Jonas Lundkvist

Proton therapy of cancer: potential clinical advantages and cost-effectiveness.

Proton therapy may offer potential clinical advantages compared with conventional radiation therapy for many cancer patients. Due to the large investment costs for building a proton therapy facility, however, the treatment cost with proton radiation is higher than with conventional radiation. It is therefore important to evaluate whether the medical benefits of proton therapy are large enough to motivate the higher costs. We assessed the cost-effectiveness of proton therapy in the treatment of four different cancers: left-sided breast cancer, prostate cancer, head and neck cancer, and childhood medulloblastoma. A Markov cohort simulation model was created for each cancer type and used to simulate the life of patients treated with radiation. Cost and quality adjusted life years (QALYs) were used as primary outcome measures. The results indicated that proton therapy was cost-effective if appropriate risk groups were chosen. The average cost per QALY gained for the four types of cancer assessed was about €10 130. If the value of a QALY was set to €55 000, the total yearly net benefit of treating 925 cancer patients with the four types of cancer was about €20.8 million. Investment in a proton facility may thus be cost-effective. The results must be interpreted with caution, since there is a lack of data, and consequently large uncertainties in the assumptions used.

Cost-effectiveness of proton radiation in the treatment of childhood medulloblastoma

Radiation therapy is an important component in the treatment of medulloblastoma; however, in many patients, it is associated with risk of late adverse events. Proton radiation therapy has potential to reduce the risk of adverse events compared with conventional radiation, but it is associated with a higher treatment cost. The objective of the current study was to assess the cost‐effectiveness of proton therapy compared with conventional radiation therapy in the treatment of childhood medulloblastoma.

Screening for Abdominal Aortic Aneurysm in 65-Year-old Men Remains Cost-effective with Contemporary Epidemiology and Management

OBJECTIVES The epidemiology and management of abdominal aortic aneurysms (AAA) has changed significantly, with lower prevalence, increased longevity of patients, increased use of endovascular aneurysm repair (EVAR), and improved outcome. The clinical and health economic effectiveness of one-time screening of 65-year-old men was assessed within this context. METHODS One-time ultrasound screening of 65-year-old men (invited) versus no screening (control) was analysed in a Markov model. Data on the natural course of AAA (risk of repair and rupture) was based on randomised controlled trials. Screening detected AAA prevalence (1.7%), surgical management (50% EVAR), repair outcome, costs, and long-term survival were based on contemporary population-based data. Incremental cost-efficiency ratios (ICER), absolute and relative risk reduction for death from AAA (ARR, RRR), numbers needed to screen (NNS), and life-years gained were calculated. Annual discounting was 3.5%. RESULTS In base case at 13-years follow-up the ICER was €14,706 per incremental quality-adjusted life-year (QALY); ARR was 15.1 per 10,000 invited, NNS was 530, and QALYs gained were 56.5 per 10,000 invited. RRR was 42% (from 0.36% in control to 0.21% in invited). In a lifetime analysis the ICER of screening decreased to €7,570/QALY. The parameters with highest impact on the cost-efficiency of screening in the sensitivity analysis were the prevalence of AAA (threshold value <0.5%) and degree of incidental detection in the control cohort. CONCLUSIONS In the face of recent changes in the management and epidemiology of AAA, screening men for AAA remains cost-effective and delivers significant clinical impact.

Similar Cost for Elective Open and Endovascular AAA Repair in a Population-Based Setting

Purpose: To compare cost differences between elective open repair (OR) and endovascular repair (EVAR) of abdominal aortic aneurysm in a population-based setting. Methods: Clinical data and hospital-related costs (pre-, peri-, and postoperative) were analyzed for 109 consecutive AAA procedures (98 men; mean age 73 years, range 48–95; mean aneurysm diameter 61 mm, range 42–120) performed from 2001 to 2005 (58 OR, 51 EVAR) in our primary catchment area. Data were obtained through case records and hospital accounting systems. Nonparametric bootstrap was used for cost comparison. Results: EVAR patients were older (76 versus 70 years, p<0.001) and had more comorbidities (ASA class 2.6 versus 2.3, p=0.025). OR patients more often had anatomically complex aneurysms (52% versus 14%, p<0.001). Comparison of data with diagnosis-based reimbursement levels nationally and internationally indicated adequate cost level in the study. No difference was observed in total cost between OR and EVAR (€29,786 versus €26,382; p=0.336). Preoperative cost was lower for OR compared to EVAR (€661 versus €1494, p=0.002). OR patients had higher cost of intensive care [36% (€8921) of perioperative cost versus 7% (€1460), p=0.001], while EVAR had higher implant cost [36% (€7468) versus 2% (€448), p<0.001]. Mean follow-up was 2.5 years (range 0.5–5.4). Mean postoperative cost was similar (OR €4613 versus EVAR €4403, p=0.209; 16% and 17% of total cost, respectively). Postoperative cost after OR was high early on, with lower cost thereafter. Postoperative cost after EVAR was more homogenously distributed, leveling off at €500 to €1000 annually over 5 years. Conclusion: In a population-based setting, total cost was similar for OR and EVAR. There were, however, important differences in patient characteristics and cost structure.

Economic evaluations of leukemia: a review of the literature.

OBJECTIVES Leukemia, together with lymphoma and multiple myeloma, are hematological malignancies, malignancies of the blood-forming organs. There are four major types of leukemia: acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). There is a growing amount of literature of the health economic aspects of leukemia. However, no comprehensive review is yet performed on the health economic evidence for the disease. Hence, our aim was to review and analyze the existing literature on economic evaluations of the different types of leukemia. METHODS A systematic literature search used electronic databases to identify published cost analyses and economic evaluations of leukemia treatments. After reviewing all identified studies, sixty studies were considered relevant for the purpose of the review. RESULTS The identified studies were published after 1990, with a few exceptions. Many of the identified economic evaluations in leukemia, particularly for ALL and AML, may be defined as cost-minimization analyses, where only the costs of different treatment strategies are compared. In CML, a new treatment, imatinib, was introduced in 2001 and several cost-effectiveness analyses have since then been conducted comparing imatinib with previous first line treatments. CONCLUSIONS This review indicates that there is a shortage of cost-effectiveness information in leukemia. The introduction of new therapies will stress the need for new economic evaluations in this group of diseases. More information about the total costs, that is, including indirect costs, and quality of life effects would be valuable in future evaluations in leukemia.

Cost-effectiveness of maintenance rituximab treatment after second line therapy in patients with follicular lymphoma in Sweden

Introduction. Rituximab has significantly improved the prognosis for patients with both indolent and aggressive non-Hodgkins lymphoma. An economic evaluation was carried out to assess the cost-effectiveness in Sweden of rituximab as maintenance therapy for patients with follicular lymphoma in remission after second line therapy. Materials and methods. The incremental cost and effectiveness of rituximab maintenance therapy versus observation were evaluated in a health-state transition model. Primary effect measures were quality-adjusted life-years (QALY) and life-years gained (LYG). Model state transitions were calculated based on progression-free and overall survival data from the EORTC20981 trial. The analysis was made from the perspective of the healthcare provider, including direct medical costs presented in €, 2007 value. Effects and costs were discounted at a 3% annual rate. The stability of the base case results were tested in one-way and probabilistic sensitivity analyses. Results. The evaluation assessed rituximab maintenance therapy to be associated with an incremental cost per QALY gained of €12 600 and an incremental cost per LYG of €11 200. The average discounted life expectancy for patients on rituximab maintenance was 1.0 year longer than for patients on observation (5.96 vs. 4.94 years). Rituximab maintenance was associated with an additional 0.9 QALY, and total costs per patient were €11 500 higher in the treatment arm, compared to observation. Discussion. The results indicate that rituximab maintenance treatment after successful induction therapy for patients with relapsed/refractory follicular lymphoma in Sweden is cost-effective compared to observation.

Cost-effectiveness of fondaparinux vs. enoxaparin as venous thromboembolism prophylaxis in Sweden

Deep-vein thrombosis and pulmonary embolism are important causes of morbidity and mortality among patients undergoing major surgery. Fondaparinux is a new antithrombotic agent for use in prophylaxis, and this study compared its cost and effect vs. enoxaparin as prophylactic treatment in patients undergoing total knee replacement, total hip replacement, or hip-fracture surgery in Sweden. The analyses were based on a simulation model. Swedish data on cost for deep-vein thrombosis and pulmonary embolism were obtained from a large sample of patients undergoing major orthopedic surgery. The relative risk reduction for treatment with fondaparinux was estimated from results of four recently published clinical trials. The base case analyses showed that fondaparinux was cost saving and more effective than enoxaparin after total knee replacement and hip-fracture surgery and had costs per prevented venous thromboembolism of about €239 after total hip replacement. Fondaparinux is thus more cost-effective than enoxaparin as prophylactic treatment in patients undergoing major surgery in Sweden.

Cost-effectiveness of extended prophylaxis with fondaparinux compared with low molecular weight heparin against venous thromboembolism in patients undergoing hip fracture surgery

A model was developed to estimate costs and clinical effectiveness of fondaparinux compared with enoxaparin after hip fracture surgery in Sweden. Outcomes and costs of venous thromboembolism (VTE)-related care from a health care perspective were incorporated, with symptomatic deep-vein thrombosis and pulmonary embolism, recurrent VTE, post-thrombotic syndrome, major haemorrhage and all-cause death being included. Event probabilities were derived from fondaparinux clinical trial data and published data. VTE-related resource use and associated costs as well as costs of prophylaxis were based on local Swedish data. Extended prophylaxis with fondaparinux could avoid an additional 28 symptomatic VTE per 1,000 patients compared with extended prophylaxis with enoxaparin in hip fracture surgery patients. Although the prophylaxis costs were higher in the fondaparinux group, these were offset by the lower costs associated with treating fewer VTE, which thus indicates that extended fondaparinux prophylaxis is the dominant alternative when compared with enoxaparin in hip fracture surgery.

Cost-effectiveness of intensive smoking cessation therapy among patients with small abdominal aortic aneurysms

INTRODUCTION Smoking cessation is one of the few available strategies to decrease the risk for expansion and rupture of small abdominal aortic aneurysms (AAAs). The cost-effectiveness of an intensive smoking cessation therapy in patients with small AAAs identified at screening was evaluated. METHODS A Markov cohort simulation model was used to compare an 8-week smoking cessation intervention with adjuvant pharmacotherapy and annual revisits vs nonintervention among 65-year-old male smokers with a small AAA identified at screening. The smoking cessation rate was tested in one-way sensitivity analyses in the intervention group (range, 22%-57%) and in the nonintervention group (range, 3%-30%). Literature data on the effect of smoking on AAA expansion and rupture was factored into the model. RESULTS The intervention was cost-effective in all tested scenarios and sensitivity analyses. The smoking cessation intervention was cost-effective due to a decreased need for AAA repair and decreased rupture rate even when disregarding the positive effects of smoking cessation on long-term survival. The incremental cost/effectiveness ratio reached the willingness-to-pay threshold value of €25,000 per life-year gained when assuming an intervention cost of > €3250 or an effect of ≤ 1% difference in long-term smoking cessation between the intervention and nonintervention groups. Smoking cessation resulted in a relative risk reduction for elective AAA repair by 9% and for rupture by 38% over 10 years of follow-up. CONCLUSIONS An adequate smoking cessation intervention in patients with small AAAs identified at screening can cost-effectively increase long-term survival and decrease the need for AAA repair.

Challenges in analysis and interpretation of cost data in vascular surgery

OBJECTIVE Health economic arguments have become increasingly important in clinical decision making, especially when new treatment modalities are introduced. This study reviews the methods used in health economic reports of abdominal aortic aneurysm (AAA) repair and uses original cost data to study how different methods affect interpretation of results in terms of cost differences and economic efficiency. DESIGN Publications referenced in PubMed from 2003 to 2008 studying cost of AAA repair were reviewed. Original population-based cost data of AAA repair were analyzed, comparing open (OR) and endovascular repair (EVAR). Means, medians, and cost distributions were calculated, and differences were analyzed with four different statistical methods. RESULTS The review showed a mixture of statistical methods used in AAA treatment cost-comparison studies. Presentation of cost data and inclusion criteria varied between studies. The analysis of original data showed skewed distribution of cost data, with large differences between mean and median cost. Although mean values indicated a lower total, perioperative, and postoperative cost for EVAR, the median values indicated OR was the least costly method. Exclusion of extreme values lowered mean perioperative cost of OR by 10%, while cost of EVAR was unaffected. Inferential testing of cost differences by means of four statistical methods showed that P values were highly dependent on test methodology. CONCLUSIONS Conclusions of health economic reports can be highly dependent on how the data are presented and the statistical methods that are used. We recommend that cost data be presented as mean values with distributions. Exclusion of outliers and focus on P values should be avoided.