Use of high dose cyproterone acetate and risk of intracranial meningioma in women: cohort study.

OBJECTIVE: To assess the risk of meningioma associated with use of high dose cyproterone acetate, a progestogen indicated for clinical hyperandrogenism. DESIGN: Observational cohort study. SETTING: Data from SNDS, the French administrative healthcare database, between 2007 and 2015. PARTICIPANTS: 253 777 girls and women aged 7-70 years living in France who started cyproterone acetate between 2007 and 2014. Participants had at least one reimbursement for high dose cyproterone acetate and no history of meningioma or benign brain tumour, or long term disease status. Participants were considered to be exposed when they had received a cumulative dose of at least 3 g during the first six months (139 222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114 555 participants). 10 876 transgender participants (male to female) were included in an additional analysis. MAIN OUTCOME MEASURE: Surgery (resection or decompression) or radiotherapy for one or more intracranial meningiomas. RESULTS: Overall, 69 meningiomas in the exposed group (during 289 544 person years of follow-up) and 20 meningiomas in the control group (during 439 949 person years of follow-up) were treated by surgery or radiotherapy. The incidence of meningioma in the two groups was 23.8 and 4.5 per 100 000 person years, respectively (crude relative risk 5.2, 95% confidence interval 3.2 to 8.6; adjusted hazard ratio 6.6, 95% confidence interval 4.0 to 11.1). The adjusted hazard ratio for a cumulative dose of cyproterone acetate of more than 60 g was 21.7 (10.8 to 43.5). After discontinuation of cyproterone acetate for one year, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group. In a complementary analysis, 463 women with meningioma were observed among 123 997 already using cyproterone acetate in 2006 (risk of 383 per 100 000 person years in the group with the highest exposure in terms of cumulative dose). Meningiomas located in the anterior skull base and middle skull base, particularly the medial third of the middle skull base, involving the spheno-orbital region, appeared to be specific to cyproterone acetate. An additional analysis of transgender participants showed a high risk of meningioma (three per 14 460 person years; 20.7 per 100 000 person years). CONCLUSIONS: A strong dose-effect relation was observed between use of cyproterone acetate and risk of intracranial meningiomas. A noticeable reduction in risk was observed after discontinuation of treatment.

Early detection and curative treatment of hepatocellular carcinoma: A cost-effectiveness analysis in France and in the United States.

Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis. Patients outside clinical trials seldom benefit from evidence-based monitoring. The objective of this study was to estimate the cost-effectiveness of complying with HCC screening guidelines. The economic evaluation compared surveillance of patients with cirrhosis as recommended by the guidelines ("gold-standard monitoring") to "real-life monitoring" from the health care system perspective. A Markov model described the history of the disease and treatment course including current first-line curative treatment: liver resection, radiofrequency ablation (RFA), and liver transplantation. Transition probabilities were derived mainly from two French cohorts, CIRVIR and CHANGH. Costs were computed using French and U.S. tariffs. Effectiveness was measured in life years gained (LYG). An incremental cost-effectiveness ratio (ICER) was calculated for a 10-year horizon and tested with one-way and probabilistic sensitivity analyses. The cost difference between the two groups was $648 ($87,476 in the gold-standard monitoring group vs. $86,829 in the real-life monitoring group) in France and $11,965 ($93,795 vs. $81,829) in the United States. Survival increased by 0.37 years (7.18 vs. 6.81 years). The ICER was $1,754 per LYG in France and $32,415 per LYG in the United States. The health gain resulted from earlier diagnosis and access to first-line curative treatments, among which RFA provided the best value for money. CONCLUSION: Our results indicate that gold-standard monitoring for patients with cirrhosis is cost-effective, attributed to a higher probability of benefiting from a curative treatment and so a higher survival probability. (Hepatology 2017;65:1237-1248).

Cost Effectiveness of Free Access to Smoking Cessation Treatment in France Considering the Economic Burden of Smoking-Related Diseases.

CONTEXT: In France more than 70,000 deaths from diseases related to smoking are recorded each year, and since 2005 prevalence of tobacco has increased. Providing free access to smoking cessation treatment would reduce this burden. The aim of our study was to estimate the incremental cost-effectiveness ratios (ICER) of providing free access to cessation treatment taking into account the cost offsets associated with the reduction of the three main diseases related to smoking: lung cancer, chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). To measure the financial impact of such a measure we also conducted a probabilistic budget impact analysis. METHODS AND FINDINGS: We performed a cost-effectiveness analysis using a Markov state-transition model that compared free access to cessation treatment to the existing coverage of €50 provided by the French statutory health insurance, taking into account the cost offsets among current French smokers aged 15-75 years. Our results were expressed by the incremental cost-effectiveness ratio in 2009 Euros per life year gained (LYG) at the lifetime horizon. We estimated a base case scenario and carried out a Monte Carlo sensitivity analysis to account for uncertainty. Assuming a participation rate of 7.3%, the ICER value for free access to cessation treatment was €3,868 per LYG in the base case. The variation of parameters provided a range of ICER values from -€736 to €15,715 per LYG. In 99% of cases, the ICER for full coverage was lower than €11,187 per LYG. The probabilistic budget impact analysis showed that the potential cost saving for lung cancer, COPD and CVD ranges from €15 million to €215 million at the five-year horizon for an initial cessation treatment cost of €125 million to €421 million. CONCLUSION: The results suggest that providing medical support to smokers in their attempts to quit is very cost-effective and may even result in cost savings.

Annual cost of stable coronary artery disease in France: A modeling study.

BACKGROUND: Few studies have analyzed the cost of treatment of chronic angina pectoris, especially in European countries. AIM: To determine, using a modeling approach, the cost of care in 2012 for 1year of treatment of patients with stable angina, according to four therapeutic options: optimal medical therapy (OMT); percutaneous coronary intervention with bare-metal stent (PCI-BMS); PCI with drug-eluting stent (PCI-DES); and coronary artery bypass graft (CABG). METHODS: Six different clinical scenarios that could occur over 1year were defined: clinical success; recurrence of symptoms without hospitalization; myocardial infarction (MI); subsequent revascularization; death from non-cardiac cause; and cardiac death. The probability of a patient being in one of the six clinical scenarios, according to the therapeutic options used, was determined from a literature search. A direct medical cost for each of the therapeutic options was calculated from the perspective of French statutory health insurance. RESULTS: The annual costs per patient for each strategy, according to their efficacy results, were, in our models, €1567 with OMT, €5908 with PCI-BMS, €6623 with PCI-DES and €16,612 with CABG. These costs were significantly different (P<0.05). A part of these costs was related to management of complications (recurrence of symptoms, MI and death) during the year (between 3% and 38% depending on the therapeutic options studied); this part of the expenditure was lowest with the CABG therapeutic option. CONCLUSION: OMT appears to be the least costly option, and, if reasonable from a clinical point of view, might achieve appreciable savings in health expenditure.

Evaluating structured care for diabetes: can calibration on margins help to avoid overestimation of the benefits? An illustration from French diabetes provider networks using data from the ENTRED Survey.

OBJECTIVE: While there is growing evidence on the effectiveness of structured care for diabetic patients in trial settings, standard population level evaluations may misestimate intervention benefits due to patient selection. In order to account for potential biases in measuring intervention benefits, we tested the impact of calibration on margins as a novel adjustment method in an evaluation context compared with simple poststratification. RESEARCH DESIGN AND METHODS: We compared the results of a before-after evaluation on HbA1c levels after 1 year of enrollment in a French diabetes provider network (DPN) using an unadjusted sample and samples adjusted by simple poststratification to results obtained after adjustment via calibration on margins to the general diabetic population's characteristics using a national cross-sectional sample of diabetic patients. RESULTS: Both with and without adjustment, patients in the DPN had significantly lower HbA1c levels after 1 year of enrollment. However, the reductions in HbA1c levels among the adjusted samples were 22-183% lower than those measured in the unadjusted sample, regardless of the poststratification method and characteristics used. Compared with simple poststratification, estimations using calibration on margins exhibited higher performance. CONCLUSIONS: Evaluations of diabetes management interventions based on uncontrolled before-after experiments may overestimate the actual benefit for patients. This can be corrected by using poststratification approaches when data on the ultimate target population for the intervention are available. In order to more accurately estimate the effect an intervention would have if extended to the target population, calibration on margins seems to be preferable over simple poststratification in terms of performance and usability.

Cost effectiveness of full coverage of the medical management of smoking cessation in France.

OBJECTIVE: To estimate the incremental cost effectiveness of full coverage of the medical management of smoking cessation from the perspective of statutory health insurance (SHI) in France. DESIGN AND POPULATION: Cost-effectiveness analysis based on a Markov state-transition decision analytic model was used to compare full SHI coverage of smoking cessation and actual coverage based on an annual €50 lump sum per insured person among current French smokers aged 15-75 years. We used a scenario approach to take into account the many different behaviours of smokers and the likely variability of SHI policy choices in terms of participation rate and number and frequency of attempts covered. INTERVENTIONS: Drug treatments for smoking cessation combined with six medical consultations including individual counselling. MAIN OUTCOMES MEASURES: The cost effectiveness of full coverage was expressed by the incremental cost-effectiveness ratio (ICER) in 2009 euros per life-year gained (LYG) at the lifetime horizon. RESULTS: The cost effectiveness per LYG for smokers ranged from €1786 to €2012, with an average value of €1911. The minimum value was very close to the maximum value with a difference of only €226. The cost-effectiveness ratio was only minimally sensitive to the participation rate, the number of attempts covered and the cessation rate. CONCLUSIONS: Compared to other health measures in primary and secondary prevention of cardiovascular disease already covered by SHI, full coverage of smoking cessation is the most cost-effective approach.

Cost of transcatheter aortic valve implantation and factors associated with higher hospital stay cost in patients of the FRANCE (FRench Aortic National CoreValve and Edwards) registry.

BACKGROUND: Currently, several anatomical approaches and intervention sites can be used to perform transcatheter aortic valve implantations (TAVIs), often with no clinical indications for choosing one or another. While these choices can have an impact on resource consumption, no costing study is available in the European context to provide information on resource use and assist decision-making. AIMS: To provide comparative data on the cost of the TAVI procedure, depending on anatomical approach and intervention site used, from a hospital perspective, and to analyze factors associated with cost of hospital stay. METHODS: Multicentre national registry data were collected in 16 centres between January and October 2009. For 287 patients, a descriptive costing study and a multivariable analysis of hospital stay cost were performed. RESULTS: The mean cost of the TAVI procedure was €22,876 and the mean initial hospital stay cost was €35,164. The procedure cost, excluding valve cost, did not differ between anatomical approaches and was highest in the hybrid room and lowest in the catheterization laboratory. Factors associated with higher hospital stay cost were transapical approach, Society of Thoracic Surgeons score>10%, warfarin use at inclusion, complications during procedure and pacemaker implantation following valve implantation. CONCLUSIONS: If clinical considerations do not interfere, hospital staff may find it economically favorable to opt for the catheterization laboratory and against the hybrid room. The mean hospital stay cost is higher than the tariff paid in 2011, a difference that has grown since the change in tariff in 2012, representing an economic disincentive for the uptake of TAVI in France.