Global spending on orphan drugs in France, Germany, the UK, Italy and Spain during 2007.

BACKGROUND: Orphan drugs are indicated for the treatment of rare diseases which, in the EU, are defined as those with a prevalence of <5 per 10000 inhabitants. Characteristically, these diseases negatively affect health-related quality of life and may be life threatening. The EU has passed legislation to encourage pharmaceutical companies to invest in research programmes into rare diseases, with the aim of developing new, safe and effective orphan drugs. OBJECTIVES: To describe the status of orphan drugs in five countries in the EU (France, Germany, the UK, Italy and Spain), estimate the mean annual cost per patient and indication of these orphan drugs, and determine the associated cost of these drugs in comparison with overall spending on drugs in each country (year 2007 values). METHODS: The analysis was limited solely to costs of orphan drugs with sales data available for 2007. The mean annual cost per patient was estimated using recommended regimens for maintenance dose and duration from the summary of product characteristics. Likewise, the ratio between annual costs per patient for treatment of each disease and its prevalence was calculated. Sales data were available for at least one of the countries studied for 38 of the 44 orphan drugs authorized by the European Medicines Agency. Only 21 products had data available for all five countries studied. RESULTS: Germany was the country with access to the largest number of orphan drugs (36), followed by the UK (34), Spain (28), France (27) and Italy (25). The mean annual cost per patient and indication of the 38 orphan drugs on the market ranged widely from €331 to €337,501. It appears that orphan drugs indicated to treat diseases with a prevalence of <2 per 10000 inhabitants have higher annual per-patient costs than those indicated to treat diseases with a higher prevalence. The percentage of total drug spending accounted for by orphan drugs in 2007 was 1.7% in France, 2.1% in Germany, 1.0% in the UK, 1.5% in Italy and 2.0% in Spain, with an average overall percentage of 1.7% for these five countries. CONCLUSIONS: In 2007, spending on orphan drugs in five European countries was acceptable in terms of the percentage of these countries' overall drug expenditure. Mean annual costs per patient of orphan drugs varied widely, with costs being related to the prevalence of the disease for which the product is indicated.

Costs of adverse events associated with erlotinib or afatinib in first-line treatment of advanced EGFR-positive non-small cell lung cancer.

OBJECTIVES: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are an established treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation. According to published meta-analyses, no significant efficacy differences have been demonstrated between erlotinib and afatinib. However, the incidence of EGFR-TKI-related adverse events (AEs) was lower with erlotinib. This study compares the cost of management of the AEs associated with these two drugs from the perspective of the Spanish National Health System (NHS). METHODS: The frequency of AEs was established from a recently published meta-analysis. In Spain, the daily cost of both drugs can be considered similar; as a result, only the costs of management of the AEs were considered. Costs and resource utilization in the management of the AEs were estimated by a panel of Spanish oncologists and from studies previously carried out in Spain. A probabilistic analysis was performed based on a Monte Carlo simulation. RESULTS: The model generated 1,000 simulations. The total cost per patient treated with erlotinib and afatinib was €657.44 and €1,272.15, respectively. With erlotinib, the cost per patient and per AE of grades ≤2 and ≥3 was €550.86 and €106.58, respectively, whereas the cost with afatinib was €980.63 and €291.52, respectively. The reduction in the number of AEs with erlotinib could avoid a mean cost for the NHS of €614.71 (95% CI: €342.57-881.29) per patient. CONCLUSION: In advanced EGFR mutation-positive NSCLC patients, first-line treatment with erlotinib could reduce health care costs for the NHS, due to a decrease in the AE rate compared with afatinib. In long-term treatments, the avoidance of complications and the lowering of costs associated with the management of AEs are relevant factors that contribute to the sustainability of the health system.

Economic evaluation of obinutuzumab in combination with chlorambucil in first-line treatment of patients with chronic lymphocytic leukemia in Spain.

OBJECTIVE: To evaluate the cost-effectiveness of obinutuzumab in combination with chlorambucil (GClb) versus rituximab plus chlorambucil (RClb) in the treatment of adults with previously untreated chronic lymphocytic leukemia (CLL) and with comorbidities that make them unsuitable for full-dose fludarabine-based therapy, from the perspective of the Spanish National Health System. METHODS: A Markov model was developed with three mutually exclusive health states: progression-free survival (with or without treatment), progression, and death. Survival time for the two treatments was modeled based on the results of CLL11 clinical trial and external sources. Each health state was associated with a utility value and direct medical costs. The utilities were obtained from a utility elicitation study conducted in the UK. Costs and general background mortality data were obtained from published Spanish sources. Deterministic and probabilistic analyses were conducted, with a time frame of 20 years. The health outcomes were measured as life years (LYs) gained and quality-adjusted life years (QALYs) gained. Efficiency was measured as the cost per LY or per QALY gained of the most effective regimen. RESULTS: In the deterministic base case analysis, each patient treated with GClb resulted in 0.717 LYs gained and 0.673 QALYs gained versus RClb. The cost per LY and per QALY gained with GClb versus RClb was €23,314 and €24,838, respectively. The results proved stable in most of the univariate and probabilistic sensitivity analyses, with a probabilistic cost per QALY gained of €24,734 (95% confidence interval: €21,860-28,367). CONCLUSION: Using GClb to treat patients with previously untreated CLL for whom full-dose fludarabine-based therapy is unsuitable allows significant gains in terms of LYs and QALYs versus treatment with RClb. Treatment with GClb versus RClb can be regarded as efficient when considered the willingness to pay thresholds commonly used in Spain.