Two year continuation rates of contraceptive methods in France: a cohort study from the French national health insurance database.

OBJECTIVE: The aim of this study was to evaluate the continuation rates of reimbursed contraceptive methods in French real-world conditions. METHODS: A retrospective cohort study using a representative sample of the national health insurance database, the General Sample of Beneficiaries (Echantillon Généralistes des Bénéficiaires [EGB]), was performed between 2006 and 2012. Selected women were ≥15 years of age and had started a reimbursed contraceptive method between 2009 and 2012 without prior reimbursement for an implant or an intrauterine contraceptive method between 2006 and 2008. The outcome of interest was the continuation rates, defined as the probability of women initiating a contraceptive method and continuing to use the same method over time. Continuation rates were assessed for up to 2 years. Only the first contraceptive method used during the study period was considered in the analysis. Non-parametric Kaplan-Meier survival analysis was used to assess continuation rates. RESULTS: A population of 42,365 women representative of the 4,109,405 French women initiating any reimbursed method between 2009 and 2012 was identified in the EGB: 74.5% of women used oral contraceptives, 12.8% the levonorgestrel-releasing intrauterine system (LNG-IUS), 9.2% the copper intrauterine device (Cu-IUD) and 3.5% the subdermal etonogestrel (ENG) implant. The 2 year continuation rates varied from 9.1% for progestin-only oral contraceptives, 27.6% for first to second generation combined oral contraceptives (COCs) and 33.4% for third generation COCs to 83.6% for the ENG implant, 88.1% for the Cu-IUD and 91.1% for the LNG-IUS. CONCLUSION: This study conducted in real-world conditions showed that long-acting reversible contraceptive (LARC) methods remain rarely used in France despite high continuation rates over 2 years. Increasing the use of LARC methods is therefore a public health priority.

[Cost-effectiveness analysis of aripiprazole once-monthly versus paliperidone palmitate once-monthly in the treatment of schizophrenia in France]. / Analyse coût-efficacité de l'aripiprazole injectable à libération prolongée (AILP) comparé au palmitate de palipéridone (PP) dans le traitement de la schizophrénie en France.

OBJECTIVE: The aim of the study was to estimate the cost-effectiveness ratio of aripiprazole once-monthly compared to once-monthly injectable paliperidone palmitate in the treatment of schizophrenia in France on the basis of results and data from the QUALIFY study. METHODS: Consumed resources data measured with a dedicated questionnaire and results on the quality of life scales from the QUALIFY study were combined with French standard unit costs of each collected consumed resources during QUALIFY to estimate the cost-effectiveness ratios of the two products. Multivariate sensitivity analyses were performed to test the combined impact of the different assumptions. RESULTS: Findings of the study showed greater efficacy on the quality of life (QLS) and psychiatric evaluation scales (CGI-S and CGI-I) observed in QUALIFY of aripiprazole compared with paliperidone palmitate. Findings also suggest a trend (P=0.0733) in the reduction of total costs linked to a statistical decrease (P<0,0001) in drug costs in the aripiprazole group. These findings are reinforced by the probabilistic sensitivity analyses. CONCLUSION: Aripiprazole appeared to be more cost-effective than paliperidone palmitate in the French context. Limits of this study are mainly related with the duration of the clinical trial and to assumptions on the transposability of measured consumed resources in the international clinical trial to the French healthcare system.

Transforming scales of measurement of visual acuity at the group level.

AIM: To provide formulae that may be used to transform sample-based estimates of group-level mean and standard deviation of visual acuity (VA) across different scales of measurement. METHODS: We focused on 3 transformations: (1) ETDRS letters - LogMAR (2) Decimal - LogMAR and (3) Snellen - LogMAR. We assumed that logMAR follows a normal distribution in the underlying population and used the empirical asymptotic normal approximation of the joint distribution of average and standard deviation in order to derive formulae for transformation of group-level estimates. We considered that the true population parameters are not known and are to be estimated using data from a sample of patients (which is essentially always the case). We compared estimates obtained with the proposed sample-based approach with those based on a "naïve" approach in which individual-level formulae are used directly for transformation of means and standard deviations at the group-level. RESULTS: Applying formulae that are appropriate for transformations of scales of measurement for data at the individual- (or patient-) level, to transform VA at the group level, can lead to biased estimates of means and standard deviations. In particular, it could lead to underestimation of the average logMAR VA in studies that use decimal VA. Such bias will be greater in magnitude when disease strongly affects VA. CONCLUSIONS: This paper provides formulae that can be easily implemented in standard spreadsheet software programs, and which allow appropriate transformations of group-level estimates of mean and standard deviation of VA across different scales of measurement. These transformations are helpful for performing meta-analyses or for comparisons of results across studies when VA is expressed in different units.

Modelling lifetime cost consequences of toric compared with standard IOLs in cataract surgery of astigmatic patients in four European countries.

OBJECTIVE: To compare the lifetime costs of freeing astigmatic patients from spectacles after bilateral cataract surgery implanting toric intraocular lenses (IOLs: i.e., Acrysof Toric) versus monofocal IOLs, in France, Italy, Germany and Spain. METHODS: A Markov model followed patient cohorts from cataract surgery until death. Prevalence rates of patients not needing spectacles and the types of spectacles prescribed for those requiring them were obtained from clinical trials and national surveys. The economic perspective was societal. Mortality rates were incorporated into the model. Discount rates were applied. A sensitivity analysis was performed on non-discounted costs. RESULTS: Fewer patients with toric IOLs needed spectacles for distance vision than patients with monofocal IOLs. With monofocal IOLs more than 66% of patients needed complex spectacles compared to less than 25% implanted with toric IOLs. In France and Italy, toric IOLs reduced overall costs relative to otherwise high spectacle costs after cataract surgery. Savings were 897.0 euros (France), 822.5 euros (Germany), 895.8 euros (Italy) and 391.6 euros (Spain), without discounting. On applying a 3% discount rate the costs became 691.7 euros, 646.4 euros, 693.9 euros and 308.2 euros, respectively. CONCLUSIONS: Bilateral toric IOL implants in astigmatic patients decreased spectacle dependence for distance vision and the need for complex spectacles. The economic consequences for patients depended on the national spectacle costs usually incurred after cataract surgery.

Intermediate visual acuity without spectacles following bilateral ReSTOR implantation.

PURPOSE: This survey determined uncorrected visual acuity (VA) at near, intermediate, and far distances in cataract patients implanted with ReSTOR, and assessed patient satisfaction. METHODS: Consecutive cataract patients implanted bilaterally with ReSTOR were followed up at least 4 months. The Early Treatment Diabetic Retinopathy Study scale was used to measure VA for near (40 cm), intermediate (50, 60, and 70 cm), and distance vision, with VAs expressed in logMAR and adjusted for distance using Bennett's (1993) formula. Satisfaction was self-rated on a visual analogue scale ranging from 0 (poor) to 10 (high). RESULTS: Twenty-four consecutive patients (mean age 67.6 years) were operated upon by a single surgeon and followed up for a mean of 336.5 days after second eye surgery. Average postoperative VAs for uncorrected distance were 0.06 logMAR and intermediate VAs were 0.21 logMAR at both 50 cm and 60 cm and 0.22 logMAR at 70 cm. These levels of uncorrected intermediate VA would allow patients to read Word computer text in Times New Roman font 8 zoomed to 100%, at 70 cm from the monitor screen. The authors found that23/24 patients (96%) no longer wore spectacles. The remaining patient required correction for astigmatism as this refraction error is not yet correctable by ReSTOR. Average selfrated satisfaction was 8.54. CONCLUSIONS: In an everyday surgical practice, none of the studied bilateral ReSTOR cataract patients without astigmatism required spectacles when followed up 6 months or later. Intermediate VA was compatible with reading and led to high patient satisfaction.

[Impact on renal function of an early switch from conventional to liposomal amphotericin B formulation in the empirical treatment of fungal infections]. / Impact sur la fonction rénale d'un relais précoce de la formulation conventionnelle de l'amphotéricine B par sa formulation liposomale dans le cadre d'un traitement empirique antifongique (Etude Nephemat).

OBJECTIVE: The authors had for aim to define the threshold of nephrotoxicity before switching to other antifungal treatment in hematological patients treated by conventional amphotericin B (AmB) as an empiric antifungal treatment. DESIGN: A prospective randomised multicenter study was made on 32 neutropenic hematological patients receiving conventional AmB for empirical antifungal treatment. The patients were randomised after a greater than or equal to 30% increase of serum creatinine (sCr). Patients in the early-switch group received liposomal AmB just after randomisation and patients in the late-switch group received liposomal AmB only when serum creatinine increase was greater or equal to 100% or sCr reached 170mumol/L. RESULTS: Thirty-one patients were analysed: 16 patients in the early-switch group and 15 patients in the late-switch group (seven switched to liposomal AmB and eight continued conventional AmB treatment). The mean age of patients was 48 years and 68% were men. The most frequent underlying haematological malignancy was acute leukemia (94%). In the late-switch group, the degradation of renal function continued after randomisation contrary to the early-switch group: median variations of calculated sCr clearance in early- and late-switch groups were -16.8 and -1.5%, respectively (P=0.03). Moreover, an early switch was cost-effective with a sCr lower duration of hospitalisation in comparison with a late switch. CONCLUSIONS: This randomised trial suggests that an early switch to Liposomal AmB improves and preserves renal function in comparison with a late switch.

Cost consequences of adjuvant capecitabine, Mayo Clinic and de Gramont regimens for stage III colon cancer in the French setting.

BACKGROUND/AIMS: To compare the cost consequences of oral capecitabine and two different intravenous regimens of 5-fluorouracil/folinic acid (de Gramont and Mayo Clinic regimens) as adjuvant therapy in stage III colon cancer in France. METHODS: Clinical efficacy and safety data were taken from published clinical trials. Medical resource use was estimated from published data and expert opinion. Direct costs (drug acquisition, inpatient and home drug administration, laboratory tests, transportation, and management of adverse events) were considered over a time horizon of 46 months (3.8 years). The perspective taken was that of the French Sickness Funds. RESULTS: In patients treated with capecitabine, relapse-free survival was 1.3 months longer than with the Mayo Clinic regimen, which has been shown to be as effective as the de Gramont regimen. In the base case analysis, capecitabine was less costly (3,654 EUR/patient) than the Mayo Clinic (10,481 EUR/ patient) and de Gramont (7,204 EUR/patient) regimens. In the sensitivity analysis, capecitabine remained dominant except when the intravenous regimens were assumed to be administered at home in all patients. CONCLUSIONS: In France, capecitabine is more effective and less costly than both the Mayo Clinic and de Gramont regimens as adjuvant therapy for colon cancer.

Costs of cardiovascular events of diabetic patients in the French hospitals.

AIMS: To test the assumption that hospital management of macro-vascular complications of Diabetes is more resource consuming in diabetic than in non-diabetic patients and to estimate, if relevant, the extra costs for diabetic patients. METHODS: The French national DRG database (PMSI- 2003) was analysed for the following cardio-vascular events (CVE): Stroke, Myocardial Infarction, Unstable Angina, Cardiac Arrest and Coronary Revascularization. Diabetic patients (Type 1 and 2) were identified using co-morbidity diagnosis. Differences in various indicators of resource consumption were tested between diabetic and non-diabetic patients. Using length of stay (LOS) as a cost driver, the extra hospital costs of each CVE were then estimated by reference to mean costs measured on the whole database. RESULTS: Average LOS of patients with diabetes were significantly longer than of non diabetic patients. (stroke: +2.5 days, myocardial infarction: +1.5 days, unstable angina: +1.3 days, revascularisation: +2.8 days; P<0.001). The mean numbers of medical procedures by stay were also higher in the diabetic group. Extra hospital costs of CVE for diabetic patients as compared with mean costs were the following: +23.9% (non fatal stroke), +10.4% (non fatal myocardial infarction), +6.1% (unstable angina), +9.1% (coronary revascularization). CONCLUSION: The hospital costs of CVE in diabetic patients are higher than average. Specific costs for these complications should be used to improve the relevance of economic studies of Diabetes.

Self-reported visual impairment and mortality: a French nationwide perspective.

PURPOSE: To estimate the association between self-reported visual impairment and mortality. METHODS: Two national surveys in community and institutionalized populations were combined. First, 2,075 institutions for children with impairments, adults with impairments aged persons, and psychiatric patients were selected randomly. The sample comprised 15,403 subjects of whom 14,603 (94.9%) were interviewed. Second, a random, stratified sample of 21,760 persons living in the community was selected, and 16,945 (77.9%) were interviewed. Types of impairment were identified by face-to-face interviews. Two years later, 14,497 subjects in institutions and 15,648 in the community were revisited. Data on death were obtained from either the National Register or households. Death rates were related to age, gender, and impairment. A logistic regression was performed including impairments, activities of daily living, age, gender, type of residence, and geographical area. RESULTS: Strong, independent associations were found between particular impairments, institutional residence, activities of daily living, age, gender, and risk of death. Associations between mortality and type of impairment could be ranked as follows: motor (OR = 1.235), brain (OR = 1.552), low vision (OR = 1.681), speech (OR = 2.090), visceral (OR = 2.233) and blindness (OR = 2.262). CONCLUSIONS: Self-reported visual impairment is an independent factor associated with mortality.

[Anogenital warts incidence, medical management and costs in women consulting gynaecologists in France]. / Incidence, prise en charge et coût des condylomes acuminés anogénitaux chez les femmes consultant leur gynécologue en France.

OBJECTIVES: The objectives of this study were to estimate the incidence of genital warts and treatment costs in women consulting gynaecologists in France in 2005. PATIENTS AND METHODS: A prospective observational study was performed through a representative sample of gynaecologists. Investigators enrolled all patients seen with genital warts during a 2-month period. A questionnaire detailing socio-demographic characteristics, case description, patient's clinical profile, past/ current management, and treatment of genital warts was completed by the investigators. RESULTS: 212 gynaecologists participated in the study. Questionnaires were completed for 263 patients including 198 (75.3%) new cases, 53 (20.2%) recurrent cases and 12 (4.5%) resistant cases. The overall incidence was estimated at 228.9/100,000 (female 15-65year old population) corresponding to 47,755 cases annually managed by gynaecologists in France. The average treatment cost was 482.70euro for society and 342.40 euro for third-party payers. The annual direct cost of genital warts management was estimated at 23,051,339euro, of which 16,351,312euro was funded by the French health care system. DISCUSSION AND CONCLUSION: The costs of treating genital warts are considerable. The introduction of a quadrivalent (type 6,11,16,18) Human Papillomavirus vaccine including types responsible for 90% of genital warts could potentially substantially reduce these costs.

Cost-effectiveness model comparing dual-mobility to fixed-bearing designs for total hip replacement in France.

BACKGROUND: Instability is among the main causes of total hip arthroplasty (THA) failure. In clinical studies, THA with a dual-mobility cup (THA-DM) decreased the risk of instability after primary THA compared to THA with a fixed-bearing design (THA-FB). However, whether THA-DM is more cost-effective than THA-FB has not been established using Markov modelling with determination of the incremental cost-effectiveness ratio (ICER). The objectives of this work were to: (1) measure the efficiency of these two options, (2) use the nationwide hospital electronic database (PMSI) to estimate direct costs of dislocations and revisions for instability, and (3) conduct deterministic and probabilistic sensitivity analyses to estimate potential mean annual cost-savings in France. HYPOTHESIS: We hypothesised that primary THA-DM was cost-saving compared to primary THA-FB. MATERIAL AND METHODS: In the database, we identified 80,405 patients who had THA in 2009 and we collected their outcomes over 4 years (2009-2012). Cost-effectiveness was assessed based on the costs of resources used for all consequences of prosthetic dislocation and paid for by the statutory health insurance system or other sources. RESULTS: THA-DM was associated with a relative risk of dislocation of 0.4 versus THA-FB. This risk difference translated into 3283 fewer dislocations per 100,000 patients with THA-DM. The corresponding cost-savings for the 140,000 primary THA procedures done in France annually was 39.62 million Euros. A relative risk of 0.2 would yield annual cost-savings of 56.28 million Euros. In the probabilistic sensitivity analysis, THA-DM was the less costly option under all hypotheses, with potential maximum cost-savings of more than 100 million Euros per year in France. DISCUSSION: This comparative cost-effectiveness analysis suggests that THA-DM may induce substantial cost-savings compared to THA-FB. This possibility should be assessed by long-term clinical studies of new-generation DM prostheses.

Factors associated with glycemic control. A cross-sectional nationwide study in 2,579 French children with type 1 diabetes. The French Pediatric Diabetes Group.

OBJECTIVE: To determine on a large scale the multiple medical and nonmedical factors that influence glycemic control in the general population of children with diabetes, we performed a nationwide French cross-sectional study. RESEARCH DESIGN AND METHODS: We enrolled 2,579 patients aged 1-19 years with type 1 diabetes of > 1 year's duration. The study was center based: 270 centers were identified, 206 agreed to participate, and 147 included at least 90% of their patients. Questionnaires were completed by physicians interviewing patients and family, and HbA1c measurements were centralized. To identify explanatory variables for HbA1c level and frequency of severe hypoglycemia, we performed multiple regression analysis using all the quantitative variables collected and stepwise logistic regression for the qualitative variables. RESULTS: Mean HbA1c value for the whole population was 8.97 +/- 1.98% (normal 4.7 +/- 0.7% [SD]). Only 19 children (0.7%) had ketoacidosis during the 6 months before the study, whereas 593 severe hypoglycemia events occurred in 338 children (13.8%). Control was better in university-affiliated hospitals and centers following > 50 patients, reflecting the importance of access to experienced diabetologists. Children had a mean of 2.3 injections, allegedly performed 2.8 glucose measurements per day, and were seen an average of 4.6 times per year at the center. In the multiple regression analysis, 94% of the variance of HbA1c was explained by our pool of selected variables, with the highest regression coefficient between HbA1c and age (Rc = 0.43, P < 0.0001), then with daily insulin dosage per kilogram (Rc = 0.28, P < 0.0001), mother's age (Rc = 0.26, P < 0.0001), frequency of glucose measurements (Rc = 0.21, P < 0.0001), and diabetes duration (Rc = 0.14, P < 0.0001). Logistic regression identified quality of family support and dietary compliance, two related qualitative and possibly subjective variables, as additional explanatory determinants of HbA1c. The frequency of severe hypoglycemia was 45 per 100 patient-years and correlated with diabetes duration, but not with HbA1c levels or other variables. CONCLUSIONS: Although overall results remain unsatisfactory, 33% of studied French children with type 1 diabetes had HbA1c < 8%, the value obtained in Diabetes Control and Complications Trial adolescents treated intensively. Diabetes management in specialized centers should be encouraged.

Economic analysis of adjuvant therapy with interferon alpha-2a in stage II malignant melanoma.

Using the trial demonstrating that interferonalpha-2a (IFNalpha-2a) is efficacious as adjuvant therapy in stage II melanoma, we evaluate its outcomes and economic consequences. Using rates observed in the 5-year trial and published figures, survival and Q-TWIST (Time Without Symptoms and Toxicity) were extrapolated to a 10-year and lifetime horizon. Cost analysis was performed using the trial's data, published literature and experts' opinions from the perspective of the French Sickness Funds. Patients in the IFNalpha-2a-group have an additional 0.26 years in life-expectancy over a 5-year time period (P=0.046), 0.67 years over a 10-year period and 2.59 years over a lifetime. Cost per life-year-gained was estimated at approximately 14400 after 5 years, 6635 after 10 years and 1716 over a lifetime. Assuming that there is an improvement in disease-free survival only, cost is 26147 per Q-TWIST. Cost-effectiveness of IFNalpha-2a in stage II melanoma compares favourably with estimates for widely used therapies in the oncological field.

Blindness, low vision, and other handicaps as risk factors attached to institutional residence.

AIMS: To estimate the risk of living in an institution and being visually impaired. METHODS: Two national surveys were pooled: (1) 2075 institutions (for children or adults with handicaps, old people, and psychiatric centres) were selected randomly, in 18 predefined strata, from the French health ministry files. From these institutions, 15 403 subjects were selected randomly and handicap was documented by interview in 14 603 (94.9%) of them; (2) level of handicap was documented in a randomised, stratified sample of 356 208 citizens living in the community; from this sample, 21 760 subjects were further selected at random and 16 945 people were interviewed. Data on handicaps (visual, auditory, speech, brain, visceral, motor, and other) and activities of daily living (ADL) were extracted. The odds ratio (OR) of living in an institution was estimated, using stepwise logistic regressions with age, geographical area, handicaps, and ADL as co-variables. RESULTS: Subjects in institutions, compared to those living at home, were, respectively, more often female (64.3% v 52.4%) and older (68.7 v 38.0 years); they more often had handicaps (ORs: speech, 6.59; brain, 10.17; motor, 8.86; visceral, 3.49; auditory, 2.66; other, 1.53); and were less often able to perform their ADL (46.2% v 97.1%) without assistance. Below 80 years, blind people were more often in institutions (ORs 0.239 to 0.306); whereas in older people the association was reversed (OR: 3.277). Low vision was always significantly associated with institutional residence (ORs from 0.262 to 0.752). CONCLUSION: Visual handicap was associated with institutional residence. The link persisted after adjustment for known confounding factors.

Cost effectiveness of hepatitis A prevention in France.

A spreadsheet simulation model of hepatitis A disease was developed to evaluate the cost effectiveness of an inactivated [corrected] hepatitis A vaccine ('Havrix', SmithKline Beecham) in high risk groups in France. Gammaglobulin prophylaxis, systematic vaccination without screening and vaccination of nonimmune persons after systematic screening were compared with the reference situation of no prevention over a 10-year period. It was found that both vaccination strategies would prevent 98% of new cases of hepatitis A, and would generate savings of FF4.2 to FF4.7 million ($US1 = FF5, 1995) in alternative service volunteers [initial seroprevalence (IS) 26%] stationed in countries with high hepatitis A endemicity. The cost per symptomatic case avoided [i.e. the cost-effectiveness ratio (CER)] was found to vary from FF177,612 with screening to FF281,463 without screening in adult tourists (IS 77%). In hospital workers, screening before vaccination (CER = FF65,108) would be about half as costly as systematic vaccination (IS 55 to 79%). Recommendations for vaccination should take into account the specific collective or individual risk, age, seroprevalence and probability of compliance with the prevention protocol.

An economic evaluation of tiludronic acid treatment in Paget's disease of bone.

The objective of this study was to evaluate the long term comparative outcome of intermittent courses of therapy with low-dosage tiludronic acid (400 mg/day) versus etidronic acid in patients with Paget's disease of bone. The long term outcome was evaluated by means of a model, as the number of complications avoided during a 5-year period. Only major complications were considered (fractures of long bones, spinal cord dysfunction, osteoarthritis of the hip), which can be cured by adequate medical intervention, and may thus be valued in terms of direct costs. Deafness was not considered and was not valued. The various additional direct costs incurred (treatment and follow-up) and avoided (complications avoided) were assessed using an extrapolation model, based on the results of a clinical study. A standard costing methodology was used, according to the patterns of care currently in use in France. Costs were calculated from a societal perspective, including social security and private insurance fund reimbursements, and out-of-pocket expenses. These were estimated in French francs (F: 1994 values). The estimated mean treatment cost per patient for the treatment of Paget's disease and its complications over a 5-year period was F34,198 with etidronic acid, and F30,754 to F36,422 with tiludronic acid, depending on whether an optimistic or a conservative view of the efficacy of tiludronic acid was assumed. Despite its higher acquisition cost, the use of tiludronic acid was less expensive in the treatment of Paget's disease and its complications, compared with the use of etidronic acid, when an optimistic view of the efficacy of tiludronic acid was assumed.