups (e.g., the U.S. Preventive Services Task Force1) have released many recommendations on the use of testing technologies in clinical care. The core purpose of these processes is to demonstrate a favorable balance of clinical benefits versus harms.

Tests based on genomics are some of the most actively emerging domains, with potentially wide applicability in screening, diagnosis, management, and prognosis. This rapid growth and potential does not mean that genomic tests should be issued a “pass” on the need for evidence. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP; is an initiative sponsored by the Centers for Disease Control and Prevention (CDC) Office of Public Health Genomics that aims to provide authoritative advice to physicians and patients about genomic tests.2 The EGAPP initiative is developing methods that are explicit, transparent, and publicly accountable, and that critically examine analytic validity, clinical validity, and clinical utility, with particular weight given to the demonstration of clinical outcomes that patients recognize and care about.3 So far, the EGAPP Working Group (EWG) has released recommendations on four applications of genomic tests.

  • Does testing for cytochrome P450 polymorphisms in adults beginning 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?4

The EWG found insufficient evidence to recommend for or against the use of CYP450 testing in adults beginning SSRI treatment for nonpsychotic depression. In the absence of supporting evidence, and with consideration of other contextual issues, the EWG discourages the use of CYP450 testing in patients beginning SSRI treatment until further clinical trials are completed.

  • Genetic testing strategies in persons newly diagnosed with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives.5

The EWG found sufficient evidence to recommend offering genetic testing for Lynch syndrome to persons with newly diagnosed colorectal cancer to reduce morbidity and mortality in relatives. There was insufficient evidence to recommend a specific genetic testing strategy among several that were examined.

  • Can tumor gene expression profiling improve outcomes in patients with breast cancer?6

The EWG found insufficient evidence to recommend for or against the use of tumor gene expression profiles to improve outcomes in defined populations of women with breast cancer. For one test, the EWG found preliminary evidence of potential benefit of testing results in some women who need to make decisions about treatment options (reduced adverse events because of low-risk women avoiding chemotherapy), but could not rule out the potential for harm in other women (breast cancer recurrence that might have been prevented). The evidence is insufficient to assess the balance of benefits and harms of the proposed uses of the tests. The EWG encourages further development and evaluation of these technologies.

  • Can UGT1A1 genotyping reduce morbidity and mortality in persons with metastatic colorectal cancer treated with irinotecan (Camptosar)?7

The EWG found insufficient evidence to recommend for or against the routine use of UGT1A1 genotyping in persons with metastatic colorectal cancer treated with irinotecan, with the intent of modifying the dose as a way to avoid adverse drug reactions (e.g., severe neutropenia).

The EGAPP initiative is a model project, which means that scope and methods are still in development. Additional topics under review include cardiogenomic profiling, factor V Leiden testing, multiple single nucleotide polymorphism testing for prostate and breast cancer, and CYP2D6 testing to direct use of tamoxifen in breast cancer. Many other tests are available, and because the EGAPP initiative is a small project, it cannot possibly evaluate all of them. The CDC hopes that the initial success of the EGAPP initiative will stimulate discussion on how to expand the project to be more comprehensive, so that patients and physicians always have somewhere to turn for authoritative advice.

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