A generally applicable cost-effectiveness model for the evaluation of vaccines against cervical cancer

OBJECTIVE: This study aimed at evaluating the cost-effectiveness of human papillomavirus virus (HPV) vaccination in France, using a generally applicable succinct cohort model. METHODS: A lifetime Markov cohort model, adapted to the French setting, simulate the natural history of oncogenic HPV infection towards cervical cancer (CC). Additional modules account for the effects of screening and vaccination. The girls’ cohort is vaccinated at age 12 and follows current screening. Costs and outcomes (discounted at 3 and 1.5%, respectively) were compared with a cohort receiving screening alone. RESULTS: The model results agreed well with real-life data. Vaccination in addition to screening would substantially reduce the incidence of and mortality from CC, compared with screening alone, at an estimated cost-effectiveness of €9,706 per quality-adjusted-life-year. Sensitivity analysis showed that the discount rate and the parameters related to the disease history have the largest impact on the results. CONCLUSION: This succinct cohort model indicated that HPV vaccination would be a cost-effective policy option in France. It uses readily available data and should be generally applicable to the evaluation of HPV vaccination in a variety of countries and settings

Cost-effectiveness of alectinib compared to crizotinib for the treatment of first-line ALK+ advanced non-small-cell lung cancer in France.

The aim of the study is to evaluate the cost-effectiveness of alectinib for first-line treatment of ALK+ advanced non-small-cell lung cancer compared to crizotinib in the French setting. This study used a partitioned survival model, with three discrete health states (progression-free survival, post-progression survival and death). Survival probabilities were derived from a randomised Phase III clinical trial comparing alectinib to crizotinib (ALEX). Beyond the length of the trial (18 months), the efficacy of both treatments was considered equivalent. Occurrence of adverse events or brain metastases were considered as inter-current events. Utilities (and disutilities for intercurrent adverse events) derived from the EQ-5D were applied. Costs were attributed using standard French national public health tariffs. Projected mean overall survival was 4.62 years for alectinib and 4.18 years for crizotinib. Projected mean progression-free survival was 30.30 months for alectinib and 16.13 months for crizotinib. The total number of quality-adjusted life years projected was 3.40 for alectinib and 2.84 for crizotinib. The projected total cost of treatment over the lifetime of the model was € 246,022 for alectinib and € 195,486 for crizotinib. This extra cost was principally attributable to treatment acquisition costs and management before progression. Alectinib was associated with lower costs related to brain metastases and to management post-progression. The incremental cost per life year gained was 115,334 €/year and the incremental cost-effectiveness ratio was 90,232 €/QALY. First-line treatment of ALK+ NSCLC with alectinib provides superior clinical outcomes to crizotinib and is cost-effective in the French context

Cost-effectiveness analysis of vaccination against rotavirus with RIX4414 in France.

International audienceBACKGROUND: It is estimated that annually 300 000 cases of rotavirus-induced gastroenteritis (RVGE) occur in children aged up to 5 years in France. A two-dose vaccine against rotavirus infection (RIX4414; Rotarix, GlaxoSmithKline), has been shown to be highly effective against severe RVGE. OBJECTIVE: This study evaluated the cost effectiveness of general vaccination against rotavirus using RIX4414 in France. METHODS: A Markov model simulated RVGE events and the associated outcomes and costs relating to general vaccination of infants against rotavirus infection using RIX4414 (Rotarix) in a birth cohort of children aged up to 5 years in France with a combined adjustment for age distribution with the seasonality of the infection. Costs and outcomes were estimated from a limited societal perspective, including direct medical costs paid out of pocket or by third-party payers, as well as the proportion of direct medical costs reimbursed by the health authorities. Indirect costs were not included in the base-case analysis. The primary outcome measure was the incremental cost per QALY. RESULTS: Vaccination with RIX4414 incurred an incremental cost of 44 583 Euro per QALY at a public price of 57 Euro per vaccine dose. Univariate sensitivity analyses showed that the parameters with the largest influence on the results were the transition probabilities of severe diarrhoea, seeking medical advice and emergency visits, utility scores of diarrhoea (mild) in children and infants, and the discount rate for benefits. Probabilistic multivariate sensitivity analysis confirmed these results. The acceptability curve indicated that 94% of the results were under an informal threshold of 50 000 Euro per QALY. Comparing our results with those of a recently published study using pooled data for two rotavirus vaccine products in France, the main differences are explained by differences in model structure and in data input values. They include a different age distribution of the infection, shorter duration of the at-risk period (3 years instead of 5 years), different vaccine efficacy, different unit cost data, different disease duration, and different disutility values for the health states in the model. There is a need for agreed standards to improve comparability of results from different studies. CONCLUSIONS: The results demonstrate that a generalized vaccination strategy with RIX4414 would be cost effective in France from a limited societal perspective, depending on the baseline assumptions for disease progression and on utility scores selected

Effect of physical activity on women at increased risk of breast cancer: results from the E3N cohort study.

PURPOSE: There is a need to investigate the type, duration, frequency, and intensity of physical activity that are critical to reduce the risk of breast cancer, and if this relation differs among subgroups of women.METHODS: We analyzed the relation between physical activity and breast cancer incidence between 1990 and 2002 (n=3,424 cases), among 90,509 women of the French E3N cohort, ages between 40 and 65 years in 1990. We gave special attention to effect modification by body mass index (BMI), family history of breast cancer, parity, and hormone replacement therapy (HRT).RESULTS: A linear decrease in risk of breast cancer was observed with increasing amounts of moderate (P(trend)<0.01) and vigorous (P(trend)<0.0001) recreational activities. Compared with women who reported no recreational activities, those with more than five weekly hours of vigorous recreational activity had a relative risk of 0.62 (0.49-0.78). This decrease was still observed among women who were overweight, nulliparous, had a family history of breast cancer, or used HRT. Compared with the whole cohort, among nulliparous women, the reduction of risk observed was of a higher magnitude, although the test for heterogeneity did not reach statistical significance.CONCLUSION: A risk reduction of breast cancer was particularly observed with vigorous recreational activity. Further investigations are needed to confirm that intensity is an important variable to consider in risk reduction and to identify the precise biological mechanisms involved in such a risk reduction

Cost-effectiveness of bevacizumab plus paclitaxel versus paclitaxel for the first-line treatment of HER2-negative metastatic breast cancer in specialist oncology centers in France

Abstract Background Evidence from clinical trials suggests that the addition of bevacizumab to chemotherapy in the first-line treatment of patients with HER2-negative metastatic breast cancer improves progression-free survival (PFS) but not overall survival (OS). However, a retrospective analysis of real-world data from the French Comprehensive Cancer Centers (FCCC) through the Epidemiological Strategy and Medical Economics (ESME) Research Program, suggested that in this setting, the addition of bevacizumab may confer a significant benefit in terms of both PFS and OS. A cost-effectiveness analysis was performed to determine the cost-effectiveness of bevacizumab plus paclitaxel versus paclitaxel alone in the first-line treatment of HER2-negative metastatic breast cancer at specialist oncology centers in France. Methods The analysis was performed using a three-state Markov model and clinical input data from N = 3426 HER2-negative metastatic breast cancer patients treated with bevacizumab plus paclitaxel or paclitaxel alone. The analysis was performed from a third party payer perspective over a 10-year time horizon; future costs and clinical outcomes were discounted at 4% per annum. Results In the overall population, the addition of bevacizumab to paclitaxel led to incremental gain of 0.72 life years and 0.48 quality-adjusted life years (QALYs) relative to paclitaxel alone. The incremental lifetime cost of the addition of bevacizumab was EUR 27,390, resulting in an incremental cost-effectiveness ratio (ICER) of EUR 56,721 per QALY gained for bevacizumab plus paclitaxel versus paclitaxel alone. In a subgroup of triple negative patients the ICER was EUR 66,874 per QALY gained. Conclusions The analysis indicated that the combination of bevacizumab plus paclitaxel is likely to be cost-effective compared with paclitaxel alone for the first-line treatment of HER2-negative metastatic breast cancer in specialized oncology centers in France

Anthropometric measurements and body silhouette of women: validity and perception.

International audienceOBJECTIVE: To examine the validity of self-reported values for current anthropometric measurements and factors related to misreporting. DESIGN: E3N, a prospective cohort study of cancer risk factors, conducted in France and part of the European Prospective Investigation on Cancer. E3N comprises 100,000 women, born between 1925 and 1950, followed with self-administered questionnaires sent every 18 to 24 months starting in 1990. SUBJECTS: 152 women for the validation study of self-reported anthropometric measurements, and 91,815 women selected to evaluate factors affecting misreporting of body silhouette. STATISTICAL ANALYSIS: Paired t tests, Pearson and Spearman correlations were applied to evaluate the validity of self-reported measures, and analysis of variance and logistic regression were used to assess the factors influencing misreporting of silhouette. RESULTS: The correlation coefficients between self- and external measurements were high. All but sitting height (r = 0.56) were more than 0.80, with weight and bust (nipples) measurement correlation coefficients attaining 0.94. The correlation between body mass index (BMI), measured by the technician and the self-reported silhouette, was 0.78. Small height was always associated with misclassification. Specific factors related to a more favorable perception of body silhouette were: being overweight, small height, younger age, and a lower level of education. These women were also more frequently unmarried, more physically active, and had had a slender body shape during adolescence. Results denoting a less favorable perception of body shape were reversed. CONCLUSION/APPLICATIONS: Self-reported measurements (made with or without help) are valid measures in epidemiological studies. Body silhouettes are simple and useful indicators of body mass index. However they should be interpreted with caution in certain instances, especially for overweight subjects

Alcohol and genetic polymorphisms: effect on risk of alcohol-related cancer

International audiencePublic health guidelines aim to limit the consumption of alcoholic beverages worldwide and the subsequent health burden. In particular, alcohol consumption is an avoidable risk factor for cancer. In human beings, ethanol in alcoholic drinks is mainly oxidised in the liver by alcohol dehydrogenases to acetaldehyde, and is further detoxified to acetate by aldehyde dehydrogenases. Functional variants in genes involved in alcohol metabolism result in differences between individuals in exposure to carcinogenic acetaldehyde, suggesting a possible interaction of genetic susceptibility and alcohol exposure in cancer. We reviewed available studies of the combined effects of alcohol drinking and genetic polymorphisms on alcohol-related cancer risk. Most available data were for polymorphisms in alcohol and folate metabolism. We give an overview of published studies on the combined effects of alcohol drinking and polymorphisms in genes for alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), cytochrome P450 2E1, and methylene-tetrahydrofolate reductase on the risk of alcohol-related cancer. Current data lend support to a role of polymorphisms ADH1B and ALDH2 combined with alcohol consumption in cancer. Other available data are insufficient or inconclusive, highlighting the need for additional studies

Comparison of two physical activity questionnaires in obese subjects:the NUGENOB study

PURPOSE: Simple instruments are needed to assess habitual physical activity (PA) in obese subjects. In a multicenter European obesity project, we tested whether PA assessments by two questionnaires were correlated and similarly associated to selected obesity-related variables. METHODS: A total of 757 obese subjects (75% female; age 37.1 [7.9] yr, BMI 35.5 [4.9] kg.m(-2), mean [SD]) completed the Baecke questionnaire (assessing work, sport, and nonsport leisure activity) and the short last 7-d version of the International Physical Activity Questionnaire (IPAQ; assessing vigorous, moderate-intensity, walking activity, and sitting). We assessed percent body fat (bioimpedance), waist circumference, and fasting plasma concentrations of glucose, insulin, leptin, and FFA. Insulin sensitivity was assessed by the HOMA index for insulin resistance (HOMAIR). RESULTS: Using the IPAQ, only about one third of men and women were classified as insufficiently active. Total habitual PA assessments by the Baecke and IPAQ were significantly related (Spearman rho = 0.51 in total sample, P < or = 0.0001, with adjustment for age, gender, and center). Using principal component analysis, we built two uncorrelated indices corresponding to general obesity (determined by high body fat and leptin) and abdominal obesity (determined by high waist circumference and HOMAIR). PA scores from both questionnaires were negatively related to general and abdominal obesity indices, except for abdominal obesity with the IPAQ in men. CONCLUSIONS: Total PA assessments by the two questionnaires were found to correlate significantly, and the general pattern of associations of PA with general obesity was similar for the two questionnaires. However, the IPAQ may capture less of the relationships between PA and abdominal obesity than the Baecke, especially in men. Reporting of habitual PA in obese subjects with the IPAQ warrants further evaluation against objective assessment methods

Growth, keratinolytic proteinase activity and thermotolerance of dermatophytes associated with alopecia in Uyo, Nigeria

Mycological research was conducted on the mycelial growth, keratinolytic proteinase activity and thermotolerance of dermatophytes associated with alopecia patients in Uyo, Nigeria. The results revealed that Microsporum sp. — AP1 , Epidermophyton sp. — AP2 , Trichophyton rubrum — AP4 , Trichophyton mentagrophytes — AP5 and a yeast Candida albicans — AP3 isolated exhibited variable growth and keratinase activity at different temperatures. Microsporum sp. — AP1 and T. mentagrophytes — AP5 survived heat treatment at 90 °C but exhibited best mycelial growth at 30 °C (with 53.41 mg/50 ml biomass dry weight) and 40 °C (with 61.32 mg/50 ml biomass dry weight) respectively, after incubation for 2 weeks. Trichophyton rubrum — AP4 and Epidermophyton sp. — AP2 could not survive heat treatment at 90 °C but grew better at 40 °C (with 38.52 mg/50 ml biomass dry weight) and 30 °C (with 48.32 mg/50 ml biomass dry weight) respectively, over the same incubation period, while C. albicans — AP3 grew better at 30 °C with 38.7 mg/50 ml biomass dry weight after 2 weeks, but failed to survive at 70 °C. All the isolates except Candida albicans — AP3 survived at 80 °C and exhibited great potential to elaborate keratinolytic enzymes, with T. mentagrophytes demonstrating the best potential at 30 °C and 40 °C. Higher temperatures tended to reduce keratinolytic activities and there were significant (P <0.05) relationships between biomass weight and enzyme productivities of all the isolates except T. mentagrophytes . This indicates that in some dermatophytes keratinolytic proteinase activity is not a function of cell multiplicity. This plus the high thermostability of the enzymes are important attributes in the consideration of preventive and therapeutic methods against dermatophytes in the tropics