Overall survival in the UK in mycosis fungoides or Sézary syndrome cutaneous T-cell lymphoma: comparative effectiveness of mogamulizumab versus current standard of care.

Aim: Due to extensive treatment switching in the MAVORIC trial, lack of UK regulatory licence for the comparator, overall survival (OS) with mogamulizumab was compared with patients with previously treated advanced mycosis fungoides/Sézary syndrome (MF/SS) in real-world setting. Design, setting & participants: Data were from the Hospital Episode Statistics database (all patients in NHS secondary care system in 2009-2019). Patients were selected according to trial inclusion criteria, then trial and HES samples were matched on selected variables with significant imbalance. Outcomes: The analysis indicated significant improvement in OS for mogamulizumab treatment compared with UK clinical practice (hazard ratio: 0.36, 95% CI: 0.24, 0.53). Conclusion: Results suggest an OS advantage for patients with advanced MF/SS treated with mogamulizumab in MAVORIC trial compared with UK clinical practice.

Cost-utility analysis of mogamulizumab in advanced mycosis fungoides and Sézary syndrome cutaneous T-cell lymphoma.

Aim: This study assessed the cost-utility of mogamulizumab, a novel monoclonal antibody, versus established clinical management (ECM) in UK patients in previously treated advanced mycosis fungoides (MF)/Sézary syndrome (SS). Materials & methods: Lifetime partitioned survival model based on overall survival, next treatment-free survival and the use of allogeneic stem cell transplant was developed. Inputs were from the pivotal MAVORIC trial, real-world evidence and published literature. Extensive sensitivity analyses were conducted. Results: Discounted incremental quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratio were 3.08, £86,998 and £28,233. Results were most sensitive to the survival extrapolations, utilities and costs after loss of disease control. Conclusion: Mogamulizumab is a cost-effective alternative to ECM in UK patients with previously treated advanced MF/SS.

Adjusting for treatment crossover in the MAVORIC trial: survival in advanced mycosis fungoides and Sézary syndrome.

Background: Relative overall survival (OS) estimates reported in the MAVORIC trial are potentially confounded by a high proportion of patients randomized to vorinostat switching to mogamulizumab; furthermore, vorinostat is not used in clinical practice in the UK. Methods: Three methods were considered for crossover adjustment. Survival post-crossover adjustment was compared with data from the Hospital Episode Statistics (HES) to contextualize estimates. Results: Following adjustment, the OS hazard ratio for mogamulizumab versus vorinostat was 0.42 (95% CI: 0.18, 0.98) using the method considered most appropriate based on an assessment of assumptions and comparison with HES. Conclusions: OS of mogamulizumab relative to vorinostat may be underestimated in MAVORIC due to the presence of crossover. The HES database was used to validate this adjustment.

Changes in treatment pattern and costs in advanced hepatocellular carcinoma (HCC).

INTRODUCTION: While essential for cost-effectiveness analyses, there are no current resource use and cost data available for advanced hepatocellular carcinoma (HCC) and selective internal radiation therapy (SIRT). The study aims to assess current resource use and costs in HCC and for SIRT compared to historical survey data. AREAS COVERED: To address this data gap, resource use was elicited via surveys and interviews with medical professionals experienced with HCC and SIRT in the United Kingdom. Unit costs were from publicly available databases. Resource use and costs were estimated and compared to prior surveys. EXPERT OPINION: From eleven responses, pre-progression costs for SIRT and systemic therapy were £256.77 and £292.27/month, respectively. One-off progression and post-progression costs were £209.98 and £522.84/month. Monthly costs were 54%-79% lower than in previous surveys, due to reduction in hospitalizations and funded social care. Furthermore, substantial differences in resource use associated with SIRT between clinical practice and clinical trials were found. In conclusion, increased availability and familiarity with systemic treatments has led to important changes in HCC care and SIRT administration. The uncertainty from the use of expert opinion and the limited number of hospitals with SIRT experience can be addressed with future research using large databases, registries.

Cost-utility analysis of selective internal radiation therapy with Y-90 resin microspheres in hepatocellular carcinoma.

Background: The study assessed the cost-utility of selective internal radiation therapy (SIRT) with Y-90 resin microspheres versus sorafenib in UK patients with unresectable hepatocellular carcinoma ineligible for transarterial chemoembolization. Materials & methods: A lifetime partitioned survival model was developed for patients with low tumor burden (≤25%) and good liver function (albumin-bilirubin grade 1). Efficacy, safety and quality of life data were from a European Phase III randomized controlled trial and published studies. Resource use was from registries and clinical surveys. Results: Discounted quality-adjusted life-years were 1.982 and 1.381, and discounted total costs were £29,143 and 30,927, for SIRT and sorafenib, respectively. Conclusion: SIRT has the potential to be a dominant (more efficacious/less costly) or cost-effective alternative to sorafenib in patients with unresectable hepatocellular carcinoma.

Cost-Effectiveness of Sarilumab Added to Methotrexate in the Treatment of Adult Patients with Moderately to Severely Active Rheumatoid Arthritis Who Have Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors.

BACKGROUND: Despite a substantial number of treatment options in rheumatoid arthritis (RA) following tumor necrosis factor inhibitor (TNFi) inadequate response or intolerance (TNF-IR), a lack of clarity on the optimal approach remains. Sarilumab, a human monoclonal anti-interleukin-6 receptor alpha antibody, can be used as monotherapy or in combination with methotrexate or other conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) in TNF-IR patients. OBJECTIVE: To conduct a cost-utility analysis from a U.S. health care system perspective for sarilumab subcutaneous 200 mg + methotrexate versus abatacept + methotrexate or a bundle of TNFi + methotrexate for treatment of adult patients with moderately to severely active RA and TNF-IR. METHODS: Analysis was conducted via individual patient simulation based on patient profiles from the TARGET trial (NCT01709578); a 6-month decision tree was followed by lifetime semi-Markov model with 6-month cycles. Treatment response at 6 months, informed by network meta-analysis, was based on American College of Rheumatology (ACR) 20/50/70 criteria; patients achieving ≥ ACR20 continued with current therapy, and other patients moved to the next line of biologic DMARD therapy or conventional synthetic DMARD palliative treatment. Direct costs included wholesale acquisition drug costs and administration and routine care costs. Routine care costs and quality-adjusted life-years (QALYs) were estimated by predicting the Health Assessment Questionnaire Disability Index score based on treatment response and were imputed from published equations. RESULTS: Sarilumab + methotrexate dominated the TNFi bundle + methotrexate, achieving lower costs ($319,324 vs. $356,096) and greater effectiveness (4.27 vs. 4.15 QALYs), and was on the cost-efficiency frontier with abatacept + methotrexate ($360,211 and 4.29 QALYs). Abatacept + methotrexate was not cost-effective versus sarilumab + methotrexate. Scenario analyses indicated the results were robust; sarilumab + methotrexate became dominant against abatacept + methotrexate after reduced model horizon, minimum response based on ACR50 or ACR70, or time to discontinuation per treatment class. Sarilumab + methotrexate was also dominant versus the TNFi bundle; when class-specific time to treatment discontinuation was specified, sarilumab remained cost-effective with an incremental cost-effectiveness ratio of $36,894. CONCLUSIONS: Sarilumab + methotrexate can be considered an economically dominant (more effective, less costly) option versus a second TNFi + methotrexate; compared with abatacept + methotrexate, it is a less costly but less effective option for patients with moderately to severely active RA who have previously failed TNFi. DISCLOSURES: This study was funded by Sanofi and Regeneron Pharmaceuticals. Kiss and Gal are employees of Evidera, which received consulting fees from Sanofi/Regeneron for conducting this study. Muszbek was employed by Evidera at the time of this study. Kuznik and Chen are current employees of and stockholders in Regeneron Pharmaceuticals. Fournier is an employee of and stockholder in Sanofi. Proudfoot is a former employee of and current stockholder in Sanofi and current employee and stockholder in ViiV Healthcare/GlaxoSmithKline. Michaud has received grant funding from Pfizer and the Rheumatology Research Foundation. The sponsors were involved in the study design, collection, analysis, and interpretation of data as well as data checking of information provided in the manuscript. The authors had unrestricted access to study data, were responsible for all content and editorial decisions, and received no honoraria related to the development of this publication.

Economic Evaluation of Sarilumab in the Treatment of Adult Patients with Moderately-to-Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Conventional Synthetic Disease-Modifying Antirheumatic Drugs.

INTRODUCTION: Assess the cost-effectiveness (US healthcare payer perspective) of sarilumab subcutaneous (SC) 200 mg + methotrexate versus conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or targeted DMARD + methotrexate for moderate-to-severe rheumatoid arthritis (RA) in adults with inadequate response to methotrexate. METHODS: Microsimulation based on patient profiles from MOBILITY (NCT01061736) was conducted via a 6-month decision tree and lifetime Markov model with 6-monthly cycles. Treatment response at 6 months was informed by a network meta-analysis and based on American College of Rheumatology (ACR) response. Responders: patients with ACR20 response who continued with therapy; non-responders: ACR20 non-responders who transitioned to the subsequent treatment. Utilities and quality-adjusted life-years (QALYs) were estimated via mapping 6-month ACR20/50/70 response to relative change in Health Assessment Questionnaire Disability Index score (short term) and based on published algorithms (long term). Direct costs considered drugs (wholesale acquisition costs), administration and routine care. RESULTS: Lifetime QALYs and costs for treatment sequences on the efficiency frontier were 3.43 and $115,019 for active csDMARD, 5.79 and $430,918 for sarilumab, and 5.94 and $524,832 for etanercept (all others dominated). Sarilumab was cost-effective versus tocilizumab and csDMARD (incremental cost-effectiveness ratios of $84,079/QALY and $134,286/QALY). Probabilistic sensitivity analysis suggested comparable costs and slightly improved health benefits for sarilumab versus tocilizumab, irrespective of threshold. CONCLUSION: In patients with moderate-to-severe RA, sarilumab 200 mg SC every 2 weeks + methotrexate can be considered a cost-effective treatment option, with lower costs and greater health benefits than alternative treatment sequences (+ methotrexate) beginning with adalimumab, certolizumab, golimumab and tofacitinib and below commonly accepted cost-effectiveness thresholds against tocilizumab + methotrexate or csDMARD active treatment. FUNDING: Sanofi and Regeneron Pharmaceuticals, Inc.

Cost-Effectiveness of Golimumab in Ankylosing Spondylitis from the UK Payer Perspective.

INTRODUCTION: Golimumab is a tumor necrosis factor-α (TNF-α) inhibitor for treatment of patients with severe, active ankylosing spondylitis. This study evaluated the cost-effectiveness of golimumab compared with conventional care and other TNF-α inhibitors in treatment of AS from the UK National Health Service perspective. METHODS: A long-term Markov model (with initial decision tree) was developed to simulate the progression of a hypothetical cohort of patients with active AS over a lifetime. The effectiveness outcome was quality-adjusted life-years (QALYs). Utilities were estimated by mapping Bath Ankylosing Spondylitis Functional Index scores, and the primary response measure was ≥50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index at 12 weeks. Direct, medication, and AS management costs were included. Costs and outcomes were discounted at 3.5%. RESULTS: All TNF-α inhibitors were comparable to each other and superior to conventional care. The incremental cost-effectiveness ratios (ICERs) for TNF-α inhibitors were £19,070-42,532 per QALY gained compared with conventional care. Analyses of the ICERs for each TNF-α inhibitor compared with conventional care demonstrated that golimumab was the most cost-effective treatment, and that adalimumab and etanercept were dominated by golimumab. Sensitivity analyses confirmed the robustness of these analyses. CONCLUSIONS: Golimumab may be considered a cost-effective treatment alternative for patients with active AS. With comparable costs and efficacy among TNF-α inhibitors, the choice of TNF-α inhibitor to treat AS is likely to be driven by patient and physician choice. FUNDING: Merck & Co., Inc.

Comparative healthcare-associated costs of methicillin-resistant Staphylococcus aureus bacteraemia-infective endocarditis treated with either daptomycin or vancomycin.

Complex infection with methicillin-resistant Staphylococcus aureus (MRSA) is associated with high healthcare and societal costs; thus, evaluation of the costs and health benefits of interventions is an important consideration in a modern healthcare system. This study estimated the cost consequences of the use of daptomycin compared with vancomycin for the first-line treatment of patients with proven MRSA-induced bacteraemia-infective endocarditis (SAB-IE) with a vancomycin minimum inhibitory concentration (MIC) >1mg/L in the UK. A decision model was developed to assess total healthcare costs of treatment, including inpatient, outpatient and drug costs. Data were sourced from the literature (treatment efficacy and safety), a physician survey (resource use) and publicly available databases (unit costs). Assuming the same length of stay for daptomycin and vancomycin, the total healthcare costs per patient were £17917 for daptomycin and £17165 for vancomycin. However, extrapolating from published studies and supported by a physician survey, daptomycin was found to require fewer therapeutic switches and a shorter length of stay. When the length of stay was reduced from 42 days to 28 days, daptomycin saved £4037 per person compared with vancomycin. In conclusion, daptomycin is an effective and efficient alternative antibiotic for the treatment of SAB-IE. However, the level of cost saving depends on the extent to which local clinical practice allows early discharge of patients before the end of their antibiotic course when responding to treatment.

The Cost-effectiveness of Pixantrone for Third/Fourth-line Treatment of Aggressive Non-Hodgkin's Lymphoma.

PURPOSE: Aggressive non-Hodgkin's lymphoma (aNHL) is associated with poor long-term survival after relapse, and treatment is limited by a lack of consensus regarding standard of care. Pixantrone was studied in a randomized trial in patients with relapsed or refractory aNHL who had failed ≥ 2 lines of therapy, demonstrating a significant improvement in complete or unconfirmed complete response and progression-free survival (PFS) compared with investigators' choice of single-agent therapy. The objective of this study was to assess the health economic implications of pixantrone versus current clinical practice (CCP) in the United Kingdom for patients with multiply relapsed or refractory aNHL receiving their third or fourth line of treatment. METHODS: A semi-Markov partition model based on overall survival and PFS was developed to evaluate the lifetime clinical and economic impact of treatment of multiply relapsed or refractory aNHL with pixantrone versus CCP. The empirical overall survival and PFS data from the PIX301 trial were extrapolated to a lifetime horizon. Resource use was elicited from clinical experts, and unit costs and utilities were obtained from published sources. The analysis was conducted from the perspective of the United Kingdom's National Health Service and personal social services. Outcomes evaluated were total costs, life-years, quality-adjusted life-years (QALYs), and cost per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty around the results. FINDINGS: Pixantrone was estimated to increase life expectancy by a mean of 10.8 months per patient compared with CCP and a mean gain of 0.56 discounted QALYs. The increased health gains were associated with an increase in discounted costs of approximately £18,494 per patient. The incremental cost-effectiveness ratio of pixantrone versus CCP was £33,272 per QALY gained. Sensitivity and scenario analyses suggest that the incremental cost-effectiveness ratio was sensitive to uncertainty in the PFS and overall survival estimates and the utility values associated with each health state. IMPLICATIONS: Pixantrone may be considered both clinically effective and cost-effective for patients with multiply relapsed or refractory aNHL who currently have a high level of unmet need.

Overview of parametric survival analysis for health-economic applications.

Health economic models rely on data from trials to project the risk of events (e.g., death) over time beyond the span of the available data. Parametric survival analysis methods can be applied to identify an appropriate statistical model for the observed data, which can then be extrapolated to derive a complete time-to-event curve. This paper describes the properties of the most commonly used statistical distributions as a basis for these models and describes an objective process of identifying the most suitable parametric distribution in a given dataset. The approach can be applied with both individual-patient data as well as with survival probabilities derived from published Kaplan-Meier curves. Both are illustrated with analyses of overall survival from the Sorafenib Hepatocellular Carcinoma Assessment Randomised Protocol trial.

Using daptomycin in hospitalised patients with cSSTI caused by Staphylococcus aureus has an impact on costs.

BACKGROUND: The aim was to assess the cost impact of daptomycin compared to vancomycin treatment in patients hospitalised for complicated skin and soft-tissue infection (cSSTI) with suspected methicillin-resistant Staphylococcus aureus infection in the UK. METHODS: A decision model was developed to estimate the costs associated with cSSTI treatment. Data on efficacy, treatment duration and early discharge from published clinical trials were used, with data gaps on standard clinical practice being filled by means of clinician interviews. RESULTS: Total health-care costs per patient were GBP 6,214 and GBP 6,491 for daptomycin and vancomycin, respectively. A sensitivity analysis suggested that modifying the parameters within a reasonable range does not impact on the conclusion that the higher cost of daptomycin is likely to be offset by lower costs of monitoring and hospitalisation. CONCLUSIONS: This study demonstrates that daptomycin not only provides an alternative treatment for multiple resistant infections, but may also reduce National Health Service costs.

Modelling survival in hepatocellular carcinoma.

OBJECTIVES: To identify the pattern of the risk of death over long-term in unresectable hepatocellular carcinoma by determining the appropriate distribution to extrapolate overall survival and to assess the role of the Weibull distribution as the standard survival model in oncology. RESEARCH DESIGN AND METHODS: To select the appropriate distribution, three types of data sources have been analysed. Patient level data from two randomized controlled trials and published Kaplan-Meier curves from a systematic literature review provided short term follow-up data. They were supplemented with patient level data, with long-term follow-up from the Cancer Institute New South Wales, Australia. Published Kaplan-Meier curves were read in and a time-to-event dataset was created. Distributions were fitted to the data from the different sources separately. Their fit was assessed visually and compared using statistical criteria based on log-likelihood, the Akaike information criterion (AIC), and the Bayesian information criterion (BIC). RESULTS: Based on both published and patient-level, and both short- and long-term follow-up data, the Weibull distribution, used very often in cost-effectiveness models in oncology, does not seem to offer a good fit in hepatocellular carcinoma among the different survival models. The best fitting distribution appears to be the lognormal, with loglogistic as the second-best fitting function. Results were consistent between the different sources of data. CONCLUSIONS: In unresectable hepatocellular carcinoma, the Weibull model, which is often treated at the gold standard, does not appear to be appropriate based on different sources of data (two clinical trials, a retrospective database and published Kaplan-Meier curves). Lognormal distribution seems to be the most appropriate distribution for extrapolating overall survival.

Economic evaluation of sorafenib in unresectable hepatocellular carcinoma.

BACKGROUND AND AIM: A double-blind, randomized phase III trial of sorafenib in advanced hepatocellular carcinoma demonstrated that sorafenib significantly prolonged overall survival compared to placebo (median overall survival = 10.7 months vs 7.9 months, P < 0.001). Sorafenib is the first and only systemic agent demonstrating survival benefit in these patients. The aim of this study was to assess the cost-effectiveness of sorafenib versus best supportive care in the treatment of advanced hepatocellular carcinoma in the USA. METHODS: A Markov model was developed following time-to-progression and survival using phase III trial data. Health effects are expressed as life-years gained. Resource utilization included drugs, physician visits, laboratory tests, scans, and hospitalizations. Unit costs, expressed in 2007 $US, came from diagnosis-related groupings, fee schedules, and the Red Book. Costs and effects were evaluated over a patient's lifetime and discounted at 3%. RESULTS: Results are presented as incremental cost/life-year gained. Deterministic and probabilistic sensitivity analyses were conducted. Life-years gained were increased for sorafenib compared to best supportive care (mean ± standard deviation: 1.58 ± 0.17 vs 1.05 ± 0.10 life-years gained/sorafenib patient and best supportive care, respectively). Lifetime total costs were $US40,639 ± $US3052 for sorafenib and $US7, 804 ± $US1349 for best supportive care. The incremental cost-effectiveness ratio was $US62,473/life-year gained. CONCLUSIONS: The economic evaluation indicates that sorafenib is cost-effective compared to best supportive care, with a cost-effectiveness ratio within the established threshold that US society is willing to pay (i.e. $US50,000-$US100,000) and significantly lower than alternative thresholds suggested in recent years ($US183,000-$US264,000/life-year gained, or $US300,000/quality-adjusted life-year) in oncology.

Economic evaluation of sorafenib in the treatment of hepatocellular carcinoma in Canada.

BACKGROUND: A randomized phase III trial of sorafenib vs. placebo in hepatocellular carcinoma (HCC) demonstrated that sorafenib significantly prolonged overall survival (OS) compared to placebo. RESEARCH DESIGN AND METHODS: A Markov model was developed to evaluate the cost-effectiveness of sorafenib vs. best supportive care (BSC) in HCC from the perspective of the Canadian provincial Ministry of Health. The model followed survival and time to progression (TTP) in monthly cycles based on the extrapolation of patient level trial data. Health effects were expressed as life-years gained (LYG). Resource use included drugs, physician visits, laboratory tests, scans, and hospitalizations. Unit costs were gathered from public sources and were expressed in 2007 Canadian Dollars. Costs and effects were evaluated over a lifetime and discounted at 5%. Results were presented as mean +/- standard deviation. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: LYG was longer for sorafenib (1.52 +/- 0.16 vs. 1.03 +/- 0.09 LYG/patient for sorafenib and BSC, respectively). The lifetime total costs were $47,511 +/- 3 656 for sorafenib and $10,376 +/- 1 649 for BSC, resulting in an incremental cost-effectiveness ratio (ICER) of $75,821/LYG, and deterministic ICER of $75,759/LYG. The results were most sensitive to OS, TTP and BSC costs after progression. Sensitivity analyses results showed that the model was robust. CONCLUSIONS: The economic evaluation indicates that sorafenib is cost-effective as compared to BSC in HCC. Limitations include multiple data sources, use of expert opinion for resource use, and the lack of utility data.

Public health value of fixed-dose combinations in hypertension.

It is well documented that reducing blood pressure (BP) in hypertensive individuals reduces the risk of cardiovascular (CV) events. Despite this, many patients with hypertension remain untreated or inadequately treated, and fail to reach the recommended BP goals. Suboptimal BP control, whilst arising from multiple causes, is often due to poor patient compliance and/or persistence, and results in a significant health and economic burden on society. The use of fixed-dose combinations (FDCs) for the treatment of hypertension has the potential to increase patient compliance and persistence. When compared with antihypertensive monotherapies, FDCs may also offer equivalent or better efficacy, and the same or improved tolerability. As a result, FDCs have the potential to reduce both the CV event rates and the non-drug healthcare costs associated with hypertension. When FDCs are adopted for the treatment of hypertension, issues relating to copayment, formulary restrictions and therapeutic reference pricing must be addressed.

Health economic implications of irbesartan treatment versus standard blood pressure control in patients with type 2 diabetes, hypertension and renal disease: a Hungarian analysis.

To perform a health economic analysis on treatment with irbesartan in patients with type 2 diabetes and hypertension. A Markov model was adapted to the Hungarian setting to simulate renal deterioration from the development of microalbuminuria to nephropathy, doubling of serum creatinine, end-stage renal disease (ESRD) and all-cause mortality. Outcomes for two treatments were evaluated: (1) a placebo regimen of standard antihypertensive medications, and (2) the addition of irbesartan 300 mg administered daily, with both treatment initiated after developing microalbuminuria. Outcomes were discounted at 5% annually to correspond with national guidelines. Treatment with irbesartan was estimated to improve undiscounted life expectancy by 0.98 +/- 0.05 years, reduce the cumulative incidence of ESRD by 7.5 +/- 0.4%, and reduce lifetime costs by Hungarian Forints (HUF) 519,993 +/- 70,814, compared to placebo. Irbesartan was projected to improved life expectancy and reduce costs compared to placebo in the Hungarian setting in hypertensive patients with type 2 diabetes and microalbuminuria.

Does therapeutic reference pricing always result in cost-containment? The Hungarian evidence.

Therapeutic reference pricing is one of the potential cost containment methods for pharmaceuticals. The most critical question of reference pricing is how to select reference product(s) if their efficacy is different, especially if different strengths of the same substance are available. Authors describe the Hungarian experience related to the introduction of therapeutic reference pricing for statin therapies as of 1 September 2003. The National Health Insurance Fund selected the reference products based on their low price per DDD. Therapeutic reference pricing was expected to reduce the expenditure on statins by switching therapy to cheaper alternatives and therefore decreasing the average price per prescribed unit. The National Health Insurance Fund expected price erosion not only for branded products directly affected by generics but even for patented ones. Despite generic price erosion of simvastatin, the average unit price of statins was reduced by only 3% at 7 months after the introduction of the reference pricing system. During the same period the average DDD per prescription was increased from 1.14 to 1.65. The price of patented statins did not change over this period. Introduction of therapeutic reference pricing neglected evidence-based medicine results and ultimately increased the expenditure on statins in Hungary. Selection of the cheapest DDD per unit as the reference product resulted in growth of DDD per prescription, and consequently increased price per prescribed unit of statins. The failure of the system could have been even more dramatic if increased utilisation of generic statins had not reduced the negative effect of therapeutic reference pricing. Based upon the first experiences of the Hungarian implementation, the method described in this paper for the extension of generic reference pricing to therapeutic categories is not justifiable.

[Economic evaluation of population-based mass screening for the early detection of cancer: a systematic review]. / Daganatos betegségek korai felismerésére irányuló populációs szintû szûrôprogramok egészség-gazdaságtani elemzése - rendszerezett irodalmi áttekintés.

PURPOSE: The increasing premature mortality due to cancer has made population based screening programs for cervical,breast and colorectal cancers inevitable in Hungary. However, when confronted with limited resources, the aim is that, within the budget constrain, the greatest possible health gain should be "produced". METHODS: The authors made a systematic review of the international literature concerning the cost-effectiveness of screening programs for the above tumours. RESULTS: In case of cervical cancer the Papanicolaou test, in case of breast cancer the mammography meet the WHO criteria for population-based mass screening. The well-designed organised screening programs are more cost-effective than the opportunistic screening. Among sexually active women, according to structure the mobile screening buses, according to age group screening of the 30-39 years old women seems the most favourable. For breast cancer, screening the 60-70 years old population every second year is the reference strategy from a health economic perspective. The cost-effectiveness results of either increasing the frequency of screening, extending the program for other age groups, or selecting a high-risk population are contradictory. In case of colorectal cancer there is no screening method, which would meet the WHO criteria. The two-day FOBT seems the most favourable, followed by colonoscopy for positive results, in the 55-74 years old population every second year. CONCLUSION: In addition to fulfilling requirements for a population-based screening method, the cost-effectiveness perspective should be taken into account.