The Clinical and Economic Impact of Attaining National HIV/AIDS Strategy Treatment Targets in the United States.

Background: The US National HIV/AIDS Strategy (NHAS) aims for 72% (90% diagnosed times 80% of those virally suppressed) viral suppression among persons with human immunodeficiency virus (HIV) by 2020. We examined the clinical and economic impact of reaching this target, in the general US population and among black men who have sex with men (MSM), the group with the highest HIV prevalence. Methods: Using a mathematical simulation, we project the 5- and 20-year clinical outcomes, costs, and incremental cost-effectiveness ratios for (1) Current Pace of detection, linkage, retention, and virologic suppression and (2) NHAS investments in expanded testing ($24-$74 per test) and adherence ($400 per person-year), calibrated to achieve 72% suppression by 2020. We examined alternative rates of testing, retention, and suppression and the efficacy and cost of adherence interventions. Results: Compared with Current Pace over 20 years, NHAS averted 280000 HIV transmissions (80000 in black MSM) and 199000 (45000) deaths and saved 2138000 (453000) years of life, while increasing costs by 23%. The incremental cost-effectiveness ratio for NHAS compared with Current Pace was $68900 per quality-adjusted life-year ($38300 for black MSM) and was most sensitive to antiretroviral therapy costs. Conclusions: Reaching NHAS targets would yield substantial clinical benefits and be cost-effective in both the general US and black MSM populations.

Sustainable Development in Surgery: The Health, Poverty, and Equity Impacts of Charitable Surgery in Uganda.

BACKGROUND: The recently adopted Sustainable Development Goals call for the end of poverty and the equitable provision of healthcare. These goals are often at odds, however: health seeking can lead to catastrophic spending, an outcome for which cancer patients and the poor in resource-limited settings are at particularly high risk. How various health policies affect the additional aims of financial wellbeing and equity is poorly understood. This paper evaluates the health, financial, and equity impacts of governmental and charitable policies for surgical oncology in a resource-limited setting. METHODS: Three charitable platforms for surgical oncology delivery in Uganda were compared to six governmental policies aimed at improving healthcare access. An extended cost-effectiveness analysis using an agent-based simulation model examined the numbers of lives saved, catastrophic expenditure averted, impoverishment averted, costs, and the distribution of benefits across the wealth spectrum. FINDINGS: Of the nine policies and platforms evaluated, two were able to provide simultaneous health and financial benefits efficiently and equitably: mobile surgical units and governmental policies that simultaneously address surgical scaleup, the cost of surgery, and the cost of transportation. Policies that only remove user fees are dominated, as is the commonly employed short-term "surgical mission trip". These results are robust to scenario and sensitivity analyses. INTERPRETATION: The most common platforms for increasing access to surgical care appear unable to provide health and financial risk protection equitably. On the other hand, mobile surgical units, to date an underutilized delivery platform, are able to deliver surgical oncology in a manner that meets sustainable development goals by improving health, financial solvency, and equity. These platforms compare favorably with policies that holistically address surgical delivery and should be considered as countries strengthen health systems.

Cost effectiveness of targeted high-dose atorvastatin therapy following genotype testing in patients with acute coronary syndrome.

BACKGROUND: Results from the PROVE IT trial suggest that patients with acute coronary syndrome (ACS) treated with atorvastatin 80 mg/day (A80) have significantly lower rates of cardiovascular events compared with patients treated with pravastatin 40 mg/day (P40). In a genetic post hoc substudy of the PROVE IT trial, the rate of event reduction was greater in carriers of the Trp719Arg variant in kinesin family member 6 protein (KIF6) than in noncarriers. We assessed the cost effectiveness of testing for the KIF6 variant followed by targeted statin therapy (KIF6 Testing) versus not testing patients (No Test) and treating them with P40 or A80 in the USA from a payer perspective. METHODS: A Markov model was developed in which 2-year event rates from PROVE IT were extrapolated over a lifetime horizon. Costs and utilities were derived from published literature. All costs were in 2010 US dollars except the cost of A80, which was in 2012 US dollars because the generic formulation was available in 2012. Expected costs and quality-adjusted life-years (QALYs) were estimated for each strategy over a lifetime horizon. RESULTS: Lifetime costs were US$31,700; US$37,100 and US$41,300 for No Test P40, KIF6 Testing and No Test A80 strategies, respectively. The No Test A80 strategy was associated with more QALYs (9.71) than the KIF6 Testing (9.69) and No Test P40 (9.57) strategies. No Test A80 had an incremental cost-effectiveness ratio (ICER) of US$232,100 per QALY gained compared with KIF6 Testing. KIF6 Testing had an ICER of US$45,300 per QALY compared with No Test P40. CONCLUSIONS: Testing ACS patients for KIF6 carrier status may be a cost-effective strategy at commonly accepted thresholds. Treating all patients with A80 is more expensive than treating patients on the basis of KIF6 results, but the modest gain in QALYs is achieved at a cost/QALY that is generally considered unacceptable compared with the KIF6 Testing strategy. Compared with treating all patients with P40, the KIF6 Testing strategy had an ICER below US$50,000 per QALY. The conclusions from this study are sensitive to the price of generic A80 and the effect on adherence of knowing KIF6 carrier status. The results were based on a post hoc substudy of the PROVE IT trial, which was not designed to test the effectiveness of KIF6 testing.

A cost-effectiveness analysis of folic acid fortification policy in the United States.

OBJECTIVE: To quantify the health and economic outcomes associated with changes in folic acid consumption following the fortification of enriched grain products in the USA. DESIGN: Cost-effectiveness analysis. SETTING: Annual burden of disease, quality-adjusted life years (QALY) and costs were projected for four steady-state strategies: no fortification, or fortifying with 140, 350 or 700 microg folic acid per 100 g enriched grain. The analysis considered four health outcomes: neural tube defects (NTD), myocardial infarctions (MI), colon cancers and B12 deficiency maskings. SUBJECTS: The US adult population subgroups defined by age, gender and race/ethnicity, with folate intake distributions from the National Health and Nutrition Examination Surveys (1988-1992 and 1999-2000), and reference sources for disease incidence, utility and economic estimates. RESULTS: The greatest benefits from fortification were predicted in MI prevention, with 16 862 and 88 172 cases averted per year in steady state for the 140 and 700 microg fortification levels, respectively. These projections were between 6261 and 38 805 for colon cancer and 182 and 1423 for NTD, while 15-820 additional B12 cases were predicted. Compared with no fortification, all post-fortification strategies provided QALY gains and cost savings for all subgroups, with predicted population benefits of 266 649 QALY gained and $3.6 billion saved in the long run by changing the fortification level from 140 microg/100 g enriched grain to 700 microg/100 g. CONCLUSIONS: The present study indicates that the health and economic gains of folic acid fortification far outweigh the losses for the US population, and that increasing the level of fortification deserves further consideration to maximise net gains.

Cost-effectiveness analysis of oxaliplatin compared with 5-fluorouracil/leucovorin in adjuvant treatment of stage III colon cancer in the US.

BACKGROUND: The MOSAIC trial demonstrated that oxaliplatin/5-fluorouracil/leucovorin (FU/LV) (FOLFOX4) as adjuvant treatment of TNM stage II and III colon cancer significantly improves disease-free survival compared with 5-FU/LV alone. For stage III patients the 4-year disease-free survival (DFS) was 69% in the FOLFOX4 arm vs 61% in the LV5FU2 arm, P = .002). The cost-effectiveness of FOLFOX4 in stage III patients was evaluated from a US Medicare perspective. METHODS: By using individual patient-level data from the MOSAIC trial (median follow-up: 44.2 months), DFS and overall survival (OS) were estimated up to 4 years from randomization. DFS was extrapolated from 4 to 5 years by fitting a Weibull model and subsequent survival was estimated from life tables. OS beyond 4 years was predicted from the extrapolated DFS estimates and observed survival after recurrence. Costs were calculated from trial data and external estimates of resources to manage recurrence. RESULTS: Patients on FOLFOX4 were predicted to gain 2.00 (95% confidence interval [CI]: 0.63, 3.37) years of DFS over those on 5-FU/LV. The predicted life expectancy of stage III patients on FOLFOX4 and 5-FU/LV was 17.61 and 16.26 years, respectively. Mean total lifetime disease-related costs were $56,300 with oxaliplatin and $39,300 with 5-FU/LV. Compared with 5-FU/LV, FOLFOX4 was estimated to cost $20,600 per life-year gained and $22,800 per quality-adjusted life-year (QALY) gained, discounting costs and outcomes at 3% per annum. CONCLUSIONS: FOLFOX4 is likely to be cost-effective compared with 5-FU/LV in the adjuvant treatment of stage III colon cancer. The incremental cost-effectiveness ratio compares favorably with other funded interventions in oncology.

Population-level changes in folate intake by age, gender, and race/ethnicity after folic acid fortification.

OBJECTIVES: We sought to quantify the impact of the 1998 US Food and Drug Administration (FDA) folic acid fortification policy by estimating folate intake at the population level. METHODS: We analyzed total folate intake levels (from food and supplements) according to gender, age, and race/ethnicity, using data from 2 National Health and Nutrition Examination Surveys. We measured pre- and postfortification folate intake distributions, adjusted for measurement error, and examined proportions of the population who reached certain thresholds of daily total folate intake. RESULTS: Mean daily food and total folate intake increased by approximately 100 microg/day after fortification. The proportion of women aged 15-44 years who consume more than 400 microg/day of folate has increased since fortification, but has not yet reached the FDA's 50% target and varies by race/ethnicity from 23% to 33%. Among persons aged 65 years and older who may be at risk for masking a vita-microg/day (the min B12 deficiency, the percentage who consume more than 1000 "tolerable upper intake level") has at least doubled among Whites and Black men, but has remained less than 5% for all groups. CONCLUSIONS: Since fortification, folic acid intake among the US population has increased, and there are substantial variations by age, gender, and race/ethnicity.

Cost-effectiveness of treating multidrug-resistant tuberculosis.

BACKGROUND: Despite the existence of effective drug treatments, tuberculosis (TB) causes 2 million deaths annually worldwide. Effective treatment is complicated by multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs. We projected the health benefits and cost-effectiveness of using drug susceptibility testing and second-line drugs in a lower-middle-income setting with high levels of MDR TB. METHODS AND FINDINGS: We developed a dynamic state-transition model of TB. In a base case analysis, the model was calibrated to approximate the TB epidemic in Peru, a setting with a smear-positive TB incidence of 120 per 100,000 and 4.5% MDR TB among prevalent cases. Secondary analyses considered other settings. The following strategies were evaluated: first-line drugs administered under directly observed therapy (DOTS), locally standardized second-line drugs for previously treated cases (STR1), locally standardized second-line drugs for previously treated cases with test-confirmed MDR TB (STR2), comprehensive drug susceptibility testing and individualized treatment for previously treated cases (ITR1), and comprehensive drug susceptibility testing and individualized treatment for all cases (ITR2). Outcomes were costs per TB death averted and costs per quality-adjusted life year (QALY) gained. We found that strategies incorporating the use of second-line drug regimens following first-line treatment failure were highly cost-effective compared to strategies using first-line drugs only. In our base case, standardized second-line treatment for confirmed MDR TB cases (STR2) had an incremental cost-effectiveness ratio of 720 dollars per QALY (8,700 dollars per averted death) compared to DOTS. Individualized second-line drug treatment for MDR TB following first-line failure (ITR1) provided more benefit at an incremental cost of 990 dollars per QALY (12,000 dollars per averted death) compared to STR2. A more aggressive version of the individualized treatment strategy (ITR2), in which both new and previously treated cases are tested for MDR TB, had an incremental cost-effectiveness ratio of 11,000 dollars per QALY (160,000 dollars per averted death) compared to ITR1. The STR2 and ITR1 strategies remained cost-effective under a wide range of alternative assumptions about treatment costs, effectiveness, MDR TB prevalence, and transmission. CONCLUSIONS: Treatment of MDR TB using second-line drugs is highly cost-effective in Peru. In other settings, the attractiveness of strategies using second-line drugs will depend on TB incidence, MDR burden, and the available budget, but simulation results suggest that individualized regimens would be cost-effective in a wide range of situations.

Do drug formulary policies reflect evidence of value?

OBJECTIVE: To investigate the extent to which preferred drug lists and tiered formularies reflect evidence of value, as measured in published cost-utility analyses (CUAs). METHODS: Using 1998-2001 data from a large registry of cost-effectiveness analyses, we examined the 2004 Florida Medicaid preferred drug list and the 2004 Harvard Pilgrim Pharmacy Program 3-tier formulary, and compared cost-utility ratios (standardized to 2002 US dollars) of drugs with preferred and nonpreferred status. RESULTS: Few drugs on the formularies had any cost-utility data available. Of those that did, median cost-utility ratios were somewhat higher (less favorable) for Florida's preferred drugs compared with the nonpreferred drugs (25,465 dollars vs 13,085 dollars; P = .09). Ratios did not differ for drugs on tiers 1 and 2 of the Harvard Pilgrim formulary, although they were higher for tier 3 and for excluded drugs (18,309 dollars, 18,846 dollars, 52,119 dollars, and 22,580 dollars, respectively; P = .01). Among therapies reported to be cost-saving or to have cost-utility ratios below 50,000 dollars, 77% had favored status in Florida Medicaid and 73% in Harvard Pilgrim. Among dominated drug interventions (reported to be more costly and less effective than alternatives), 95% had favored status in Florida Medicaid and 56% in Harvard Pilgrim. CONCLUSIONS: This study underscores the paucity of published cost-utility data available to formulary committees. Some discrepancies prevail between the value of drugs, as reflected in published cost-utility ratios, and the formulary placement policies of 2 large health plans.

Should resistance testing be performed for treatment-naive HIV-infected patients? A cost-effectiveness analysis.

BACKGROUND: Data from the United States and Europe show a population prevalence of baseline drug resistance of 8%-10% among human immunodeficiency virus (HIV)-infected patients who are antiretroviral naive. Our objective was to determine the clinical impact and cost-effectiveness of genotype resistance testing for treatment-naive patients with chronic HIV infection. METHODS: We utilized a state-transition model of HIV disease to project life expectancy, costs, and cost-effectiveness in a hypothetical cohort of antiretroviral-naive patients with chronic HIV infection. On the basis of a US survey of treatment-naive patients from the Centers for Disease Control and Prevention, we used a baseline prevalence of drug resistance of 8.3%. RESULTS: A strategy of genotype-resistance testing at initial diagnosis of HIV infection increased per-person quality-adjusted life expectancy by 1.0 months, with an incremental cost-effectiveness ratio of 23,900 dollars per quality-adjusted life-year gained, compared with no genotype testing. The cost-effectiveness ratio for resistance testing remained less than 50,000 dollars per quality-adjusted life-year gained, unless the prevalence of resistance was < or =1%, a level lower than those reported in most regions of the United States and Europe. In sensitivity analyses, the cost-effectiveness remained favorable through wide variations in baseline assumptions, including variations in genotype cost, prevalence of resistance overall and to individual drug classes, and sensitivity of resistance testing. CONCLUSIONS: Genotype-resistance testing of chronically HIV-infected, antiretroviral-naive patients is likely to improve clinical outcomes and is cost-effective, compared with other HIV care in the United States. Resistance testing at the time of diagnosis should be the standard of care.

Optimal allocation of testing dollars: the example of HIV counseling, testing, and referral.

BACKGROUND: Health screening programs can be represented as a pathway of sequential processes: offering a test, obtaining consent, conducting the test, providing results, and linking to appropriate care. Using the example of HIV testing, the authors explore the optimal targeting of funds within this pathway. METHODS: The authors develop a microsimulation of HIV testing services and decompose the likelihood that an unidentified HIV-infected person will receive care into the probability of testing [P(test)] and the probability of follow-up [P(follow)] defined as returning for results and linking to care. The authors examine the clinical impact and cost-effectiveness of alternative investments in these component probabilities. RESULTS: At 1% undiagnosed HIV prevalence, cost-effectiveness ratios for HIV testing cluster around $33,000/QALY (quality-adjusted life year) gained. A program with a yield of 0.16 via P(test)=0.20 and P(follow)=0.80 has a cost-effectiveness ratio of $32,900/QALY compared with $36,300/QALY for a program where P(test)=0.80 and P(follow)=0.20. Interventions that improve the probability of success in later stages in the testing pathway [P(follow)] are more cost-effective than investments devoted to earlier stages [P(test)]. CONCLUSIONS: Equivalent pathway outcomes in a screening program do not confer equal value. Limited screening resources are best targeted toward returning for results and linkage among those already identified with disease rather than offering testing to additional people.

Metastatic colorectal carcinoma: cost-effectiveness of percutaneous radiofrequency ablation versus that of hepatic resection.

PURPOSE: To evaluate the relative cost-effectiveness of radiofrequency (RF) ablation and hepatic resection in patients with metachronous liver metastases from colorectal carcinoma (CRC) and compare the outcomes, cost, and cost-effectiveness of a variety of treatment and follow-up strategies. MATERIALS AND METHODS: A state-transition decision model for evaluating the (societal) cost-effectiveness of RF ablation and hepatic resection in patients with CRC liver metastases was developed. The model tracks the presence, number, size, location, growth, detection, and removal of up to 15 individual metastases in each patient. Survival, quality of life, and cost are predicted on the basis of disease extent. Imaging, ablation, and resection affect outcomes through detection and elimination of individual metastases. Several patient care strategies were developed and compared on the basis of cost, effectiveness, and incremental cost-effectiveness (expressed as dollars per quality-adjusted life-year [QALY]). Extensive sensitivity analysis was performed to evaluate the impact of alternative scenarios and assumptions on results. RESULTS: A strategy permitting ablation of up to five metastases with computed tomographic (CT) follow-up every 4 months resulted in a gain of 0.65 QALYs relative to a no-treat strategy, at an incremental cost of $2400 per QALY. Compared with this ablation strategy, a strategy permitting resection of up to four metastases, one repeat resection, and CT follow-up every 6 months resulted in an additional gain of 0.76 QALYs at an incremental cost of $24 300 per QALY. Across a range of model assumptions, more aggressive treatment strategies (ie, ablation or resection of more metastases, treatment of recurrent metastases, more frequent follow-up imaging) were superior to less aggressive strategies and had incremental cost-effectiveness ratios of less than $35 000 per QALY. Findings were insensitive to changes in most model parameters; however, results were somewhat sensitive to changes in size thresholds for RF ablation, the number of metastases present, and surgery and treatment costs. CONCLUSION: RF ablation is a cost-effective treatment option for patients with CRC liver metastases. However, in most scenarios, hepatic resection is more effective (in terms of QALYs gained) than RF ablation and has an incremental cost-effectiveness ratio of less than $35 000 per QALY.

HER-2 testing and trastuzumab therapy for metastatic breast cancer: a cost-effectiveness analysis.

PURPOSE: Trastuzumab therapy has been shown to benefit metastatic breast cancer patients whose tumors exhibit HER-2 protein overexpression or gene amplification. Several tests of varying accuracy and cost are available to identify candidates for trastuzumab. We estimated the cost-effectiveness of alternative HER-2 testing and trastuzumab treatment strategies. PATIENTS AND METHODS: We performed a decision analysis using a state-transition model to simulate clinical practice in a hypothetical cohort of 65-year-old metastatic breast cancer patients. Outcomes were quality-adjusted life-years (QALYs), lifetime cost, and incremental cost-effectiveness ratio (ICER). Interventions included testing with the HercepTest (DAKO, Carpinteria, CA) immunohistochemical assay alone, fluorescence in situ hybridization (FISH) alone, and both tests, followed by trastuzumab and chemotherapy for patients with positive test results and chemotherapy alone for patients with negative test results. RESULTS: In the base case, initial HercepTest with FISH confirmation of all positive results had an ICER of $125,000 per QALY gained. The incremental cost-effectiveness of initial FISH was $145,000 per QALY gained. Other strategies yielded the same or poorer effectiveness at a higher cost, or lower effectiveness at a lower cost, but with a less favorable ICER. These findings persisted under a range of assumptions, and only changes in test characteristics substantially altered results. CONCLUSION: It is more cost-effective to use FISH alone or as confirmation of all positive HercepTest results, rather than using FISH to confirm only weakly positive results or using HercepTest alone. When multiple tests are available to identify treatment candidates, test characteristics may have a substantial impact on the aggregate costs and effectiveness of treatment.

Cost-effectiveness analysis of predischarge monitoring for apnea of prematurity.

OBJECTIVE: It is standard practice to defer discharge of premature infants until they have achieved a set number of days without experiencing apnea. The duration of this period, however, is highly variable across institutions, and there is scant literature on its effectiveness or value-for-money. Our objective was to establish the economic impact of varying durations of predischarge observation for apnea of prematurity. METHODS: Using computer simulation, we compared the alternatives of hospital monitoring for 1 to 10 days, after apparent cessation of apnea, with no monitoring and with the next longest period of monitoring. The daily probability of apnea requiring stimulation after a given number of apnea-free days was obtained from chart review of 216 infants, beginning on the day they attained both full feeds and temperature stability in an open crib. Baseline rates of survival or impairment, utilities for calculation of quality-adjusted life years (QALYs), outcomes for respiratory arrest at home, and long-run costs for neurodevelopmental impairment were derived from the literature. Hospital expenditures were obtained from itemized billing records for infants on each of the final 10 days of hospitalization and converted to costs using Medicare cost-to-charge ratios. Costs are reported in 2000 US dollars. RESULTS: For infants born at 24 to 26 weeks' gestation, each additional day of monitoring cost from $41000 per QALY saved for the first day to >$130000 per additional QALY gained for the tenth day. Cost-effectiveness was poorer for infants who were born at gestational ages >30 weeks. Results were sensitive to the proportion of charted apneas requiring stimulation that would actually progress, without intervention, to respiratory arrest. CONCLUSIONS: In this model, the cost-effectiveness of predischarge monitoring for apnea of prematurity declined significantly as the duration of monitoring was increased. Consideration should be given to alternative uses for resources in formulating neonatal discharge guidelines.