5 Things Clinicians Should Know About the Complex World of Genetic Testing

Selecting the appropriate genetic test can be daunting, and busy clinicians can be hard pressed to stay up to date regarding the rapidly-evolving landscape of genomic medicine. They need to know what a test does, what diseases or conditions a test targets, what tests have evidence showing a benefit to patient management, and what tests are covered by payers. ECRI’s Genetic Test Assessment service focuses on assessing clinical evidence on genetic tests and deciphering a test’s intended purpose and methodology.

Below are some frequently asked questions from healthcare professionals who use ECRI to guide utilization of genetic testing. 

1. What is the difference between genetic and genomic testing? Are they the same?
   While technically different, the terms genetic and genomic testing are often used interchangeably. “Genetic test” is broad and encompasses a constellation of analyses in the molecular diagnostics field, but significant differences exist in these tests’ potential implications. It can be useful to think of molecular diagnostics in two overarching categories that typically serve different, and sometimes overlapping, purposes: germline testing and somatic testing.
   
   Germline testing examines DNA in a patient’s cells (usually from blood or saliva) to identify inherited genetic variants that may increase an individual’s risk for cancer or other conditions and inform whether a current condition is inherited. Genetic testing, described as “germline,” “risk assessment,” or “hereditary,” examines DNA in a patient’s cells (usually from a blood or saliva sample) to identify inherited genetic variants that may increase an individual’s risk for cancer or other conditions and inform whether a current condition is inherited. Genomic testing, described as “somatic,” “biomarker,” or “personalized medicine,” is performed on diseased tissue.
   
   
2. How can we measure the accuracy of genetic tests?
   The evidence supporting use of genetic testing can be broadly classified into three categories based on its ability to:
   - Reliably detect genetic variants (analytic validity)
   - Accurately predict the presence or absence of a condition or predisposition to disease (clinical validity)
   - Provide useful information to medical practice (clinical utility)
   
   A test without sufficient validity or utility has little value, so it is not surprising that much of the research on genetic testing focuses on establishing analytic and clinical validity and clinical utility. For clinicians to want to use it, the test must help patient care in some way.
   
   
3. Why do test results often seem convoluted?
   Genetic testing results are often not black and white. Gene sequencing generally provides three types of results: positive, negative, and uncertain. Positive and negative results are typically straightforward, but an uncertain/unknown result can be a source of stress and confusion for patients and providers.
   
   A variant of unknown significance (VUS) represents a variation in a gene that differs from what is currently understood as “normal.” A VUS has no definitive link to a particular disease or condition; rather, it implies that the scientific community does not have enough information to interpret what the variation represents. As the scientific community observes VUSs in enough healthy individuals or individuals with disease, the interpretation may change and be “upgraded” to pathogenic or “downgraded” to benign.
   
   
4. How accurate and useful are direct-to-consumer (DTC) genetic tests?
   Test kits for sale in pharmacies, big-box retailers, and online shopping sites lure consumers: discover your ancestry, find family members you never knew existed, and uncover information about disease predispositions that may be lurking in your genes. For years, 23andMe® and Ancestry® dominated the DTC marketplace; more recently, however, laboratories started offering new tests that use newer methodologies and physician-mediated “clinical grade" testing that is ordered or approved by a clinician who deems it appropriate to assess a particular patient's health status. Many tests purport to analyze genes associated with cancer risk, cardiovascular disease predisposition, drug response, and other personal health and wellness traits.
   
   Despite physician involvement, “clinical grade" tests raise concerns for patients, providers, and the healthcare system regardless of testing methodology. These tests can be confusing for patients who may lack the clinical knowledge to know whether testing for various health conditions is appropriate. Also, patients may not realize that test results can be inaccurate or yield incomplete information, which can be a source of distress and worry. If patients seek help from their providers, the clinicians may need to decipher and act on unfamiliar tests that may have been inappropriate at the outset. In turn, the healthcare system can become encumbered with the cost of confirmatory testing, screening, and treating conditions or disease predispositions that may not alter a patient's clinical course.​
   
   
5. Where can I find support for selecting the appropriate genetic test?
   This information simply scratches the surface of the complex and quickly evolving world of genetic testing. But there is help. You can make more confident utilization decisions about genetic tests with evidence-based assessments and data-driven guidance from ECRI's doctoral-level scientists and genetic counselor. ECRI’s clinical evidence team assessed the data on genetic tests to determine:
   - Which tests are best and which should be avoided?
   - Which tests have robust clinical utility evidence?
   - How will a test benefit a given patient?
   - Which payers cover a specific test?

Learn more about how payers and providers can rely on ECRI Genetic Test Assessment to make unbiased coverage and utilization decisions.