Julie Ann Lynch

Utilization of genetic tests: analysis of gene-specific billing in Medicare claims data

Purpose:We examined the utilization of precision medicine tests among Medicare beneficiaries through analysis of gene-specific tier 1 and 2 billing codes developed by the American Medical Association in 2012.Methods:We conducted a retrospective cross-sectional study. The primary source of data was 2013 Medicare 100% fee-for-service claims. We identified claims billed for each laboratory test, the number of patients tested, expenditures, and the diagnostic codes indicated for testing. We analyzed variations in testing by patient demographics and region of the country.Results:Pharmacogenetic tests were billed most frequently, accounting for 48% of the expenditures for new codes. The most common indications for testing were breast cancer, long-term use of medications, and disorders of lipid metabolism. There was underutilization of guideline-recommended tumor mutation tests (e.g., epidermal growth factor receptor) and substantial overutilization of a test discouraged by guidelines (methylenetetrahydrofolate reductase). Methodology-based tier 2 codes represented 15% of all claims billed with the new codes. The highest rate of testing per beneficiary was in Mississippi and the lowest rate was in Alaska.Conclusions:Gene-specific billing codes significantly improved our ability to conduct population-level research of precision medicine. Analysis of these data in conjunction with clinical records should be conducted to validate findings.Genet Med advance online publication 26 January 2017

BRCA Genetic Testing and Receipt of Preventive Interventions Among Women Aged 18–64 Years with Employer-Sponsored Health Insurance in Nonmetropolitan and Metropolitan Areas — United States, 2009–2014

Problem/Condition Genetic testing for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene mutations can identify women at increased risk for breast and ovarian cancer. These testing results can be used to select preventive interventions and guide treatment. Differences between nonmetropolitan and metropolitan populations in rates of BRCA testing and receipt of preventive interventions after testing have not previously been examined. Period Covered 2009–2014. Description of System Medical claims data from Truven Health Analytics MarketScan Commercial Claims and Encounters databases were used to estimate rates of BRCA testing and receipt of preventive interventions after BRCA testing among women aged 18–64 years with employer-sponsored health insurance in metropolitan and nonmetropolitan areas of the United States, both nationally and regionally. Results From 2009 to 2014, BRCA testing rates per 100,000 women aged 18–64 years with employer-sponsored health insurance increased 2.3 times (102.7 to 237.8) in metropolitan areas and 3.0 times (64.8 to 191.3) in nonmetropolitan areas. The relative difference in BRCA testing rates between metropolitan and nonmetropolitan areas decreased from 37% in 2009 (102.7 versus 64.8) to 20% in 2014 (237.8 versus 191.3). The relative difference in BRCA testing rates between metropolitan and nonmetropolitan areas decreased more over time in younger women than in older women and decreased in all regions except the West. Receipt of preventive services 90 days after BRCA testing in metropolitan versus nonmetropolitan areas throughout the period varied by service: the percentage of women who received a mastectomy was similar, the percentage of women who received magnetic resonance imaging of the breast was lower in nonmetropolitan areas (as low as 5.8% in 2014 to as high as 8.2% in 2011) than metropolitan areas (as low as 7.3% in 2014 to as high as 10.3% in 2011), and the percentage of women who received mammography was lower in nonmetropolitan areas in earlier years but was similar in later years. Interpretation Possible explanations for the 47% decrease in the relative difference in BRCA testing rates over the study period include increased access to genetic services in nonmetropolitan areas and increased demand nationally as a result of publicity. The relative differences in metropolitan and nonmetropolitan BRCA testing rates were smaller among women at younger ages compared with older ages. Public Health Action Improved data sources and surveillance tools are needed to gather comprehensive data on BRCA testing in the United States, monitor adherence to evidence-based guidelines for BRCA testing, and assess receipt of preventive interventions for women with BRCA mutations. Programs can build on the recent decrease in geographic disparities in receipt of BRCA testing while simultaneously educating the public and health care providers about U.S. Preventive Services Task Force recommendations and other clinical guidelines for BRCA testing and counseling.

Genetic tests to identify risk for breast cancer

OBJECTIVES To describe the currently available genetic tests that identify hereditary risk for breast cancer. DATA SOURCES Systematic review of scientific literature, clinical practice guidelines, and data published by test manufacturers. CONCLUSION Changes in gene patent laws and advances in sequencing technologies have resulted in rapid expansion of genetic testing. While BRCA1/2 are the most recognized genes linked to breast cancer, several laboratories now offer multi-gene panels to detect many risk-related mutations. IMPLICATIONS FOR NURSING PRACTICE Genetic testing will be increasingly important in the prevention, diagnosis, and treatment of breast cancer. Oncology and advanced practice nurses must understand risk factors, significance of various genetic tests, and patient counseling.

Trends in utilization and costs of BRCA testing among women aged 18–64 years in the United States, 2003–2014

PurposeWe examined 12-year trends in BRCA testing rates and costs in the context of clinical guidelines, national policies, and other factors.MethodsWe estimated trends in BRCA testing rates and costs from 2003 to 2014 for women aged 18–64 years using private claims data and publicly reported revenues from the primary BRCA testing provider.ResultsThe percentage of women with zero out-of-pocket payments for BRCA testing increased during 2013–2014, after 7 years of general decline, coinciding with a clarification of Affordable Care Act coverage of BRCA genetic testing. Beginning in 2007, family history accounted for an increasing proportion of women with BRCA tests compared with personal history, coinciding with BRCA testing guidelines for primary care settings and direct-to-consumer advertising campaigns. During 2013–2014, BRCA testing rates based on claims grew at a faster rate than revenues, following 3 years of similar growth, consistent with increased marketplace competition. In 2013, BRCA testing rates based on claims increased 57%, compared with 11% average annual increases over the preceding 3 years, coinciding with celebrity publicity.ConclusionThe observed trends in BRCA testing rates and costs are consistent with possible effects of several factors, including the Affordable Care Act, clinical guidelines and celebrity publicity.

Molecular Diagnostic Testing in Breast Cancer

OBJECTIVES An overview of molecular tests used in the treatment of breast cancer, organized by stage and clinical condition. DATA SOURCES Systematic review of scientific literature, guideline recommendations, and data published by test manufacturers. CONCLUSION Several molecular tests that analyze expression of cancer-related genes have been validated in clinical trials and are recommended by clinical practice guidelines to inform diagnosis and treatment decisions for personalized interventions. IMPLICATIONS FOR NURSING PRACTICE Molecular testing has become an important part of patient care for those with breast cancer. Oncology nurses must understand this methodology to prescribe tests, interpret the results, and provide guidance to patients.

Implementation of the 21-gene recurrence score test in the United States in 2011

Purpose:We examined hospital use of the 21-gene breast cancer test in the United States. We report state-level differences in utilization and propose a model for predicting implementation of guideline-recommended genomic testing.Methods:Genomic Health provided test orders for calendar year 2011.We summarized utilization at the hospital and state levels. Using logistic regression, we analyzed the association between the likelihood to order the test and the hospital’s institutional and regional characteristics.Results:In 2011, 45% of 4,712 acute-care hospitals ordered the test, which suggests that 25% of newly diagnosed invasive female breast cancer cases were tested. Significant predictors of testing included participation in National Cancer Institute (NCI) clinical research cooperative groups (odds ratio (OR) 3.73; 95% confidence interval, 2.96–4.70), advanced imaging (OR, 2.19; CI, 1.78–2.68), high-complexity laboratory (OR, 2.15; CI, 1.24–3.70), affiliation with a medical school (OR, 1.57; CI, 1.31–1.88), and reconstructive surgery (OR, 1.23; CI, 1.01–1.50). Significant regional predictors included metropolitan county (OR, 3.77; CI, 2.83–5.03), above-mean income (OR, 1.37; CI, 1.11–1.69), and education (OR, 1.26; CI, 1.03–1.54). Negative predictors included designation as a critical-access hospital (OR, 0.10; CI, 0.07–0.14) and distance from an NCI cancer center (OR, 0.998; CI, 0.997–0.999), with a 15% decrease in likelihood for every 100 miles.Conclusion:Despite considerable market penetration of the test, there are significant regional and site-of-care differences in implementation, particularly in rural states.Genet Med 18 10, 982–990.

Epidermal Growth Factor Receptor Mutational Testing and Erlotinib Treatment Among Veterans Diagnosed With Lung Cancer in the United States Department of Veterans Affairs

Introduction We examined mutational testing of the epidermal growth factor gene (EGFR) and erlotinib treatment among veterans diagnosed with non–small‐cell lung cancer in the United States Department of Veterans Affairs (VA). Our objectives were to identify the prevalence of clinically actionable EGFR mutations, to determine whether testing and treatment were guideline concordant, to evaluate the impact of testing and treatment on survival, and to estimate the rate of testing. Patients and Methods Test results were linked to electronic health records from VA Corporate Data Warehouse and the VA Central Cancer Registry. We analyzed patient demographic and clinical characteristics, prevalence of EGFR mutations, and timing of EGFR mutational testing and erlotinib treatment based on pharmacy records. Overall survival was assessed by Kaplan‐Meier analysis. Results Among 973 patients tested at 70 VA medical centers between 2011 and 2013, 64 (7%) had sensitizing EGFR mutations, 694 (71%) were EGFR wild type, and 168 (17%) had clinically insignificant polymorphisms or variants of unknown significance. Results were not documented in 47 tests (5%). Erlotinib administration was in agreement with test results in 843 cases (87%). Conclusion Veterans have a much lower rate of sensitizing EGFR mutations than the reported average of 10% to 15%, which correlates with a high rate of smoking among veterans. This may partially explain clinicians’ reluctance to prescribe EGFR testing, which results in underutilization. Although test results appear to have influenced erlotinib treatment decisions, we documented a substantial number of cases where treatment was not applied in accordance with clinical guidelines, potentially resulting in worse outcomes and unnecessary cost. Micro‐Abstract We examined epidermal growth factor receptor gene (EGFR) testing and erlotinib treatment among veterans with non–small‐cell lung cancer. Veterans had a low (7%) prevalence of EGFR mutations. There were several patients where EGFR testing and erlotinib treatment departed from clinical practice guidelines. Integration of decision support tools into the electronic health record could improve the quality of cancer care.

Race and Genomics in the Veterans Health Administration

Clinical implementation of genomic medicine is gaining momentum. Since 2003, there has been a 25% yearly increase in the number of genes linked to specific diseases or treatments. Genetic testing is quickly and steadily being incorporated into clinical practice guidelines across a wide range of health indications, including cancer, cardiology, infectious diseases, mental health, and primary care. Within the Veterans Health Administration (VHA), from 2011 through 2013, more than 80 000 veterans underwent at least 1 of 110 different genetic tests. Tests that have high levels of utilization within the VHA include Factor V Leiden gene to identify patients at risk for venous thrombosis, HLA-B*5701 to identify patients at risk for a hypersensitivity reaction to abacavir (a treatment for HIV), IL28B to evaluate potential responsiveness to peginterferon-α-2b treatment for HCV, and several tests to inform risk, prognosis, or treatment for cancer, including BCR-ABL1, FLT3, JAK2, BRAF, BRCA, c-KIT, EGFR, EML4-ALK, KRAS, MLH1, MSH2, MSH6, among others.

21-Gene recurrence score testing among Medicare beneficiaries with breast cancer in 2010–2013

Purpose:We evaluated national patient-level utilization of the 21-gene recurrence score (21-gene RS) test among Medicare beneficiaries with breast cancer. We analyzed clinical, demographic, and regional factors that predict testing.Methods:Using 2010–2013 Medicare claims, we conducted a retrospective study of breast cancer patients. The outcome variable was whether the patient underwent testing. Independent variables expected to predict testing were age, gender, race, Medicaid status, clinical characteristics, and hospital referral region (HRR).Results:From 2010 to 2013, the number of test orders increased by 23.0%. Of the 256,818 patients identified in 2011–2012 claims, 25,352 (9.9%) underwent the 21-gene RS test. Estrogen receptor–positive status was the strongest positive predictor of testing (odds ratio (OR) 2.58, 95% confidence interval (CI) 2.48–2.69). White patients were more likely to be tested than minorities (OR 1.46, 95% CI 1.39–1.52). Secondary cancer was the strongest negative predictor. Medicaid recipients were less likely to be tested (OR 0.74, 95% CI 0.71–0.78). The likelihood of testing decreased with increasing age and comorbidities.Conclusions:Despite widespread implementation of the 21-gene RS test, minorities and Medicaid recipients had less access to testing. Many patients with serious comorbidities or advanced age were tested even though the risk algorithm may not have been applicable to them.Genet Med advance online publication 23 March 2017

Clinical decisions surrounding genomic and proteomic testing among United States veterans treated for lung cancer within the Veterans Health Administration

BackgroundCurrent clinical guidelines recommend epidermal growth factor receptor (EGFR) mutational testing in patients with metastatic non-small cell lung cancer (NSCLC) to predict the benefit of the tyrosine kinase inhibitor erlotinib as first-line treatment. Proteomic (VeriStrat) testing is recommended for patients with EGFR negative or unknown status when erlotinib is being considered. Departure from this clinical algorithm can increase costs and may result in worse outcomes. We examined EGFR and proteomic testing among patients with NSCLC within the Department of Veterans Affairs (VA). We explored adherence to guidelines and the impact of test results on treatment decisions and cost of care.MethodsProteomic and EGFR test results from 2013 to 2015 were merged with VA electronic health records and pharmacy data. Chart reviews were conducted. Cases were categorized based on the appropriateness of testing and treatment.ResultsOf the 69 patients with NSCLC who underwent proteomic testing, 33 (48%) were EGFR-negative and 36 (52%) did not have documented EGFR status. We analyzed 138 clinical decisions surrounding EGFR/proteomic testing and erlotinib treatment. Most decisions (105, or 76%) were concordant with clinical practice guidelines. However, for 24 (17%) decisions documentation of testing or justification of treatment was inadequate, and 9 (7%) decisions represented clear departures from guidelines.ConclusionEGFR testing, the least expensive clinical intervention analyzed in this study, was significantly underutilized or undocumented. The records of more than half of the patients lacked information on EGFR status. Our analysis illustrated several clinical scenarios where the timing of proteomic testing and erlotinib diverged from the recommended algorithm, resulting in excessive costs of care with no documented improvements in health outcomes.