Treatment of high risk medulloblastomas in children above the age of 3 years: a SFOP study.

AIM: Improvement of EFS of children older than 3 years with high risk medulloblastoma. METHODS: Between 1993 and 1999, 115 patients (3-18 years, mean 8 years) with high risk medulloblastoma were included. After surgery treatment consisted of chemotherapy ('8in1' and etoposide/carboplatin) before and after craniospinal radiotherapy. RESULTS: Patients were staged using Chang-criteria (PF residue only, M1 and M2/M3) by local investigator as well as by central review panel (82.4% concordance). Chemotherapy was well tolerated without major delays in radiotherapy. With a mean follow up of 81 months (9-119), 5-year EFS was 49.8% and OS 60.1%. In detail according to subgroups EFS was 68.8% for PF residue only, 58.8% for M1 disease and 43.1% for M2/M3. CONCLUSION: M1 patients are legitimate high risk patients. Survival rates are still very low for high risk medulloblastoma patients and future trials should therefore focus on more intensive (chemotherapy/radiotherapy) treatment.

Standard-risk medulloblastoma treated by adjuvant chemotherapy followed by reduced-dose craniospinal radiation therapy: a French Society of Pediatric Oncology Study.

OBJECTIVE: The primary objective of this study was to decrease the late effects of prophylactic radiation without reducing survival in standard-risk childhood medulloblastoma. PATIENTS AND METHODS: Inclusion criteria were as follows: children between the ages of 3 and 18 years with total or subtotal tumor resection, no metastasis, and negative postoperative lumbar puncture CSF cytology. Two courses of eight drugs in 1 day followed by two courses of etoposide plus carboplatin (500 and 800 mg/m(2) per course, respectively) were administered after surgery. Radiation therapy had to begin 90 days after surgery. Delivered doses were 55 Gy to the posterior fossa and 25 Gy to the brain and spinal canal. RESULTS: Between November 1991 and June 1998, 136 patients (median age, 8 years; median follow-up, 6.5 years) were included. The overall survival rate and 5-year recurrence-free survival rate were 73.8% +/- 7.6% and 64.8% +/- 8.1%, respectively. Radiologic review showed that 4% of patients were wrongly included. Review of radiotherapy technical files demonstrated a correlation between the presence of a major protocol deviation and treatment failure. The 5-year recurrence-free survival rate of patients included in this study with all optimal quality controls of histology, radiology, and radiotherapy was 71.8% +/- 10.5%. In terms of sequelae, 31% of patients required growth hormone replacement therapy and 25% required special schooling. CONCLUSION: Reduced-dose craniospinal radiation therapy can be proposed in standard-risk medulloblastoma provided staging and radiation therapy are performed under optimal conditions.

[Medical and economic evaluation of organ transplantation in France. The example of liver transplantation]. / L'évaluation médico-économique des greffes d'organe en France. L'exemple de la transplantation hépatique.

BACKGROUND: Organ transplantation is an expensive and risky medical procedure. Estimating the cost is difficult because the care is complex and involves many actors. We present a methodological framework for the economic evaluation of organ transplantation in France which include a detailed collection of all the direct costs and the simultaneous analysis of health status. It was applied to evaluate the cost of liver transplantation in France. METHODS: All consecutive adults transplanted or placed on the waiting list of liver transplantation in the Department of Surgery of Cochin Hospital, Paris, between 1994 and 1996 were included. All resource use was measured during one year: staff wages, pharmacy and blood, laboratory and radiology, supplies, overhead hospital services. Mean quality of life was estimated by the survival weighted by the Karnofsky index. RESULTS: Transplantation: 38 patients were included. The first year mean cost after transplantation was 561,000FF (included rehospitalizations cost of 120,000FF). Care outside the hospital induced 10% of the total cost. Mean quality of life was 63% (from 0% to 93%) and increased with time, whereas cost decreased. Waiting list: 26 of 33 patients on waiting list were transplanted. The first year mean cost was 95,000FF (included 32,000FF for first evaluation) and increased with time. 44% of cost was supported by another hospital than the transplanting one. Sickness allowance added 20% to the cost. The mean quality of life was 56% during the first year. CONCLUSIONS: This complete approach of organ transplantation cost respected the medical procedure over the time. Detailed costs take into account the care outside the hospital. This method can be used in other countries and generalised to all surgical or medical procedure as heavy as the organ transplantation.

Cost-effectiveness of monolayers and human papillomavirus testing compared to that of conventional Papanicolaou smears for cervical cancer screening: protocol of the study of the French Society of Clinical Cytology.

The French Society of Clinical Cytology is conducting a study to compare the cost-effectiveness of monolayers and human papillomavirus (HPV) testing with that of conventional Papanicolaou (Pap) smears for cervical cancer screening. The protocol of this study is presented. It includes 3,000 women who will be evaluated by the three methods (conventional Pap smears, or monolayers with or without HPV testing) and by the reference method: colposcopy followed, in cases with abnormalities, by cervical biopsy. Efficacy or performance of the methods will be compared on the basis of sensitivity. Cost comparisons and cost-effectiveness modeling will be based on the costs associated with methods themselves and also the costs of "false positives." This will require specific collection of data concerning the costs of the three methods, as these costs have not previously been accurately documented. Patient recruiting and data collection started in September 1999 and will be complete in June 2000. The first results are expected to be available in spring 2001.

Costs and outcomes of liver transplantation in adults: a prospective, 1-year, follow-up study. GRETHECO study group.

BACKGROUND: Orthotopic liver transplantation (OLT) is widely used to treat patients with end-stage liver disease. However, data on the cost of the procedure are fragmentary. We evaluated the costs, as calculated from resource use, and outcomes of OLT in adults, from registration on the transplant waiting list to the end of the 1st-year of follow-up after the transplant. METHODS: Two parallel cohort studies were conducted from 1994 to 95. All patients ages 18 years and older, on the waiting list (n=33) according to national criteria or having undergone transplants (n=38) were followed for 1 year or until either the transplant (waiting list cohort) or death (waiting list and transplantation cohorts). RESULTS: Eighty percent of the patients undergoing transplants were alive after 1 year, and no patient died while on the waiting list. However, the estimated cost of the procedure was high: more than 55,000 pound silver for the 1st year after OLT, to be added to 5,500 pound silver for evaluation and further costs motivated by the planned transplant during an average 6.5 months on the waiting list. Age over 40 and a baseline Child-Pugh score of 10 and over were predictive of high costs. The proportion of costs associated with immunosuppressive therapy and rejection were very high. CONCLUSIONS: This medical and economic cohort study suggests that OLT is still expensive; the study identifies sources of extra cost that could be limited either by improved selection of patients or, in the future, by technological advances in immunosuppressive therapy that help avoid medical complications. It also suggests the situation is precarious, with outcomes and costs being very sensitive to variation in graft availability.

Cross-cultural adaptation of a health status classification system in children with cancer. First results of the French adaptation of the Health Utilities Index Marks 2 and 3.

Our objective was to adapt and validate the Health Utilities Index Mark 2 (HUI 2) and HUI 3 health status classification systems self-report questionnaire in a population of children with cancer, a group of 42 children already included in a multi-centre database designed by the Group on Brain Tumors in Children of the French Society for Pediatric Oncology. Children were recruited during a routine consultation. Most of them had completed treatment. The version of the questionnaire for French adults was adapted linguistically for children. Open-ended queries by children about the comprehensiveness of the questions and very low non-response rates showed a good acceptability of the questionnaire. The main psychometric properties of the HUI 2 and HUI 3 classification systems were assessed in 3 groups of raters (child, parent, physician): construct validity was tested against the rating of the child's health state on a Likert scale and through comparison with clinical data, and internal consistency was determined through multi-trait analysis. Weighted and unweighted kappa values were used to measure the inter-rater agreement between the child's, parent's and physician's assessment of the child's health state. The convergent validity was satisfactory, with better results when the physician's assessment was used. The most affected attributes were the expected ones (i.e., cognition, pain and emotion). Disagreement was observed between the 3 raters, more often in the same direction: taking the child's assessment as the reference, the parents tended to under-estimate the health status while physicians tended to over-estimate it.

Social and economic aspects of osteoporosis.

The first part of this article draws together descriptive studies on the direct medical costs of osteoporosis. The second part is devoted to economic evaluation of 1) osteoporosis treatment on the basis of clinical criteria and 2) preventive strategies, some of them including bone mineral density screening. These analyses point out the importance of taking into account quality of life and compliance issues. Research into dependency of the elderly has made it possible to obtain knowledge of the long-term economic consequences of osteoporosis. Development of research into dependency and its causes leads to the question as to whether the treatment and prevention of osteoporosis should be regulated in an isolated manner or whether it should be part of a larger health care policy with respect to aging.

French cross-cultural adaptation of the Health Utilities Indexes Mark 2 (HUI2) and 3 (HUI3) classification systems. Clinical and Economic Working Groups.

The McMaster Health Utilities Indexes Mark 2 (HUI2) and 3 (HUI3) are multiattribute health classification systems, for which multiattribute preference functions have been developed in Canada. They provide a comprehensive instrument for use in economic evaluations and population health survey studies. This paper reports on the first results on the adaptation of the HUI2 and HUI3 systems cross-culturally and the assessment of the validity and reliability of the French self-report questionnaire in different patient populations. The cross-cultural adaptation included translation, backtranslations, an expert consensus meeting and pre-test with a few patients and healthy subjects in order to produce a conceptually equivalent French version of the 15 question self-report questionnaire and the HUI2 and HUI3 classification systems. Different groups of patients attending specialized clinics (n = 709) completed the questionnaire and another generic questionnaire (the Sickness Impact Profile (SIP)) for validity assessment. Physicians and patients were also asked for a global subjective assessment of the patient's health status. The French questionnaire was well received by the patients. The criterion and convergent validities of both classification systems (correlations with the patients' and physicians' assessments and with the responses to the SIP questionnaire) were satisfactory. The internal consistency was acceptable too (Cronbach's alpha = 0.81), as was the 3 day test-retest reproducibility. These first results authorize careful use of the 15 question self-report questionnaire in French. An assessment of the multiattribute preference function for the HUI3 system in France will be the study's next objective.

[Conditions of use and access to care of sickle cell anemia patients. Analysis of the literature]. / Conditions d'usage et d'accès aux soins des drépanocytaires. Analyse de la littérature.

In order to identify the care access and life conditions and non-compliance risk factors of sickle-cell patients, we performed a literature survey on these subjects, and on other chronic pathologies and care systems used as references. The data showed a positive influence of good quality of life, social support and family environment on diabetes mellitus patients compliance, and the negative effect of poor socioeconomic status on adequate prenatal care. Concerning sickle-cell disease, there were few data on the non-compliance risk factors. However, the authors identified factors which influence the patient health status and showed the negative result of the disease on the quality of life of the patient and his family. A new study has been induced by these conclusions on the sickle-cell disease cohort of Guadeloupe reference center.

[Cost-effectiveness analysis of the treatment of chronic hepatitis C]. / Analyse coût-efficacité du traitement de l'hépatite chronique C.

OBJECTIVES: Chronic active hepatitis C is an important public health issue because of its prevalence, evolution, and overall cost. Treatment by recombinant alpha-interferon is both expensive and exacting and its effectiveness is limited. We report the results of a cost-effectiveness analysis of alpha-interferon treatment in patients with chronic active hepatitis C. METHODS: Direct medical costs of caring for patients with chronic active hepatitis C and its complications, based on treatment or no treatment, were assessed with retrospective data collected from the files of 137 hospital patients. Seventy-seven patients were treated with alpha-interferon between 1988 and 1994. The overall costs of caring for chronic active hepatitis C patients, without treatment or with alpha-interferon treatment (3 millions units three times a week) for 6 months (strategy A), 12 months (strategy B), or 12 months but discontinuing treatment when there was no response (strategy C), was reported and compared to the respective effectiveness of each. RESULTS: With an actualization rate of 5%, the real overall cost of caring for a chronic active hepatitis C patient was 143290 FF. Considering the contraindication rate (15%), the treatment acceptance (85%), the response rate to treatment (50%), and the prolonged response rate (25 to 30%), treating patients with strategy A induced a real overall cost of caring to 140731 FF to avoid 0.11 cases of cirrhosis, to 150277 FF to avoid 0.13 cases of cirrhosis with strategy B, and to 136947 FF to avoid 0.13 cases of cirrhosis with strategy C. CONCLUSION: Alpha-interferon treatment in patients with chronic active hepatitis C provides a long-term saving compared to cases which receive no treatment. Strategy C was the most cost-effective, inducing the reduction of both the number of cases of cirrhosis and the cost of care.

[Medical costs associated with the risk of maternal-fetal contamination by HIV. Results of a prospective survey]. / Coûts médicaux associés au risque de contamination maternofoetale par le VIH. Résultats d'une enquête prospective.

BACKGROUND: Assessment of economic implications of pediatric HIV infection allows to document efforts which are devoted by health care system to the care of children born to HIV infected women. This paper presents the results of the first analysis, in the French health care context, of direct medical costs related to HIV mother-to-child risk of transmission. MATERIAL AND METHODS: Statistical prospective analysis was performed on 853 files concerning 152 children followed in three medical centers. Because the medical consumptions data were linked to clinical status, average direct medical costs per medical contact could be defined for each center. RESULTS: Results were consistent with the hypothesis that more medical care is necessary when the clinical picture is uncertain (indeterminate status) or reflects health state deterioration. However, results are very different according to HIV clinical status and disparities may be so large that costs per clinical status hierarchy may be disrupted. Explicative factors for these variabilities are expressed in terms of patient recruitment, medical uncertainty management and resources disponibility.

[Economic analysis of neonatal screening for drepanocytosis in metropolitan France]. / Analyse économique du dépistage néonatal de la drépanocytose en France métropolitaine.

There is indisputable evidence that mortality and morbidity can be significantly reduced by programmes that screen newborns for sickle cell disease. But in the French epidemiological context, national decision regarding generalization of local screening programmes to all newborns must take into account economic considerations as at-risk populations represent, in most geographic areas, a few percent of the total population. Targeted screening can be considered but raises ethical and practical issues. In order to compare alternative screening strategies, a cost-effectiveness analysis has been performed. The analysis is based on a screening programme of newborns conducted in the south-eastern suburb of Paris. Strategies have been defined in terms of laboratory procedures (isoelectrofocalisation, electrophoresis on citrate agar, high pressure liquid chromatography, BIORAD technique,...) and methods for blood collection (dried paper, micro-tube). An evaluation of all the necessary costs have been performed for each strategy in the biochemistry laboratory in charge of the neonatal programme. Costs have been estimated from detailed observation of physical quantities of capital and labour involved in each case. Evolution of unit and marginal costs according to the level of annual production has been assessed. Effectiveness has been measured in terms of number of sickle cell cases detected. Screening of at-risk babies in Paris region would permit detection of 80 to 215 babies each year at a unit cost per case found varying from 1 to 2,800 US$ (according to hypothesis of prevalence). When compared with other programmes of prevention, results of selected screening of newborns in whole metropolitan France suggest that this action might be discussed by public health authorities.

Economic assessment of maternal serum screening for Down's syndrome using human chorionic gonadotropin.

The effectiveness and costs of prenatal screening programmes for Down's syndrome using maternal serum markers will vary significantly depending on the biological cut-off values chosen in order to select women, at each maternal age, who will be sent for amniocentesis. On the basis of the first French prospective study of human chorionic gonadotropin (hCG) measurement in maternal serum, this paper shows that the screening protocol currently used in France, where hCG cut-off values are defined in order to offer amniocentesis to women of all ages with a 1 per cent fetal risk of Down's syndrome, would detect 64.06 per cent of all cases of trisomy 21 at birth and would be highly profitable for the French social security system. On the basis of a representative sample of 100,000 pregnant women, the total costs of screening would reach $8,302,000 but would generate net potential savings of $32,186,000 in terms of life-long costs of care for trisomic 21 children which would be 'avoided' by termination of pregnancy following a positive diagnosis of Down's syndrome. Economic assessment shows that cost-benefit analysis would justify lower hCG cut-off values and a higher detection rate of fetal Down's syndrome (74.45 per cent) than the current French protocol. This paper concludes that it is ethical and value-laden issues, such as the consequences for women and couples of false positives and false negatives of screening, rather than economic and financial arguments that may set limits to the utilization of screening for Down's syndrome using maternal serum markers like hCG.

[Cost-benefit analysis of prenatal screening for trisomy 21 through analysis of HCG in maternal blood]. / Analyse coût-bénéfice du dépistage prénatal de la trisomie 21 par dosage de l'hCG sérique maternelle.

Introduction of maternal serum markers for prenatal screening of Down's syndrome implies a redefinition of the criteria used for identifying at risk women for screening by amniocentesis, which are currently based on maternal age. On the basis of the first French prospective study of human chorionic gonadotropin measurement in maternal serum as a predictor of Down's syndrome, this paper shows that a screening policy combining maternal age with hCG measurement was more cost-effective than one relying on maternal age alone. A cost-benefit analysis (using the "avoided" lifelong costs of care for a trisomic 21 child that are allowed by prenatal screening) would justify lower hCG cut-off values and an higher detection rate of Down's syndrome (74.5%) than other decision rules based on alternative principles such as: equalization to 1% of fetal risk of Down's syndrome for access to amniocentesis at all maternal ages or equalization to 1/1000 of fetal risk of Down's syndrome among women not undergoing amniocentesis. However, results of the cost-benefit analysis are very sensitive to other factors such as the cost associated with loss of a normal fetus due to iatrogenic risk of amniocentesis (false positives of hCG). Ethical and value-laden issues that necessarily underlie economic evaluation of screening programmes, as well as other decision rules based on equalization of acceptable risk for each maternal age, are discussed.

[Cost effectiveness analysis of prenatal screening of trisomy 21 by maternal serum markers (hCG)]. / Analyse coût-efficacité du dépistage prénatal de la trisomie 21 par marqueur sérique maternel (le cas de l'hCG).

Introduction of maternal serum markers for prenatal screening of Down's syndrome leads to a redefinition of the criteria used for identifying at risk women (i.e. in France, mainly based on maternal age of 38 and over). Effectiveness and costs of prenatal screening of Down's syndrome using such maternal serum markers will vary depending on the biological cut-off values defined, at each maternal age, to identify the population of pregnant women that will be sent to amniocentesis. On the basis of the first French prospective study of the use of human chorionic gonadotropin (hCG) measurement in maternal serum as a predictor of an increased risk of Down's syndrome, this paper shows that a screening policy combining maternal age with hCG measurement is more cost-effective than screening on the basis of maternal age alone. However, final decisions about hCG cut-off values should take into account the complex ethical dilemmas involved, especially the potential consequences of "false positives" and "false negatives", of this marker.

[Economic evaluation of interventions in public health: potentials and limitations]. / L'évaluation économique des interventions en santé publique: principes et limites.

One of the main principles of economic evaluation refers to the scarcity of resources. So, choices must and will be made concerning the commitment of these resources to one use instead another. Economic evaluation can assume different methodological forms regarding the kind and complexity of programme to be assessed and the issue of outcome valuation, but each analytic technique compares the resources consumed by different relevant alternatives with the health improvements and other consequences arising from them. From a pragmatic point of view, four types of economic evaluation can be distinguished associated with different measurement and valuation of consequences: cost-minimization, cost-effectiveness, cost-utility and cost-benefit analysis. A first step of economic appraisal is definition and description of each competing alternative. Then, there are difficulties associated with measurement and valuation of both costs and effectiveness of alternatives. The assessment of public health interventions poses some special problems in terms of time profiles of cost and consequences. Most of the costs of a health programme incurred in the present while benefits will come later in the future. Therefore, cost and consequences must be discounted to reflect the existence of time preference. The last important point concerns the assessment of health consequences. Ideally, evaluation of efficacy takes the form of a well controlled randomized trial designed for this purpose. But, in many situations, this approach is not relevant, appropriate or feasible and efficacy appraisal must be developed on the basis of available data and "realistic" assumptions. So, every evaluation will contain some degree of uncertainty or imprecision and a sensibility analysis must be performed in order to test sensitivity of the results to alternative assumptions and uncertainty.

Cost-effectiveness of HIV screening of pregnant women in hospitals of the Paris area. The Paris-Tours study group of antenatal transmission of HIV, Group '9 maternites'.

In the context of an epidemiologic multicentric study about perinatal transmission of HIV, screening was systematically proposed to all pregnant women attending nine maternities clinics of the Paris region (n = 7600, between August 1987 and July 1988) at their first prenatal visit. Among them, 2145 had already been tested and 45 were known to be HIV positive. So, 5660 tests were performed during the first 6 months (period 1), and 17 pregnant women were discovered to be positive. The total cost of screening has been estimated between FF. 720,000 and 775,000, resulting in a mean cost per pregnant woman found to be HIV positive of about FF. 42,000 to 45,000. A similar calculation over the following 5 months (period 2) gave a mean cost of between FF. 165,000 and 178,000. Since the women, before being screened, had to answer a short questionnaire about risk factors; cost and effectiveness of a selective screening strategy could be simulated. The preference of systematic screening to selective screening enabled the discovery of two HIV positive cases in each period, the marginal cost, i.e., cost per extra pregnant woman found to be HIV positive was thus FF. 303,320 to 327,540 for period 1, and FF. 572,240 to 619,000 for period 2. Although these figures seem high, an estimation of the cost-effectiveness does not allow us to conclude whether it is in society's interest to devote the funds necessary to move away from selective screening towards systematic screening.(ABSTRACT TRUNCATED AT 250 WORDS)

Socio-cultural inequities in access to prenatal diagnosis: the role of insurance coverage and regulatory policies.

The article presents the results of a 4-month-period survey by questionnaire among all women attending the Marseille Centre for Prenatal Diagnosis for amniocentesis. Socio-cultural status of women getting access to amniocentesis is significantly higher than in the general population of pregnant women in the same geographic area of south-eastern France. Socio-cultural status is also higher among women who have to cover costs of procedure to get access to amniocentesis than among those who benefit from it free-of-charge according to French Social Security regulations. In contrast, risk perception and attitudes toward termination of pregnancy are similar in these two groups. A total of 24.4 per cent of respondents declared that they got access to amniocentesis 'on their own initiative', the remaining 75.6 per cent declaring that they 'were following medical advice'. Multidimensional analysis shows that the women who do not benefit from free-of-charge amniocentesis, and who have a high level of education and no antecedents of fetal and perinatal deaths, are more likely to perceive themselves as 'self-referring'. The study indicates that institutional coverage may be effective in reducing socio-cultural inequities in access to prenatal diagnosis. But such a policy may conflict with the respect of women's individual autonomy in the amniocentesis decision.

Searching for consensus through multi-criteria decision analysis. Assessment of screening strategies for hemoglobinopathies in southeastern France.

Until now, no systematic strategy for the prevention of major hemoglobinopathies has been implemented in southeastern France, in spite of frequencies of beta-thalassemia trait and HbS trait as high as 2.5-8% in some ethnic populations. The purpose of the study was to help a group of experts, brought together by the Regional Center for Disease Control, to reach a consensus about screening for carriers of heterozygote hemoglobinopathies. A multicriteria decision-analysis model was used to take into account not only the costs and effectiveness of potential screening strategies, but also five other qualitative criteria: technical and practical feasibilities, ethical acceptability, information follow-up in time, and global impact on health education. Conclusions differ significantly from those of a pure cost-effectiveness analysis, but a multicriteria approach seems best suited to medical experts' preferences.

[Cost-benefit analysis of amniocentesis in the prenatal diagnosis of chromosome abnormalities]. / Analyse coût-bénéfice du diagnostic prénatal des anomalies chromosomiques par amniocentèse.

The article presents a cost-benefit analysis of amniocentesis for detection of chromosomal anomalies based on data (1985/87) collected in the Marseille area. In this geographic area, it is possible to confront, in an exhaustive manner, pregnant women's access to amniocentesis and incidence of fetal anomalies due to chromosomal aberrations. Results show that prenatal diagnosis is highly cost-beneficial, the average cost of one "avoided" case of Down's syndrome being lower than the lifelong costs of care for such a child. However, the study emphasizes that the cost-benefit ratio is highly sensitive to the implicit value society affects to the loss of "normal" fetuses through spontaneous abortions provoked by amniocentesis and because of terminations of pregnancy following diagnosis of minor fetal anomalies. The study also shows that lowering maternal age limit for access to free-of-charge amniocentesis from the current 38 years of age to 35 would have been cost-beneficial. Such lowering of the maternal age limit is discussed and compared with other indications which might be used for systematic access to amniocentesis.