[Budget impact of self-testing in the national cervical cancer screening program]. / Impact budgétaire de l'utilisation de l'autotest dans le cadre du programme national de dépistage du cancer du col de l'utérus.

OBJECTIVES: A nationwide screening program for cervical cancer (CC) was organized in 2018 as part of the 2014-2019 French cancer plan, with the objective of reducing CC incidence and mortality in France by reaching an 80 % coverage rate. As an alternative to pap smear, vaginal self-sampling (VSS) aimed at identifying high-risk HPV carriage could help to achieve this goal. The objective of the present study is to compare the respective budgetary impacts of several self-sampling strategies. METHOD: A budget impact model was developed to compare non-use of self-sampling in CC screening to the 5-year costs of 5 VSS strategies viewed from an all-payer perspective. While the first strategy was based on mailing the VSS kit with a reminder to participate in the screening program, the second was based on accompanying the mailed kit with an invitation to participate. The third and fourth strategies were based on providing health professionals with the kit, and thereby offering self-sampling as an alternative to pap smears for women undergoing CC screening and having previously received the kits. Finally, the fifth strategy was based on self-sampling as the one and only CC screening modality. The parameters of the model were based on past screening participation data and experiments in France on organized screening and VSS use. The costs included those of procedures associated with screening and program organization. RESULTS: All in all, the costs associated with cervical cancer screening would represent approximately 1 billion euros over 5 years. All strategies would be associated with participation ranging from 81% to 84%, which would represent an increase of 4.7% to 5.2% of lesions diagnosed by screening and a cost reduction between €30M and €87M over 5 years, with the exception of the strategy based on sending the kit (with the reminder associated or not) to the health professionals offering this option (+€23M and +€6M). CONCLUSIONS: In conclusion, the use of self-sampling as an alternative to pap smears for non-participating women would increase participation, with only a moderate budgetary impact and could, in some cases, even induce savings.

[Estimated impact of the current colorectal screening program in France]. / Estimation de l'impact du programme actuel de dépistage organisé du cancer colorectal.

BACKGROUND: Colorectal cancer is the third most common cancer and the second most deadly in France. A Cochrane meta-analysis has confirmed the benefits of colorectal cancer screening. A nationwide colorectal screening program was set up in France in 2009 for medium-risk, asymptomatic people aged 50 to 74 years. It has been based, since 2015, on the Fecal Immunochemical Test. The participation rate for 2016-2017 was 34%, which is lower than the European objectives. The objective of this study was to evaluate the impact of the program at the current participation rate and at rates of 45% and 65%. METHODS: The epidemiological impact of the program was estimated from the results of an individual simulation model adapted from the Microsimulation Screening Analysis Colon model, calibrated and transposed to the French context. An initial analysis was conducted to estimate the individual impact of screening and a second for the entire eligible population, at various participation rates. RESULTS: The test is associated with a lifetime reduction in the risk of colorectal cancer of 24% for men and 21% for women, and a reduction in the risk of death from colorectal cancer of 51% and 43% respectively. At the current level of participation, the program reduces incidence by 5% and mortality by 14% compared to no organized screening. The impact would be reduced by an additional 3% and 8% for participation rates of 45% and 65% respectively. Similarly, mortality would decrease by an additional 8% and 22%. CONCLUSION: These results confirm that in a population at medium risk for colorectal cancer, the organised programme is an effective strategy for reducing its incidence. They also confirm that the achievement of European objectives remains a key issue for improving the effectiveness of organized screening. An evolution of immunological test delivery modalities could help to achieve these participation objectives.

Comparison of 48-week efficacies of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide and nucleoside/nucleotide reverse transcriptase inhibitor-sparing regimens: a systematic review and network meta-analysis.

OBJECTIVES: To compare nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-sparing regimens with tenofovir alafenamide (TAF)-based combinations in HIV-1-infected adults, we performed a network meta-analysis (NMA) to provide estimates of relative efficacy for these two regimens. METHODS: A systematic literature review (SLR) was performed to identify phase 3/4 randomized controlled clinical trials evaluating the efficacy of commonly used combination antiretroviral therapy (cART) including an NRTI backbone or that of commonly used NRTI-sparing regimens. A Bayesian random-effect model was used to compare virological suppression rates at 48 weeks for NRTI-sparing regimens and elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF). RESULTS: Twenty-three studies in treatment-naïve patients identified by the SLR were included in the NMA, including four studies assessing NRTI-sparing regimens. In treatment-naïve patients, the probability of achieving virological suppression at 48 weeks was between 40% and 60% higher with E/C/F/TAF than with NRTI-sparing strategies. The credible interval vs. darunavir/ritonavir (DVR/r) + raltegravir (RAL) and LPV/r monotherapy did not include 1. In the subgroup of naïve patients with viral load < 100 000 HIV-1 RNA copies/mL, a credible difference was found between NRTI-sparing treatments and E/C/F/TAF. Studies in treatment-experienced patients were too heterogeneous to allow for an NMA. CONCLUSIONS: The NMA results suggest that E/C/F/TAF represents a more effective option than NRTI-sparing regimens in terms of 48-week efficacy in treatment-naïve patients. Furthermore, TAF pharmacological properties, as well as tolerability results in clinical studies, suggest a safety profile similar to that of NRTI-sparing regimens. Thus, the E/C/F/TAF combination might represent a more appropriate option than NRTI-sparing regimens for initiation of antiretroviral therapy in treatment-naïve HIV-infected patients.

[Cost-effectiveness of transurethral resection of the bladder with blue light in patients with non muscle invasive bladder cancer in France]. / Coût-efficacité de la résection transurétrale de vessie en lumière bleue chez les patients atteints d'un cancer de la vessie non infiltrant en France.

OBJECTIVE: Photodynamic diagnosis after instillation of hexylaminolevulinate (Hexvix(®)) during transurethral resection of the bladder (TURB) helps in the detection of tumors and results in a reduction of recurrence. The medical and economic impact of fluorescence compared to conventional white light TURB needed to be analyzed in the French healthcare system. The aim of this study was to evaluate the medical and economic impact of the blue light TURB in the treatment of NMIBC. MATERIALS AND METHODS: A cost-utility model, based on data from the literature and expert opinions, combining a decision tree and a Markov model was used to simulate the initial management after a first TURB of all new patients diagnosed with symptoms consistent with NMIBC and outcomes at short and long terms. In this model, the initial TURB could be achieved either with fluorescence in addition to white light, or with white light only. The main criteria of the model was based on the quality adjusted life years (QALY). The economic evaluation focused on the direct costs. The test's results and costs were determined from diagnosis until death of patients. RESULTS: The use of photodynamic diagnosis during TURB resulted in an improvement in QALYs (0.075) and a reduction of € 670 of the costs compared to the conventional treatment with white light. Thus, the blue light resection was defined as a strategy called "dominant" over the TURB in white light. CONCLUSION: In the context of the French health system, the model of the study showed that the blue light cystoscopy during TURB was associated with increased QALYs and reduced health spending. This kind of result is rare in oncology. This health economic analysis confirms the interest of hexylaminolevulinate acid in initial management of NMIBC, according to studies conducted in United Kingdom, Italy and Poland.

Cost-effectiveness of sofosbuvir in the treatment of patients with hepatitis C.

In France, 190,306 patients were suffering from chronic hepatitis C in 2012. These patients have a decreased life expectancy and are susceptible to complications associated with chronic hepatitis. Current treatments are poorly tolerated and their effectiveness varies depending on the genotype of the virus. Sofosbuvir, a new class of treatment, has demonstrated in five phase III trials sustained viral response (SVR) rates of over 90% across genotypes, higher than current treatments and has a tolerance profile similar to placebo. The objective was to determine the cost-effectiveness of using sofosbuvir in the treatment of chronic HCV infection. A Markov model was used to compare treatment strategies with and without sofosbuvir. The model simulated the natural history of HCV infection. SVR rates were based on data from clinical trials. Utilities associated with different stages of disease were based on data from the literature. French direct medical costs were used. Price for sofosbuvir was the price used in the early access program for severe fibrosis stages. The incremental cost-effectiveness ratio for sofosbuvir versus current reference treatments was € 16,278/QALY and varied from 40,000 €/QALY for F0 stages to 12,080 €/QALY for F4 stages. The sensitivity analyses carried out confirmed the robustness of this result. Sofosbuvir is a cost-effective treatment option for patients with hepatitis C.

Poor longitudinal continuity of care is associated with an increased mortality rate among patients with mental disorders: results from the French National Health Insurance Reimbursement Database.

BACKGROUND: Research on the impact of the continuity of care (COC) on health outcomes in patients with mental illness is limited. This observational study examined whether the longitudinal COC is associated with a decreased likelihood of death among patients with mental disorders in the French general population. METHOD: Data were derived from the French National Health Insurance (NHI) reimbursement database. Patients with any mental disorder who visited a psychiatrist at least twice within 6 months were included. The primary endpoint was death by all causes. We measured longitudinal COC with a psychiatrist twice a year between 2007 and 2010, using the COC index developed by Bice and Boxerman. The COC index was analysed as a time-dependent variable in a survival analysis after adjustments for age, gender and stratifying on comorbidities and social status. RESULTS: Among 14,515 patients visiting a psychiatrist at least twice in 6 months and tracked over 3 years, likelihood of death was significantly lower in patients with higher continuity of care (hazard ratio for an increase in 0.1 of continuity, adjusted for age, sex, and stratified on comorbidities and social status: 0.83 [0.83-0.83]), particularly in those with bipolar disorder, major depressive disorder and schizophrenia. CONCLUSION: Improving longitudinal continuity of care in mental health care may contribute to substantially decrease mortality.

[Development and validation of indicators relating to the quality of prevention and early management of postpartum haemorrhage (COMPAQ-HPST research project)]. / Développement et validation d'indicateurs relatifs à la qualité de la prévention et de la prise en charge initiale des hémorragies du postpartum (programme COMPAQ-HPST).

OBJECTIVES: To develop and validate a set of quality indicators (QIs) relating to the prevention and early management of postpartum haemorrhage (PPH) in maternity wards. The ultimate aim was to use these QIs for hospital comparison and public diffusion of results. MATERIALS AND METHODS: In 2009, COMPAQ-HPST developed a set of five QIs from consensus guidelines with the aid of experts and professional associations, relating to: i) the prevention of PH (three QIs) and ii) the initial management of PPH (two QIs). We also tested a questionnaire about the presence of written protocols in maternity wards. RESULTS: Ninety-seven voluntary maternity wards were included in the study. All five QIs showed wide variations in implementation among hospitals, revealing substantial room for improvement. Results of the questionnaire were variable according to the item considered. CONCLUSION: We validated five process QIs relating to the prevention and early management of PPH. All these five QIs have been transmitted to HAS for nationwide generalization. They should allow hospitals to implement quality of care improvement in this setting, adapted to their individual and comparative results.

Parameters of control when facing stochastic demand: a DEA approach applied to Bangladeshi vaccination sites.

An aim of vaccination programs is near-complete coverage. One method for achieving this is for health facilities providing these services to operate frequently and for many hours during each session. However, if vaccine vials are not fully used, the remainder is often discarded, considered as waste. Without an active appointment schedule process, there is no way for facility staff to control the stochastic demand of potential patients, and hence reduce waste. And yet reducing the hours of operation or number of sessions per week could hinder access to vaccination services. In lieu of any formal system of controlling demand, we propose to model the optimal number of hours and sessions in order to maximize outputs, the number and type of vaccines provided given inputs, using Data Envelopment Analysis (DEA). Inputs are defined as the amount of vaccine wastage and the number of full-time equivalent staff, size of the facility, number of hours of operation and the number of sessions. Outputs are defined as the number and type of vaccines aimed at children and pregnant women. This analysis requires two models: one DEA model with possible reallocations between the number of hours and the number of sessions but with the total amount of time fixed and one model without this kind of reallocation in scheduling. Comparing these two scores we can identify the "gain" that would be possible were the scheduling of hours and sessions modified while controlling for all other types of inefficiency. By modeling an output-based model, we maintain the objective of increasing coverage while assisting decision-makers determining optimal operating processes.

Sensitivity of fetal anomaly detection as a function of time.

In this paper, we show that the ratio of the number of fetal anomalies detected by ultrasounds (US) to the total number of cases is not a consistent estimator of the US sensitivity. As Eddy pointed out, when the disease evolves over time, the sensitivity of a test also varies over time according to the development of the disease. To assess correctly the detection capability of a test, it is therefore necessary to estimate a time continuous function (sensitivity function) instead of a single parameter. From a methodological point of view, by considering the "detectability" time of a fetal anomaly as a random variable and parametrizing its distribution function, we estimate the probability that an anomaly is detected conditional upon the precise timing of actually performed US during pregnancy. We fit this model with Eurofetus data (about 7,300 abnormal fetuses), and we compare estimations for different kinds of anomalies (classification based on the system involved and/or severity of the handicap). To allow for heterogeneity of anomalies regarding the detectability time, we generally adopt mixture models. For instance, we select a bi-gamma distribution for major malformations and estimate that 63% of such anomalies are detectable quite early in pregnancy (conditional mean: 15.2 weeks of amenorrhea (WA) +/- 4.2 WA), the others becoming detectable later (30.3 WA +/- 6.4 WA). Such results are then integrated in a cost-effectiveness analysis.

[Determination of the sensitivity of echography in prenatal diagnosis of fetal malformations. Methodological aspects]. / Détermination de la sensibilité de l'échographie dans le diagnostic anténatal des malformations foetales. Aspects méthodologiques.

In the article, following Eddy's work we show that the ratio of the number of cases detected by echography to the total number of cases is not a consistent estimator of test sensitivity of the pathology over time. In such conditions, the sensitivity of the test function is the only correct way to evaluate the test's ability to detect pathologic cases in an asymptomatic population. From a methodological point of view, if the time of detectability of the condition is considered as a random variable, then the function of sensitivity is estimated by fitting a distribution function to the observed date. In order to illustrate the feasibility and the consistency of our methodology, we present results based on simulated data.