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Transcatheter aortic valve implantation (TAVI) has become the therapy of choice for treating severe aortic stenosis in patients at high-risk for surgery or where it is considered too risky to attempt. This uptake varies across geographies however, and its cost or value has frequently been cited as the reason for this. We sought to evaluate the potential cost and clinical impact of TAVI in intermediate risk patients from a French collective perspective.The analysis was performed using a novel Markov model with data derived from the PARTNER II randomized controlled trial for survival, clinical event rates, and quality-of-life. The simulated time horizon was 15 years, costs were from French sources and presented in 2016 Euros. Discounting of all outcomes was at 4% annually and the effect of uncertainty in model parameters was explored by deterministic and probabilistic sensitivity analysis (PSA).In comparison to surgery, TAVI resulted in improved clinical outcomes (life expectancy and quality-adjusted life expectancy) and lower costs over a lifetime time horizon. The base case results showed increases of 0.42 years and 0.41 QALYs with lifetime cost savings of €439 for TAVI compared to surgery. PSA results showed a50% likelihood of cost-effectiveness at €0 willingness-to-pay and a 100% likelihood at ∼€15,000.Clinically, survival projections are based on limited follow-up data and introduce uncertainty into the outcomes from the model. Economically, procedure costs are derived from a heterogeneous mix of patient risk groups, although this is much more likely to bias against TAVI and under-estimate overall cost savings.In our analyses of intermediate risk patients, TAVI is associated with superior clinical outcomes compared to surgery and is cost saving. It could be expected that cost savings are conservative and likely to increase over time.

This study assesses the cost-effectiveness of Technology Lipido-Colloid with Nano Oligo Saccharide Factor (TLC-NOSF) wound dressings versus neutral dressings in the management of diabetic foot ulcers (DFUs) from a French collective perspective. We used a Markov microsimulation cohort model to simulate the DFU monthly progression over the lifetime horizon. Our study employed a mixed method design with model inputs including data from interventional and observational studies, French databases and expert opinion. The demographic characteristics of the simulated population and clinical efficacy were based on the EXPLORER double-blind randomized controlled trial. Health-related quality of life, costs, and resource use inputs were taken from the literature relevant to the French context. The main outcomes included life-years without DFU (LYsw/DFU), quality-adjusted life-years (QALYs), amputations, and lifetime costs. To assess the robustness of the results, sensitivity and subgroup analyses based on the wound duration at treatment initiation were performed. Treatment with the TLC-NOSF dressing led to total cost savings per patient of EUR 35,489, associated with gains of 0.50 LYw/DFU and 0.16 QALY. TLC-NOSF dressings were established as the dominant strategy in the base case and all sensitivity analyses. Furthermore, the model revealed that, for every 100 patients treated with TLC-NOSF dressings, two amputations could be avoided. According to the subgroup analysis results, the sooner the TLC-NOSF treatment was initiated, the better were the outcomes, with the highest benefits for ulcers with a duration of two months or less (+0.65 LYw/DFU, +0.23 QALY, and cost savings of EUR 55,710). The results from the French perspective are consistent with the ones from the German and British perspectives. TLC-NOSF dressings are cost-saving compared to neutral dressings, leading to an increase in patients’ health benefits and a decrease in the associated treatment costs. These results can thus be used to guide healthcare decisionmakers. The potential savings could represent EUR 3,345 per treated patient per year and even reach EUR 4,771 when TLC-NOSF dressings are used as first line treatment. The EXPLORER trial is registered with ClinicalTrials.gov, number NCT01717183.

Objectives Biologic disease-modifying antirheumatic drugs (bDMARDs) are prescribed sequentially in the treatment of rheumatoid arthritis (RA). Healthcare decision makers continue to debate their use, mainly because of their high costs. Our aim was to perform an economic evaluation for France of bDMARD sequences for treatment of moderate-to-severe RA after inadequate response or intolerance to conventional DMARDs (eg, methotrexate). Methods A discretely integrated condition event simulation was developed to track the course of patients from first bDMARD through switches to further lines in a sequence. The model included 11 events, 91 conditions, and 21 controlling equations. Inputs were obtained from a meta-analysis of clinical trials, a French registry, national drug lists, and databases. Survival, time with minimal activity, quality-adjusted life-years (QALYs), and total costs were output. Structural and probabilistic sensitivity analyses were conducted. Results Sequences starting with etanercept biosimilars (ETB) cost less, with ETB–abatacept–infliximab the least expensive: the mean lifetime discounted total cost was €116 912 per patient, with a mean of 11.166 QALYs. Most other strategies were dominated or led to small QALY gains (0.0008-0.0329). Only ETB–tocilizumab–abatacept made it onto the efficiency frontier, but at €955 778 per QALY gained. These results were confirmed in several scenarios and uncertainty analyses. Conclusion Given minor differences in QALYs gained between bDMARD sequences with large cost differences, starting with biosimilars was more efficient than starting with branded products. Our model and findings should provide French and other decision makers with useful tools to address the challenges of comparing sequences of treatments for RA.

International audience

Background Patient characteristics and survival outcomes in randomized trials may be different from those in real-life clinical practice. The objective of this study was to describe treatment pathways, safety, drug costs and survival in patients with metastatic Renal Cell Carcinoma (mRCC) in a real world setting. Methods A retrospective analysis was performed using IQVIA real world oncology cross-sectional survey data, a retrospective treatment database collecting anonymized patient-level data in Europe. Data on treatment naïve patients with mRCC who received a first-line targeted therapy in France were extracted for the period 2005–2015. Descriptive analyses were performed on treatment patterns, patient characteristics and safety profiles. Progression Free Survival (PFS) was determined using Kaplan-Meier survival analysis. Results One thousand three hundred thirty-one patients with mRCC who received a first-line targeted therapy were included. The male/female sex ratio was 2.5 and 66% of patients were aged > 60 years. 83% of patients had clear cell adenocarcinoma. 83% of patients underwent a surgical procedure, 10% had radiotherapy. In patients who received a first-line targeted therapy, 73% received sunitinib. The mean time from diagnosis to first-line treatment by targeted therapies in patients initially diagnosed with metastatic disease was 3.3 months [95% CI:2.5–4.1]. In patients who received second-line targeted therapy n = 257 (19%), the most frequently observed treatment sequences were sunitinib-everolimus (33%) and sunitinib-sorafenib (27%). Adverse events data were available for 501 patients and adverse events were documented in 70% of patients, most frequently diarrhoea. The overall median PFS was 13 months [95% CI:11.5–16]. Conclusion Patient characteristics were consistent with the literature. Treatment patterns appeared to follow current practice guidelines. Despite some variations, PFS in our study seems to be consistent with findings from other real world studies. Nevertheless, PFS results were higher than those observed in clinical trials. Due to the use of cross-sectional data, PFS in our study should be interpreted with caution. Electronic supplementary material The online version of this article (10.1186/s12885-018-4117-z) contains supplementary material, which is available to authorized users.

Objective To assess the cost-effectiveness of the elbasvir/grazoprevir (EBR/GZR) regimen in patients with genotype 1 chronic hepatitis C virus (HCV) infection with severe and end-stage renal disease compared to no treatment. Design This study uses a health economic model to estimate the cost-effectiveness of treating previously untreated and treatment experienced chronic hepatitis C patients who have severe and end stage renal disease with the elbasvir-grazoprevir regimen versus no treatment in the French context. The lifetime homogeneous markovian model comprises of forty combined health states including hepatitis C virus and chronic kidney disease. The model parameters were from a multicentre randomized controlled trial, ANRS CO22 HEPATHER French cohort and literature. 1000 Monte Carlo simulations of patient health states for each treatment strategy are used for probabilistic sensitivity analysis and 95% confidence intervals calculations. The results were expressed in cost per quality-adjusted life year (QALY) gained. Patients The mean age of patients in the HEPATHER French cohort was 59.6 years and 56% of them were men. 22.3% of patients had a F0 fibrosis stage (no fibrosis), 24.1% a F1 stage (portal fibrosis without septa), 7.1% a F2 stage (portal fibrosis with few septa), 21.4% a F3 stage (numerous septa without fibrosis) and 25% a F4 fibrosis stage (compensated cirrhosis). Among these HCV genotype 1 patients, 30% had severe renal impairment stage 4, 33% had a severe renal insufficiency stage 5 and 37% had terminal severe renal impairment stage 5 treated by dialysis. Intervention Fixed-dose combination of direct-acting antiviral agents elbasvir and grazoprevir compared to no-treatment. Results EBR/GZR increased the number of life years (6.3 years) compared to no treatment (5.1 years) on a lifetime horizon. The total number of QALYs was higher for the new treatment because of better utility on health conditions (6.2 versus 3.7 QALYs). The incremental cost-utility ratio (ICUR) was of €15,212 per QALY gained for the base case analysis. Conclusions This cost-utility model is an innovative approach that simultaneously looks at the disease evolution of chronic hepatitis C and chronic kidney disease. EBR/GZR without interferon and ribavirin, produced the greatest benefit in terms of life expectancy and quality-adjusted life years (QALY) in treatment-naive or experienced patients with chronic hepatitis C genotype 1 and stage 4-5 chronic kidney disease including dialysis patients. Based on shape of the acceptability curve, EBR/GZR can be considered cost-effective at a willingness to pay of €20,000 /QALY for patients with renal insufficiency with severe and end-stage renal disease compared to no treatment.

International audience; Existence conditions of permanental distributions are deeply connected to existence conditions of multivariate negative binomial distributions. The aim of this paper is double. It answers several questions generated by recent works on this subject, but it also goes back to the roots of this field and fixes existing gaps in older papers concerning conditions of infinite divisibility for these distributions.

Objectives: The objective of this study was to describe treatment patterns, survival, healthcare use and costs in patients with metastatic renal cell carcinoma (mRCC) in a real-world setting. Research design and methods: We used the National Health Insurance (NHI) claims database for the Ile-de-France region to perform a retrospective cohort analysis of patients with mRCC treated by a first-line targeted therapy. Treatment naïve patients were identified combining the 10th revision of the International Classification of Diseases (ICD-10) codes (C64 & C77-C79) and a first prescription of targeted therapies. Descriptive analyses were performed on treatment patterns and patients’ characteristics. Progression free survival (PFS) and overall survival (OS) were determined using Kaplan–Meier actuarial survival analysis. All healthcare resource use and costs were estimated on a per patient per month (PPPM) basis (€2016). Results: A total of 327 treatment naïve patients with mRCC were included. Median follow-up was 13.4 months. Sunitinib accounted for 73% of first-line treatments. The most frequently observed treatment sequence for the first two lines was sunitinib–everolimus (16%; n = 137) and for the first three lines sunitinib–everolimus–axitinib (20%; n = 49). First-line PFS for sunitinib, everolimus, pazopanib, sorafenib and other was 8.7, 6.2, 10.7, 5.7 and 11.2 months, respectively. Median OS for patients treated by first-line sunitinib, everolimus, pazopanib, sorafenib and other was respectively 14.7, 8.1, 21.1, 8.9 and 14.0 months. From the NHI’s perspective, the mean PPPM was €5546. The average PPPM in pre-progression was €5597 compared to €5541 beyond progression of the disease. Oral targeted therapies accounted for 53% of the total PPPM. Conclusion: This descriptive study showed that the economic burden of mRCC is substantial with oral targeted therapies accounting for 53% of the PPPM. OS and PFS in real life are poorer than observed in clinical trials.

International audience

Background & Objectives The aim of this study was to assess the economic burden of hospitalisations for metastatic renal cell carcinoma (mRCC), to describe the patterns of prescribing expensive drugs and to explore the impact of geographic and socio-demographic factors on the use of these drugs. Methods We performed a retrospective analysis from the French national hospitals database. Hospital stays for mRCC between 2008 and 2013 were identified by combining the 10th revision of the International Classification of Diseases (ICD-10) codes for renal cell carcinoma (C64) and codes for metastases (C77 to C79). Incident cases were identified out of all hospital stays and followed till December 2013. Descriptive analyses were performed with a focus on hospital stays and patient characteristics. Costs were assessed from the perspective of the French National Health Insurance and were obtained from official diagnosis-related group tariffs for public and private hospitals. Results A total of 15,752 adult patients were hospitalised for mRCC, corresponding to 102,613 hospital stays. Of those patients, 68% were men and the median age at first hospitalisation was 69 years [Min-Max: 18–102]. Over the study period, the hospital mortality rate reached 37%. The annual cost of managing mRCC at hospital varied between 28M€ in 2008 and 42M€ in 2012 and was mainly driven by inpatient costs. The mean annual per capita cost of hospital management of mRCC varied across the study period from 8,993€ (SD: €8,906) in 2008 to 10,216€ (SD: €10,527) in 2012. Analysis of the determinants of prescribing expensive drugs at hospital did not show social or territorial differences in the use of these drugs. Conclusion This study is the first to investigate the in-hospital economic burden of mRCC in France. Results showed that in-hospital costs of managing mRCC are mainly driven by expensive drugs and inpatient costs.

We give necessary and sufficient conditions for existence and infinite divisibility of α-determinantal processes. For that purpose we use results on negative binomial and ordinary binomial multivariate distributions.

Objective To model the cost-effectiveness impact of routine use of an antimicrobial chlorhexidine gluconate-containing securement dressing compared to non-antimicrobial transparent dressings for the protection of central vascular lines in intensive care unit patients. Design This study uses a novel health economic model to estimate the cost-effectiveness of using the chlorhexidine gluconate dressing versus transparent dressings in a French intensive care unit scenario. The 30-day time non-homogeneous markovian model comprises eight health states. The probabilities of events derive from a multicentre (12 French intensive care units) randomized controlled trial. 1,000 Monte Carlo simulations of 1,000 patients per dressing strategy are used for probabilistic sensitivity analysis and 95% confidence intervals calculations. The outcome is the number of catheter-related bloodstream infections avoided. Costs of intensive care unit stay are based on a recent French multicentre study and the cost-effectiveness criterion is the cost per catheter-related bloodstream infections avoided. The incremental net monetary benefit per patient is also estimated. Patients 1000 patients per group simulated based on the source randomized controlled trial involving 1,879 adults expected to require intravascular catheterization for 48 hours. Intervention Chlorhexidine Gluconate-containing securement dressing compared to non-antimicrobial transparent dressings. Results The chlorhexidine gluconate dressing prevents 11.8 infections /1,000 patients (95% confidence interval: [3.85; 19.64]) with a number needed to treat of 85 patients. The mean cost difference per patient of €141 is not statistically significant (95% confidence interval: [€-975; €1,258]). The incremental cost-effectiveness ratio is of €12,046 per catheter-related bloodstream infection prevented, and the incremental net monetary benefit per patient is of €344.88. Conclusions According to the base case scenario, the chlorhexidine gluconate dressing is more cost-effective than the reference dressing. Trial Registration This model is based on the data from the RCT registered with www.clinicaltrials.gov (NCT01189682).

Objectifs L’evaluation de l’efficience permet de comparer les couts et les consequences de strategies alternatives. Cet outil d’aide a la decision repose sur des modeles mathematiques qui requierent des donnees d’efficacite, de tolerance, de qualite de vie et de couts des technologies de sante evaluees. Cependant, la disponibilite et la qualite des donnees demeurent problematiques et contribuent a l’incertitude sur le resultat de l’efficience. L’utilisation des donnees individuelles des essais cliniques (evaluation ex. ante) ou d’etudes observationnelles et des donnees de cout collectees en vie reelle (evaluation ex. post) demeure le gold standard au regard des recommandations de la HAS en matiere d’evaluation medico-economique, mais l’acces a ces donnees reste difficile, d’ou le recours alternatif aux donnees agregees, moins precises mais souvent publiees et, aux dires d’experts, considerees comme etant moins robustes. Il semble donc opportun de s’interroger sur l’impact de l’utilisation des donnees d’efficacite et de tolerance (individuelles versus agregees) et de couts (estimees en vie reelle versus estimees lors des essais cliniques et/ou a dires d’experts) issues de differentes sources sur les resultats d’efficience. Cette etude vise a analyser cet impact avec une application dans le cancer du rein metastatique et le melanome metastatique. Methodes Une comparaison des resultats issus d’analyses cout-utilite reposant sur l’utilisation de jeux de donnees differents sera realisee : donnees individuelles d’efficacite issues des essais (scenario 1) versus donnees agregees d’efficacite disponibles dans la litterature (scenario 2) ; donnees de cout estimees en vie reelle (scenario 3) versus donnees de cout estimees lors des essais cliniques et completees par une analyse du PMSI et/ou de dires d’experts (scenario 4). Pour les deux pathologies d’interet, les donnees agregees d’efficacite seront collectees a travers une revue systematique de la litterature et les donnees individuelles seront collectees a partir des bases de donnees des essais cliniques mises en ligne sur un portail dedie. Les donnees de cout en vie reelle seront estimees a travers une analyse de la base Donnees de consommation inter-regimes (DCIR) d’Ile-de-France, les autres donnees de couts seront estimees a partir des donnees de consommation des ressources recueilles dans les essais cliniques et completees par une analyse PMSI et/ou de dires d’experts. Resultats L’acces aux donnees agregees d’efficacite ne presente pas de difficultes particulieres en dehors des biais de publication et des delais entre la disponibilite des donnees et leurs publications. En revanche et malgre la volonte des industriels et des pouvoirs publics de faciliter l’acces aux donnees individuelles des essais cliniques ou aux donnees de l’Assurance maladie pour les chercheurs, l’acces a ces donnees reste complexe et necessite une evaluation prealable du protocole de recherche ainsi que des delais importants d’instruction des dossiers. Par ailleurs, bien que le PMSI soit plus accessible, il ne comporte pas de donnees sur la consommation de ressources en ville. Conclusion L’acces aux donnees de sante dans un temps opportun demeure important pour l’evaluation medico-economique, notamment dans un domaine comme l’oncologie ou les avancees therapeutiques progressent vite, rendant l’evaluation medico-economique rapidement obsolete.

International audience; Finding a biomarker of long length-of-stay (LOS) would provide a simple solution to target frail older inpatients at such risk. The aim of this study was to determine whether serum 25-hydroxyvitamin D (25OHD) deficiency, defined as serum concentration = 14 days; n = 120) versus the other two tertiles combined (

International audience; BACKGROUND: There is a need for a brief geriatric assessment (BGA) tool to screen elderly patients admitted to the Emergency Department (ED) for their risk of a long hospital stay. OBJECTIVE: To examine whether a BGA administered to elderly patients admitted to the ED may predict the risk of a long hospital stay in the geriatric acute care unit.METHODS: This study had a prospective cohort study design, enrolling 424 elderly patients (mean age 84.0 +/- 6.5 years, 31.6% male) who were evaluated in the ED using a BGA composed of the following items: age, gender, number of medications taken daily, history of falls during the past 6 months, Mini-Mental State Examination (MMSE) score, and non-use of home-help services (i.e., living alone without using any formal or informal home services or social help). The length of stay (LOS) was calculated in days. Patients were separated into three groups based on LOS: low (13 days).RESULTS: The prevalence of male gender was higher among patients with the longest LOS compared to those with intermediate LOS (p = 0.002). There were more patients with a history of falls in the high LOS group compared to the intermediate LOS group (p = 0.001) and the low LOS group (p < 0.001). The classification tree showed that male patients with an MMSE score CONCLUSIONS: The combination of a history of falls, male gender, cognitive impairment, and age under 85 years identified elderly ED patients at high risk of a long hospital stay.

• A retrospective analysis was performed using the French national hospital database (PMSI), an exhaustive hospital discharge database that covers all hospital stays in public and private hospitals in France. For each hospital stay, the PMSI provides a compilation of administrative data (i.e. age, gender, residence code) and medical data (i.e. diagnosis, medical procedures performed during hospital stays). Each hospital stay is then classified in a diagnosis related group (DRG) and can be linked to a patient using the unique patient identification number. • We extracted all hospital stays from 2007 to 2013 with the ICD-10 codes for both renal cell carcinoma (C64*) and metastasis (C77*, C78*,C79*). Among hospital stays for mRCC, we extracted incident cases identified by the absence of hospitalization for mRCC and the absence of metastasis in the previous year. Hospital stays for which the patient identification number was not adequately recorded as well as hospital stays that could not be classified into a DRG were excluded. Hospital stays for non incident cases and patients aged under 18 were also excluded. • Included patients were followed until death and data were censored on December 2013 for living patients. • Descriptive analysis were performed in terms of hospital stays and patients. • The cost of hospitalizations for mRCC was calculated from the perspective of the French national health insurance. For this purpose, the DRG tariffs for both public and private settings were used. Context & Objective • Kidney cancer accounts for approximately 3% of all cancers in France(1). In 2012, there were 11,573 new cases of kidney cancer and 3,957 deaths in France(2). • Renal cell carcinoma (RCC) accounts for 85% to 92% of kidney cancer cases (1,3–4). Approximately 25% to 30% of patients with RCC have metastasis at diagnosis and up to 50% of patients who undergo curative renal resection are likely to develop metastatic renal cell carcinoma (mRCC)(4).

Contexte : La retinopathie diabetique (RD) est la cause la plus frequente des cecites observees chez les personnes de moins de 60 ans dans la population generale. L’objectif de la recherche etait d’evaluer la pertinence du depistage preventif de la retinopathie diabetique par photographie du fond d’œil et ses modalites de mise en œuvre.Methodes : Un modele de Markov a ete construit pour evaluer l’efficacite de 17 strategies. Le modele simule le devenir d’une cohorte de patients avec ou sans retinopathie diabetique, sur une periode de 10 ans. Quatorze etats de sante sont decrits dont six reproduisent l’histoire naturelle de la maladie : « Pas de retinopathie », « Retinopathie de fond », « Retinopathie preproliferante debutante », « Retinopathie a hauts risques », « Deficience visuelle severe » et « Deces ». Trois criteres ont ete retenus pour definir les strategies alternatives de depistage : le type de materiel utilise dans le cadre du depistage organise (camera non mydriatique avec ou sans dilatation) et a l’occasion d’un depistage individuel (biomicroscopie), le rythme (annuel, biennal ou triennal) et le seuil d’adressage au specialiste en fonction du stade de severite de la maladie. Les probabilites de transition annuelles ont ete estimees a partir de la Liverpool Diabetic Eyes Study (LDES). Les calculs de couts ont ete realises en se placant du point de vue des depenses de prevention et de soins ophtalmologiques financees ou remboursees par l’assurance maladie. Les tarifs ont ete extraits de la base de donnees Amelie. Un taux d’actualisation de 4% par an a ete applique aux donnees de couts et d’efficacite. Le nombre de deficiences visuelles severes evitees a ete choisi comme critere clinique. L’efficience a ete defini en termes de processus de production. Une analyse de sensibilite deterministe a ete conduite.Resultats : Six strategies sont finalement apparues comme etant efficientes : le depistage biennal par camera non mydriatique avec dilatation et seuil d’adressage au specialiste > a 10 sur le score LDES, le depistage biennal par camera non mydriatique avec dilatation et seuil d’adressage > a 20 sur le score LDES, le depistage annuel par camera non mydriatique avec dilatation et seuil d’adressage > a 30 sur le score LDES, depistage annuel par camera non mydriatique sans dilatation et seuil d’adressage au specialiste > a 10 sur le score LDES, et le depistage opportuniste biennal ou triennal. Le depistage opportuniste annuel tout en etant efficient, constitue la strategie la moins efficace et la moins couteuse. Le cout moyen cumule par patient sur 10 ans est compris entre 277 € (depistage triennal par camera non mydriatique avec dilatation) et 477 € (depistage annuel par camera non mydriatique sans dilatation). Le pourcentage de deficiences visuelles severes evitees est compris entre 35% (depistage triennal par camera non mydriatique avec dilatation) et 58% (depistage opportuniste annuel).Conclusion : Notre etude a permis de mettre en evidence 6 strategies efficientes. Bien qu’il ne soit possible de les departager en l’absence de definition d’un seuil d’effort collectif socialement acceptable, une simple analyse de productivite raisonnee nous a amene a recommander le choix de trois d’entre elles en premiere intention. Le depistage en population generale ne se justifie que s’il atteint des taux de participation beaucoup plus eleves que ceux observes actuellement.

Objectif : L’objectif de cette etude est d’evaluer sous un angle economique l’impact d’une structure d’accompagnement et d’education a la sante des assures sociaux de la Sarthe. Cette structure, denommee « Club Sante Active » (CSA), a ete creee par la Caisse Primaire d’Assurance Maladie de la Sarthe en janvier 2006. L’analyse economique est proposee dans la perspective de l’Assurance maladie. Il s’agit d’une etude observationnelle retrospective fondee sur l’exploitation des donnees de remboursement de soins sollicites entre 2005 et 2009 par les assures sociaux du regime general de la Sarthe. Methode : 563 patients ont ete inclus dans le groupe CSA et 832 dans le groupe temoin. Une methode statistique comparable a celle du score de propension a ete utilisee afin d’assurer la comparabilite des deux groupes etudies a partir de la prise en compte de neuf covariables disponibles. Aussi, une analyse statistique des series temporelles de consommation medicale des assures de chaque groupe a-t-elle ete realisee afin d’evaluer l’impact economique tendanciel du Club Sante Active. Les depenses de sante remboursees par l’Assurance maladie (couts directs medicaux et non medicaux, indemnites journalieres) constituent le critere final de jugement de l’efficacite economique de la strategie evaluee et la nonadhesion au Club Sante Active definit la strategie de reference. Resultats : Une moindre evolution tendancielle des consommations par rapport au groupe temoin (hors CSA) a ete relevee chez les membres du CSA sur les categories de personnes et groupes de prestations suivants : les personnes en affection de longue duree (ALD) âgees de 40 a 60 ans pour les analgesiques et le recours aux soins de medecine generale, les personnes en ALD âgees de plus de 60 ans pour les analgesiques et les inhibiteurs de la pompe a proton (IPP), les personnes sans ALD âgees de 40 a 60 ans pour les IPP, les psychotropes, le recours aux soins de kinesitherapie et le nombre d’indemnites journalieres versees. A l’inverse, un seul cas d’evolution superieure pour les adherents du Club a ete recense : il s’agit du recours aux soins infirmiers pour les personnes en ALD de plus de 60 ans. Ce dernier resultat doit toutefois etre mis en perspective avec la particularite de la demographie medicale des infirmiers en Sarthe, ou l’acces a ce type de soins n’est a priori pas satisfaisant, le departement etant l’un des moins bien pourvus de toute la France. Conclusion : Les signes d’evolution constates sur les soins de ville ne sont pas la contrepartie d’un report de depenses sur les soins hospitaliers, ces prestations ayant ete controlees. Ces resultats tendent ainsi a confirmer que l’accompagnement des assures peut aboutir a une modification significative des comportements de recours au systeme de soins, notamment sur le champ des soins de ville.

L’objectif de cette etude est d’evaluer sous un angle medico-economique l’impact du parcours de soins coordonnes de patients traites chroniquement par corticosteroides inhales, dans la perspective de l’Assurance maladie (reforme de l’Assurance maladie du 13 aout 2004). Il s’agit d’une etude observationnelle retrospective fondee sur l’exploitation des donnees de remboursement de soins sollicites en 2007 par les assures sociaux du regime general.METHODE : 290 patients ont ete inclus dans chaque groupe (un groupe ayant declare un medecin traitant et un groupe n’ayant pas declare de medecin traitant), des hommes et des femmes âges de 16 a 50 ans traites par corticosteroides inhales durant au moins trois mois consecutifs. La methode du score de propension a ete utilisee afin d’assurer la comparabilite des deux groupes etudies a partir de la prise en compte de douze covariables disponibles. Aussi, une modelisation semi-markovienne a-t-elle ete realisee afin d’evaluer l’evolution du controle de la pathologie respiratoire a partir de l’evolution des prescriptions journalieres de corticosteroides inhales (critere intermediaire de l’efficacite). Le nombre d’annees de vie gagnees pondere par la qualite de vie (QALY) constitue le critere final de jugement de l’efficacite de la strategie evaluee et la non-inscription dans un parcours de soins coordonnes definit la strategie de reference.RESULTATS : Une simulation sur 10 000 echantillons, par bootstrap non parametrique, fondee sur les donnees longitudinales observees sur douze mois, a estime un intervalle de confiance a 95 % du ratio cout-efficacite incremental compris entre 30 699 euros et 31 401 euros par QALY gagne.CONCLUSION : La coordination annuelle, par un medecin traitant, de patients traites par corticosteroides inhales est donc consideree comme une strategie cout-efficace au regard des seuils d’acceptabilite des strategies de sante recommandes par l’Organisation Mondiale de la Sante en 2009 (entre une fois et trois fois le produit interieur brut par habitant).

In the first part of this dissertation we consider several problems of finite-dimensional parameter estimation for Markov sequences in the asymptotics of large samples. The asymptotic behavior of the Bayesian estimators and the estimators of the method of moments are described. It is shown that under regularity conditions these estimators are consistent and asymptotically normal. We show that the Bayesian estimator is asymptotically efficient. The one-step and two-step maximum likelihood estimator-processes are studied. These estimators allow us to construct the asymptotically efficient estimators based on some preliminary estimators, say, the estimators of the method of moments or Bayes estimator and the one-step maximum likelihood estimator structure. We propose particular non-linear autoregressive processes as examples and we illustrate the properties of these estimators with the help of numerical simulations. In the second part we give theapplications of Markov processes in health economics. We compare homogeneous and non-homogeneous Markov models for cost-effectiveness analysis of routine use of transparent dressings containing a chlorhexidine gluconate gel pad versus standard transparent dressings. The antimicrobial dressing protects central vascular accesses reducing the risk of catheter-related bloodstream infections. The impact of the modeling approach on the decision of adopting antimicrobialdressings for critically-ill patients is discussed., Dans la première partie de cette thèse, nous considérons plusieurs problèmes d'estimation de paramètre de dimension finie pour les séquences de Markov dans l'asymptotique des grands échantillons. Le comportement asymptotique des estimateurs bayésiens et les estimateurs obtenus par la méthode des moments sont décrits. Nous montrons que sous les conditions de régularité ces estimateurs sont consistants et asymptotiquement normaux et que l'estimateur bayésien est asymptotiquement efficace. Les estimateur-processus du maximum de vraisemblance un-pas et deux-pas sont étudiés. Ces estimateurs nous permettent de construire des estimateurs asymptotiquement efficaces sur la base de certainsestimateurs préliminaires, par exemple, les estimateurs obtenus par la méthode des moments ou l'estimateur deBayes et la structure de l'estimateur du maximum de vraisemblance un-pas. Nous proposons notamment des processus autorégressifs non linéaires comme exemple et nous illustrons les propriétés de ces estimateurs à l'aide de simulations numériques. Dans la deuxième partie, nous donnons les applications de processus de Markov en économie de la santé. Nous comparons les modèles de Markov homogènes et non-homogènes pour l'analyse coût-efficacité de l'utilisation depansements transparents contenant un gel de gluconate de chlorhexidine par rapport aux pansements transparents standard. Le pansement antimicrobien protège les accès vasculaire centrale et réduit le risque de bactériémies liées aux cathéters. L'impact de l'approche de modélisation sur la décision d'adopter des pansements antimicrobiens pour les patients gravement malades est discuté.

In the first part of this dissertation we consider several problems of finite-dimensional parameter estimation for Markov sequences in the asymptotics of large samples. The asymptotic behavior of the Bayesian estimators and the estimators of the method of moments are described. It is shown that under regularity conditions these estimators are consistent and asymptotically normal. We show that the Bayesian estimator is asymptotically efficient. The one-step and two-step maximum likelihood estimator-processes are studied. These estimators allow us to construct the asymptotically efficient estimators based on some preliminary estimators, say, the estimators of the method of moments or Bayes estimator and the one-step maximum likelihood estimator structure. We propose particular non-linear autoregressive processes as examples and we illustrate the properties of these estimators with the help of numerical simulations. In the second part we give theapplications of Markov processes in health economics. We compare homogeneous and non-homogeneous Markov models for cost-effectiveness analysis of routine use of transparent dressings containing a chlorhexidine gluconate gel pad versus standard transparent dressings. The antimicrobial dressing protects central vascular accesses reducing the risk of catheter-related bloodstream infections. The impact of the modeling approach on the decision of adopting antimicrobialdressings for critically-ill patients is discussed., Dans la première partie de cette thèse, nous considérons plusieurs problèmes d'estimation de paramètre de dimension finie pour les séquences de Markov dans l'asymptotique des grands échantillons. Le comportement asymptotique des estimateurs bayésiens et les estimateurs obtenus par la méthode des moments sont décrits. Nous montrons que sous les conditions de régularité ces estimateurs sont consistants et asymptotiquement normaux et que l'estimateur bayésien est asymptotiquement efficace. Les estimateur-processus du maximum de vraisemblance un-pas et deux-pas sont étudiés. Ces estimateurs nous permettent de construire des estimateurs asymptotiquement efficaces sur la base de certainsestimateurs préliminaires, par exemple, les estimateurs obtenus par la méthode des moments ou l'estimateur deBayes et la structure de l'estimateur du maximum de vraisemblance un-pas. Nous proposons notamment des processus autorégressifs non linéaires comme exemple et nous illustrons les propriétés de ces estimateurs à l'aide de simulations numériques. Dans la deuxième partie, nous donnons les applications de processus de Markov en économie de la santé. Nous comparons les modèles de Markov homogènes et non-homogènes pour l'analyse coût-efficacité de l'utilisation depansements transparents contenant un gel de gluconate de chlorhexidine par rapport aux pansements transparents standard. Le pansement antimicrobien protège les accès vasculaire centrale et réduit le risque de bactériémies liées aux cathéters. L'impact de l'approche de modélisation sur la décision d'adopter des pansements antimicrobiens pour les patients gravement malades est discuté.