Epidemiological Impact and Cost-Effectiveness of Varicella Vaccination Strategies in the United Kingdom.

BACKGROUND: Despite the burden of varicella, there is no universal varicella vaccination (UVV) program in the United Kingdom (UK) due to concerns that it could increase herpes zoster (HZ) incidence. We assessed the cost-utility of a first-dose monovalent (varicella [V]) or quadrivalent (measles-mumps-rubella-varicella [MMRV]) followed by a second-dose MMRV UVV program. GSK and MSD varicella-containing vaccines (VCVs) were considered. METHODS: Dynamic transmission and cost-effectiveness models were adapted to the UK. Outcomes measured included varicella and HZ incidences and the incremental cost-utility ratio (ICURs) over a lifetime horizon. Payer and societal perspectives were evaluated. RESULTS: The impact of V-MMRV and MMRV-MMRV UVV programs on varicella incidence was comparable between both VCVs at equilibrium. HZ incidence increased by 1.6%-1.7% over 7 years after UVV start, regardless of the strategies, then decreased by >95% at equilibrium. ICURs ranged from £5665 (100 years) to £18 513 (20 years) per quality-adjusted life-year (QALY) gained with V-MMRV and from £9220 to £27 101 per QALY gained with MMRV-MMRV (payer perspective). MMRV-MMRV was cost-effective in the medium- and long-terms with GSK VCV and only cost-effective in the long term with MSD VCV at a £20 000 per QALY gained threshold. Without the exogenous boosting hypothesis, HZ incidence decreased through UVV implementation. ICURs were most sensitive to discount rates and MMRV price. CONCLUSIONS: A 2-dose UVV was demonstrated to be a cost-effective alternative to no vaccination. With comparable effectiveness as MSD VCV at lower costs, GSK VCV may offer higher value for the money.

Genomic signature to guide adjuvant chemotherapy treatment decisions for early breast cancer patients in France: a cost-effectiveness analysis.

Introduction: Chemotherapy (CT) is commonly used as an adjuvant treatment for women with early breast cancer (BC). However, not all patients benefit from CT, while all are exposed to its short- and long-term toxicity. The Oncotype DX® test assesses cancer-related gene expression to estimate the risk of BC recurrence and predict the benefit of chemotherapy. The aim of this study was to estimate, from the French National Health Insurance (NHI) perspective, the cost-effectiveness of the Oncotype DX® test compared to standard of care (SoC; involving clinicopathological risk assessment only) among women with early, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC considered at high clinicopathological risk of recurrence. Methods: Clinical outcomes and costs were estimated over a lifetime horizon based on a two-component model that comprised a short-term decision tree representing the adjuvant treatment choice guided by the therapeutic decision support strategy (Oncotype DX® test or SoC) and a Markov model to capture long-term outcomes. Results: In the base case, the Oncotype DX® test reduced CT use by 55.2% and resulted in 0.337 incremental quality-adjusted life-years gained and cost savings of €3,412 per patient, compared with SoC. Being more effective and less costly than SoC, Oncotype DX® testing was the dominant strategy. Discussion: Widespread implementation of Oncotype DX® testing would improve patient care, provide equitable access to more personalized medicine, and bring cost savings to the health system.

Social Preferences for Orphan Drugs: A Discrete Choice Experiment Among the French General Population.

Objectives: While several authors have suggested using a multi-criteria approach for orphan drug assessment and proposed lists of determinants of orphan drug value, studies on social preferences regarding these determinants remain limited. The current study aimed to identify preferences of the French general population regarding attributes characterizing the value of orphan drugs in a discrete choice experiment. Methods: The list of attributes was formed based on a literature search and was refined through expert interviews, a focus group, and a pilot study. The final list included nine attributes: disease-associated disability, disease-associated mortality, number of patients, availability of alternative treatments, treatment impact on disease disability, treatment impact on mortality, treatment safety, uncertainty around therapeutic effect, and annual treatment cost per patient. Members of the General Public were presented with 12 choice sets containing two drug profiles described according to the attributes and an option to fund neither of these treatments. The questionnaire was disseminated online. A conditional logit model with random effects was used to estimate the weight of each attribute. Results: A total of 958 persons participated in the study (48.7% male, mean age: 47.5 years). All attributes except for disease-associated disability had a statistically significant influence on the choices made by participants. The attribute with the highest weight was treatment impact on mortality (p < 0.0001), followed by uncertainty around therapeutic effect (p < 0.0001). The direction of results was generally consistent with intuition: patients preferred a drug with a larger impact on mortality, a larger impact on disability, with mild or no adverse events, with less uncertainty. Although patients appeared to prefer drugs with a lower budget impact, the relationship between patient preferences and costs was more complex. Conclusions: Preferences of the general public between orphan drugs are mostly driven by the impact on mortality and the degree of certainty regarding the available evidence.

Health economic evaluation of rivaroxaban in the treatment of patients with chronic coronary artery disease or peripheral artery disease.

AIMS: In the COMPASS trial, rivaroxaban 2.5 mg twice daily (bid) plus acetylsalicylic acid (ASA) 100 mg once daily (od) performed better than ASA 100 mg od alone in reducing the rate of cardiovascular disease, stroke, or myocardial infarction (MI) in patients with coronary artery disease (CAD) and peripheral artery disease (PAD). A Markov model was developed to assess the cost-effectiveness of rivaroxaban plus ASA vs. ASA alone over a lifetime horizon, from the UK National Health System perspective. METHODS AND RESULTS: The base case analysis assumed that patients entered the model in the event-free health state, with the possibility to experience ≤2 events, transitioning every three-month cycle, through acute and post-acute health states of MI, ischaemic stroke (IS), or intracranial haemorrhage (ICH), and death. Costs, quality-adjusted life-years (QALYs), life years-all discounted at 3.5%-and incremental cost-effectiveness ratios (ICERs) were calculated. Deterministic and probabilistic sensitivity analyses were conducted, as well as scenario analyses. In the model, patients on rivaroxaban plus ASA lived for an average of 14.0 years with no IS/MI/ICH, and gained 9.7 QALYs at a cost of £13 947, while those receiving ASA alone lived for an average of 12.7 years and gained 9.3 QALYs at a cost of £8126. The ICER was £16 360 per QALY. This treatment was cost-effective in 98% of 5000 iterations at a willingness-to-pay threshold of £30 000 per QALY. CONCLUSION: This Markov model suggests that rivaroxaban 2.5 mg bid plus ASA is a cost-effective alternative to ASA alone in patients with chronic CAD or PAD.

Cost-effectiveness of pirfenidone compared to all available strategies for the treatment of idiopathic pulmonary fibrosis in France.

Objective: To update the health economic evaluation of pirfenidone in the treatment of idiopathic pulmonary fibrosis (IPF) compared to all available alternatives strategies (Best supportive care - BSC and nintedanib), based on a cost-utility model previously validated by the CEESP's (French Committee for Economic Evaluation) in 2014. Methods: A standard Markov cohort model, adapted to French methodology guidelines, was used to simulate the therapeutic management and the course of IPF patients (including potential adverse events) using the collective perspective. Cost-effectiveness was evaluated regarding life years (LY); quality-adjusted life-years (QALY); average cumulative costs; the incremental cost-effectiveness ratio (ICER) expressed in cost per QALY gained. Data were retrieved from trials, meta-analysis, literature, health insurance and hospitalisation databases, and national tariffs. Results: Over 15 years, total costs accumulated in the pirfenidone strategy were estimated at €99,477 per patient, €104,610 in nintedanib, and €14,177 in Best Supportive Care (BSC). The total number of QALYs accumulated equalled 5.20 (6.91 LYs), 4.52 (5.98 LYs), and 3.79 (4.98 LYs), respectively. Pirfenidone was estimated to be dominant over nintedanib with incremental costs of -€5,133 and 0.67 more QALYs accumulated. Incremental cost versus BSC was €85,300 and 1,404 QALY gained. The cost-effectiveness ratio was estimated at 60,738€/QALY when compared to BSC. Conclusion: Pirfenidone is likely to be a cost-effective strategy compared to BSC and seems more efficient and less costly compared to nintedanib for the treatment of patients with IPF in France.

Treatment patterns and healthcare resource utilization and costs in heavy menstrual bleeding: a Japanese claims database analysis.

AIMS: Heavy menstrual bleeding (HMB) is a highly prevalent condition, characterized by excessive menstrual blood loss and cramping, that interferes with activities of daily life. The aim of this study was to investigate treatment patterns in HMB in Japan, and to assess healthcare resource utilization and costs among women newly-diagnosed with the condition. MATERIALS AND METHODS: This study retrospectively analyzed health insurance data available in the Japan Medical Data Center (JMDC) database on women aged 18-49 years who were newly-diagnosed with primary or secondary HMB. Treatment patterns were analyzed, and healthcare utilization and costs were evaluated and compared to matched controls. RESULTS: The study included a total of 635 patients, 210 with primary HMB and 425 with secondary HMB. In the primary HMB cohort, 60.0% of patients received one or more pharmacological or surgical treatments, compared with 76.2% in the secondary HMB cohort. The most commonly prescribed medications in all patients were hemostatic agents (28.7%), traditional Chinese medicine (TCM) (12.1%), and low-dose estrogen progestins (LEPs) (10.1%). After adjustment for patient baseline characteristics, healthcare costs were 1.93-times higher in primary HMB cases (p < .0001) and 4.44-times higher in secondary HMB cases (p < .0001) vs healthy controls. Outpatient care was the main cost driver. LIMITATIONS: The main limitations of this study are related to its retrospective nature, and the fact that only reimbursed medications were captured in the source database. CONCLUSIONS: A substantial proportion of HMB patients did not receive the recommended treatments. Healthcare costs were considerably increased in the presence of an HMB diagnosis.

Key drivers for market penetration of biosimilars in Europe.

Background & Objectives: Potential drivers and barriers of biosimilar uptake were mainly analysed through qualitative approaches. The study objective was to conduct a quantitative analysis and identify drivers of biosimilar uptake of all available biosimilars in the European Union (EU). Methods: A three-step process was established to identify key drivers for the uptake of biosimilars in the top 10 EU member states (MS) pharmaceutical markets (Belgium, France, Germany, Greece, Hungary, Italy, Poland, Spain, Sweden, and the UK): (1) literature review to identify incentive policies in place to enhance biosimilars adoption; (2) assessment of biosimilar market dynamics based on database analysis; (3) regression model analysis on price using the following explicative variables: incentive policies; price difference between the biosimilar and the originator product; distribution channel; generic uptake and generic price cut; pharmaceutical expenditure per capita; and market competition. Results: At the study cut-off date, 20 biosimilars were available on the market. Incentive policies applied to biosimilars were found to be heterogeneous across countries, and uptakes of biosimilars were also very heterogeneous between different therapeutic classes and countries. Results from the model demonstrated that incentive policies and the date of first biosimilar market entry were correlated to biosimilar uptake. Pharmaceutical expenditure per capita and the highest generic uptake were inversely correlated with biosimilar uptake. Average generic price discount over originator and the number of biosimilars showed a trend toward statistical significance for correlation with biosimilar uptake, but did not reach the significance threshold. Biosimilar price discount over original biologic price, the number of analogues, and the distribution channel were not correlated with the biosimilar uptake. Conclusions: Understanding drivers of biosimilar uptake becomes a critical issue to inform policy decision-makers. This study showed that incentive policies to enhance uptake remain an important driver of biosimilar penetration, while biosimilar price discounts have no impact. Future research is warranted when the biosimilar market gains maturity.

Evaluation of the treatment patterns and economic burden of dysmenorrhea in Japanese women, using a claims database.

PURPOSE: This study aimed to describe treatment patterns and estimate health care resource utilization and associated costs among Japanese women with dysmenorrhea, using a claims database. METHODS: This was a retrospective analysis using health insurance data from the Japan Medical Data Center, assessing female patients aged 18-49 years with newly diagnosed primary or secondary dysmenorrhea. Treatment pattern analyses focused on hormonal medications, analgesics, hemostatic agents, traditional Chinese medicine (TCM), and gynecological surgeries. Data were collected on health care resource utilization and costs associated with medications, imaging procedures, and inpatient and outpatient care in both patients and matched controls. RESULTS: The analysis included 6,315 women with dysmenorrhea (3,441 primary; 2,874 secondary). The most commonly prescribed initial therapies were low-dose estrogen progestins (LEPs, 37.7%) and TCM (30.0%), with substantial differences between primary (LEPs: 27.4%, TCM: 38.8%) and secondary (LEPs: 50.2%, TCM: 19.5%) dysmenorrhea cohorts. Surgery was conducted in <5% of all patients. Both primary and secondary cohorts of dysmenorrhea had significantly higher mean total health care costs compared to controls within the 1-year period following diagnosis (Case-primary: 191,680 JPY [1,916 USD]; secondary: 246,488 JPY [2,465 USD], Control-primary: 83,615 JPY [836 USD]; secondary: 90,711 JPY [907 USD]) (p<0.0001). After adjusting for baseline characteristics, these costs were 2.2 and 2.9 times higher for primary and secondary dysmenorrhea cohorts, respectively, compared with matched controls, (both p<0.0001). The main driver of these excess costs was outpatient care, with eight additional physician visits per year among dysmenorrhea patients compared to controls (p<0.0001). CONCLUSION: Considerable heterogeneity in treatment patterns was observed, with relatively low utilization of LEPs in patients with primary dysmenorrhea and those treated by internal medicine physicians. Total annual health care costs were approximately 2-3 times higher in patients with dysmenorrhea compared to women without the condition.

A Trial-Based Predictive Microsimulation Assessing the Public Health Benefits of Nalmefene and Psychosocial Support for the Reduction of Alcohol Consumption in Alcohol Dependence.

BACKGROUND: Alcohol dependence causes considerable harm to patients. Treatment with nalmefene, aiming to reduce consumption rather than maintain complete abstinence, has been licensed based on trials demonstrating a reduction in total alcohol consumption and heavy drinking days. Relating these trial outcomes to harmful events avoided is important to demonstrate the clinical relevance of nalmefene treatment. METHODS: A predictive microsimulation model was developed to compare nalmefene plus brief psychosocial intervention (BRENDA) versus placebo plus BRENDA for the treatment of patients with alcohol dependence and a high or very high drinking risk level based on three pooled clinical trials. The model simulated patterns and level of alcohol consumption, day-by-day, for 12 months, to estimate the occurrence of alcohol-attributable diseases, injuries and deaths; assessing the clinical relevance of reducing alcohol consumption with treatment. RESULTS: The microsimulation model predicted that, in a cohort of 100,000 patients, 971 (95 % confidence interval [CI] 904-1038) alcohol-attributable diseases and injuries and 133 (95 % CI 117-150) deaths would be avoided with nalmefene versus placebo. This level of benefit has been considered clinically relevant by the European Medicines Agency. CONCLUSIONS: This microsimulation model supports the clinical relevance of the reduction in alcohol consumption, and has estimated the extent of the public health benefit of treatment with nalmefene in patients with alcohol dependence and a high or very high drinking risk level.

A Comparison of Markov and Discrete-Time Microsimulation Approaches: Simulating the Avoidance of Alcohol-Attributable Harmful Events from Reduction of Alcohol Consumption Through Treatment of Alcohol Dependence.

BACKGROUND AND OBJECTIVE: When modelling the pathophysiology of a disease, it is important to select a modelling approach that can adequately replicate its course. The objective of this paper was to compare the outcomes obtained by the Markov and discrete-time microsimulation modelling approaches using nalmefene clinical trial data. METHODS: Markov and microsimulation modelling approaches assessing alcohol dependence treatment with psychosocial support with or without nalmefene were compared in terms of the modelled evolution of patients' alcohol consumption and the resulting occurrence of alcohol-attributable harmful events over 1 year. RESULTS: Comparison of the proportion of the modelled population at different levels of alcohol consumption over time revealed systematic differences arising from the different modelling techniques: a lower number of patients reaching abstinence, a higher number of patients at higher drinking levels, and, overall, a smoother evolution of alcohol consumption in the microsimulation. Reasons are discussed in the paper. While the models produced similar occurrences of alcohol-attributable harmful events as a whole, distinct results for the individual events were observed, explained by the specific pathophysiology of occurrence of these events and how their implementation was adapted to fit the limitations of the compared modelling approaches; however, these differences were only statistically significant for one of the eight events. CONCLUSIONS: For a general public health or health economic assessment of alcohol use disorders, it is possible to achieve similar results with the compared approaches. To assess a patients' disease course, taking into consideration alcohol-attributable harmful events, the microsimulation approach may provide more precise results. However, further external validation of the models is needed and this additional precision may be outweighed by the greater computational burden of a microsimulation approach.