Does genomic profiling to assess Type 2 Diabetes risk improve health outcomes?

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It has been suggested that genomic profiling in the general population or in high-risk populations for type 2 diabetes (T2D) might lead to management changes (e.g., earlier initiation or higher rates of medical interventions, or targeted recommendations for behavioral change) that improve T2D outcomes or prevent T2D. EWG found no direct evidence to support this possibility, so this review sought indirect evidence aimed at documenting the extent to which genomic profiling alters T2D risk estimation, alone and in combination with traditional risk factors, and the extent to which risk classification improves health outcomes.

EGAPP Recommendation Statement:The EGAPP Working Group (EWG) found insufficient evidence to recommend testing for predictive variants in 28 variants (listed in Table 1 of the recommendation) to assess risk for Type 2 Diabetes in the general population, based on studies in populations of northern European descent. The EWG found that the magnitude of net health benefit from use of any of these tests alone or in combination is close to zero. The EWG discourages clinical use unless further evidence supports improved clinical outcomes.

The EGAPP Working Group (EWG) found insufficient evidence to recommend testing for the TCF7L2 gene to assess risk for Type 2 Diabetes in high-risk individuals. The EWG found that the magnitude of net health benefit from use of this test is close to zero. The EWG discourages clinical use unless further evidence supports improved clinical outcomes.

Based on the available evidence for both scenarios, the overall certainty of net health benefit is deemed ‘Low’.

EGAPP Recommendation (May 2013)

Evidence Report (March 2013)

Key Questions:

Clinical Scenario 1 – Does the use of a Multigene Panel to Estimate Lifetime Risk of Developing Type 2 Diabetes (T2D) Improve Patient Outcomes?

  • Question 1: Does the use of the T2D Multigene Panel test lead to improved outcomes for the patient/consumer, or is it useful in medical or personal decision making? (overarching question)?

  • Question 2: What is known about the analytic validity of the test(s) used to identify the variations in the genes in the T2D Multigene Panel, including the analytic sensitivity and specificity, reproducibility, assay robustness (e.g., failure rates, resistance to changes in variables such as sample quality), and other factors?

  • Question 3: What is the clinical validity of the T2D Multigene Panel, including clinical sensitivity and specificity and positive and negative predictive values?

    A. What is the strength of association of the variants in these specific genes with risk for T2D (e.g., odds ratios)?

    B. How well does this testing alone predict risk for T2D?

    C. How well does this testing in combination with other clinical factors (e.g., family history, age, BMI/obesity, glucose levels) predict risk for T2D?

    D. How do other genetic and environmental factors (e.g., race/ethnicity, family history, smoking, diet, exercise level, other conditions) affect the clinical validity of this test?

  • Question 4: What are the issues relating to the use of the T2D Multigene Panel test in the general population and its impact on patient/consumer outcomes?

    A. What are the current management options for patients/consumers at risk for T2D based on a positive T2D Multigene Panel result in a medical model? How would recommendations differ from routine health messages? How would outcomes change based on use of this test in a direct to consumer model?

    B. How could the results of the T2D Multigene Panel for risk of T2D in the general population impact health behaviors or inform decision-making by patients and their healthcare providers that affect outcomes?

    C. In what ways could the use of the T2D Multigene Panel in the general population impact clinical outcomes (e.g., morbidity / mortality)?

    D. What is known about other contextual issues, such as cost-effectiveness, likelihood of behavioral change, and family history considerations?

  • Question 5: What are the potential harms associated with use of the T2D Multigene Panel (e.g., marketing direct to consumers, distress or stigma for a “poor prognosis” result, misinterpretation of results leading to excessive or inadequate treatment, exploitation of hyper-vigilant people)?

 

Clinical Scenario 2 – Does the use of TCF7L2 Testing in a High Risk Population to Determine Short Term (3-4 yrs) Risk of Developing Type 2 Diabetes (T2D) Improve Outcomes?

  • Question 1: Does the use of TCF7L2 testing lead to improved outcomes for the patient/consumer, or is it useful in medical or personal decision making? (overarching question)

  • Question 2. What is known about the analytic validity of the test(s) used to identify the variation in the TCF7L2 gene, including the analytic sensitivity and specificity, reproducibility, assay robustness (e.g., failure rates, resistance to changes in variables such as sample quality), and other factors?

  • Question 3. What is the clinical validity of TCF7L2 testing, including clinical sensitivity and specificity and positive and negative predictive values?

    A. What is the strength of association of the variant in this specific gene with short-term risk for T2D (e.g., odds ratios)?

    B. How well does this testing alone predict risk for T2D?

    C. How well does this testing in combination with other clinical factors (e.g., family history, age, BMI/obesity, glucose levels) predict risk for T2D?

    D. How do other genetic and environmental factors (e.g., race/ethnicity, family history, smoking, diet, exercise level, other conditions) affect the clinical validity of this test?

  • Question 4. What are the issues relating to the use of TCF7L2 testing in this high risk population and its impact on patient/consumer outcomes?

    A. What are the current management options for high risk patients/consumers who have a positive TCF7L2 test result in the usual medical model? Would recommendations differ from routine health messages? How might the outcomes change in a direct to consumer model?

    B. How could the results of TCF7L2 testing for risk of T2D in this high risk population impact health behaviors or inform decision-making by patients and their healthcare providers that affect outcomes?

    C. In what ways could the use of TCF7L2 testing in this high risk population impact clinical outcome (e.g., morbidity / mortality)?

    D. What is known about other contextual issues, such as cost-effectiveness, likelihood of behavioral change, and family history considerations?

  • Question 5.What are the potential harms associated with TCF7L2 testing (e.g., marketing direct to consumers, distress or stigma for a “poor prognosis” result, misinterpretation of results leading to excessive or inadequate treatment, exploitation of hyper-vigilant people)?

Why EGAPP Selected this Topic for Review:

Key Criteria: Prevalence and severity of T2D; testing is offered through both clinical and direct-to-consumer models, each with unique considerations.

Other Considerations: Estimating risk of T2D based on variants in multiple genes, individually and in combination, challenges risk assessment and EGAPP evidence review methods. Review considers two distinct populations.