Cost-effectiveness of clopidogrel in STEMI patients in the Netherlands: a model based on the CLARITY trial.

OBJECTIVE: This study assesses the costs and effects of combination treatment with clopidogrel and aspirin in comparison to aspirin alone in patients with an ST-segment elevation myocardial infarction (STEMI) in a Dutch setting. METHODS: A decision tree model is used to combine data from different sources about efficacy, epidemiology and costs. In the short-run, cost-effectiveness is based on efficacy data derived from the CLARITY trial. The cost-effectiveness of continued treatment is addressed by analysing which conditions need to be fulfilled to deem the strategy 'cost-effective', and discussing whether it is likely that it is. Estimates concerning the benefits of preventing events are derived from Swedish registries. Approximations of both direct and indirect costs are derived from the literature. Effects are expressed as life years gained and Quality Adjust Life Years (QALYs). Uncertainties are addressed by uni- and multivariate sensitivity analyses with and without taking account of the dependency between the separate ischaemic events. RESULTS: A treatment regimen similar to that of the CLARITY trial, including patients similar to those in the trial, is estimated to result in 0.05 additional life years and 0.062 additional quality adjusted life years for a cost that is euro1929 lower than aspirin therapy. Continuation of treatment outside the trial period is expected to result in ICERs of below euro20,000 per QALY as long as the real risk reduction of combination treatment is greater than 0.487% per year. CONCLUSION: The results indicate that clopidogrel therapy combined with aspirin, according to the regimen seen in CLARITY, and using data from Swedish registries to inform the model, is cost-effective. Sensitivity analyses suggest that the model is robust to a wide range of parameter estimates, including those based on data from Swedish registries. Continued treatment is very likely to be cost effective in light of all the indirect evidence.

Patients' representations of their end-stage renal disease: relation with mortality.

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

Efficacy of recombinant activated factor VII vs. activated prothrombin complex concentrate for patients suffering from haemophilia complicated with inhibitors: a Bayesian meta-regression.

The optimal on-demand treatment of joint bleeds in haemophilia patients with inhibitors is a source of debate, with studies reporting various efficacy levels for different drugs and dosage regimens. To analyse, in a unified Bayesian meta-regression model, the published efficacy of recombinant activated factor VII (rFVIIa) and/or activated prothrombin complex concentrate (aPCC) as on-demand treatments for joint bleeds in haemophilia patients with inhibitors. A systematic search was carried out to identify studies reporting on dosage and efficacy of rFVIIa and aPCC in the treatment of joint bleeds in the target patient population. Data were abstracted and included in the model and adjusted for potential sources of heterogeneity. Pooled efficacy levels for typical rFVIIa and aPCC regimens were estimated. Seventeen studies, collectively reporting on >2000 joint bleeds, were included. Medication type combined with dosage was the only significant explanatory parameter. The model predicts that a typical regimen of 90 microg kg(-1) rFVII repeated every 3 h if needed results in cumulative joint bleed resolution of 66%, 88% and 95% after 12, 24 and 36 h, respectively. In comparison, a typical regimen of 75 IU kg(-1) aPCC repeated every 12 h if needed results in cumulative joint bleed resolution of 39%, 62% and 76%, respectively. These differences were statistically significant and were also robust in sensitivity analyses. This analysis suggests that a typical rFVIIa regimen will resolve joint bleeds more effectively than a typical aPCC regimen after 12, 24 and 36 h.

Comparison of hemodialysis and peritoneal dialysis survival in The Netherlands.

Considerable geographic variation exists in the relative use of hemodialysis (HD) vs peritoneal dialysis (PD). Studies comparing survival between these modalities have yielded conflicting results. Our aim was to compare the survival of Dutch HD and PD patients. We developed Cox regression models using 16 643 patients from the Dutch End-Stage Renal Disease Registry (RENINE) adjusting for age, gender, primary renal disease, center of dialysis, year of start of renal replacement therapy, and included several interaction terms. We assumed definite treatment assignment at day 91 and performed an intention-to-treat analysis, censoring for transplantation. To account for time dependency, we stratified the analysis into three time periods, >3-6, >6-15, and >15 months. For the first period, the mortality hazard ratio (HR) of PD compared with HD patients was 0.26 (95% confidence interval (CI) 0.17-0.41) for 40-year-old non-diabetics, which increased with age and presence of diabetes to 0.95 (95% CI 0.64-1.39) for 70-year-old patients with diabetes as primary renal disease. The HRs of the second period were generally higher. After 15 months, the HR was 0.86 (95% CI 0.74-1.00) for 40-year-old non-diabetics and 1.42 (95% CI 1.23-1.65) for 70-year-old patients with diabetes as primary renal disease. We conclude that the survival advantage for Dutch PD compared with HD patients decreases over time, with age and in the presence of diabetes as primary disease.

Increased end-stage diabetic nephropathy in Indo-Asian immigrants living in the Netherlands.

AIMS/HYPOTHESIS: We aimed to investigate the risk of end-stage diabetic nephropathy due to Type II (non-insulin-dependent) diabetes mellitus in Indo-Asian immigrants from Surinam. METHODS: A demographically based case-control study was carried out in Surinamese Indo-Asian immigrants and Dutch Caucasian subjects. All patients with end-stage diabetic nephropathy who had started dialysis between 1990 and 1998 were identified through a national registry of all patients entering a renal replacement program in the Netherlands. The general population of native Dutch and Surinamese Indo-Asians were considered the control subjects. RESULTS: Among Indo-Asian immigrants, the age adjusted relative risk of end-stage diabetic nephropathy was 38 (95 % CI 16 to 91) compared with the native Dutch population. The duration of diabetes until the start of dialysis treatment was similar in both ethnic groups, about 17 years. CONCLUSION/INTERPRETATION: The Indo-Asian subjects had a nearly 40-fold increase in the risk for end-stage diabetic nephropathy due to Type II diabetes, compared with the native Dutch population. This was higher than expected on the basis of the eightfold higher prevalence of diabetes in the Indo-Asian population. The similar duration of diabetes until the start of dialysis treatment in both ethnic groups supports the hypothesis of a higher incidence of diabetic nephropathy in the Indo-Asian diabetic population. Early and frequent screening for diabetes and microalbuminuria is recommended in Indo-Asian subjects.

EQ-5D: a measure of health status from the EuroQol Group.

Established in 1987, the EuroQol Group initially comprised a network of international, multilingual and multidisciplinary researchers from seven centres in Finland, the Netherlands, Norway, Sweden and the UK. Nowadays, the Group comprises researchers from Canada, Denmark, Germany, Greece, Japan, New Zealand, Slovenia, Spain, the USA and Zimbabwe. The process of shared development and local experimentation resulted in EQ-5D, a generic measure of health status that provides a simple descriptive profile and a single index value that can be used in the clinical and economic evaluation of health care and in population health surveys. Currently, EQ-5D is being widely used in different countries by clinical researchers in a variety of clinical areas. EQ-5D is also being used by eight out of the first 10 of the top 50 pharmaceutical companies listed in the annual report of Pharma Business (November/December 1999). Furthermore, EQ-5D is one of the handful of measures recommended for use in cost-effectiveness analyses by the Washington Panel on Cost Effectiveness in Health and Medicine. EQ-5D has now been translated into most major languages with the EuroQol Group closely monitoring the process.

A comparison of quality of life of patients on automated and continuous ambulatory peritoneal dialysis.

OBJECTIVE: Data on health-related quality of life (HRQOL) of automated peritoneal dialysis (APD) patients are scarce. The objectives of this study were (1) to explore HRQOL of APD patients and compare it with HRQOL of continuous ambulatory peritoneal dialysis (CAPD) patients and a general population sample, and (2) to study the relationship between HROOL assessment outcomes and background variables. DESIGN: Home interviews of APD and CAPD patients. HRQOL, social-demographic, clinical, and treatment-related background data were collected at the interview and from patient charts. Multiple regression analysis and logistic regression analysis were used to study the relationship of HRQOL assessment outcomes with background variables. SETTING: Sixteen Dutch dialysis centers. PATIENTS: Convenience sample of 37 APD patients and 59 CAPD patients matched for total time on dialysis. MAIN OUTCOME MEASURES: Four HRQOL instruments: Short-Form 36, EuroQol EQ-5D, Standard Gamble, and Time Trade Off. RESULTS: Physical functioning of both APD and CAPD patients was impaired compared with the general population; mental functioning was not different. In multivariate analyses, the mental health of APD patients was found to be better than that of CAPD patients. In addition, APD patients were less anxious and depressed than CAPD patients. With respect to physical aspects of HRQOL and role-functioning, no differences were observed between APD and CAPD patients. Other variables to explain HRQOL assessment outcomes were age, the number of comorbid diseases, and primary kidney disease. CONCLUSIONS: HRQOL of APD patients is at least equal to HRQOL of CAPD patients.

Renal replacement therapy in Europe: the results of a collaborative effort by the ERA-EDTA registry and six national or regional registries.

BACKGROUND: In June 2000 a new ERA-EDTA Registry Office was opened in Amsterdam. This Registry will only collect core data on renal replacement therapy (RRT) through national and regional registries. This paper reports the technical and epidemiological results of a pilot study combining the data from six registries. METHODS: Data from the national renal registries of Austria, Finland, French-Belgium, The Netherlands, Norway, and Scotland were combined. Patients starting RRT between 1980 and 1999 (n=57371) were included in the analyses. Cox proportional hazards regression was used to predict survival. RESULTS: The use of different coding systems for ESRD treatment by the registries made it difficult to merge the data. Incidence and prevalence of RRT showed a continuous increase with a marked variation in rates between countries. The 2-, 5- and 10-year patient survival was 67, 35 and 11% in dialysis patients and 90, 81 and 64% after a first renal allograft. Multivariate analysis showed a slightly better survival on dialysis in the 1990-1994 (RR 0.94, 95% CI 0.90-0.98) and the 1995-1999 cohort (RR 0.88, 95% CI 0.84-0.92) compared to the 1980-1984 cohort. In contrast, there was a much greater improvement in transplant-patient survival, resulting in a 56% reduction in the risk of death within the 1995-1999 cohort (RR 0.44, 95% CI 0.39-0.50) compared to the 1980-1984 cohort. CONCLUSIONS: This study provides support for the feasibility of a "new style" ERA-EDTA registry and the collection of data is now being extended to other countries. The improvement in patient survival over the last two decades has been much greater in transplant recipients than in dialysis patients.

The effect of medical care by a helicopter trauma team on the probability of survival and the quality of life of hospitalised victims.

In 1995, an experiment was started to give extra medical help by helicopter to patients who needed emergency treatment. The aim of the experiment was not to reduce the transportation time to the hospital, but to bring specialised medical care directly to patients as soon as possible. An evaluation study was carried out to assess the effect of the treatment given by the Helicopter Trauma Team (HTT) on survival and quality of life. The study focused on hospitalised patients suffering from polytrauma. A direct comparison between an experimental and control group was not possible, because the HTT group consisted of more severely injured patients. A refined severity index was constructed on the basis of the Revised Trauma Scale (RTS) and the Injury Severity Scale (ISS) and their sub-scores. Using this index, it was possible to make a clear distinction between three groups of patients, i.e. those with a high probability of survival (with or without special medical treatment), those with a very low probability of survival and the patients in between. It was shown that the HTT-treatment was effective. The survival rate increased for patients in the 'in between' group, but not for patients with a low probability of survival. There was no difference in the quality of life of patients from the HTT and non-HTT groups 15 months after the accident. These findings refute the hypothesis that only the most severely injured patients with a low quality of life profit from HTT-treatment.

Sensitivity and perspective in the valuation of health status: whose values count?

The literature was studied on the existence of differences in valuation for hypothetical and actual health states between patients and other-rater groups. It was found that nine different study designs have been used to study this question and two of these designs were applied in a study involving dialysis patients and other rater groups. In the first study, both dialysis patients and students had to value hypothetical health states with Standard Gamble (SG) and Time Trade Off (TTO). Patients assigned higher values to hypothetical health states than students did. In the second study, dialysis patients who were being treated with four different dialysis modalities were asked to value their own health state with SG, TTO and a visual analogue scale (EQ(VAS)), and to describe their health state on the EQ-5D(profile). Several EQ-5D(index) values (health index values derived from general population samples) were calculated for the four dialysis treatment groups, based on the EQ-5D(profile). These health indexes could discriminate between treatment groups, according to clinical impressions. Treatment groups could not be differentiated based on patients' valuations of own health state. The results suggest that general population samples, using EQ-5D(index) values, may be more able to discriminate between patient groups than the patients themselves are. The implications of this finding for valuation research and policy-making are discussed.

Effect of simultaneous pancreas-kidney transplantation on mortality of patients with type-1 diabetes mellitus and end-stage renal failure.

BACKGROUND: Long-term prognosis of patients with type-1 diabetes mellitus and end-stage renal failure appears to be better after kidney transplantation compared with dialysis. Controversy exists about the additional benefit of a simultaneously transplanted pancreatic graft. We studied the effect on mortality of simultaneous pancreas-kidney transplantation compared with kidney transplantation alone from regional differences in transplantation protocols. METHODS: All 415 patients with type-1 diabetes (aged 18-52 years) who started renal-replacement therapy in the Netherlands between 1985 and 1996 were included in the analysis. Patients were allocated to a centre based on their place of residence at onset of renal failure. In the Leiden area, the primary intention to treat was with a simultaneous pancreas-kidney transplantation, whereas in the non-Leiden area, kidney transplantation alone was the predominant type of treatment. All patients were followed up to July, 1997. Analyses, mortality, and graft failure were by Cox proportional-hazard model adjusted for age and sex. FINDINGS: Simultaneous pancreas-kidney transplantation was done in 41 (73%) of 56 transplanted patients in the Leiden area compared with 59 (37%) of 158 transplanted patients in the non-Leiden area (p<0.001). The hazard ratio for mortality after the start of renal-replacement therapy was 0.53 (95% CI, 0.36-0.77, p<0.001) in the Leiden area compared with the non-Leiden area. When just the transplanted patients were analysed the mortality ratio was 0.4 (95% CI 0.20-0.77, p=0.008) and was independent of duration of dialysis and early transplant-related deaths. Equal survival was found for patients on dialysis only. INTERPRETATION: These data support the hypothesis that simultaneous pancreas-kidney transplantation prolongs survival in patients with diabetes and end-stage renal failure.

Economic evaluation of end stage renal disease treatment.

This paper examines the cost-effectiveness of end stage renal disease (ESRD) treatments. Empirical data on costs of treatment modalities and quality of life of patients were gathered alongside a clinical trial and combined with data on patient and technique survival from the Dutch Renal Replacement Registry. A Markov-chain model, based on the actual Dutch ESRD program as of January 1st 1997, predicted the cost-effectiveness and cost-utility of dialysis and transplantation over the 5-year period 1997-2001. Total annual costs amounted to DFL 650 million (1.1% of the health care budget). Centre Haemodialysis was found to be the least cost-effective treatment, while transplantation and Continuous Ambulatory Peritoneal Dialysis (CAPD) were the most cost-effective treatments. The Markov-chain model was used to study the influence of substitutive policies on the overall cost-effectiveness of the ESRD treatment program. The influence of such policies was found to be modest in the Dutch context, where a high percentage of patients is already being treated with more cost-effective treatment modalities. In countries where Centre Haemodialysis is still the only or the major treatment option for ESRD patients, substitutive policies might have a more substantial impact on cost-effectiveness of ESRD treatment.

Quality of life in short adults.

The use of (costly) growth hormone (GH) treatment in short children is often justified by the assumption that short stature considerably reduces quality of life in adults. We tested this assumption in 5 groups of short adults: 25 patients with isolated GH deficiency; 17 male patients with childhood onset renal failure; 25 women with Turner syndrome and 26 patients who were presented as a child to a paediatrician for idiopathic short stature. A group of 44 short individuals with presumably idiopathic short stature, who had not been presented to a paediatrician for short stature, was sampled from the general population ('normal shorts'). We measured quality of life in terms of socio-economic variables, the Nottingham Health Profile and time trade-off. The mean height of most groups was close to the 3rd percentile. The chance of having a partner was low for all groups, except for the normal shorts. Problems with job application were only reported in Turner syndrome. The scores on the Nottingham Health Profile were all within the normal range, but GH-deficient adults had a higher score on the domain energy than normal shorts. Women with Turner syndrome, individuals with renal failure, and those with idiopathic short stature had a wish to be taller, with an estimated reduction in quality of life of 2-4% (time trade-off). As the normal shorts did not show any sign of a reduced quality of life, we falsify the assumption of a direct relation between short stature and quality of life. The complaints of patients with idiopathic short stature around the 3rd percentile seem to be the result of unsuccessful coping strategies.

Measuring the quality of life before and after bilateral lung transplantation in patients with cystic fibrosis.

Lung transplantation is an important topic today in healthcare policy because the technique is new and costly. One of the important issues in the evaluation of lung transplantation is quality of life. The quality of life after lung transplantation must be relatively high compared with other forms of medical care to legitimize the high costs of transplantation. Quantifying the quality of life after lung transplantation and other medical therapies is possible with general measurements of quality of life. In a pilot study of six patients with cystic fibrosis, the quality of life, both before and after lung transplantation, was measured by the following five instruments: (1) standard gamble, (2) time trade-off, (3) the Karnofsky performance status, (4) the EuroQol visual analog scale, and (5) the Nottingham health profile. This pilot study demonstrates that the introduced methodology is feasible. The preliminary results suggest that the improvement in quality of life for patients with cystic fibrosis after bilateral lung transplantation is comparable to the improvement in quality of life after heart transplantation.

Systems of donor transfer.

The development of medical knowledge has resulted in a demand in society for donor organs, but the recruitment of donor organs for transplantation is difficult. This paper aims to provide some general insights into the complex interaction processes involved. A laissez-faire policy, in which market forces are relied on, is not acceptable from an ethical and legal point of view in most western European countries. Especially at the demand side of the exchange of donor organs, commercialism is to be opposed. We judge the use of commercial incentives at the supply side less unacceptable in theory but not feasible in western European countries. Since market forces are deemed unacceptable as instruments for coordinating demand and supply of donor organs, donor procurement has to be considered as a collective good, and therefore governments are faced with the responsibility of making sure that alternative interaction and distribution mechanisms function. The role of organ procurement agencies (OPAs) in societal interaction concerning postmortem organ donation is described using a two-dimensional conceptualisation scheme. Medical aspects of living organ donation are described. An international comparative description of legal systems to regulate living organ donation in western European countries completes this survey.

The utility of health at different stages in life: a quantitative approach.

Thirty students and thirty-five elderly people compared the quality of life of imaginary patients of different ages suffering from end-stage renal disease. By manipulating the time the imaginary patients had to be on a transplantation waiting list, the utility of health at different periods of life could be compared. Except for the very young, respondents found health in the early periods of life to be twice as important as in the last decade of life. Health at age 35 had an utility somewhere between these two extremes. The responses of the elderly people showed remarkable resemblance to the students' responses, suggesting that the results reflect a general ethical standard. The values found were tested by means of a factorial design and found to fulfill the qualifications of an interval scale.

Heart transplantation in the Netherlands; costs, effects and scenarios.

The Dutch heart transplantation programme was subjected to a prospective economic evaluation and costs and effects with or without such programme were estimated. The no-programme estimates were derived from pretransplant patient data. Future projections of both options were based on micro-stimulation using additional data on severe heart disease prevalence and on multi-organ donation. Costs per life year gained are estimated at NLG 57,650 (quality adjusted: NLG 71,900). Sensitivity analysis showed these results to depend highly on long term incidence of costs and on quality of life after transplantation.