Importance of Patient Health Insurance Coverage and Out-of-Pocket Costs for Genomic Testing in Oncologists' Treatment Decisions.

PURPOSE: Use of genomic testing, especially multimarker panels, is increasing in the United States. Not all tests and related treatments are covered by health insurance, which can result in substantial patient out-of-pocket (OOP) costs. Little is known about oncologists' treatment decisions with respect to patient insurance coverage and OOP costs for genomic testing. METHODS: We identified 1,049 oncologists who used multimarker tumor panels from the 2017 National Survey of Precision Medicine in Cancer Treatment. Separate multivariable ordinal logistic regressions examined associations of oncologist-, practice-, and area-level characteristics and oncologists' ratings of importance (very, somewhat, or a little/not important) of insurance coverage and OOP costs for genomic testing in treatment decisions, adjusting for oncologist years of experience, sex, race and ethnicity, specialty, use of next-generation sequencing (NGS) tests, region, tumor boards, patient insurance mix, and area-level socioeconomic characteristics. RESULTS: Among oncologists, 47.3%, 32.7%, and 20.0% reported that patient insurance coverage for genomic testing was very, somewhat, or a little/not important, respectively, in treatment decisions. In addition, 56.9%, 28.0%, and 15.2% reported that OOP costs for testing were very, somewhat, or a little/not important, respectively. In adjusted analyses, oncologists who used NGS tests were more likely to report patient insurance and OOP costs as important (odds ratio [OR], 2.00 [95% CI, 1.16 to 3.45] and OR, 2.12 [95% CI, 1.22 to 3.68], respectively) in treatment decisions compared with oncologists who did not use these tests, as were oncologists who treated solid tumors, rather than only hematological cancers. More years of experience and higher percentages of Medicaid or self-paid/uninsured patients in the practice were associated with reporting insurance coverage (OR, 1.43 [95% CI, 1.09 to 1.89]) and OOP costs (OR, 1.51 [95% CI, 1.13 to 2.01]) as important. Oncologists in practices with molecular tumor boards for genomic tests were less likely to report coverage (OR, 0.63 [95% CI, 0.47 to 0.85]) and OOP costs (OR, 0.72 [95% CI, 0.53 to 0.97]) as important than their counterparts in practices without these tumor boards. CONCLUSION: Most oncologists rate patient health insurance and OOP costs for genomic tests as important considerations in subsequent treatment recommendations. Modifiable factors associated with these ratings can inform interventions to support patient-physician decision making about care.

Population-based utilization and costs associated with tyrosine kinase inhibitors for first-line treatment of chronic myelogenous leukemia among elderly patients.

BACKGROUND: Following approval of imatinib, a breakthrough tyrosine kinase inhibitor (TKI), survival significantly improved by more than 20% since 2001 among treated chronic myelogenous leukemia (CML) patients. Subsequently, more expensive second-generation TKIs with varying selectivity profiles have been approved. Population-based studies are needed to evaluate the real-world utilization of TKI therapies, particularly given their escalating costs and recommendations for maintenance therapy. OBJECTIVE: To assess the utilization patterns of first-line TKIs, overall and by specific agent, among elderly CML patients in the United States, and the cost implications. METHODS: CML patients aged 65 years and older at diagnosis between 2007 and 2015 were identified from population-based cancer registries in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The percentage of CML patients receiving imatinib, dasatinib, or nilotinib within the first year of diagnosis was calculated along with time to first-line treatment initiation. Bivariate comparisons and Cox proportional hazards models were used to identify factors associated with TKI initiation. Average monthly patient responsibility, including patient out-of-pocket (OOP) costs, stratified by Part D low-income subsidy (LIS) status were also calculated. RESULTS: Among the 1,589 CML patients included, receipt of any TKI within 1 year of diagnosis increased from 66.2% to 78.9%. In 2015, the distribution of first-line TKI therapies was 41.3% imatinib, 28.3% dasatinib, and 9.3% nilotinib. Almost 60% of patients initiated TKI treatment within 3 months of diagnosis. Multivariable analysis indicated that TKI use in the first year was lower among the very elderly (aged > 75 years vs. 65-69 years: HR = 0.72; 95% CI = 0.63-0.83), patients with more comorbidities (Hierarchical Condition Category risk score > 2 vs. HR = 0.74, 95% CI = 0.62-0.88), and patients ineligible for LIS (HR = 0.75; 95% CI = 0.65-0.87). Average monthly patient OOP cost was significantly lower for LIS-eligible versus LIS-ineligible patients: imatinib (2016: $12 vs. $487), dasatinib (2016: $34 vs. $557), and nilotinib (2016: $1 vs. $526). CONCLUSIONS: TKI use has increased significantly since 2007. While imatinib remained the most frequently prescribed first-line agent, by 2015 newer TKIs represented one third of the market share. Utilization patterns indicated persistent age, comorbidity, and financial barriers. TKI use is indicated for long-term therapy, and increased adoption of newer, more expensive agents raises concerns about the sustained affordability of CML treatment, particularly among unsubsidized patients. DISCLOSURES: No outside funding supported this study. There are no reported conflicts of interest.

Factors Associated With Oncologist Discussions of the Costs of Genomic Testing and Related Treatments.

BACKGROUND: Use of genomic testing is increasing in the United States. Testing can be expensive, and not all tests and related treatments are covered by health insurance. Little is known about how often oncologists discuss costs of testing and treatment or about the factors associated with those discussions. METHODS: We identified 1220 oncologists who reported discussing genomic testing with their cancer patients from the 2017 National Survey of Precision Medicine in Cancer Treatment. Multivariable polytomous logistic regression analyses were used to assess associations between oncologist and practice characteristics and the frequency of cost discussions. All statistical tests were two-sided. RESULTS: Among oncologists who discussed genomic testing with patients, 50.0% reported often discussing the likely costs of testing and related treatments, 26.3% reported sometimes discussing costs, and 23.7% reported never or rarely discussing costs. In adjusted analyses, oncologists with training in genomic testing or working in practices with electronic medical record alerts for genomic tests were more likely to have cost discussions sometimes (odds ratio [OR] = 2.09, 95% confidence interval [CI] = 1.19 to 3.69) or often (OR = 2.22, 95% CI = 1.30 to 3.79), respectively, compared to rarely or never. Other factors statistically significantly associated with more frequent cost discussions included treating solid tumors (rather than only hematological cancers), using next-generation sequencing gene panel tests, having higher patient volume, and working in practices with higher percentages of patients insured by Medicaid, or self-paid or uninsured. CONCLUSIONS: Interventions targeting modifiable oncologist and practice factors, such as training in genomic testing and use of electronic medical record alerts, may help improve cost discussions about genomic testing and related treatments.

Comparative effectiveness research in cancer genomics and precision medicine: current landscape and future prospects.

A major promise of genomic research is information that can transform health care and public health through earlier diagnosis, more effective prevention and treatment of disease, and avoidance of drug side effects. Although there is interest in the early adoption of emerging genomic applications in cancer prevention and treatment, there are substantial evidence gaps that are further compounded by the difficulties of designing adequately powered studies to generate this evidence, thus limiting the uptake of these tools into clinical practice. Comparative effectiveness research (CER) is intended to generate evidence on the "real-world" effectiveness compared with existing standards of care so informed decisions can be made to improve health care. Capitalizing on funding opportunities from the American Recovery and Reinvestment Act of 2009, the National Cancer Institute funded seven research teams to conduct CER in genomic and precision medicine and sponsored a workshop on CER on May 30, 2012, in Bethesda, Maryland. This report highlights research findings from those research teams, challenges to conducting CER, the barriers to implementation in clinical practice, and research priorities and opportunities in CER in genomic and precision medicine. Workshop participants strongly emphasized the need for conducting CER for promising molecularly targeted therapies, developing and supporting an integrated clinical network for open-access resources, supporting bioinformatics and computer science research, providing training and education programs in CER, and conducting research in economic and decision modeling.

Population sciences, translational research, and the opportunities and challenges for genomics to reduce the burden of cancer in the 21st century.

Advances in genomics and related fields are promising tools for risk assessment, early detection, and targeted therapies across the entire cancer care continuum. In this commentary, we submit that this promise cannot be fulfilled without an enhanced translational genomics research agenda firmly rooted in the population sciences. Population sciences include multiple disciplines that are needed throughout the translational research continuum. For example, epidemiologic studies are needed not only to accelerate genomic discoveries and new biological insights into cancer etiology and pathogenesis, but to characterize and critically evaluate these discoveries in well-defined populations for their potential for cancer prediction, prevention and response to treatment. Behavioral, social, and communication sciences are needed to explore genomic-modulated responses to old and new behavioral interventions, adherence to therapies, decision making across the continuum, and effective use in health care. Implementation science, health services, outcomes research, comparative effectiveness research, and regulatory science are needed for moving validated genomic applications into practice and for measuring their effectiveness, cost-effectiveness, and unintended consequences. Knowledge synthesis, evidence reviews, and economic modeling of the effects of promising genomic applications will facilitate policy decisions and evidence-based recommendations. Several independent and multidisciplinary panels have recently made specific recommendations for enhanced research and policy infrastructure to inform clinical and population research for moving genomic innovations into the cancer care continuum. An enhanced translational genomics and population sciences agenda is urgently needed to fulfill the promise of genomics in reducing the burden of cancer.

Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older.

PURPOSE: The Study of Tamoxifen and Raloxifene (STAR) demonstrated that raloxifene was as effective as tamoxifen in reducing the risk of invasive breast cancer (IBC) in postmenopausal women and had lower risks of thromboembolic events, endometrial cancer, and cataracts but had a nonstatistically significant higher risk of noninvasive breast cancer. There is a need to summarize the risks and benefits of these agents. PATIENTS AND METHODS: Baseline incidence rates of IBC and other health outcomes, absent raloxifene and tamoxifen, were estimated from breast cancer chemoprevention trials; the Surveillance, Epidemiology and End Results Program; and the Women's Health Initiative. Effects of raloxifene and tamoxifen were estimated from STAR and the Breast Cancer Prevention Trial. We assigned weights to health outcomes to calculate the net benefit from raloxifene compared with placebo and tamoxifen compared with placebo. RESULTS: Risks and benefits of treatment with raloxifene or tamoxifen depend on age, race, breast cancer risk, and history of hysterectomy. Over a 5-year period, postmenopausal women with an intact uterus had a better benefit/risk index for raloxifene than for tamoxifen. For postmenopausal women without a uterus, the benefit/risk ratio was similar. The benefits and risks of raloxifene and tamoxifen are described in tables that can help identify groups of women for whom the benefits outweigh the risks. CONCLUSION: We developed a benefit/risk index to quantify benefits from chemoprevention with tamoxifen or raloxifene. This index can complement clinical evaluation in deciding whether to initiate chemoprevention and in comparing the benefits and risks of raloxifene versus tamoxifen.

Cancer risk prediction models: a workshop on development, evaluation, and application.

Cancer researchers, clinicians, and the public are increasingly interested in statistical models designed to predict the occurrence of cancer. As the number and sophistication of cancer risk prediction models have grown, so too has interest in ensuring that they are appropriately applied, correctly developed, and rigorously evaluated. On May 20-21, 2004, the National Cancer Institute sponsored a workshop in which experts identified strengths and limitations of cancer and genetic susceptibility prediction models that were currently in use and under development and explored methodologic issues related to their development, evaluation, and validation. Participants also identified research priorities and resources in the areas of 1) revising existing breast cancer risk assessment models and developing new models, 2) encouraging the development of new risk models, 3) obtaining data to develop more accurate risk models, 4) supporting validation mechanisms and resources, 5) strengthening model development efforts and encouraging coordination, and 6) promoting effective cancer risk communication and decision-making.

Estimates of the number of US women who could benefit from tamoxifen for breast cancer chemoprevention.

BACKGROUND: The Breast Cancer Prevention Trial demonstrated that tamoxifen treatment produced a 49% reduction in the risk of invasive breast cancer among women at elevated risk for the disease. The U.S. Food and Drug Administration (FDA) subsequently approved tamoxifen for women aged 35 years or older with a 5-year breast cancer risk of 1.67% or higher for breast cancer chemoprevention. However, tamoxifen use has been associated with adverse outcomes, and not all eligible women have a positive benefit/risk ratio. METHODS: We used weighted data from the year 2000 National Health Interview Survey Cancer Control Module to estimate the total number of U.S. women, aged 35-79 years, who were eligible for tamoxifen chemoprevention based on the FDA eligibility criteria. We also estimated the numbers of white and black women who would benefit from tamoxifen chemoprevention on the basis of a positive benefit/risk index developed by Gail et al. RESULTS: Of the 65,826,074 women aged 35-79 years without reported breast cancer in the United States in 2000, 10,232 816 women (15.5%, 95% confidence interval [CI] = 14.7% to 16.3%) would be eligible for tamoxifen chemoprevention. The percentage of U.S. women who would be eligible varied dramatically by race, with 18.7% (95% CI = 17.8% to 19.7%) of white women, 5.7% (95% CI = 4.3% to 7.5%) of black women, and 2.9% (95% CI = 2.1% to 3.9%) of Hispanic women being eligible. Of the 50,104,829 white U.S. women aged 35-79 years, 2,431,911 (4.9%, 95% CI = 4.3% to 5.4%) would have a positive benefit/risk index for tamoxifen chemoprevention. Of the 7,481,779 black U.S. women aged 35-79 years, only 42,768 (0.6%, 95% CI = 0.2% to 1.3%) would have a positive benefit/risk index. Among white women, 28,492 (95% CI = 24,693 to 32,292) breast cancers would be prevented or deferred if those women who have a positive net benefit index took tamoxifen over the next 5 years. CONCLUSION: A substantial percentage of U.S. women would be eligible for tamoxifen chemoprevention according to FDA criteria, but a much smaller percentage would have an estimated net benefit. Nevertheless, this latter percentage corresponds to more than two million women.