Photocoagulation or sham laser in addition to conventional anti-VEGF therapy in macular edema associated with TelCaps due to diabetic macular edema or retinal vein occlusion (TalaDME): a study protocol for a multicentric, French, two-group, non-commercial, active-control, observer-masked, non-inferiority, randomized controlled clinical trial.

BACKGROUND: Macular edema (ME) results from hyperpermeability of retinal vessels, leading to chronic extravasation of plasma components into the retina and hence potentially severe visual acuity loss. Current standard of care consists in using intravitreal injections (IVI), which results in a significant medical and economic burden. During diabetic retinopathy (DR) or retinal vein occlusion (RVO), it has recently been shown that focal vascular anomalies (capillary macro-aneurysms, also termed TelCaps) for telangiectatic capillaries may play a central role in the onset, early recurrence, and/or persistence of ME. Since targeted photocoagulation of TelCaps may improve vision, identification, and photocoagulation of TelCaps, it may represent a way to improve management of ME. OBJECTIVE: The Targeted Laser in (Diabetic) Macular Edema (TalaDME) study aims to evaluate whether ICG-guided targeted laser (IGTL), in association with standard of care by IVI, allows reducing the number of injections during the first year of treatment compared with IVI only, while remaining non-inferior for visual acuity. METHODS: TalaDME is a French, multicentric, two-arms, randomized, sham laser-controlled, double-masked trial evaluating the effect of photocoagulation of TelCaps combined to IVI in patients with ME associated with TelCaps. Patients with vision loss related to center involved ME secondary to RVO or DR and presenting TelCaps are eligible. Two hundred and seventy eyes of 270 patients are randomized in a 1:1 ratio to standard care, i.e., IVI of anti-VEGF solely (control group) or combined with IGTL therapy (experimental group). Stratification is done on the cause of ME (i.e., RVO versus diabetes). Anti-VEGF IVI are administered to both groups monthly for 3 months (loading dose) and then with a pro re nata regimen with a monthly follow-up for 12 months. The primary endpoint will be the number of IVI and the change in visual acuity from baseline to 12 months. Secondary endpoints will be the changes in central macular thickness, impact on quality of life, cost of treatment, and incremental cost-utility ratio in each groups. KEY SAFETY: Rare but severe AE linked to the use of IVI and laser, and previously described, are expected. In the sham group, rescue laser photocoagulation may be administered by the unmasked investigator if deemed necessary at month 3. DISCUSSION: The best management of ME associated with TelCaps is debated, and there have been no randomized study designed to answer this question. Given the fact that TelCaps may affect 30 to 60% of patients with chronic ME due to DR or RVO, a large number of patients could benefit from a specific management of TelCaps. TalaDME aims to establish the clinical and medico-economic benefits of additional targeted laser. The results of TalaDME may raise new recommendations for managing ME and impact healthcare costs. TRIAL REGISTRATION: EudraCT: 2018-A00800-55/ NCT03751501. Registration date: Nov. 23, 2018.

14-day tailored PCR-guided triple therapy versus 14-day non-Bismuth concomitant quadruple therapy for Helicobacter pylori eradication: A multicenter, open-label randomized noninferiority controlled trial.

BACKGROUND: The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established. AIM: To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication. PATIENTS AND METHODS: We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication. RESULTS: We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at -0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population. CONCLUSION: In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).

The cost of illness and burden of suicide and suicide attempts in France.

BACKGROUND: With 11,558 deaths and 200,000 suicide attempts in 2019, France is among the European countries most affected. The aim of this study was to determine the costs and burden of suicides and suicide attempts in France (population 67 million). METHODS: We estimated direct costs, comprising healthcare, as well as post-mortem costs including autopsy, body removal, funeral expenses, police intervention and support groups; indirect costs comprised lost productivity, daily allowances; the burden of disease calculations used a monetary value for death and disability based on incidence data. Data was obtained from the national statistics, health and social care database, registries, global burden of disease, supplemented by expert opinion. We combined top down and bottom up approaches. RESULTS: The total costs and burden of suicides and suicide attempts was estimated at €18.5 billion and €5.4 billion, respectively. Direct costs were €566 million and €75 million; indirect costs were €3.8 billion and €3.5 billion; monetary value for death and disability was €14.6 billion and €1.3. The monetary value for death and disability represented 79.1% and 24.8% of total costs for suicide and suicide attempt respectively. Some costs were based upon expert opinion, caregivers' burden was not counted and pre COVID data only is reported. CONCLUSIONS: In France, the total cost and burden of suicides and suicide attempts was several billion €, suggesting major potential savings from public health interventions.

An eye on equity: faricimab-driven health equity improvements in diabetic macular oedema using a distributional cost-effectiveness analysis from a UK societal perspective.

BACKGROUND/OBJECTIVES: Diabetic macular oedema (DMO) is a leading cause of blindness in developed countries, with significant disease burden associated with socio-economic deprivation. Distributional cost-effectiveness analysis (DCEA) allows evaluation of health equity impacts of interventions, estimation of how health outcomes and costs are distributed in the population, and assessments of potential trade-offs between health maximisation and equity. We conducted an aggregate DCEA to determine the equity impact of faricimab. METHODS: Data on health outcomes and costs were derived from a cost-effectiveness model of faricimab compared with ranibizumab, aflibercept and off-label bevacizumab using a societal perspective in the base case and a healthcare payer perspective in scenario analysis. Health gains and health opportunity costs were distributed across socio-economic subgroups. Health and equity impacts, measured using the Atkinson inequality index, were assessed visually on an equity-efficiency impact plane and combined into a measure of societal welfare. RESULTS: At an opportunity cost threshold of £20,000/quality-adjusted life year (QALY), faricimab displayed an increase in net health benefits against all comparators and was found to improve equity. The equity impact increased the greater the concerns for reducing health inequalities over maximising population health. Using a healthcare payer perspective, faricimab was equity improving in most scenarios. CONCLUSIONS: Long-acting therapies with fewer injections, such as faricimab, may reduce costs, improve health outcomes and increase health equity. Extended economic evaluation frameworks capturing additional value elements, such as DCEA, enable a more comprehensive valuation of interventions, which is of relevance to decision-makers, healthcare professionals and patients.

Outcomes and costs with the introduction of robotic-assisted thoracic surgery in public hospitals.

Robotic-assisted thoracic surgery (RATS) is an effective treatment of non-small cell lung cancer (NSCLC) but the effects of its implementation in university hospital networks has not been described. We analyzed the early clinical outcomes, estimated costs, and revenues associated with three robotic systems implemented in the Paris Public Hospital network. A retrospective study included patients who underwent RATS for NSCLC in 2019 and 2020. Ninety-day morbidity, mortality, hospital costs, and hospital revenues were described. Economic analyses were conducted either from the hospital center or from the French health insurance system perspectives. Cost drivers were tested using univariate and multivariable analyses. Sensitivity analyses were performed to assess uncertainty over in-hospital length of stay (LOS), number of robotic surgeries per year, investment cost, operating room occupancy time, maintenance cost, and commercial discount. The study included 188 patients (65.8 ± 9.3 years; Charlson 4.1 ± 1.4; stage I 76.6%). Median in-hospital LOS was 6 days [5-9.5], 90-day mortality was 1.6%. Mean hospital expenses and revenues were €12,732 ± 4914 and €11,983 ± 5708 per patient, respectively. In multivariable analysis, factors associated with hospital costs were body mass index, DLCO, major complications, and transfer to intensive care unit. Sensitivity analyses showed that in-hospital LOS (€11,802-€15,010) and commercial discounts on the list price (€11,458-€12,732) had an important impact on costs. During the first 2 years following the installation of three robotic systems in Paris Public Hospitals, the clinical outcomes of RATS for NSCLC have been satisfactory. Without commercial discount, hospital expenses would have exceeded hospital revenues.Clinical registration number CNIL, N°2221601, CERC-SFCTCV-2021-07-20-Num17_MOPI_robolution.

Weight telemonitoring of heart failure versus standard of care in a real-world setting: Results on mortality and hospitalizations in a 6-month nationwide matched cohort study.

AIMS: Evaluating the benefit of telemonitoring in heart failure (HF) management in real-world settings is crucial for optimizing the healthcare pathway. The aim of this study was to assess the association between a 6-month application of the telemonitoring solution Chronic Care Connect™ (CCC) and mortality, HF hospitalizations, and associated costs compared with standard of care (SOC) in patients with a diagnosis of HF. METHODS AND RESULTS: From February 2018 to March 2020, a retrospective cohort study was conducted using the largest healthcare insurance system claims database in France (Système National des Données de Santé) linked to the CCC telemonitoring database of adult patients with an ICD-10-coded diagnosis of HF. Patients from the telemonitoring group were matched with up to two patients from the SOC group based on their high-dimensional propensity score, without replacement, using the nearest-neighbour method. A total of 1358 telemonitored patients were matched to 2456 SOC patients. The cohorts consisted of high-risk patients with median times from last HF hospitalization to index date of 17.0 (interquartile range: 7.0-66.0) days for the telemonitoring group and 27.0 (15.0-70.0) days for the SOC group. After 6 months, telemonitoring was associated with mortality risk reduction (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.56-0.89), a higher risk of first HF hospitalization (HR 1.81, 95% CI 1.55-2.13), and higher HF healthcare costs (relative cost 1.38, 95% CI 1.26-1.51). Compared with the SOC group, the telemonitoring group experienced a shorter average length of overnight HF hospitalization and fewer emergency visits preceding HF hospitalizations. CONCLUSION: The results of this nationwide cohort study highlight a valuable role for telemonitoring solutions such as CCC in the management of high-risk HF patients. However, for telemonitoring solutions based on weight and symptoms, consideration should be given to implement additional methods of assessment to recognize imminent worsening of HF, such as impedance changes, as a way to reduce mortality risk and the need for HF hospitalizations. Further studies are warranted to refine selection of patients who could benefit from a telemonitoring system and to confirm long-term benefits in high-risk and stable HF patients.

Study protocol for FASTRAK: a randomised controlled trial evaluating the cost impact and effectiveness of FAST-MRI for HCC suRveillance in pAtients with high risK of liver cancer.

INTRODUCTION: The surveillance of hepatocellular carcinoma (HCC) using semi-annual liver ultrasound (US) is justified in patients with cirrhosis. In this context, US has a low sensitivity (<30%) for the detection of HCC at the very early stage (ie, Barcelona clinic liver cancer (BCLC) 0, uninodular tumour <2 cm). The sensitivity of abbreviated liver MRI (AMRI) is reported to exceed 80%, but its use is hampered by costs and availability. Our hypothesis is that AMRI used as a screening examination in patients at high risk of HCC (>3% per year) could increase the rates of patients with a tumour detected at an early stage accessible to curative-intent treatment, and demonstrate its cost-effectiveness in this population. METHODS AND ANALYSIS: The FASTRAK trial is a multicentre, randomised controlled trial with two parallel arms, aiming for superiority and conducted on patients at high risk for HCC (yearly HCC incidence >3%). Randomisation will be conducted on an individual basis with a centralised approach and stratification by centre. After inclusion in the trial, each patient will be randomly assigned to the experimental group (semi-annual US and AMRI) or the control group (semi-annual US alone). The main objective is to assess the cost/quality-adjusted life year and cost/patient detected with a BCLC 0 HCC in both arms. A total of 944 patients will be recruited in 37 tertiary French centres during a 36-month period and will be followed-up during 36 months. ETHICS AND DISSEMINATION: The FASTRAK trial received ethical approval on 4 April 2022. Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences. TRIAL REGISTRATION NUMBER: Clinical trial number (ClinicaTrials.gov) NCT05095714.

Cost-effectiveness of stepwise provisional versus systematic dual stenting strategies in patients with distal bifurcation left main stem lesions: economic analysis of the EBC MAIN trial.

BACKGROUND: In patients with distal bifurcation left main stem lesions requiring intervention, the European Bifurcation Club Left Main Coronary Stent Study trial found a non-significant difference in major adverse cardiac events (MACEs, composite of all-cause death, non-fatal myocardial infarction and target lesion revascularisation) favouring the stepwise provisional strategy, compared with the systematic dual stenting. AIMS: To estimate the 1-year cost-effectiveness of stepwise provisional versus systematic dual stenting strategies. METHODS: Costs in France and the UK, and MACE were calculated in both groups to estimate the incremental cost-effectiveness ratio (ICER). Uncertainty was explored by probabilistic bootstrapping. The analysis was conducted from the perspective of the healthcare provider with a time horizon of 1 year. RESULTS: The cost difference between the two groups was €-755 (€5700 in the stepwise provisional group and €6455 in the systematic dual stenting group, p value<0.01) in France and €-647 (€6728 and €7375, respectively, p value=0.08) in the UK. The point estimates for the ICERs found that stepwise provisional strategy was cost saving and improved outcomes with a probabilistic sensitivity analysis confirming dominance with an 80% probability. CONCLUSION: The stepwise provisional strategy at 1 year is dominant compared with the systematic dual stenting strategy on both economic and clinical outcomes.

Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial.

RATIONALE: Mechanical thrombectomy (MT) associated with the best medical treatment (BMT) has recently shown efficacy for the management of acute ischemic stroke (AIS) secondary to a large vessel occlusion. However, evidence is lacking regarding the benefit of MT for more distal occlusions. AIM: To evaluate the efficacy in terms of good clinical outcome at 3 months of MT associated with the BMT over the BMT alone in AIS related to a distal occlusion. METHODS: The DISCOUNT trial is a multicenter open-label randomized controlled trial involving French University hospitals. Adult patients (⩾18 years) with an AIS involving the anterior or posterior circulation secondary to a distal vessel occlusion within 6 h of symptom onset or within 24 h if no hyperintense signal on fluid attenuation inversion recovery acquisition will be randomized 1:1 to receive either MT associated with the BMT (experimental group) or BMT alone (control group). The number of patients to be included is 488. STUDY OUTCOMES: The primary outcome is the rate of good clinical outcome at 3 months defined as a modified Rankin scale (mRS) ⩽2 and evaluated by an independent assessor blinded to the intervention arm. Secondary outcomes include recanalization of the occluded vessel within 48 h, angiographic reperfusion in the experimental group, 3-month excellent clinical outcome (mRS ⩽ 1), all adverse events, and death. A cost utility analysis will estimate the incremental cost per quality-adjusted life year (QALY) gained. DISCUSSION: If positive, this study will open new insights in the management of AISs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05030142 registered on 1 September 2021.

The clinical and financial burden of nonhepatocellular carcinoma focal lesions detected during the surveillance of patients with cirrhosis.

BACKGROUND AND AIMS: HCC surveillance is challenged by the detection of hepatic focal lesions (HFLs) of other types. This study aimed to describe the incidence, characteristics, outcomes, and costs of non-HCC HFL detected during surveillance. APPROACH AND RESULTS: We retrospectively analyzed nonstandardized workup performed in French patients included in HCC surveillance programs recruited in 57 French tertiary centers (ANRS CirVir and CIRRAL cohorts, HCC 2000 trial). The overall cost of workup was evaluated, with an estimation of an average cost per patient for the entire population and per lesion detected. A total of 3295 patients were followed up for 59.8 months, 391 (11.9%) patients developed HCCs (5-year incidence: 12.1%), and 633 (19.2%) developed non-HCC HFLs (5-year incidence: 21.8%). Characterization of non-HCC HFL required a median additional of 0.7 exams per year. A total of 11.8% of non-HCC HFLs were not confirmed on recall procedures, and 19.6% of non-HCC HFLs remained undetermined. A definite diagnosis of benign liver lesions was made in 65.1%, and malignant tumors were diagnosed in 3.5%. The survival of patients with benign or undetermined non-HCC HFL was similar to that of patients who never developed any HFL (5-year survival 92% vs. 88%, p = 0.07). The average cost of the diagnostic workup was 1087€ for non-HCC HFL and €1572 for HCC. CONCLUSIONS: Non-HCC HFLs are frequently detected in patients with cirrhosis, and do not impact prognosis, but trigger substantial costs. This burden must be considered in cost-effectiveness analyses of future personalized surveillance strategies.

Real-World Treatment Patterns and Effectiveness of Patients With Advanced Renal Cell Carcinoma: A Nationwide Observational Study.

BACKGROUND: Treatment landscape for advanced renal cell carcinoma (aRCC) has evolved quickly and few data about the real-world treatment patterns are available. This study aimed at describing the real-world treatment patterns and effectiveness of all systemic treatments available for aRCC in first and second-line treatment. MATERIALS AND METHODS: A cohort of patients initiating a first-line systemic treatment for aRCC in 2016 was extracted from the French nationwide healthcare insurance system database (SNDS). The first-line treatment initiation date constituted the index date and patients were followed until death, loss to follow-up, or December 31, 2019, whichever occurred first. aRCC was identified using hospital diagnosis, long-term disease, or renal biopsy before index date. All analyses were performed for first and second-line treatment. Overall survival (OS) and time-to-next treatment or death (TNT-D) were estimated using Kaplan-Meier approach. RESULTS: In 2016, 1629 patients initiated a first-line treatment for aRCC. Most of them were male (75.9%) and the median age was 67 years. Most of patients (91.7%) had received a tyrosine kinase inhibitor as first-line treatment, mainly sunitinib (64.4%), and 53.5% received a second-line, among which 43.7% nivolumab. Median OS (95% confidence interval [CI]) was 20.7 (95% CI:18.2-22.4) months from first-line treatment initiation and 15.4 (13.9-17.5) months from second-line treatment initiation. Median TNT-D were respectively 9.3 (9.7-12.1) months and 6.9 (5.9-7.7) months. CONCLUSION: This study highlights the limited survival of aRCC patients These results provide a valuable baseline and highlight the need for innovation, such as immune checkpoint inhibitor-based combinations that have recently became first-line standard of care.

The Cost-Effectiveness of Rivaroxaban Plus Aspirin Compared with Aspirin Alone in the COMPASS Trial: A US Perspective.

BACKGROUND: Rivaroxaban 2.5 mg twice daily with aspirin 100 mg daily was shown to be better than aspirin 100 mg daily for preventing cardiovascular (CV) death, stroke or myocardial infarction in patients with either stable coronary artery disease (CAD) or peripheral artery disease (PAD). The cost-effectiveness of this regimen in this population is essential for decision-makers to know. METHODS: US direct healthcare system costs (in USD) were applied to hospitalized events, procedures and study drugs utilized by all patients. We determined the mean cost per participant for the full duration of the trial (mean follow-up of 23 months) plus quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) over a lifetime using a two-state Markov model with 1-year cycle length. Sensitivity analyses were performed on the price of rivaroxaban and the annual discontinuation rate. RESULTS: The costs of events and procedures were reduced for Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) patients who received rivaroxaban 2.5 mg orally (BID) plus acetylsalicylic acid (ASA) compared with ASA alone. Total costs were higher for the combination group ($7426 versus $4173) after considering acquisition costs of the study drug. Over a lifetime, patients receiving rivaroxaban plus ASA incurred $27,255 more and gained 1.17 QALYs compared with those receiving ASA alone resulting in an ICER of $23,295/QALY. ICERs for PAD only and polyvascular disease subgroups were lower. CONCLUSION: Rivaroxaban 2.5 mg BID plus ASA compared with ASA alone was cost-effective (high value) in the USA. COMPASS ClinicalTrials.gov identifier: NCT01776424.

Costs of purchase, maintenance, microbiological control, and reprocessing of a reusable duodenoscope.

Background and study aims The costs of reusable endoscope reprocessing have been evaluated, yet external validity of the findings remains challenging. The aim of this study was to assess the costs of purchase, maintenance, microbiological control, and reprocessing of a reusable duodenoscope per endoscopic retrograde cholangiopancreatography (ERCP) in France. Study findings exclude the costs of infection, downtime due to breakdown, reprocessing single-use material disposal, and device disposal, all of which should also be considered. Materials and methods The study encompassed both observational and theoretical approaches. Observational data were collected in four hospitals, from December 2019 to December 2020, with an ad hoc survey, based on 2016 and 2018 national guidelines for duodenoscope reprocessing. Costs were modeled, using the same guidelines, assuming a mean workload of 223 ERCP/duodenoscope/year. Results The mean observed cost of purchase, maintenance, microbiological control, reprocessing (human resources and consumables), and overhead (additional 35%) with a reusable duodenoscope was €80.23 (standard deviation €3.77) per ERCP. The corresponding mean theoretical cost was €182.71 for manual reprocessing without endoscope drying cabinet (EDC), €191.36 for manual reprocessing with EDC, €235.25 for automated endoscope reprocessing (AER) without EDC, and €253.62 for AER with EDC. Conclusions Because procedures, equipment, volume activity, number of duodenoscopes, human resources, and internal work organizations are hospital-dependent, observed costs varied between hospitals. Theoretical costs were higher than observed costs, showing that the theoretical approach is not sufficient. Hypotheses to explain the difference between the two approaches include failing to measure some costs in the survey and challenges in guideline implementation.

Cost-effectiveness of modified diagnostic strategy to safely rule-out pulmonary embolism in the emergency department: a non-inferiority cluster crossover randomized trial (MODIGLIA-NI).

BACKGROUND: The aim of this trial-based economic evaluation was to assess the incremental costs and cost-effectiveness of the modified diagnostic strategy combining the YEARS rule and age-adjusted D-dimer threshold compared with the control (which used the age-adjusted D-dimer threshold only) for the diagnosis of pulmonary embolism (PE) in the Emergency Department (ED). METHODS: Economic evaluation from a healthcare system perspective alongside a non-inferiority, crossover, and cluster-randomized trial conducted in 16 EDs in France and two in Spain with three months of follow-up. The primary endpoint was the additional cost of a patient without failure of the diagnostic strategy, defined as venous thromboembolism (VTE) diagnosis at 3months after exclusion of PE during the initial ED visit. Mean differences in 3-month failure and costs were estimated using separate generalized linear-regression mixed models, adjusted for strategy type, period, and the interaction between strategy and period as fixed effects and the hospital as a random effect. The incremental cost-effectiveness ratio (ICER) was obtained by dividing the incremental costs by the incremental frequency of VTE. RESULTS: Of the 1,414 included patients, 1,217 (86%) were analyzed in the per-protocol analysis (648 in the intervention group and 623 in the control group). At three months, there were no statistically significant differences in total costs (€-46; 95% CI: €-93 to €0.2), and the failure rate was non inferior in the intervention group (-0.64%, one-sided 97.5% CI: -∞ to 0.21%, non-inferiority margin 1.5%) between groups. The point estimate of the incremental cost-effectiveness ratio (ICER) indicating that each undetected VTE averted in the intervention group is associated with cost savings of €7,142 in comparison with the control group. There was a 93% probability that the intervention was dominant. Similar results were found in the as randomized population. CONCLUSIONS: Given the observed cost decrease of borderline significance, and according to the 95% confidence ellipses, the intervention strategy has a potential to lead to cost savings as a result of a reduction in the use of chest imaging and of the number of undetected VTE averted. Policy-makers should investigate how these monetary benefits can be distributed across stakeholders. CLINICALTRIALS: Trial registration number ClinicalTrials.gov Identifier: NCT04032769; July 25, 2019.

The role of quantitative bias analysis for nonrandomized comparisons in health technology assessment: recommendations from an expert workshop.

The use of treatment effects derived from nonrandomized studies (NRS) in health technology assessment (HTA) is growing. NRS carry an inherently greater risk of bias than randomized controlled trials (RCTs). Although bias can be mitigated to some extent through appropriate approaches to study design and analysis, concerns around data availability and quality and the absence of randomization mean residual biases typically render the interpretation of NRS challenging. Quantitative bias analysis (QBA) methods are a range of methods that use additional, typically external, data to understand the potential impact that unmeasured confounding and other biases including selection bias and time biases can have on the results (i.e., treatment effects) from an NRS. QBA has the potential to support HTA bodies in using NRS to support decision-making by quantifying the magnitude, direction, and uncertainty of biases. However, there are a number of key aspects of the use of QBA in HTA which have received limited discussion. This paper presents recommendations for the use of QBA in HTA developed using a multi-stakeholder workshop of experts in HTA with a focus on QBA for unmeasured confounding.

Prevalence and cost of sickle cell disease in France: real-world analysis using data from the Echantillon Généraliste des Bénéficiaires.

Sickle cell disease (SCD) is a genetic disorder of the hemoglobin resulting in chronic anemia, hemolysis, and vaso-occlusions. Its treatment mostly relies on hydroxycarbamide, transfusions, and stem cell transplantation. This study aimed at describing the epidemiology and management of SCD in adolescent and adult patients in France. This was a retrospective study performed among SCD patients aged ≥12 years between 2016 and 2018 and controls. SCD patients were matched on a 1:3 ratio with a group of individuals with no diagnosis of SCD, referred as control group. The matching of SCD patients and controls was a direct matching based on age, sex, CMU-c status (which corresponds to free-of-charge complementary coverage for people with low resources) and geographical region of residence. SCD patients and their matched controls were followed-up for the same amount of time by adjusting controls' follow-up period to that of the associated patients. This study used claims data from the French representative 1/97th sample of health data system. The main outcomes were the patients' characteristics and treatments received, healthcare consumptions and related costs among SCD cases and controls. Between 2016 and 2018, 151 patients with ≥6 months of follow-up were identified out of the total population of 732,164 individuals. SCD prevalence extrapolated to the entire population [95% CI] was 19,502 [19,230, 19,778] in 2018. The median (Q1-Q3) age at inclusion date was 37.0 (25.0-48.0) years, with 69.5% of patients being female. The mean (SD) reimbursed cost over follow-up was €24,310 (89,167), mostly represented by hospitalization costs accounting for €21,156 (86,402). A switch in SCD management was observed with age, as younger patients presented more frequent hospitalizations and acute procedures, while older ones had more frequent medical visits and paramedical care. Mean (SD) annual costs were €25,680 (91,843) and vs. €3,227 (23,372) for patients and controls, respectively (p < 0.001), representing an extra cost of almost €150 million over the entire SCD population. This study highlighted the important costs related to SCD and the related medical need with treatment alternatives, which could be filled by the emergence of new therapies.

End-of life medical spending and care pathways in the last 12 months of life: A comprehensive analysis of the national claims database in France.

BACKGROUND: To inform policy makers on efficient provision of end-of-life care, we estimated the 12-month medical expenditures of French decedents in 2015. METHODS: We estimated total medical expenditures by service type and diagnosis category, and analyzed care pathways for breast cancer, dementia, chronic obstructive lung disease. RESULTS: 501,121 individuals died in 2015, 59% of whom were in a hospital at the time of death. The aggregated spending totaled 9% of total health expenditures, a mean of €28,085 per capita, 44% of which was spent during the last 3 months of life. Hospital admissions represented over 70% of total expenditures; 21.3% of the population used hospital palliative care services in their last year of life. Analyses performed on breast cancer, dementia and lung disease found that differences in care pathways markedly influenced spending and were not simply explained by patients characteristics. CONCLUSION: Diagnoses and care trajectories, including repeated hospital stays, are the main drivers of the last year of life expenditures. Our data suggests that early identification of patients requiring palliative care and community-based end-of-life service delivery is feasible and could better support patients, families and caregivers with constant or reduced costs.

Multicentre medicoeconomic evaluation of cardiac magnetic resonance imaging for predicting coronary artery disease in left ventricular dysfunction: The CAMAREC study design.

BACKGROUND: Cardiac magnetic resonance imaging may provide a non-invasive alternative to coronary angiography for differentiating between ischaemic and non-ischaemic cardiomyopathy in cases of unexplained reduced left ventricular ejection fraction. AIM: The CAMAREC study aims to evaluate the diagnostic accuracy of cardiac magnetic resonance imaging in predicting significant coronary artery disease in patients with reduced left ventricular ejection fraction, using coronary angiography as the gold standard for comparison. METHODS: CAMAREC is a prospective cohort study of 406 patients in 10 centres with newly diagnosed, unexplained left ventricular ejection fraction ≤ 45%. Cardiac magnetic resonance imaging and coronary angiography will be conducted within a 2-week interval, starting with cardiac magnetic resonance imaging; independent committees will review the results blindly. Primary outcome is sensitivity of detecting ischaemic scar on cardiac magnetic resonance imaging for predicting significant coronary artery disease on coronary angiography according to Felker's criteria. Secondary outcomes include specificity and positive and negative predictive values (with 95% confidence intervals) of cardiac magnetic resonance imaging for predicting significant coronary artery disease in patients with reduced left ventricular ejection fraction, kappa concordance coefficient between cardiac magnetic resonance imaging and coronary angiography for diagnosing the affected myocardial territory, and the impact of cardiac magnetic resonance imaging on revascularization decisions. Two ancillary studies will evaluate the incremental cost-effectiveness of using cardiac magnetic resonance imaging first versus coronary angiography first, and the sensitivity of pre- and postcontrast T1-mapping for predicting significant coronary artery disease in patients with reduced left ventricular ejection fraction. CONCLUSION: Our study protocol is designed to rigorously evaluate cardiac magnetic resonance imaging as a non-invasive alternative to coronary angiography in patients with unexplained reduced left ventricular ejection fraction. The results will have significant implications for patient management, and may support growing evidence for the clinical utility of cardiac magnetic resonance imaging.