Alena M. Pfeil

Cost-Effectiveness Analysis of Sofosbuvir Compared to Current Standard Treatment in Swiss Patients with Chronic Hepatitis C

In clinical trials, sofosbuvir showed high antiviral activity in patients infected with hepatitis C virus (HCV) across all genotypes. We aimed to determine the cost-effectiveness of sofosbuvir-based treatment compared to current standard treatment in mono-infected patients with chronic hepatitis C (CHC) genotypes 1–4 in Switzerland. Cost-effectiveness was modelled from the perspective of the Swiss health care system using a lifetime Markov model. Incremental cost-effectiveness ratios (ICERs) used an endpoint of cost per quality-adjusted life year (QALY) gained. Treatment characteristics, quality of life, and transition probabilities were obtained from published literature. Country-specific model inputs such as patient characteristics, mortality and costs were obtained from Swiss sources. We performed extensive sensitivity analyses. Costs and effects were discounted at 3% (range: 0–5%) per year. Sofosbuvir-containing treatment in mixed cohorts of cirrhotic and non-cirrhotic patients with CHC genotypes 1–4 showed ICERs between CHF 10,337 and CHF 91,570 per QALY gained. In subgroup analyses, sofosbuvir dominated telaprevir- and boceprevir-containing treatment in treatment-naïve genotype 1 cirrhotic patients. ICERs of sofosbuvir were above CHF 100,000 per QALY in treatment-naïve, interferon eligible, non-cirrhotic patients infected with genotypes 2 or 3. In deterministic and probabilistic sensitivity analyses, results were generally robust. From a Swiss health care system perspective, treatment of mixed cohorts of cirrhotic and non-cirrhotic patients with CHC genotypes 1–4 with sofosbuvir-containing treatment versus standard treatment would be cost-effective if a threshold of CHF 100,000 per QALY was assumed.

Determinants of quality of life of patients with heart failure and iron deficiency treated with ferric carboxymaltose : FAIR-HF sub-analysis

BACKGROUND Heart failure (HF) is a burden to patients and health care systems. The objectives of HF treatment are to improve health related quality of life (HRQoL) and reduce mortality and morbidity. We aimed to evaluate determinants of health-related quality of life (HRQoL) in patients with iron deficiency and HF treated with intravenous (i.v.) iron substitution or placebo. METHODS A randomised, double-blind, placebo-controlled trial (n = 459) in iron-deficient chronic heart failure (CHF) patients with or without anaemia studied clinical and HRQoL benefits of i.v. iron substitution using ferric carboxymaltose (FCM) over a 24-week trial period. Multivariate analysis was carried out with various clinical variables as independent variables and HRQoL measures as dependent variables. RESULTS Mean change from baseline of European Quality of Life - 5 Dimensions (EQ-5D) (value set-based) utilities (on a 0 to 100 scale) at week 24 was 8.91 (i.v. iron) and 0.68 (placebo; p < 0.01). In a multivariate analysis excluding baseline HRQoL, a higher exercise tolerance and i.v. iron substitution positively influenced HRQoL, whereas impaired renal function and a history of stroke had a negative effect. The level of HRQoL was also influenced by country of residence. When baseline HRQoL was factored in, the multivariate model remained stable. CONCLUSION In this study, i.v. iron substitution, exercise tolerance, stroke, country of residence and renal function influenced measures of HRQoL in patients with heart failure and iron deficiency.

Efficacy, effectiveness and safety of long-acting granulocyte colony-stimulating factors for prophylaxis of chemotherapy-induced neutropenia in patients with cancer : a systematic review

PurposePegfilgrastim was introduced over a decade ago. Other long-acting granulocyte colony-stimulating factors (G-CSFs) have recently been developed. We systematically reviewed the efficacy, effectiveness and safety of neutropenia prophylaxis with long-acting G-CSFs in cancer patients receiving chemotherapy.MethodsWe performed a systematic literature search of the MEDLINE, EMBASE and Cochrane Library databases, and abstracts from key congresses. Studies of long-acting G-CSFs for prophylaxis of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) were identified by two independent reviewers. Abstracts and full texts were assessed for final inclusion; risk of bias was evaluated using the Cochrane’s tool. Effectiveness and safety results were extracted according to study type and G-CSF used.ResultsOf the 839 articles identified, 41 articles representing different studies met the eligibility criteria. In five randomised controlled trials, 11 clinical trials and 17 observational studies across several tumour types and chemotherapy regimens, pegfilgrastim was used alone or compared with daily G-CSF, no G-CSF, no upfront pegfilgrastim or placebo. Studies generally reported lower incidence of CIN (4/7 studies), FN (11/14 studies), hospitalisations (9/13 studies), antibiotic use (6/7 studies) and adverse events (2/5 studies) with pegfilgrastim than filgrastim, no upfront pegfilgrastim or no G-CSF. Eight studies evaluated other long-acting G-CSFs; most (5/8) were compared to pegfilgrastim and involved patients with breast cancer receiving docetaxel-based therapy. Efficacy and safety profiles of balugrastim and lipegfilgrastim were comparable to pegfilgrastim in phase 3 studies. Efficacy and safety of other long-acting G-CSFs were mixed.ConclusionsPegfilgrastim reduced the incidence of FN and CIN compared with no prophylaxis. Most studies showed better efficacy and effectiveness for pegfilgrastim than filgrastim. Efficacy and safety profiles of lipegfilgrastim and balugrastim were similar to pegfilgrastim.

Cost per patient and potential budget implications of denosumab compared with zoledronic acid in adults with bone metastases from solid tumours who are at risk of skeletal-related events: an analysis for Austria, Sweden and Switzerland

Objectives To assess cost implications per patient, per year, and to predict the potential annual budget impact when patients with bone metastases secondary to solid tumours at risk of skeletal-related events (SREs) transition from zoledronic acid (ZA; 4 mg every 3–4 weeks) to denosumab (120 mg every 4 weeks) in Austria, Sweden and Switzerland. Methods Country specific costs for medication and administration, patient management and SREs (defined as pathologic fracture, radiation to bone, surgery to bone and spinal cord compression) were assessed over a 1-year time horizon. Drug administration and patient management costs were taken from available public sources. SRE costs were based on local unit costs applied to country specific healthcare resources obtained from a multinational retrospective chart review study. Due to lack of real world data for the included countries, SRE rates were derived from phase III clinical trials in patients with advanced cancer and bone metastases. These trials demonstrated that denosumab was superior to ZA in the reduction of SREs. Results Estimated total annual cost savings for each patient transitioned from ZA to denosumab varied by country and cancer type, ranging from €1583 to €2375 in Austria, from €1980 to €2319 in Sweden (9.1 SEK/€) and from €3408 to €3857 in Switzerland (1.2 CHF/€). Cost savings were mainly driven by the lower SRE related costs and lower administration costs of denosumab compared with ZA. Conclusions Denosumab offers superior efficacy compared with ZA in patients with solid tumours and bone metastases. Cost savings are predicted in the Austrian, Swedish and Swiss healthcare systems following treatment transition from ZA to denosumab.

Alzheimer's dementia: budget impact and cost-utility analysis of a combination treatment of a cholinesterase inhibitor and memantine in Switzerland

QUESTIONS UNDER STUDY The objective of this study was to estimate the potential budget impact and cost-effectiveness of the combination treatment of a cholinesterase inhibitor and memantine in Switzerland. METHODS The prevalence of dementia according to European sources and future Swiss population data were used to estimate the number of patients with Alzheimers dementia in Switzerland. Both direct and indirect costs calculated from Swiss sources were included. Utility estimates and transition probabilities were obtained from the published literature. A Markov model was used for the cost-utility analysis in order to calculate incremental cost-effectiveness ratios from a health care and a societal perspective. RESULTS Assuming mono treatment (either a cholinesterase inhibitor or memantine), treatment costs would increase from CHF 22.7 million in 2012 to CHF 26.1 million in 2016, the additional yearly treatment costs for the combination treatment (cholinesterase inhibitor and memantine) would be between CHF 1.7 million and CHF 1.9 million. The Markov model compared health care costs of the mono treatment to costs of the combination treatment over five years. From a health care perspective, the combination treatment saved CHF 27,655 per patient over five years and CHF 248,895/quality adjusted life year compared to the mono treatment. CONCLUSIONS Implementation of the reimbursed combination treatment would incur additional treatment costs of about CHF 10 million over five years. From a health care perspective, the combination treatment would decrease costs over five years by CHF 50 million. Based on long term considerations, the combination treatment was the dominant strategy over the mono treatment.

Estimating the potential annual welfare impact of innovative drugs in use in Switzerland

Expenditures of health care systems are increasing from year to year. Therefore, this study aimed to estimate the difference in costs and benefits of innovative pharmaceuticals launched 2000 onward compared to standard treatment on the national economy of Switzerland in 2010. The approach and formula described in the pilot study by Tsiachristas et al. (1), which analyzed the situation of welfare effects in the Netherlands, served as a model for our own calculations. A literature search was performed to identify cost–utility or cost-effectiveness studies of drugs launched 2000 onward compared to standard treatment. All parameters required for the calculation of welfare effects were derived from these analyses. The base-case threshold value of a quality-adjusted life year was set to CHF 100,000. Overall, 31 drugs were included in the welfare calculations. The introduction of innovative pharmaceuticals since 2000 onward to the Swiss market led to a potential welfare gain of about CHF 781 million in the year 2010. Univariate sensitivity analysis showed that results were robust. Probably because of the higher benefits of new drugs on health and quality of life compared to standard treatment, these drugs are worth the higher costs. The literature search revealed that there is a lack of information about the effects of innovative pharmaceuticals on the overall economy of Switzerland. Our study showed that potential welfare gains in 2010 by introducing innovative pharmaceuticals to the Swiss market were substantial. Considering costs and benefits of new drugs is important.

Benzodiazepine Use and Risk of Developing Alzheimer’s Disease: A Case-Control Study Based on Swiss Claims Data

BackgroundA possible association between benzodiazepine use and Alzheimer’s disease (AD) has been hypothesized in previous studies.ObjectivesUsing claims data from the Helsana Group, a large Swiss health insurance provider, we examined the association between previous benzodiazepine use and the risk of AD.MethodsWe conducted a matched case-control study and identified 1438 incident AD cases between 2013 and 2014 based on recorded first-time use of drugs used to treat AD [i.e., acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and the N-methyl-d-aspartate receptor antagonist memantine] and matched one control to each case on age, sex, index date, and residence (canton). Because the initiation of benzodiazepine use shortly before the AD diagnosis date may occur as a result of symptomatic treatment of prodromal symptoms of early major neurocognitive disorder, we introduced an induction period of 2 years before the AD diagnosis date. Additionally, we categorized medication use by duration of use prior to the index date using prescriptions. We applied conditional logistic regression analyses to calculate odds ratios with 95% confidence intervals and adjusted for use of antidepressants.ResultsThe crude odds ratio (95% confidence interval) of developing AD for patients starting benzodiazepine treatment was 1.71 (1.17–2.99) in the year before diagnosis and 1.19 (0.82–1.72) in the third year before diagnosis. After accounting for benzodiazepine use initiated during the prodromal phase, benzodiazepine use was not associated with an increased risk of developing AD; long-term benzodiazepine use (≥30 prescriptions) yielded an adjusted odds ratio of 0.78 (0.53–1.14).ConclusionsAfter taking into consideration a possible protopathic bias in the 2 years preceding the AD diagnosis date, benzodiazepine use was not associated with an increased risk of developing AD.

External validation of a risk model of febrile neutropenia occurrence in patients with non-Hodgkin lymphoma

Abstract Febrile neutropenia (FN) is a common and serious complication of chemotherapy treatment. Clinical risk models may help to identify patients at high risk of FN but must undergo external validation before implementation in medical practice. Therefore, this study externally validated previously published clinical models of FN occurrence during chemotherapy in 240 patients with non-Hodgkin lymphoma by using an independent observational dataset (n = 1829). The models demonstrated predictive ability, and validation criteria for predicting any cycle of FN were partially met but a larger than expected decrease in performance was noted (area under the receiver operating characteristic curve was 0.71 in the validation dataset and 0.83 in the training dataset). Age, weight, baseline white blood cell count and planned chemotherapy parameters were confirmed to predict FN risk. Chemotherapy dose reductions, dose delays and colony-stimulating factor use were confirmed as risk modifiers during treatment. Further work is needed to improve the predictive ability of FN risk models.

Cost-effectiveness of sacubitril/valsartan in chronic heart-failure patients with reduced ejection fraction

AIMS We aimed to assess the cost effectiveness of sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors (ACEIs) for the treatment of individuals with chronic heart failure and reduced-ejection fraction (HFrEF) from the perspective of the Swiss health care system. METHODS The cost-effectiveness analysis was implemented as a lifelong regression-based cohort model. We compared sacubitril/valsartan with enalapril in chronic heart failure patients with HFrEF and New York-Heart Association Functional Classification II-IV symptoms. Regression models based on the randomised clinical phase III PARADIGM-HF trials were used to predict events (all-cause mortality, hospitalisations, adverse events and quality of life) for each treatment strategy modelled over the lifetime horizon, with adjustments for patient characteristics. Unit costs were obtained from Swiss public sources for the year 2014, and costs and effects were discounted by 3%. The main outcome of interest was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life years (QALYs) gained. Deterministic sensitivity analysis (DSA) and scenario and probabilistic sensitivity analysis (PSA) were performed. RESULTS In the base-case analysis, the sacubitril/valsartan strategy showed a decrease in the number of hospitalisations (6.0% per year absolute reduction) and lifetime hospital costs by 8.0% (discounted) when compared with enalapril. Sacubitril/valsartan was predicted to improve overall and quality-adjusted survival by 0.50 years and 0.42 QALYs, respectively. Additional net-total costs were CHF 10 926. This led to an ICER of CHF 25 684. In PSA, the probability of sacubitril/valsartan being cost-effective at thresholds of CHF 50 000 was 99.0%. CONCLUSION The treatment of HFrEF patients with sacubitril/valsartan versus enalapril is cost effective, if a willingness-to-pay threshold of CHF 50 000 per QALY gained ratio is assumed.