Estimating Public Economic Gains from Early Breast Cancer and Curative Treatment: A Case Study in Human Epidermal Growth Factor Receptor (HER-2) Positive Targeted Therapies.

INTRODUCTION: Cancer diagnosis influences the choices that patients make regarding current and future labor market activity. These choices have implications for governments based on resulting changes in taxes paid and benefits received. In this analysis we explore how human growth receptor 2 (HER2)-positive residual invasive breast cancer and different treatments influence government accounts excluding health costs. METHODS: HER2-positive early breast cancer (eBC) health states from a published disease model were used to establish likelihood of working and wage impact at different stages of disease. The indirect productivity losses for an average woman aged 49 years were translated into fiscal consequences to government by applying an established government perspective-modeling framework. The fiscal projections (discounted) include gross tax revenue by disease stage, government transfer costs related to time off work and early retirement ,and net fiscal balance (e.g., gross taxes-transfers) in three countries Canada, Portugal, and Brazil. RESULTS: The net fiscal balance in Canada for a healthy woman was C$109,551 compared with a HER2-positive eBC woman treated with trastuzumab emtansine (C$69,767) or trastuzumab (C$62,971). A similar pattern was observed in the three countries but reflecting the overall tax burden in each country, labor force activity, and available public benefits. Age at diagnosis was an important determinant of the likely net fiscal balance, as this influences the remaining working years. DISCUSSION: Women diagnosed with HER2-positive eBC were estimated to pay less lifetime gross taxes and receive more in sickness benefits compared with healthy women. Treatments that improve outcomes are likely to offer fiscal gains for government from improved work force participation.

Costs Analysis of Fibrin Sealant for Prevention of Anastomotic Leakage in Lower Colorectal Surgery.

INTRODUCTION: Postoperative anastomotic leaks remain a common and serious complication of colorectal surgeries and are a major cause of mortality and morbidity of these procedures. Anastomotic leaks (AL) have been extensively studied; however, there has been no significant reduction in their prevalence over time. In addition, there is a significant economic burden from AL attributed to the need for repeat surgery, radiologic intervention and lengthened hospital stay. We conducted a comparative cost analysis of patients undergoing colorectal surgery with anastomosis, with the application of fibrin sealant (FS) to the sutured anastomosis versus not treating the sutured anastomosis with FS. METHODS: The deterministic decision-tree model was populated with clinical data including operating room time, hospitalization days, occurrence of AL, need for revision surgery, blood products and radiologic interventions to treat the AL in lower colorectal surgery. A systematic literature review was conducted to identify appropriate studies with these variables. RESULTS: The average cost per case treated lower colorectal surgery with fibrin sealant glue 10 mL Tisseel® and those not treated with a fibrin sealant after suturing the anastomoses was €3233 and €4130, respectively, for resource expenses paid by the healthcare system. This would suggest potential savings of €897 per surgery, achieved through the application of FS to the sutured anastomosis for preventing AL following colorectal surgery. CONCLUSION: Application of FS to the sutured anastomosis in lower colorectal surgery resulted in a decrease in post-operative AL, and cost savings based on a reduction in hospitalization days, a reduction needing: revision surgery, radiologic intervention and blood products to treat AL.

Estimating the fiscal impact of rare diseases using a public economic framework: a case study applied to hereditary transthyretin-mediated (hATTR) amyloidosis.

BACKGROUND: A wide range of rare diseases can have fiscal impacts on government finances that extend beyond expected healthcare costs. Conditions preventing people from achieving national lifetime work averages will influence lifetime taxes paid and increase the likelihood of dependence on public income support. Consequently, interventions that influence projected lifetime work activity, morbidity and mortality can have positive and negative fiscal consequences for government. The aim of this study was to apply a public economic framework to a rare disease that takes into consideration a broad range of costs that are relevant to government in relation to transfers received and taxes paid. As a case study we constructed a simulation model to calculate the fiscal life course of an individual with hereditary transthyretin-mediated (hATTR) amyloidosis in The Netherlands. In this lethal disease different progressive disease scenarios occur, including polyneuropathy and/or cardiomyopathy. RESULTS: Due to progressive disability, health care resource use, and early death, hATTR amyloidosis with polyneuropathy receives more transfers from government compared to the general population. In a scenario where a patient is diagnoses with hATTR at age 45, an individual pays €180,812 less in lifetime taxes and receives incrementally €111,695 in transfers from the government, compared to a person without hATTR. Patients suffering from cardiomyopathy die after median 4 years. The health costs of this scenario are therefore lower than that of the other polyneuropathy-based scenarios. CONCLUSIONS: The fiscal analysis illustrates how health conditions influence not only health costs, but also the cross-sectorial public economic burden attributed to lost tax revenues and public disability allowances. Due to the progressive nature of hATTR amyloidosis used in this study, public costs including disability increase as the disease progresses with reduced lifetime taxes paid. The results indicate that halting disease progression early in the disease course would generate fiscal benefits beyond health benefits for patients. This analysis highlights the fiscal consequences of diseases and the need for broader perspectives applied to evaluate health conditions. Conventional cost-effectiveness framework used by many health technology assessment agencies have well-documented limitations in the field of rare diseases and fiscal modeling should be a complementary approach to consider.

Assessing the costs and benefits of perioperative iron deficiency anemia management with ferric carboxymaltose in Germany.

BACKGROUND: Perioperative administration of ferric carboxymaltose (FCM) was previously shown to reduce both the need for transfusions and the hospital length of stay in patients with preoperative iron deficiency anemia (IDA). In this study, we estimated the economic consequences of perioperative administration using FCM vs usual care in patients with IDA from the perspective of a German hospital using decision-analytic modeling. MATERIALS AND METHODS: The model was populated with clinical inputs (transfusion rates, blood units transfused, hospital length of stay) from a previously reported randomized trial comparing FCM vs usual care for managing IDA patients undergoing elective abdominal surgery. We applied a hospital perspective to all costs, excluding surgery-related costs in both treatment arms. One-way sensitivity analyses were undertaken to evaluate key drivers of cost analysis. RESULTS: The average costs per case treated using FCM compared to usual care were €2,461 and €3,246, respectively, for resource expenses paid by hospital per case. This would suggest potential savings achieved with preoperative intravenous iron treatment per patient of €786 per case. A sensitivity analysis varying the key input parameters indicated the cost analysis is most sensitive to changes in the length of stay and the cost of hospitalization per day. CONCLUSION: Perioperative administration of FCM results in cost savings to hospitals based on reduced blood transfusions and length of stay following elective abdominal surgery.

Fiscal Impact of Smoking Cessation in Thailand: A Government Perspective Cost-Benefit Analysis.

We evaluate the broader public economic consequences of investments in smoking cessation that change lifetime productivity, which can influence future government tax revenue and social transfer costs and health care spending. The analysis applies a government perspective framework for assessing the intergenerational relationships between morbidity and mortality and lifetime tax revenue and social transfers received. Applying smoking prevalence in Thailand, a cohort model was developed for smoker and former smokers to estimate impact on lifetime direct taxes and tobacco taxes paid. Age-specific earnings for males and wage appropriate tax rates were applied to estimate net taxes for smokers and former smokers. Introducing smoking cessation leads to lifetime public economic benefits of THB13 998 to THB43 356 per person depending on the age of introducing smoking cessation. Factoring in the costs of smoking cessation therapy, an average return on investment of 1.35 was obtained indicating fiscal surplus generated for government from the combined effect of increased tax revenues and of averting smoking-attributable health care costs.

Estimating the public economic consequences of introducing varenicline smoking cessation therapy in South Korea using a fiscal analytic framework.

BACKGROUND AND AIMS: Smoking gives rise to many cross-sectorial public costs and benefits for government. Costs arise from increased healthcare spending and work-related social benefits, while smoking itself provides significant revenue for government from tobacco taxes. To better understand the public economic impact of smoking and smoking cessation therapies, this study developed a government perspective framework for assessing smoking-attributable morbidity and mortality and associated public costs. This framework includes changes in lifetime tax revenue and health costs, as well as changes in tobacco tax revenue, from fewer smokers. METHODS: A modified generational accounting framework was developed to assess relationships between smoking-attributable morbidity and mortality and public economic consequences of smoking, including lifetime tax revenue gains/losses, government social transfers, and health spending. Based on the current prevalence of smoking in South Korean males, a cohort model was developed for smokers, former-smokers, and never-smokers. The model simulated the lifetime discounted fiscal transfers for different age cohorts in 5 year age bands, and the return on investment (ROI) from smoking cessation therapy. RESULTS: Former smokers are estimated to generate higher lifetime earnings and direct tax revenues and lower lifetime healthcare costs due to the reduction of smoking-attributable mortality and morbidity compared to smokers, even after accounting for reduced tobacco taxes paid. Based on the costs of public investments in varenicline, this study estimated a ROI from 1.4-1.7, depending on treatment age, with higher ROI in younger cohorts, with an average ROI of 1.6 for those aged less than 65. CONCLUSIONS: This analysis suggests that reductions in smoking can generate positive public economic benefits for government, even after accounting for lost tobacco tax revenues. The results described here are likely applicable to countries having similar underlying smoking prevalence, comparable taxation rates, and social benefit protection provided to individuals with smoking-related conditions.

Systematic review and meta-analysis of secondary prophylaxis for prevention of HIV-related toxoplasmic encephalitis relapse using trimethoprim-sulfamethoxazole.

A recent systematic literature and meta-analysis reported relative efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of toxoplasmic encephalitis (TE) in HIV-infected adults. Here, we estimated relapse rates during secondary prophylaxis with TMP-SMX, and further explored differences in relapse rates prior to introduction of highly active antiretroviral therapy (HAART) and the widespread adoption of HAART. A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials yielded 707 studies whereby 663 were excluded after abstract screening, and 38 were excluded after full review leaving 6 studies for extraction. We performed double data extraction with a third-party adjudicator. Study designs varied with only one randomized study, four prospective cohorts and one retrospective cohort. Relapse rates were transformed using the Freeman-Tukey method and pooled using both fixed-effect and random-effects meta-analysis models. The TMP-SMX relapse rate was 16.4% (95% CI = 6.2% to 30.3%) based on random-effects models. When the disaggregated pre-HAART studies (n = 4) were included, the relapse rate was 14.9% (random effects; 95% CI = 3.7% to 31.9%). Analysis of two post-HAART studies indicated a relapse rate of 19.2% (random effects; 95% CI = 2.8% to 45.6%). Comparing the relapse rates between pre- and post-HAART studies were contrary to what might be expected based on known benefits of HAART therapy in this population. Nevertheless, cautious interpretation is necessary considering the heterogeneity of the included studies and a limited number of subjects receiving TMP-SMX reported in the post-HAART era.

Assessment of the Broader Economic Consequences of HPV Prevention from a Government-Perspective: A Fiscal Analytic Approach.

BACKGROUND: Cervical cancer poses a substantial burden in terms of morbidity, mortality, and economic losses, especially in low/middle-income countries. HPV vaccination and/or cervical cancer screening among females may reduce the burden of HPV-related diseases, including cervical cancer. However, limited funds may impede the implementation of population-based programmes. Governmental investments in the prevention of infectious disease may have broader economic and fiscal benefits, which are not accounted in conventional economic analyses. This study estimates the broader economic and fiscal impacts of implementing HPV vaccination and/or cervical cancer screening in Indonesia from the perspective of the government. METHODS: A government-perspective quantitative analytic framework was applied to assess the Net Present Value (NPV) of investment on cervical cancer prevention strategies including HPV vaccination, cervical screening and its combination in Indonesia. All monetary values were presented in International Dollars (I$). RESULTS: Based on a cohort of 10,000,000 Indonesian 12-year-old females, it was estimated that HPV vaccination and/or cervical cancer screening result in a positive NPV for the Indonesian government. The combination of cervical screening and HPV vaccination generated a substantial reduction of cervical cancer incidence and HPV-related mortality of 87,862 and 19,359, respectively. It was estimated that HPV vaccination in combination with cervical screening is the most favorable option for cervical cancer prevention (NPV I$2.031.786.000), followed by HPV vaccination alone (NPV I$1.860.783.000) and cervical screening alone (NPV I$375.244.000). CONCLUSION: In addition to clinical benefits, investing in HPV vaccination and cervical screening may yield considerable fiscal benefits for the Indonesian governments due to lifelong benefits resulting from reduction of cervical cancer-related morbidity and mortality.

Quantifying the broader economic consequences of quadrivalent human papillomavirus (HPV) vaccination in Germany applying a government perspective framework.

HPV infections can cause substantial burden in females and males as it is associated with several genital cancers, in addition to genital warts. Traditional economic evaluations often focus on quantifying cost-effectiveness, however, it is increasingly recognized that vaccinations may generate broader benefits not captured in cost-effectiveness analysis. Τhe aim of this study was to evaluate the broader economic consequences associated with HPV vaccination in males and females and to conduct a lifetime cost-benefit analysis of investing in universal vaccination in Germany from the perspective of government. Methodologies from generational accounting, human capital and health economics were combined to estimate the broader economic consequences of HPV vaccination including the fiscal impact for the government. A cohort model was developed simulating the medical costs and average lifetime fiscal transfers between the government and 12-year-old immunized and non-immunized males and females. To estimate tax revenue attributed to vaccination-related changes in morbidity and mortality, direct and indirect tax rates were linked to differences in age- and gender-specific earnings. Based on HPV vaccination costs, the base case cost-benefit analysis demonstrated that investing 1 in universal HPV vaccination could yield 1.7 in gross tax revenue over the lifetime of the cohorts. After taking into consideration the governmental transfers, universal HPV vaccination in Germany could result in incremental positive net discounted taxes (i.e. tax revenue-transfers) from 62 million for the German government. The vaccination of males and females with the quadrivalent HPV vaccine is likely to have positive effects on public finances.

Health utility of patients with advanced gastrointestinal stromal tumors (GIST) after failure of imatinib and sunitinib: findings from GRID, a randomized, double-blind, placebo-controlled phase III study of regorafenib versus placebo.

BACKGROUND: In this analysis we report patients with advanced gastrointestinal stromal tumors (GIST) refractory to imatinib and sunitinib therapy as derived from the EuroQol-5D (EQ-5D) for progression-free (PF) and progressive disease health status. METHODS: Data were analyzed from a phase III trial conducted at 57 hospitals in 17 countries (trial registration number, NCT01271712). Patients with advanced GIST were randomized (2:1) to receive blinded treatment using oral regorafenib 160 mg daily or placebo, plus best supportive care (BSC) in both groups, for the first 3 weeks of each 4-week cycle. EQ-5D-3L was administered on day 1 of each cycle before contact with their physician and before any study-related procedures. The effect of disease progression on the utility of EQ-5D was tested with paired-samples comparison and general linear mixed modeling (GLMM). RESULTS: One hundred and eighty five patients [93 % of the intention-to-treat (ITT) population] completed 803 EQ-5D questionnaires: 77.7 % in progression-free (PF) state, 6.5 % at progression, 13.9 % following first progression, and 1.9 % after second progression. Mean baseline utility was 0.767 (SD 0.221) with no significant between-group differences for active treatment and BSC. The first post-progression health state was 0.647 (SD 0.343), suggesting significantly impaired health-related quality of life after confirmed disease progression showed a decrease of -0.120 (paired samples t test, p = 0.001). GLMM showed no effect of study treatment or cycle number on utility. CONCLUSIONS: We demonstrate a significant and clinically meaningful difference in health state utility values between PF and progression. Utility values remained stable over successive regorafenib cycles after controlling for disease status and treatment type.

An economic evaluation comparing concomitant oral and topical mesalazine versus oral mesalazine alone in mild-to-moderately active ulcerative colitis based on results from randomised controlled trial.

INTRODUCTION: A previous randomised controlled trial has demonstrated that oral plus topical mesalazine enema is more effective than oral mesalazine alone for achieving clinical remission in mild-to-moderately active extensive ulcerative colitis (UC). To evaluate whether this strategy is cost-effective we conducted an economic evaluation comparing 1 g topical mesalazine in combination with 4 g oral mesalazine compared to 4 g mesalazine monotherapy in mild-to-moderately active UC. METHODS: The economic evaluation was based on the ability to achieve remission using changes from baseline in the ulcerative colitis disease activity instrument (UCDAI). A cost-utility analysis was used where the main outcome was quality-adjusted life years to reflect improved quality of life associated with achieving remission compared with active disease. A simulated Markov model with five health states was constructed to model cost and outcome changes over time: (1) active UC; (2) mesalazine-refractory active UC; (3) steroid-refractory active UC; (4) infliximab-responsive active UC; and (5) remission. To reflect parameter uncertainty in the cost-effectiveness analysis probabilistic sensitivity analysis (PSA) was conducted by varying relevant clinical parameters. RESULTS: Average treatment costs required to transition a patient from active UC to remission using oral and topical mesalazine compared with oral alone were £1812 and £2390, respectively. Improved remission rates attributed to oral and topical mesalazine resulted in moderate improvements in quality-adjusted life years (QALYs) compared to oral mesalazine alone. Disaggregation of medical costs indicated that medical consultations and diagnostic costs were similar for both treatment arms. An abbreviated analysis which considered costs up to steroid-refractory patients in subacute UC indicated that combination therapy offered a cost-savings of £285 over 16 weeks of therapy compared with monotherapy. CONCLUSIONS: The results indicate that the addition of 1 g topical mesalazine results in significant cost-savings and moderate quality of life improvements. We have also shown that irrespective of which treatment modality is used in steroid-refractory patients (eg, infliximab, azathioprine, ciclosporine) that topical mesalazine is cost-saving.