Hialy Gutierrez

Clinical Validity/Utility, Change in Practice Patterns, and Economic Implications of Risk Stratifiers to Predict Outcomes for Early-Stage Breast Cancer: A Systematic Review

BACKGROUND At least 14 stratifiers exist to assess recurrence risk, chemotherapy response, and overall survival (OS) in women with early-stage breast cancer (ESBC). These stratifiers have not been compared using a recently developed rigorous framework. We performed a systematic review of the literature on clinical validity/utility, change in clinical practice, and economic implications of ESBC stratifiers. METHODS A systematic literature search was performed using PubMed, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Database of Systematic Reviews, and bibliographies of relevant studies. Data were extracted by two investigators and graded using a previously published framework. The Level-of-Evidence determination for each study was summarized, and the studies that provide evidence on change in clinical practice and economic implications are reported. RESULTS Fifty-six articles published original evidence addressing the 21-gene recurrence score (n = 31), 70-gene signature (n = 14), Adjuvant! Online (n = 12), 5-antibody immunohistochemistry panel (n = 3), 5-gene expression index (n = 1), and 14-gene signature (n = 1). The 21-gene recurrence score satisfied Level I evidence (the highest level of evidence among five levels) for estimating distant recurrence risk (DRR), OS, and response to adjuvant chemotherapy, and Level II for estimating local recurrence risk. The 5-antibody immunohistochemistry panel and 70-gene signature satisfied Level II evidence for estimating DRR and OS. Adjuvant! Online satisfied Level II evidence for estimating DRR, OS, and chemotherapy response. The 5-gene expression index satisfied Level III evidence for predicting DRR. The 14-gene signature satisfied Level III evidence for predicting DRR and OS. Ten studies reported changes in clinical practice patterns; seven studies reported economic implications. CONCLUSION The available evidence on the ability of stratifiers to predict risks of recurrence and response to chemotherapy in ESBC is growing. Level-of-Evidence determinations using the newer framework provide a solid scientific foundation for clinical recommendations.

Cost-effectiveness of adding rituximab to fludarabine and cyclophosphamide for the treatment of previously untreated chronic lymphocytic leukemia

Abstract A recent phase III trial demonstrated improved progression-free survival (PFS) and overall survival (OS) associated with adding rituximab to fludarabine and cyclophosphamide (R-FC) compared to FC in treatment of previously untreated chronic lymphocytic leukemia (CLL). A cost-effectiveness analysis of R-FC over FC was performed from a US third-party payer perspective over a lifetime horizon in the base case. One-way, two-way and probabilistic sensitivity analyses were conducted to assess the robustness of the results. A secondary analysis was performed by also considering a societal perspective. R-FC was associated with an incremental 1.15 quality-adjusted life-years (QALYs) compared to FC and resulted in an incremental cost-effectiveness ratio of

Health Care Coverage Decision Making in Low- and Middle-Income Countries: Experiences from 25 Coverage Schemes.

23 530 per QALY in the base case and

Cost-Effectiveness of Gene-Expression Profiling for Tumor-Site Origin

31 513 per QALY considering a societal perspective. Results were most sensitive to time horizon, discount rate and unit drug cost for rituximab. Within the limitations of modeling long-term outcomes, R-FC is cost-effective for previously untreated CLL.

Abstract B9: Cost effectiveness of gene expression profiling for tumor site origin

Lessons learned by countries that have successfully implemented coverage schemes for health services may be valuable for other countries, especially low- and middle-income countries (LMICs), which likewise are seeking to provide/expand coverage. The research team surveyed experts in population health management from LMICs for information on characteristics of health care coverage schemes and factors that influenced decision-making processes. The level of coverage provided by the different schemes varied. Nearly all the health care coverage schemes involved various representatives and stakeholders in their decision-making processes. Maternal and child health, cardiovascular diseases, cancer, and HIV were among the highest priorities guiding coverage development decisions. Evidence used to inform coverage decisions included medical literature, regional and global epidemiology, and coverage policies of other coverage schemes. Funding was the most commonly reported reason for restricting coverage. This exploratory study provides an overview of health care coverage schemes from participating LMICs and contributes to the scarce evidence base on coverage decision making. Sharing knowledge and experiences among LMICs can support efforts to establish systems for accessible, affordable, and equitable health care.

Clinical utility of gene-expression profiling for tumor site origin.

OBJECTIVES Gene-expression profiling (GEP) reliably supplements traditional clinicopathological information on the tissue of origin (TOO) in metastatic or poorly differentiated cancer. A cost-effectiveness analysis of GEP TOO testing versus usual care was conducted from a US third-party payer perspective. METHODS Data on recommendation changes for chemotherapy, surgery, radiation therapy, blood tests, imaging investigations, and hospice care were obtained from a retrospective, observational study of patients whose physicians received GEP TOO test results. The effects of chemotherapy recommendation changes on survival were based on the results of trials cited in National Comprehensive Cancer Network and UpToDate guidelines. Drug and administration costs were based on average doses reported in National Comprehensive Cancer Network guidelines. Other unit costs came from Centers for Medicare & Medicaid Services fee schedules. Quality-of-life weights were obtained from literature. Bootstrap analysis estimated sample variability; probabilistic sensitivity analysis addressed parameter uncertainty. RESULTS Chemotherapy regimen recommendations consistent with guidelines for final tumor-site diagnoses increased significantly from 42% to 65% (net difference 23%; P<0.001). Projected overall survival increased from 15.9 to 19.5 months (mean difference 3.6 months; two-sided 95% confidence interval [CI] 3.2-3.9). The average increase in quality-adjusted life-months was 2.7 months (95% CI 1.5-4.3), and average third-party payer costs per patient increased by

Clinical utility of gene-expression profiling for tumor-site origin in patients with metastatic or poorly differentiated cancer: impact on diagnosis, treatment, and survival

10,360 (95% CI

Erratum: Cost-effectiveness of gene-expression profiling for tumor-site origin (Value in Health 16:1 (46-56))

2,982-

Changes in management and survival outcomes for patients receiving gene-expression-based tissue-of-origin test results for difficult-to-diagnose primary cancers.

19,192). The cost per quality-adjusted life-year gained was

PHP105 HOW ARE COVERAGE DECISIONS MADE IN PUBLICLY FUNDED HEALTH CARE PROGRAMS IN LOW- AND MIDDLE-INCOME COUNTRIES?

46,858 (95% CI