The costs of treating glaucoma with combinations of topical drugs in Spain.

PURPOSE: This study describes the treatment in ordinary clinical practice in Spain of patients with glaucoma with a two-drug combination therapy. The authors present the treatment outcome as endof-period intraocular pressure (IOP) and the calculated direct medical costs over a 2-year period. METHODS: Data were extracted retrospectively from patient charts recording the use of all medical resources related to glaucoma. Costs were estimated using unit costs from public sources (2005). Descriptive cost analysis according to combination treatment at baseline was performed. RESULTS: The study included 216 patients from 21 centers. Around half of the patients were started on a beta-blocker/prostaglandin analogue combination, while the rest received various other combinations containing either an alpha2-agonist or a carbonic anhydrase inhibitor. Across the seven groups considered, there was a statistically significant difference in the costs of the least and the two most costly groups, while the confidence intervals were overlapping in all other pairwise comparisons. The least costly drug combination was brimonidine/timolol. Assessing IOP at the end of follow-up, all the groups were equally effective (overlapping confidence intervals). In a multivariate regression analysis, the drug combination did not have an independent, significant impact on total direct medical costs, drug costs, or end-of-period IOP. Significant determinants of these variables were surgical interventions and one or more changes of drug combination during the follow-up. CONCLUSIONS: Costs are determined by the response to treatment. Inadequate response triggers treatment changes and sometimes eventually surgical interventions, thereby increasing costs significantly.

Strontium(89) chloride versus palliative local field radiotherapy in patients with hormonal escaped prostate cancer: a phase III study of the European Organisation for Research and Treatment of Cancer, Genitourinary Group.

OBJECTIVES: To compare toxicity, subjective response rate, time to subjective progression and overall survival in patients with painful bone metastases of hormone-resistant prostate cancer (HRPC) treated with a single intravenous injection of 150MBq (4mCi) Strontium(89) Chloride (S) or palliative local field radiotherapy (R) with the usual radiotherapy regimen used at each centre. The costs of both treatments were also assessed. PATIENTS AND METHODS: 101 patients were randomized to S and 102 to R. Time to event endpoints were compared with the Logrank test and Kaplan-Meier curves, in the intent-to-treat population (2-sided alpha=0.05). RESULTS: Baseline characteristics of both groups were comparable. There was a borderline statistically significant difference in overall survival in favour of the local field radiotherapy (R: 11 months; S: 7.2 months; p=0.0457). There was no difference in progression-free survival or time to progression. Subjective response was seen in 34.7% in the S-arm and in 33.3% in the R-arm. A biochemical response was observed in 10% and 13% of the R- and S-groups, respectively. There was no difference in treatment toxicity between the two groups. CONCLUSION: In symptomatic HRPC, pain treatment with local field radiotherapy is associated with a better overall survival compared to Strontium(89). The lower costs of local field radiotherapy also favour the use of this treatment in patients with HRPC. The reason for the apparent survival benefit of localised radiation treatment is not clear.

Estimating survival gain for economic evaluations with survival time as principal endpoint: a cost-effectiveness analysis of adding early hormonal therapy to radiotherapy in patients with locally advanced prostate cancer.

The problem of estimating expected outcomes for the economic evaluation of treatments for which the outcome of principal interest is (quality adjusted) survival time has so far not received sufficient attention in the literature. The best estimate of expected survival is mean survival time, but with censored survival data, the true survival time for all the subjects is not known, so the mean is not defined.A possible solution to this estimation problem is illustrated by a retrospective cost-effectiveness analysis of the addition of hormonal therapy to standard radiotherapy for patients with locally advanced prostate cancer. A recently proposed method is used to approach the problem caused by censored cost data, and the impact of uncertainty is assessed by bootstrap resampling techniques. Mean survival time is estimated by a restricted means analysis with the time point of restriction determined by statistical criteria. When average total costs and mean survival time is evaluated at this time point of restriction, the result is that the combined therapy (radiotherapy plus hormonal therapy) increases mean survival time by about 1 year, while reducing the costs per patient for the French health insurance system by 12 700 FF. The time point of restriction may also be determined by other criteria and mean survival time may be estimated by extrapolating the survival curves by means of various parametric survival distributions. We show that the exact results of the economic evaluation are decisively determined by the restriction time point chosen and the approach taken to estimate mean survival time.

Health Economics Unit achievements.

This article describes the activities of the EORTC Health Economics Unit since its inception in early 1994. The aim of the unit is to carry out economic evaluations of competing treatment options in common cancers in order to provide health care decision makers with useful information about the relative benefits and costs of the therapies they have to choose between. These assessments are mainly carried out by integrating collection of economic data in selected phase III randomized controlled clinical trials conducted by the EORTC collaborative groups. Studies with an economic evaluation integrated are currently becoming mature enough for analysis and several publications have resulted or are in press. Some studies with data from other sources than EORTC trials have also been performed and published. In addition, the unit has actively followed and contributed to the continuous methodological development in the field of economic evaluation of health care interventions.

Cost-effectiveness of the addition of early hormonal therapy in locally advanced prostate cancer: results decisively determined by the cut-off time-point chosen for the analysis.

We present a retrospective cost-effectiveness analysis using data from a randomised controlled trial (EORTC 22863) of the addition of early hormonal therapy with a luteinising hormone-releasing hormone (LHRH) analogue to radiotherapy in the treatment of patients with locally advanced prostate cancer. Data on the use of medical resources were extracted from the hospital charts of 90 patients recruited into the trial by one French hospital. Costs are assessed from the viewpoint of the French healthcare financing system and adjusted for censoring. Expected costs per patient of each treatment is related to the expected outcome, mean survival time, estimated by a restricted means analysis. The time point of restriction is determined by statistical criteria. In the base case analysis with a cut-off time point at 8.58 years, the combined therapy group (COMB) had a gain in mean survival time of 1.06 years (7.05 versus 5.99 years) and a reduction of average total costs of 12700 French francs (FF) (58300 FF versus 71000 FF). The analysis of uncertainty uses bootstrap techniques with 5000 replicates to examine the joint distribution of cost and survival outcomes. In 76% of the cases, COMB results in longer mean survival time and lower costs than the radiotherapy group (RT). In cases where COMB therapy raises costs (13% of the cases), it is rarely by more than 20000 FF per patient, no matter the size of the associated survival gain. It is thus highly likely that COMB should be considered a cost-effective option compared with RT for these patients. The exact result of the economic evaluation is decisively determined by the restriction time point selected for the determination of mean survival time, partly also because the average total costs of the two treatments develop entirely differently as a function of the survival time.

Assessment of the economic value of epoetin use in anemic cancer patients.

Anemia is a common occurrence in cancer patients, as a consequence of the disease process and treatment. Until recently, the only treatment available for anemia was red blood cell transfusions, but this was withheld until the development of severe anemia because of the risks associated with transfusion. Since the mid 1990s, recombinant human erythropoietin (rHuEPO) has been available as an alternative treatment option, which could be used to treat mild-to-moderate anemia and to prevent severe anemia. Many clinicians currently believe that anemia should be treated vigorously, because this is thought to improve patient quality of life, partly because of new research indicating that anemia may be an independent risk-factor for survival. Possible mechanisms behind such an association are not yet completely elucidated, but some clinicians argue that rHuEPO is an ideal drug for the treatment of mild and moderate anemia, as it is perceived to be without serious negative side effects. However, rHuEPO is an expensive drug and the evidence on how to use it optimally, is still highly incomplete.

Patient management strategies and transplantation techniques in european stem cell transplantation centers offering breast cancer patients high-dose chemotherapy with peripheral blood stem cell support: a joint report from the EORTC and EBMT.

BACKGROUND AND OBJECTIVES: It is increasingly being realized that there are very considerable variations in individual hospitals' strategies for managing a particular group of patients, even if using similar therapeutic regimens. Such variations make it impossible to generalize estimations of treatment costs from one setting to others. The objective of this study is to examine the extent of variation in the current approaches in Europe to peripheral blood stem cell transplantation (PBSCT) in breast carcinoma. DESIGN AND METHODS: A questionnaire was developed and sent to the EBMT member institutions. The questionnaire comprised 85 questions covering the technical and clinical issues involved and the strategies followed for the management of the patients. This paper reports the results of the survey primarily by means of descriptive, univariate frequency distributions. The results of a more analytical approach, aiming at explaining patterns in the variations observed are also presented. RESULTS: A completed questionnaire was returned by 162 centers; 60% university hospitals, 14% cancer centers and the rest general hospitals. Considerable variations are observed between the centers with respect to all aspects of patient management and technical procedures investigated. In many respects, general hospitals follow different routines from university hospitals and dedicated cancer centers. INTERPRETATION AND CONCLUSIONS: Variability to the extent observed indicates an important scope for optimization of the procedures and a large potential for reduction of costs and perhaps for improvement of outcomes. Economic evaluations, for instance comparing PBSCT with autologous BMT as support for high dose chemotherapy, can not be generalized from one setting to another without careful examination of the procedures and strategies followed in each setting. European hospitals treating breast cancer patients with high dose chemotherapy supported by transplantation of peripheral blood stem cells use very different technical procedures for mobilization, harvest and re-implantation of stem cells. In addition, there are also wide variations in the way they manage the patients, e.g. with regard to the criteria for discharge from hospital after re-implantation.

Impact of the treating institution on survival of patients with "poor-prognosis" metastatic nonseminoma. European Organization for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group and the Medical Research Council Testicular Cancer Working Party.

BACKGROUND: Because metastatic nonseminomatous germ cell cancer is a rare but treatable cancer, we have explored whether there is an association between the experience of the treating institution with this disease and the long-term clinical outcome of the patients, particularly patients with a poor prognosis. METHODS: We analyzed data on 380 patients treated in one of 49 institutions participating in the European Organization for Research and Treatment of Cancer/ Medical Research Council randomized trial of four cycles of bleomycin-etoposide-cisplatin followed by two cycles of etoposide-cisplatin versus three cycles of bleomycin-vincristine-cisplatin followed by three cycles of etoposide-ifosfamide-cisplatin-bleomycin, both treatment regimens given with or without filgrastim (granulocyte colony-stimulating factor). Institutions were divided into four groups based on the total number of patients entered in the trial. The groups were compared by use of the Cox proportional hazards model stratified for treatment with filgrastim and for patient prognosis as defined by the International Germ Cell Consensus Classification Group. With the use of this classification, only 65 % of the patients had a poor prognosis. RESULTS: Patients treated in the 26 institutions that entered fewer than five patients into the trial had an overall survival that was statistically significantly worse (two-sided P = .010; hazard ratio = 1.85; 95% confidence interval = 1.16-3.03) than that of patients treated in the 23 institutions that entered five patients or more. Overall survival and failure-free survival were similar among institutions that entered at least five patients. The observed effect may be related to differences in adherence to the chemotherapy protocol and in the frequency and extent of surgery for residual masses, although only the differences in dose intensity achieved statistical significance. CONCLUSIONS: Patients treated in institutions that entered fewer than five patients into the trial appeared to have poorer survival than those treated in institutions that entered a larger number of patients with "poor-prognosis" nonseminoma.

The costs of managing patients with advanced colorectal cancer in 10 different European centres.

With the aim of estimating and comparing the direct hospital costs of managing patients with advanced colorectal cancer in various countries, data on resource utilisation and unit prices were collected. Data on the consumption of medical resources were collected by a retrospective examination of the hospital charts for 20 patients in each of 10 centres in five European countries. To make cost comparisons meaningful, a complete and consistent set of unit prices for all the medical resources used in each of the countries would be required, but this could not be achieved. As an alternative method of comparison, the most complete set of unit prices (from Belgium) was used here to estimate the imputed average total cost of patient management in each centre. By using this approach, a summary index was created, which reflected only differences in resource utilisation. This index showed that there were considerable differences in the amounts of resources used for treating these patients, between, as well as within, countries. Differences of the same order of magnitude were found, when the treatment of subgroups of patients, according to site and stage of disease, were examined.

How should treatment costs impact on physician's decisions?

This article first discusses at what level of clinical decision making cost considerations may be most pertinent and important. It is argued that cost assessments will be of most relevance and value at an intermediate level of clinical decision making i.e. at a level where so-called policy decisions are made. These are decisions such as which drugs to include in a hospital formulary or which standard treatment 'protocols' to choose for particular types of patients. The personal encounter between individual patients and physicians will take place within the framework of available treatment options determined by these policy decisions, which must necessarily be based on a prior assessment of the expected costs and benefits of treatments. The article goes on to give a brief introduction to the various methods of economic evaluation that have been developed in order to provide the decision makers with the means to make policy decisions on the basis of the most reliable and pertinent information possible.

Cost-minimization analysis of treatment options for T1N0 glottic squamous cell carcinoma: comparison between external radiotherapy, laser microsurgery and partial laryngectomy.

BACKGROUND AND PURPOSE: A cost minimization analysis of radiotherapy (RT), laser microsurgery (L) or partial laryngectomy (PL), which are equally effective options for T1N0 glottic SCC was carried out from the perspective of the National Health Care System. METHODS: For each modality, the various events associated with the diagnostic procedure, the primary treatment, the complications, and the salvage treatment were individualized. The charges of each of these events weighted for the frequency of occurrence were then determined using the 'fee for service' policy established by the National Health Insurance of Belgium. RESULTS: A total cost of 5172, 5847 and 11563 EURO were calculated for RT, L and PL, respectively. For L, cost included post-operative RT applied in case of positive margins (30%). For PL, the cost of the primary treatment accounted for 68% of the total cost whereas it only accounted for 50 and 43% for L and RT, respectively. For RT, L or PL, complications accounted for less than 10% of the total cost. The cost of salvage treatment reached 19, 14 and 8% of the total cost for RT, L and PL, respectively. A sensitivity analysis indicated that reduction of the duration of hospitalization decreases the costs without affecting the ranking between the three options. Also, the cost of L could be reduced even slightly below the cost of RT by decreasing the need for post-operative RT. CONCLUSIONS: RT and L have almost the same expected average cost for the treatment of T1N0 glottic SCC, whereas PL is twice as expensive.

Methodological and statistical issues of quality of life (QoL) and economic evaluation in cancer clinical trials: report of a workshop.

In recent years, quality of life (QoL) and economic evaluations have become increasingly important as additional outcome measures in cancer clinical trials. However, both fields of research are relatively new and in need of finding solutions to a substantial number of specific methodological problems. This paper reports on the proceedings of a symposium aimed at summarising and discussing some of the most contentious methodological and statistical issues in QoL and economic evaluations. In addition, possible solutions are indicated and the most pertinent areas of research are identified. Issues specific to QoL evaluations that are addressed include clinically meaningful changes in QoL scores; how to analyse QoL data and to handle missing and censored data and integration of length of life and QoL outcomes. Issues specific to economic evaluations are the advantages and disadvantages of various outcome measures; statistical methods to analyse economic data and choice of decision criteria and analytical perspective. How to perform QoL and economic evaluations in large and simple trials and whether the gap between QoL and utility measures can be bridged are also discussed.

Economics of urinary tract cancers: state of the art.

The guiding principles of the predominant methods of economic evaluation, cost-effectiveness analysis and cost-utility analysis, are briefly outlined, stressing the usefulness of the methods as a systematic approach to a structured and consistent analysis of decision problems, e.g. involving choices between treatment alternatives. The paper continues with an assessment of state of the art of economic evaluations of urinary tract cancers, based on a comprehensive survey of the available publications, which are limited to bladder cancer and advanced prostate cancer. Following a description of the methods employed in the relatively few existing studies and their results, it is concluded that they are of very dubious value in providing reliable guidance on the relative costs and benefits of treatment alternatives, as they are very rudimentary and usually based on data of low quality. Considering the high and growing incidence of both prostate and bladder cancer, there is an urgent need for economic assessment of a high methodological standard and based on data of a good quality.