[Cost of high-throughput sequencing (NGS) technologies: Literature review and insights]. / Coût des technologies de séquençage haut débit (NGS) : revue de la littérature et enseignements.

Although high-throughput sequencing technologies (Next-Generation Sequencing [NGS]) are revolutionizing medicine, the estimation of their production cost for pricing/tariffication by health systems raises methodological questions. The objective of this review of cost studies of high-throughput sequencing techniques is to draw lessons for producing robust cost estimates of these techniques. We analyzed, using an eleven item analysis framework, micro-costing studies of high-throughput sequencing technologies (n=17), including two studies conducted in the French context. The factors of variability between the studies that we identified were temporality (early evaluation of the innovation vs. evaluation of a mature technology), the choice of cost evaluation method (scope, micro- vs. gross-costing technique), the choice of production steps observed and the transposability of these studies. The lessons we have learned are that it is necessary to have a comprehensive vision of the sequencing production process by integrating all the steps from the collection of the biological sample to the delivery of the result to the clinician. It is also important to distinguish between what refers to the local context and what refers to the general context, by favouring the use of mixed methods to calculate costs. Finally, sensitivity analyses and periodic re-estimation of the costs of the techniques must be carried out in order to be able to revise the tariffs according to changes linked to the diffusion of the technology and to competition between reagent suppliers.

Economic Evaluation of Telerehabilitation: Systematic Literature Review of Cost-Utility Studies.

BACKGROUND: Telerehabilitation could benefit a large population by increasing adherence to rehabilitation protocols. OBJECTIVE: Our objective was to review and discuss the use of cost-utility approaches in economic evaluations of telerehabilitation interventions. METHODS: A review of the literature on PubMed, Scopus, Centres for Review and Dissemination databases (including the HTA database, the Database of Abstracts of Reviews of Effects, and the NHS Economic Evaluation Database), Cochrane Library, and ClinicalTrials.gov (last search on February 8, 2021) was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The inclusion criteria were defined in accordance with the PICOS (population, intervention, comparison, outcomes, and study design) system: the included studies had to evaluate patients in rehabilitation therapy for all diseases and disorders (population) through exercise-based telerehabilitation (intervention) and had to have a control group that received face-to-face rehabilitation (comparison), and these studies had to evaluate effectiveness through gain in quality of life (outcome) and used the design of randomized and controlled clinical studies (study). RESULTS: We included 11 economic evaluations, of which 6 concerned cardiovascular diseases. Several types of interventions were assessed as telerehabilitation, consisting in monitoring of rehabilitation at home (monitored by physicians) or a rehabilitation program with exercise and an educational intervention at home alone. All studies were based on randomized clinical trials and used a validated health-related quality of life instrument to describe patients' health states. Four evaluations used the EQ-5D, 1 used the EQ-5D-5L, 2 used the EQ-5D-3L, 3 used the Short-Form Six-Dimension questionnaire, and 1 used the 36-item Short Form survey. The mean quality-adjusted life years gained using telerehabilitation services varied from -0.09 to 0.89. These results were reported in terms of the probability that the intervention was cost-effective at different thresholds for willingness-to-pay values. Most studies showed results about telerehabilitation as dominant (ie, more effective and less costly) together with superiority or noninferiority in outcomes. CONCLUSIONS: There is evidence to support telerehabilitation as a cost-effective intervention for a large population among different disease areas. There is a need for conducting cost-effectiveness studies in countries because the available evidence has limited generalizability in such countries. TRIAL REGISTRATION: PROSPERO CRD42021248785; https://tinyurl.com/4xurdvwf.

Perioperative time and economic impact of an intracameral combination of mydriatics and anaesthetics in routine cataract surgery.

PURPOSE: The aim of this study was to compare the perioperative time and economic impact of a licensed intracameral anaesthetic/mydriatic combination (Mydrane) during routine cataract surgery. METHODS: A real-life, prospective, comparative study was performed in 3 clinical centres in France. Preoperative, surgical, and post-operative times were determined for two mydriasis strategies using conventional preoperative mydriatics/anaesthetics eye drops (control regimen) or Mydrane administered at time of surgery. Staff, surgery schedules and drugs utilisation were collected over 12 surgery half-days. The total cost of each strategy was estimated based on treatment cost and nursing costs. RESULTS: The analysis included 112 routine cataract surgeries (57 surgeries using Mydrane and 55 using the topical regimen) without protocol deviations or complicated surgery. Overall, the mean time between administration of the first mydriatic eye drops or Mydrane and the end of the surgery was 27.4 ± 21.1 min in the Mydrane group vs. 90.3 ± 30.4 min in the control group (P < 0.0001). The total time of the procedure (from admission to discharge) was not significantly different between groups (P = 0.1611). On average, the extra cost of drugs per patient in the Mydrane group (€5.81) was almost balanced by the reduced nursing time (€5.57) with some variations between centres, due to different organisation including staff resource and consumable. CONCLUSIONS: The Mydrane strategy produced perioperative nursing time saving and cost reduction provided that adaptation and reorganisation of routine cataract surgery are implemented.

Absenteeism and indirect costs during the year following the diagnosis of an operable breast cancer: A prospective multicentric cohort study.

BACKGROUND: Diseases consequence on individual work as much as consequences of being absent from work are matters of interest for decision makers. METHODS: We analyzed lengths of absenteeism and related indirect costs for patients with a paid activity in the year following the diagnosis of early stage breast cancer, in the prospective OPTISOINS01 cohort. Both human capital and friction costs approach were considered for the valuation of lost working days (LWD). For the analysis, the friction period was estimated from recent French data. The statistical analysis included simple and multiple linear regression to search for the determinants of absenteeism and indirect costs. RESULTS: 93 % of the patients had at least one period of sick leave, with on average 2 period and 186 days of sick leave. 24 % of the patients had a part-time resumption after their sick leave periods, during 114 days on average (i.e. 41 LWD). Estimated indirect costs were 22,722.00 € and 7,724.00 € per patient, respectively for the human capital and the friction cost approach. In the multiple linear regression model, factors associated with absenteeism were: the invasive nature of the tumor (p = .043), a mastectomy (p = .038), a surgery revision (p = .002), a chemotherapy (p = .027), being a manager (p = .025) or a craftsman (p = .005). CONCLUSION: Breast cancer lead to important lengths of absenteeism in the year following the diagnosis, but almost all patients were able to return to work. Using the friction cost or the human capital approach in the analysis led to an important gap in the results, highlighting the importance of considering both for such studies.

Cost-effectiveness of emicizumab vs bypassing agents in the prevention of bleeding episodes in haemophilia A patients with anti-FVIII inhibitors in France.

INTRODUCTION: The development of an anti-FVIII inhibitor is the most serious complication of haemophilia A occurring in up to 30% of severe haemophilic patients. The current management of haemophilia A with inhibitor uses bypassing agents (BPA) and represents a significant therapeutic burden together with a limited adherence to prophylactic treatment. Emicizumab is the first monoclonal antibody developed in haemophilia A approved for the prevention of bleeding episodes in patients with anti-FVIII inhibitor. AIM: The purpose of this study is to evaluate the incremental cost-effectiveness ratio (ICER) of emicizumab versus BPAs. METHODS: A Markov model was developed over a five-year time horizon to estimate the comparative costs and benefits of the different therapeutic approaches in this rare disease. Model inputs were clinical, including annual bleeding rate and quality of life, and economical including mainly costs of prophylaxis, bleeds and adverse events. RESULTS: Emicizumab treatment is dominant, ie lest costly and more effective, in the base-case analysis saving 234 191 € for a gain of 0.88 QALY. This is confirmed by both the deterministic and probabilistic sensitivity analyses. The main limit of the study remains the absence of long-term clinical data allowing to relate treatment consumption to clinical benefit, especially in the progression of haemophilic arthropathy. CONCLUSION: Our results show that emicizumab is a cost-effective treatment allowing to consider an easy to implement prophylactic treatment for haemophilia A patients with anti-FVIII inhibitors.

From prospective clinical trial to reducing social inequalities in health: The DESSEIN trial, concept and design of a multidisciplinary study in precarious patients with breast cancer.

BACKGROUND: In France during the last 15 years, precariousness among women has increased. In breast cancer, precariousness has been associated with an increase in mortality, but the links between precariousness, stage at diagnosis and care pathway are little explored. Our study aims to evaluate the impact of precariousness on care pathways, treatment and recovery phase according to a multidisciplinary analysis. METHODS AND DESIGN: Comparative prospective observational multicenter study of exposed / unexposed category. Patients with breast cancer are recruited in the Ile de France area. Three scores are used to identify precarious patients. Precarious patients are matched to non-precarious patients by age group. Questionnaires are distributed to patients at different times of care. The main objective is to compare the stage of the disease at diagnosis between two groups. The secondary objectives are: comparison of socio-economic and geographical characteristics, direct and indirect costs, personal trajectories of care and health. Analysis include multidisciplinary approaches. A geographical information systems method will evaluate the accessibility to health facilities and the characteristics of the places of residence of the patients. An anthropological analysis will be conducted through observation of consultations and semi-directed interviews with patients. These methods will allow to analyze the diagnostic and therapeutic routes, placing it in a life history and an economic, socio-cultural and health environment. The economic analysis will include a comparison of direct, indirect costs and out-off pocket costs, from the patient's point of view and from the societal perspective. DISCUSSION: Conducted in a clinical setting and coupled with a qualitative study, this study will provide a better understanding of how contextual factors, combined with individual factors, can influence the course of health and thus the stage of the disease at diagnosis. The multidisciplinary approach, involving clinicians, geographers, an anthropologist, an economist and a health epidemiologist, will allow a multidimensional approach to the impact of precariousness on breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02948478 registered October 28, 2016. ID RCB: 2016-A00589-42. protocol version: 2.1. decembre 13, 2018.

Direct medical and non-medical costs of a one-year care pathway for early operable breast cancer: Results of a French multicenter prospective study.

INTRODUCTION: The organization of health care for breast cancer (BC) constitutes a public health challenge to ensure quality of care, while also controlling expenditure. Few studies have assessed the global care pathway of early BC patients, including a description of direct medical costs and their determinants. The aims of this multicenter prospective study were to describe care pathways of BC patients in a geographic territory and to calculate the global direct costs of early stage BC during the first year following diagnosis. METHODS: OPTISOINS01 was a multicenter, prospective, observational study including early BC patients from diagnosis to one-year follow-up. Direct medical costs (in-hospital and out-of-hospital costs, supportive care costs) and direct non-medical costs (transportation and sick leave costs) were calculated by using a cost-of-illness analysis based on a bottom-up approach. Resources consumed were recorded in situ for each patient, using a prospective direct observation method. RESULTS: Data from 604 patients were analyzed. Median direct medical costs of 1 year of management after diagnosis in operable BC patients were €12,250. Factors independently associated with higher direct medical costs were: diagnosis on the basis of clinical signs, invasive cancer, lymph node involvement and conventional hospitalization for surgery. Median sick leave costs were €8,841 per patient and per year. Chemotherapy was an independent determinant of sick leave costs (€3,687/patient/year without chemotherapy versus €10,706 with chemotherapy). Forty percent (n = 242) of patients declared additional personal expenditure of €614/patient/year. No drivers of these costs were identified. CONCLUSION: Initial stage of disease and the treatments administered were the main drivers of direct medical costs. Direct non-medical costs essentially consisted of sick leave costs, accounting for one-half of direct medical costs for working patients. Out-of-pocket expenditure had a limited impact on the household.

Multidimensional impact of breast cancer screening: Results of the multicenter prospective optisoins01 study.

Breast cancer (BC) screening has been developed to detect earlier stage tumors associated with better prognosis. The aim of study was to evaluate the impact of BC screening on therapeutic management of patients with first operable BC, and on costs, patients' needs, and working life. OPTISOINS01 was a multicenter, prospective observational study which aimed to identify the main care pathway of early BC. Among patients aged from 50 to 74 years-old, 2 groups were defined: the "Clinical signs" group and the "Screening" group (national organized screening and individual screening). We compared between these 2 groups: locoregional and systemic treatments, direct medical and non-medical costs from a National Health Insurance perspective, patients' needs assessed by the validated SCNS-BR8 "breast cancer" module of the SCNS-SF34 supportive care needs survey and the duration of sick leave. The "Clinical signs" group included 89 patients, while the"Screening" group included 290 patients. More axillary lymph node dissections and radical breast surgery were performed in the "Clinical signs". The rate of adjuvant chemotherapy was dramatically higher in the "Clinical signs" group. The median direct medical costs of the "Screening" group were €11,860 (€3,643-€41,030) per year and per patient, much lower than in the "Clinical signs" group (€14,940; €5,317-€41,070). Finally, needs specifically assessed by the SCNS-BR8 questionnaire were significantly higher for the postoperative and post-adjuvant periods in the "Clinical signs" group. This study highlighted the benefit of BC screening in terms of reduced therapies and positive impact on work and social life.

Correction: Cost of cancer diagnosis using next-generation sequencing targeted gene panels in routine practice: a nationwide French study.

Since the publication of the article, it has been noted that there is an error in Table 2. Where 543€ is listed in the final column of the table, this should have been written as 550€.

Determinants of return at work of breast cancer patients: results from the OPTISOINS01 French prospective study.

INTRODUCTION: Return to work (RTW) after breast cancer (BC) is still a new field of research. The factors determining shorter sick leave duration of patients with BC have not been clearly identified. The aim of this study was to describe work during BC treatment and to identify factors associated with sick leave duration. MATERIALS AND METHODS: An observational, prospective, multicentre study was conducted among women with operable BC. A logbook was given to all working patients to record sociodemographic and work-related data over a 1-year period. RESULTS: Work-related data after BC were available for 178 patients (60%). The median age at diagnosis was 50 years (27-77), 87.9% of patients had an invasive form of BC and 25.3% a lymph node involvement. 25.9% had a radical surgery and 24.2% had an axillary dissection. Radiotherapy was performed in 90.9% of patients and chemotherapy in 48.1%. Sick leave was prescribed for 165 patients (92.7%) for a median of 155 days. On univariate analysis, invasive BC (p=0.025), lymph node involvement (p=0.005), radical surgery (p=0.025), axillary dissection (p=0.004), chemotherapy (p<0.001), personal income <€1900/month (p=0.03) and not having received the patient information booklet on RTW (p=0.047) were found to be associated with a longer duration of sick leave. On multivariate analysis, chemotherapy was found to be associated with longer sick leave (OR: 3.5; 95% CI 1.6 to 7.9; p=0.002). The cost of sick leave to French National Health Insurance was fourfold higher in the case of chemotherapy (p<0.001). CONCLUSION: Advanced disease and chemotherapy are major factors that influence sick leave duration during the management of BC. TRIAL REGISTRATION NUMBER: NCT02813317.