Survival after transfusion in the Netherlands.

BACKGROUND: Cost-effectiveness analyses of blood safety interventions require estimates of the life expectancy after blood product transfusion. These are best derived from survival after blood transfusion, per age group and blood component type. STUDY DESIGN AND METHODS: In the PROTON (PROfiles of TransfusiON recipients) study transfusion recipient data was collected from a hospital sample covering 28% of the total blood use between 1996 and 2006 in the Netherlands. The dataset includes date of transfusion, blood component type transfused and recipient identification details. PROTON data were individually matched to mortality data of the Netherlands. Survival after first transfusion and after any transfusion was calculated, per blood component type and age group. PROTON mortality rates were compared to mortality rates in the general population. The results were used to estimate survival beyond the study period and to estimate life expectancy after transfusion. RESULTS: Of all 2,405,012 blood product transfusions in the PROTON dataset, 92% was matched to the national Dutch Municipal Population Register, which registers all deaths. After 1 year, survival after any transfusion was 65·4%, 70·4% and 53·9% for RBC, FFP and PLT respectively. After 5 years, this was 46·6%, 58·8% and 39·3% for RBC, FFP and PLT, respectively. Ten years after transfusion, mortality rates of recipients are still elevated in comparison with the general population. CONCLUSION: Mortality rates of transfusion recipients are higher than those of the general population, but the increase diminishes over time. The mortality rates found for the Netherlands are lower than those found in comparable studies for other countries.

Economic evaluation of zoledronic acid for the prevention of osteoporotic fractures in postmenopausal women with early-stage breast cancer receiving aromatase inhibitors in the UK.

BACKGROUND: Aromatase inhibitors are used as adjuvant therapy for breast cancer (BC) and are associated with accelerated bone loss. Zoledronic acid (ZOL) prevents aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women with BC. This analysis assessed the cost-effectiveness of ZOL for prevention of fractures in postmenopausal women with BC. MATERIALS AND METHODS: A Markov model was developed to project lifetime incidence of fractures, quality-adjusted life years (QALY), and costs as a function of bone mineral density (BMD) for women with early-stage BC receiving letrozole alone or with ZOL. Two strategies of ZOL therapy were compared with no treatment: starting ZOL treatment only when BMD levels decreased ('delayed ZOL') and starting ZOL simultaneously with letrozole therapy ('upfront ZOL'). RESULTS: Delayed ZOL therapy was estimated to cost 16,069 pounds per QALY, when compared with not administering bisphosphonates for AIBL prevention. The corresponding cost per QALY gained for upfront ZOL versus no treatment was estimated at 21,973 pounds. The cost-effectiveness ratio for upfront versus delayed therapy was estimated at 24,868 pounds per QALY gained. CONCLUSION: Both delayed and upfront therapy with ZOL for the prevention of AIBL and fractures in BC patients in the UK appear to result in highly acceptable cost-effectiveness ratios.

The PROTON study: profiles of blood product transfusion recipients in the Netherlands.

BACKGROUND: Transfusion recipient data are needed for correct estimation of cost-effectiveness in terms of recipient outcomes after transfusion. Also, such data are essential for monitoring blood use, estimation of future blood use and benchmarking. STUDY DESIGN AND METHODS: A sample of 20 of 93 Dutch hospitals was selected. Datasets containing all blood product transfusions between 1996 and 2006 were extracted from hospital blood bank computer systems, containing transfusion date, blood product type and recipient characteristics such as gender, address, date of birth. The datasets were appended and matched to national hospitalization datasets including primary discharge diagnoses (ICD-9). Using these data, we estimated distributions of blood recipient characteristics in the Netherlands. RESULTS: The dataset contains information on 290,043 patients who received 2,405,012 blood products (1,720,075 RBC, 443,697 FFP, 241,240 PLT) from 1996 to 2006. This is 28% of total blood use in the Netherlands during this period. Comparable diagnosis and age distributions of all hospitalizations indicate included hospitals to be representative, per hospital category, for the Netherlands. Of all red blood cells (RBC), fresh-frozen plasma (FFP) and platelets (PLT), respectively 1.7%, 2.5% and 4.5% were transfused to neonates. Recipients of 65 years or older received 57.6% of RBC, 41.4% of FFP and 29.0% of PLT. Most of the blood products were transfused to patients with diseases of the circulary system (25.1%) or neoplasms (22.0%). CONCLUSION: Transfusion data from a limited sample of hospitals can be used to estimate national distributions of blood recipient characteristics.

Cost-effectiveness of additional hepatitis B virus nucleic acid testing of individual donations or minipools of six donations in the Netherlands.

BACKGROUND: To further reduce the risk of hepatitis B virus (HBV) transmission by blood transfusion, nucleic acid testing (NAT) can be employed. The aim of this study is to estimate the incremental cost-effectiveness ratio (ICER) in the Netherlands of employing a triplex NAT assay aimed at HBV nucleic acid detection in individual donations (ID-NAT) or in minipools of 6 donations (MP-6-NAT), compared to a triplex NAT assay in minipools of 24 donations (MP-24-NAT). STUDY DESIGN AND METHODS: A mathematical model was made of the whole transfusion chain from donors to recipients of blood in the Netherlands. The annual number of avoided HBV transmissions was estimated with the window-period incidence model. The natural history of a HBV infection in recipients is described by a Markov model. RESULTS: The ICER of adding HBV MP-6-NAT or HBV ID-NAT in the Netherlands is Euro303,218 (95% confidence interval [CI], Euro233,001-Euro408,388) and Euro518,995 (95% CI, Euro399,359-Euro699,120) per quality-adjusted life-year, respectively. The ICER strongly correlates with the age of transfusion recipients. CONCLUSION: The cost-effectiveness of additional HBV NAT is limited by the limited loss of life caused by HBV transmission. Despite a higher effectiveness, HBV ID-NAT is less cost-effective than MP-6-NAT due to higher costs. A future equivalent participation of immigrants from HBV-endemic countries in the donor base renders HBV NAT only slightly more cost-effective.

Monitoring viral incidence rates: tools for the implementation of European Union regulations.

BACKGROUND AND OBJECTIVES: European legislation requires manufacturers of plasma products to report epidemiological data on human immunodeficiency virus, hepatitis B virus and hepatitis C virus in donor populations. The incidence rates of such infections are directly related to the risk of infection transmission. We propose two statistical tests to evaluate these incidence rates. MATERIALS AND METHODS: Infection data of the four Dutch blood collection centres from 2003 through 2006 were analysed. For transversal comparison of centres and detection of increased incidence rates, a new statistical test was developed (outlier test). For longitudinal detection of trends in incidence rates, a generic test for trend is proposed. The power and risk of non-detection are evaluated for both tests. RESULTS: Application of the outlier test did not reveal any significantly increased incidence rates among centres in The Netherlands. The test for trend showed no significant increase in incidence rates in individual centres, but on national level a statistically significant increase in hepatitis C virus incidence was observed (P-value of 0.01). CONCLUSION: The proposed tests allow signalling of outlier centres and trends in incidence rates both at individual centre and at national levels. Graphical support and the use of as much relevant historical data as possible is recommended. The statistical tests described are generic and can be applied by any blood establishment and plasma fractionation institute.

Recommendations for reporting economic evaluations of haemophilia prophylaxis: a nominal groups consensus statement on behalf of the Economics Expert Working Group of The International Prophylaxis Study Group.

BACKGROUND: The need for clearly reported studies evaluating the cost of prophylaxis and its overall outcomes has been recommended from previous literature. OBJECTIVES: To establish minimal ''core standards'' that can be followed when conducting and reporting economic evaluations of hemophilia prophylaxis. METHODS: Ten members of the IPSG Economic Analysis Working Group participated in a consensus process using the Nominal Groups Technique (NGT). The following topics relating to the economic analysis of prophylaxis studies were addressed; Whose perspective should be taken? Which is the best methodological approach? Is micro- or macro-costing the best costing strategy? What information must be presented about costs and outcomes in order to facilitate local and international interpretation? RESULTS: The group suggests studies on the economic impact of prophylaxis should be viewed from a societal perspective and be reported using a Cost Utility Analysis (CUA) (with consideration of also reporting Cost Benefit Analysis [CBA]). All costs that exceed $500 should be used to measure the costs of prophylaxis (macro strategy) including items such as clotting factor costs, hospitalizations, surgical procedures, productivity loss and number of days lost from school or work. Generic and disease specific quality of lífe and utility measures should be used to report the outcomes of the study. CONCLUSIONS: The IPSG has suggested minimal core standards to be applied to the reporting of economic evaluations of hemophilia prophylaxis. Standardized reporting will facilitate the comparison of studies and will allow for more rational policy decisions and treatment choices.

The use of a surgical sealant (CoSeal) in cardiac and vascular reconstructive surgery: an economic analysis.

AIM: We designed a study to estimate the economic impact of CoSeal Surgical Sealant for the prevention of anastomotic bleeding in cardiac and vascular surgery. We also explored the potential economic value of CoSeal as a means of inhibiting the formation of pericardial tissue adhesions. METHODS: A Delphi panel of 6 expert vascular and cardiac surgeons provided the assumptions and estimates needed to develop a decision analysis model to assess the impact of sealant on the costs associated with low- and high-risk forms of cardiac (valve replacement/reconstruction) and vascular (abdominal aortic aneurysm [AAA] repair, femoral bypass grafting) surgery. The primary outcome was incremental cost per patient. RESULTS: For valve repair/replacement surgery, sealant was expected to confer cost-savings in high-risk but not low-risk procedures. Predicted cost savings for high-risk AAA repairs were substantial, but minimal in the overall AAA group. Cost-savings were predicted for sealant use in all femoral-popliteal ePTFE bypass grafts, but in high-risk femoral-femoral ePTFE bypass grafts only. CONCLUSIONS: According to our decision analysis model, routine use of surgical sealant in select subgroups may confer considerable economic benefits to health service budgets. Future research should aim at testing this model in a real-world hospital setting. Assessment of the value of CoSeal in the prevention of postsurgical adhesions showed that expert surgeons see a need for effective prophylaxis. Further research into the clinical and economic benefit of this intervention is required.

Hip fracture prediction in elderly men and women: validation in the Rotterdam study.

The aim of our study was to validate a hip fracture risk function, composed of age and femoral neck bone mineral density (BMD). This estimate of the 1-year cumulative risk was previously developed on the basis of Dutch hip fracture incidence data and BMD in men and women. A cohort of 7046 persons (2778 men) aged 55 years and over was followed for an average of 3.8 years. The 1-year hip fracture risk estimate was calculated for each participant according to the risk function and categorized as low (<0.1%), moderate (0.1 to < 1%), or high (> or =1%). Observed first hip fracture incidence was then analyzed for each of these risk categories by age and gender. Additionally, we calculated the relative risk per standard deviation (SD) decrease in femoral neck BMD in this population. At baseline, 2360 individuals were categorized as low risk, 2567 as moderate risk, and 378 as high risk During follow-up, 110 first hip fractures were observed corresponding to an incidence rate of 4.1/1000 person-years (pyrs) (95% confidence interval 3.4-5.0). The observed incidence rate in the low risk group was 0.2/1000 pyrs (0.1-0.9), 2.7/1000 pyrs (1.8-3.9) in the moderate risk group, and 18.4/1000 pyrs (12.4-27.2) in the high risk group. Below the age of 70 years, incidence was low in all categories, and very few individuals were considered at high risk Above the age of 70 years, the observed incidence was high in the high risk group, while in the low and moderate risk groups, the incidence remained low even over 80 years of age. In women, the age-adjusted relative risk for hip fractures was 2.5 per SD decrease in femoral neck BMD (1.8-3.6), while in men this relative risk was 3.0 per SD (1.7-5.4). In conclusion, we observed a similar relation of hip fracture with femoral neck BMD in men and women and were able to predict accurately hip fracture rates over a period of almost 4 years.

Meta-analysis: comparing the efficacy of proton pump inhibitors in short-term use.

BACKGROUND: Proton pump inhibitors have a prominent role in the management of acid-related diseases. Controlling expenses on proton pump inhibitors would yield great economic benefits for Dutch health care. AIM: To investigate whether clinical differences in proton pump inhibitors exist. METHODS: We searched Medline, EMBASE and the Cochrane Library. We identified papers in English, German, French or Dutch in which two or more proton pump inhibitors were compared under the same clinical conditions in gastro-oesophageal reflux disease, peptic ulcer disease or Helicobacter pylori eradication. The pooled relative risks were calculated using the Mantel-Haenszel method. RESULTS: Two significant differences were found in the proton pump inhibitors compared. In gastro-oesophageal reflux disease, esomeprazole 40 mg was superior to omeprazole 20 mg (relative risk, 1.18; 95% confidence interval, 1.14-1.23). In peptic ulcer disease, pantoprazole 40 mg was superior to omeprazole 20 mg (relative risk, 1.07; 95% confidence interval, 1.02-1.13). In Helicobacter pylori eradication, no significant differences were found. CONCLUSIONS: Both significant differences found were in favour of the highest dose of proton pump inhibitor on a milligram basis. This indicates that the difference may be dose dependent and not proton pump inhibitor specific. Therefore, when prescribing proton pump inhibitors, arguments other than clinical efficacy, such as those related to pharmaco-economics, may be considered.

Cost-effectiveness of perioperative mupirocin nasal ointment in cardiothoracic surgery.

OBJECTIVE: To assess the cost-effectiveness of perioperative intranasal application of mupirocin calcium ointment in cardiothoracic surgery. DESIGN: Cost-effectiveness analysis based on results of an intervention study with historical controls. SETTING: University Hospital Rotterdam, a tertiary referral center for cardiac and pulmonary surgery. PATIENTS: Consecutive patients undergoing cardiothoracic surgery between August 1, 1989, and February 1, 1991 (control group, n = 928), and between March 1, 1991, and August 1, 1992 (intervention group, n = 868). INTERVENTION: Perioperative nasal application of mupirocin calcium ointment started on the day before surgery, continued for 5 days, twice daily. RESULTS: Postoperative costs were increased significantly in patients with a surgical-site infection (SSI), compared with uninfected patients (P < .001). Mean SSI-attributable costs were estimated at $16,878 (95% confidence interval, $15,575-$18,181). The incidence of SSIs was 7.3% in the control group and 2.8% in the intervention group, mupirocin effectiveness being 62%. The costs of mupirocin were $11 per patient. Thus, the savings per SSI prevented were $16,633. To validate this comparative estimate of SSI-attributable costs, a noncomparative analysis of the postoperative length of stay (POLS) was performed, according to the Appropriateness Evaluation Protocol. Approximately 50% of the comparative SSI-attributable POLS were judged SSI-attributable in the noncomparative analysis. Sensitivity analyses, testing for the robustness of our conclusions, indicated that the presented model is rather insensitive to variations in the incidence of SSIs and for the effectiveness and costs of mupirocin. SSI-attributable costs were shown to be the only variable with substantial effect on the cost-effectiveness ratio. Perioperative mupirocin would result in net costs instead of savings only if SSI-attributable costs were less than $245. CONCLUSIONS: SSIs in patients undergoing cardiothoracic surgery are associated with a substantial increase in postoperative costs. Provided that perioperative mupirocin reduces the SSI rate, this measure will be highly cost-effective in most centers providing cardiothoracic surgical services.

Economic evaluation of benazepril in chronic renal insufficiency.

A prospective, randomized, double-blind trial recently demonstrated that treating patients with chronic renal insufficiency with benazepril significantly decelerates the rate of progression of the disease. We tested the hypothesis that preventative treatment with the angiotensin converting enzyme (ACE) inhibitor benazepril in patients with chronic renal insufficiency is cost-effective. A Markov chain model was used that considered regular treatment, hemodialysis, continuous ambulant peritoneal dialysis, transplantation, rejection and death. Clinical trial data were used to estimate the effects of benazepril treatment and to estimate the duration until renal replacement therapy was needed. Epidemiologic parameters were derived on the basis of Dutch registries of renal diseases, costs are estimated by updating former estimates, literature review and expert opinion. We found that preventative treatment with benazepril decreased the percentage of patients who died or developed end-stage renal disease. Total costs per patient are expected to decrease in three years with more than $4,000 US per patient. Extrapolated to ten years, the savings are estimated at $23,500 US per patient. Benazepril treatment is not only an effective treatment in patients with chronic renal failure. By increasing the years spent without dialysis, it is also a cost-effective treatment.

Estimating parametric relationships between health description and health valuation with an application to the EuroQol EQ-5D.

Generic health status measures classify patients into different health states. For example, the EQ-5D descriptive system developed by the EuroQol Group classifies patients into 243 health states. Empirical values for the health states are available for only a selection (mostly 12 to 45) of these health states. Several parametric relationships between the descriptive system and the known values can be formulated to estimate the values for the unrecorded health states. This paper describes several of these modeling exercises in a comprehensible way, using the EQ-5D as an illustration. It is shown that the estimation task does not depend on the meaning of the values, but does depend on the selection of the empirically valued health states and the assumptions about the relationship between these values and the descriptive system.

Effects of ACE inhibitors on heart failure in The Netherlands: a pharmacoeconomic model.

A modelling approach is used to analyse the cost effectiveness of prescribing angiotensin converting enzyme (ACE) inhibitors, compared with standard practice, as first-line therapeutic agents in the treatment of heart failure in The Netherlands. Data concerning costs, incidence, prevalence and survival are used to construct an age-dependent semi-Markov-chain model. Two scenarios are compared. The first reflects the continuation of common practice. The second, containing assumptions made on the basis of results from randomised clinical trials, reflects the situation in which ACE inhibitors are given as first-line pharmacotherapy. Conditional on the estimates and assumptions made, it is shown that prescribing ACE inhibitors as first-line pharmacotherapy will improve survival by about 4% over the first 10 years, and will save about 17% in costs over the first 10 years. Sensitivity analysis shows the robustness of the conclusions to all major parameters.

Simulation models in the planning of health care facilities: an application in the case of neonatal extracorporeal membrane oxygenation.

OBJECTIVES: To investigate whether modelling techniques can be used in the planning of health care facilities for patients requiring neonatal extracorporeal membrane oxygenation (ECMO). METHODS: In a micro-simulation model the number of patients that will have to be referred to facilities abroad is estimated for any number of neonatal ECMO patients presenting annually for treatment in The Netherlands, and any number of ECMO facilities. The inputs to the model consist of the number of ECMO facilities, the number of patients presenting annually, the duration of treatment and the date on which patients present for ECMO treatment. The model is estimated on data from The Netherlands for 1992, during which 29 patients were treated in three facilities. Several future scenarios are modelled, principally one in which a potential increase to 56 patients per year is foreseen. RESULTS: The model indicates that, if such an increase takes place, no additional ECMO facilities will be necessary in The Netherlands if between three and four referrals annually to centres outside the region (or abroad) are considered acceptable and feasible. In that situation, it is expected that on 22 occasions each year two patients will be treated simultaneously, for a total of 81 days. On ten occasions, all three facilities will be occupied at the same time, for 21 days in total. On 199 days, at least one of the facilities will be occupied. CONCLUSION: The current study shows that the acceptability and feasibility of patient referrals to ECMO centres abroad is an important issue which health care planners will have to consider. The study also shows that modelling techniques can provide information that is useful to policy-makers in the planning of health care facilities.

Diabetes nephropathy in the Netherlands: a cost effectiveness analysis of national clinical guidelines.

BACKGROUND: In the Netherlands a program on quality assurance in medical care has started in 1996. Clinical professionals, patient organizations and health services researchers formulate evidence based guidelines with a concomitant cost-effectiveness analysis. OBJECTIVES: To examine the cost-effectiveness of guideline recommendations for prevention of nephropathy in diabetes mellitus type 1 and 2. RESEARCH DESIGN: A semi-Markov compartment model was developed. Data from international publications on epidemiological surveys and randomized trials, together with national data on health care use and costs, were used to feed the model. A cohort of diabetes patients without renal disease enters the model. MEASURES: Complication (end-stage renal disease) free years, QALY's, and life-time medical costs per patient treated according to guideline recommendations or current anti-diabetic strategy. RESULTS: Guideline treatment for type 1 diabetes yields 4.2 complication free life years, at a cost-effectiveness ratio of 13 500 (Dutch guilders) NLG per QALY. Type 2 diabetes patients gain 0.2 complication free life years at a cost-effectiveness ratio of 31 000 NLG per QALY. CONCLUSION: Guideline development for diabetes nephropathy, with concomitant cost-effectiveness calculations, has resulted in a transparent guideline with explicit information on long-term cost and effects. The project has brought health care providers and health services researchers together.

Costs in the last year of life in The Netherlands.

The costs of health care in the last year of life are a subject of debate and myth. Expensive interventions at the end of life often are blamed for the rapid increase in health care spending, but evidence about the existence of such exceptionally high expenditures at the end of life is rare and faulty. This investigation examines the development and composition of health care costs at the end of life for all age groups in The Netherlands. In contrast with earlier studies, this research analyzes both acute care (cure) and long-term care (care) costs. As an alternative for the frequently used concept of calendar years, we employed the concept of life years for calculating the costs at the end of life. We found that when life approaches its end, health care expenditures indeed rise sharply, especially in the last months. However, when we compared total cure costs in the last year of life to the total cure costs for the entire population, we concluded that the end-of-life share was only about 10%. Results of this study show that interventions to reduce costs in the last year of life will have only a modest impact compared to the total health care budget.

Bone density and risk of hip fracture in men and women: cross sectional analysis.

OBJECTIVE: To determine the relative contribution of decline in bone density to the increase in risk of hip fracture with age in men and women. DESIGN: Incidence data of hip fracture from the general population were combined with the bone density distribution in a sample from the same population and with a risk estimate of low bone density known from literature. SETTING: The Netherlands. SUBJECTS: All people with a hospital admission for a hip fracture in 1993, and bone density measured in a sample of 581.4 men and women aged 55 years and over in a district of Rotterdam. MAIN OUTCOME MEASURE: One year cumulative risk of hip fracture by age, sex, and bone density measured at the femoral neck. RESULTS: A quarter of all hip fractures occurred in men. Men reached the same incidence as women at five years older. Controlled for age, the risk of hip fracture by bone density was similar in men and women. The risk of hip fracture increased 13-fold from age 60 to 80; decrease in bone density associated with age contributed 1.9 (95% confidence interval 1.5 to 2.4) in women and 1.6 (1.3 to 1.8) in men. CONCLUSIONS: The risk of hip fracture by age and bone density is similar in men and women. The decrease in bone density associated with age makes a limited contribution to the exponential increase of the risk of hip fracture with age.

Coping with multiple morbidity in a life table.

PIP: "We present the proportional multi-state life table method, that makes the inclusion of multiple diseases better manageable and allows for comorbidity implicitly, without the need to define additional states. We implement the method for heart disease and stroke [among Dutch males in 1988], and look at the effect of hypothetical but not unrealistic changes in incidence and survival on disease prevalence and comorbidity. Finally we discuss limitations and extensions of the method." (EXCERPT)^ieng

[Is the use of helicopters with a trauma team in severely injured accident victims in The Netherlands cost effective? A modelling approach]. / Is het inzetten van helikopters met een traumateam bij ernstig gewonde ongevalsslachtoffers in Nederland kosteneffectief? Een modelmatige benadering.

OBJECTIVE: The assessment of the cost-effectiveness of helicopter medical crews for patients with major trauma in the Dutch situation. DESIGN: A modelling approach, combining available information with plausible assumptions. SETTING: Institute for Medical Technology Assessment, Rotterdam. METHODS: First, a baseline scenario was developed, implementing information that was available in the literature and a few assumptions. The sensitivity of the cost-effectiveness for the various assumptions was evaluated in alternative scenarios. END-POINTS. The relation between the costs per life year gained and the expected increase in the number of patients surviving an accident is established for the separate scenarios. RESULTS: In the baseline scenario the number of victims with a trauma score < or = 12 is estimated at 4500 per year, it is assumed that victims who die at the scene of the accident are unsalvageable and that hospital treatment costs Dfl. 27,000.--per patient. As a result costs per life year saved are only under Dfl. 50,000.--when more than 29 patients per year (9.23% gain in survival) are additionally saved. Sensitivity analysis shows that the cost-effectiveness depends highly on the expected gain in survival and on the estimate of the costs of hospital treatment. Both variables are surrounded with a lot of uncertainty. CONCLUSIONS: Relying on the information that is available at this moment, no definite conclusions can be drawn on the cost-effectiveness of this facility, because too many essential data are missing. Empirical research is necessary.

[Cost-effectiveness analysis of human monoclonal antibody HA-1A in patients with sepsis syndrome]. / Kosten-effectiviteitsanalyse van het humane monoklonale antilichaam HA-1A bij patiënten met het sepsissyndroom.

The efficiency of prescribing HA-1A for sepsis patients is analysed by comparing direct medical costs and effects. Effects are estimated on the basis of published data from a randomised clinical trial. Costs are analysed by combining data from the same trial with expectations about hospital days. Average costs per life year gained are estimated at DF1. 25,000. Sensitivity analysis is applied and the efficiency of treating patients with HA1A is shown to depend highly on the expected duration of survival after successful treatment. This leads to the advice to take epidemiologic knowledge into special account before setting the indication for using HA-1A.