Assessing real-world effectiveness of therapies: what is the impact of incretin-based treatments on hospital use for patients with type 2 diabetes?

BACKGROUND: Managing type 2 diabetes represents a major public health concern due to its important and increasing prevalence. Our study investigates the impact of taking incretin-based medication on the risk of being hospitalized and the length of hospital stay for individuals with type 2 diabetes. METHOD: We use claim panel data from 2011 to 2015 and provide difference-in-differences (DID) estimations combined with matching techniques to better ensure the treatment and control groups' comparability. Our propensity score selects individuals according to their probability of taking an incretin-based treatment in 2013 (N = 2,116). The treatment group includes individuals benefiting from incretin-based treatments from 2013 to 2015 and is compared to individuals not benefiting from such a treatment but having a similar probability of taking it. RESULTS: After controlling for health-related and socio-economic variables, we show that benefiting from an incretin-based treatment does not significantly impact the probability of being hospitalized but does significantly decrease the annual number of days spent in the hospital by a factor rate of 0.621 compared with the length of hospital stays for patients not benefiting from such a treatment. CONCLUSION: These findings highlight the potential implications for our health care system in case of widespread use of these drugs among patients with severe diabetes.

Pharmacist-led medication reconciliation at patient discharge: a tool to reduce healthcare utilization? an observational study in patients 65 years or older.

BACKGROUND: Older patients often experience adverse drug events (ADEs) after discharge that may lead to unplanned readmission. Medication Reconciliation (MR) reduces medication errors that lead to ADEs, but results on healthcare utilization are still controversial. This study aimed to assess the effect of MR at discharge (MRd) provided to patients aged over 65 on their unplanned rehospitalization within 30 days and on both patients' experience of discharge and their knowledge of their medication. METHODS: An observational multicenter prospective study was conducted in 5 hospitals in Brittany, France. RESULTS: Patients who received both MR on admission (MRa) and MRd did not have significantly fewer deaths, unplanned rehospitalizations and/or emergency visits related to ADEs (OR = 1.6 [0.7 to 3.6]) or whatever the cause (p = 0.960) 30 days after discharge than patients receiving MRa alone. However, patients receiving both MRa and MRd were more likely to feel that their discharge from the hospital was well organized (p = 0.003) and reported more frequently that their community pharmacist received information about their hospital stay (p = 0.036). CONCLUSIONS: This study found no effect of MRd on healthcare utilization 30 days after discharge in patients over 65, but the process improved patients' experiences of care continuity. Further studies are needed to better understand this positive impact on their drug care pathway in order to improve patients' ownership of their drugs, which is still insufficient. Improving both the interview step between pharmacist and patient before discharge and the transmission of information from the hospital to primary care professionals is needed to enhance MR effectiveness. TRIAL REGISTRATION: NCT04018781 July 15, 2019.

Multicentric randomized evaluation of a tricuspid valve percutaneous repair system (clip for the tricuspid valve) in the treatment of severe secondary tricuspid regurgitation Tri.Fr Design paper.

AIMS: Tricuspid regurgitation (TR) is associated with significant morbidity and mortality. Its independent prognostic role has been repeatedly demonstrated. However, this valvular heart condition is largely undertreated because of the increased risk of surgical repair. Recently, transcatheter techniques for the treatment of TR have emerged, but their implications for the clinical endpoints are still unknown. METHODS AND RESULTS: The Tri.fr trial will be a multicentre, controlled, randomized (1:1 ratio), superior, open-label, and parallel-group study conducted in 300 patients with severe secondary TR that is considered non-surgical by heart teams. Inclusion will be possible only after core laboratory review of transthoracic and transoesophageal echocardiography and after validation by the clinical eligibility committee. A description of the mechanisms of the TR will be conducted by the core laboratory. Atrial or ventricular impacts on the severity of the secondary TR will be taken into account for the randomization. The patients will be followed for 12-month, and the primary outcome will be the Packer composite clinical endpoint [combining New York Heart Association class, patient global assessment (PGA), and major cardiovascular events]. It will test the hypothesis that a tricuspid valve percutaneous repair strategy using a clip dedicated to the tricuspid valve is superior to best guideline-directed medical therapy in symptomatic patients with severe secondary TR. CONCLUSION: Tri.fr will be the first randomized, academic, multicentre study testing the value of percutaneous correction in patients with severe secondary TR.

The French National Authority for Health (HAS) Guidelines for Conducting Budget Impact Analyses (BIA).

BACKGROUND: Budget impact analysis (BIA) provides short- and medium-term estimates on changes in budgets and health outcomes resulting from the adoption of new health interventions. OBJECTIVE: The purpose of this study is to present the newly developed French National Authority for Health (HAS) guidelines on budget impact analysis as follows: process, literature review, recommendations and comparisons with other guidelines. METHODS: The development process of the HAS guidelines included a literature review (search dates: January 2000 to June 2016), a retrospective investigation of BIA previously submitted to HAS, a public consultation, international expert reviews and approval from the HAS Board and the Economic and Public Health Evaluation Committee of HAS. RESULTS: Documents identified in the literature review included 12 national guidelines, 5 recommendations for good practices developed by national and international society of health economics and 14 methodological publications including recommendations for conducting BIA. Based on its research findings, HAS developed its first BIA guidelines, which include recommendations on the following topics: BIA definition, perspective, populations, time horizon, compared scenarios, budget impact models, costing, discounting, choice of clinical data, reporting of results and uncertainty exploration. CONCLUSION: It is expected that the HAS BIA guidelines will enhance the usefulness, quality and transparency of BIA submitted by drug manufacturers to HAS. BIA is becoming an essential part of a comprehensive economic assessment of healthcare interventions in France, which also includes cost-effectiveness analysis and equity of access to healthcare.

[HAS budget impact analysis guidelines: A new decision-making tool]. / Le guide d'analyse d'impact budgétaire de la HAS : un nouvel outil d'aide à la décision.

INTRODUCTION: Budget impact analysis (BIA) provides short and medium-term estimates on changes in budgets and resources resulting from the adoption of new health interventions. OBJECTIVE: The objective of this article is to present the main messages of the newly developed French National Authority for Health (HAS) guidelines on budget impact analysis : issues, recommendations and perspectives. METHODS: The HAS guidelines development process was based on data derived from a literature review on BIA (search dates : January 2000 to June 2016), an HAS retrospective investigation, a public consultation, international expert advice, and approval from the HAS Board and the Economic and Public Health Evaluation Committee. RESULTS: Based on its research findings, HAS developed its first BIA guidelines, which include recommendations on the following topics : BIA definition, perspective, populations, time horizon, compared scenarios, budget impact models, costing, discounting, choice of clinical data, reporting of results and uncertainty analysis. CONCLUSION: The HAS BIA guidelines are expected to enhance the usefulness of BIA as an essential part of a comprehensive economic assessment of healthcare interventions, which itself includes cost-effectiveness analysis and equity of access to healthcare.

Exploring Uncertainty in Economic Evaluations of Drugs and Medical Devices: Lessons from the First Review of Manufacturers' Submissions to the French National Authority for Health.

OBJECTIVES: The objective of this paper was to evaluate how uncertainty has been accounted for in the cost-effectiveness analyses (CEAs) submitted by manufacturers to the French National Authority for Health (HAS) and to identify recurring concerns in these submissions. METHODS: We used a cross-sectional design to evaluate manufacturers' submissions from the beginning of the evaluation process in October 2013 to the end of May 2015 (n = 28). The sources of uncertainty attached to these CEAs were categorized and assessed. Relevant data were extracted independently by two assessors. RESULTS: Adherence to the HAS reference case was generally considered to be acceptable. Methodological uncertainty and parameter uncertainty were the sources of uncertainty that were most frequently explored by manufacturers. The quality of reporting of deterministic sensitivity analysis and probabilistic sensitivity analysis varied substantially across submissions, with a frequent lack of justification of the plausible range of parameter point estimates in 12 submissions (43 %). Structural uncertainty was explored much less frequently. Concerns related to omission of either important clinical events or relevant health states or extrapolation of the effects of the technology beyond the time horizon of the clinical trials were identified in 16 submissions (57 %). CONCLUSIONS: This study presented a characterization of the treatment of uncertainty for the first 28 manufacturers' submissions to the HAS. This work identified important concerns regarding the exploration of sources of uncertainty. The findings may help manufacturers to improve the quality of their submissions and may provide useful insights for extending guidelines on uncertainty analysis in CEAs submitted to the HAS.

HTA agencies facing model biases: the case of type 2 diabetes.

When evaluating new drugs or treatments eligible for reimbursement, health technology assessment (HTA) agencies are repeatedly faced with cost-effectiveness analyses that evidence lack of adequate data and modeling biases. The case of type 2 diabetes illustrates this difficulty. In spite of its high disease burden, type 2 diabetes is poorly documented through existing cost-effectiveness analyses. We support this statement by an exhaustive literature review that enables us to precisely pinpoint the limitations of models used for the assessment of newly marketed (and expensive) drugs. We find that models are mostly restricted to surrogate endpoints and based on non-inferiority clinical trial data; they also show biases in the choice of comparators and inclusion criteria. Such limitations undermine the scope and applicability of HTA practice guidelines based on cost-effectiveness evidence. Nevertheless, cost-effectiveness models remain an opportunity to better inform decision makers and to reduce the uncertainty surrounding their decisions. HTA agencies are best placed to provide incentives for companies to improve the quality of the cost-effectiveness studies submitted for pricing and reimbursement decisions. One such incentive is to include stages of discussion between the company and the health authority during the evaluation process.

The influence of waiting times on cost-effectiveness: a case study of colorectal cancer mass screening.

When a cost-effectiveness analysis is implemented, the health-care system is usually assumed to adjust smoothly to the proposed new strategy. However, technological innovations in health care may often induce friction in the organization of care supply, implying the congestion of services and subsequent waiting times. Our objective here is to measure how these short run rigidities can challenge cost-effectiveness recommendations favorable to an innovative mass screening test for colorectal cancer. Using Markov modeling, we compare the standard Guaiac fecal occult blood test (gFOBT) with an innovative screening test for colorectal cancer, namely the immunological fecal occult blood test (iFOBT). Waiting time can occur between a positive screening test and the subsequent confirmation colonoscopy. Five scenarios are considered for iFOBT: no further waiting time compared with gFOBT, twice as much waiting time for a period of 5 or 10 years, and twice as much waiting time for a period of 5 or 10 years combined with a 25% decrease in participation to confirmation colonoscopies. According to our modeling, compared with gFOBT, iFOBT would approximately double colonoscopy demand. Probabilistic sensitivity analysis enables concluding that the waiting time significantly increases the uncertainty surrounding recommendations favorable to iFOBT if it induces a decrease in the adherence rate for confirmation colonoscopy.

Incremental net benefit and acceptability of alternative health policies: a case study of mass screening for colorectal cancer.

The incremental net benefit (INB) and the related acceptability curves for public health programs provide valuable tools for decision making. We proposed to apply them to the assessment of mass screening of colorectal cancer. The now standard guaiac fecal occult blood test (FOBT) is already implemented in several countries. We considered the innovative immunological FOBT and computed tomography colonography (CTC) as competing screening technologies. Using biennial guaiac FOBT as the reference strategy, we estimated the cost-effectiveness of the following alternatives: biennial immunological FOBT, CTC every 5 years (strategy CTC5), and CTC every 10 years (strategy CTC10). Over a 30-year horizon and from the perspective of a third-party payer, we developed a Markov model on a hypothetical cohort of 100,000 subjects at average risk of colorectal cancer. Close expected net benefits between immunological FOBT and CTC5 induced uncertainty in the choice of the optimal strategy. Probabilistic sensibility analysis then suggested that below a willingness to pay (WTP) per life-years gained (LYG) of 8,587 €/LYG, CTC10 was optimal, while CTC5 would be preferred beyond a WTP of 8,587 €/LYG.

Cost-effectiveness of colorectal cancer screening with computed tomography colonography or fecal blood tests.

OBJECTIVE: To assess the cost-effectiveness of colorectal cancer screening using computed tomography colonography (CTC) and immunological fecal occult blood test (iFOBT). METHODS: CTC and iFOBT strategies were compared with Nn screening or guaiac FOBT (gFOBT) using Markov modeling. CTC was proposed at 50, 60, and 70 years, whereas gFOBT and iFOBT were performed every 2 years beginning at 50 years until 74 years of age with a 30-year time horizon. We calculated incremental cost-effectiveness ratios and efficiency ratios (ERs). Then, we performed univariate and probabilistic sensitivity analyses. RESULTS: With gFOBT as reference, colorectal cancer prevention rate was 18% for CTC and 11% for iFOBT. The incremental cost-effectiveness ratio of CTC and iFOBT were respectively 3204 and 5458 euro per life years gained (LYG), the ER for CTC was 0.22 and the ER for iFOBT was 2.08 colonoscopies per LYG. Cost-effectiveness results were sensitive to CTC cost. In the probabilistic sensitivity analysis, compared with CTC, iFOBT strategy was cost-effective for 84.6% of simulations when we assumed a willingness to pay (WTP) of 20,000 euro/LYG. CONCLUSION: CTC requires substantially less colonoscopies than iFOBT and is cost-effective for low values of WTP. However, iFOBT is the preferred screening strategy for a WTP greater than 6207 euro/LYG.

Cost-effectiveness of colorectal cancer screening with computed tomography colonography according to a polyp size threshold for polypectomy.

OBJECTIVE: Computed tomography colonography (CTC) has an acceptable accuracy in detecting colonic lesions, especially for polyps at least 6 mm. The aim of this analysis is to determine the cost-effectiveness of population-based screening for colorectal cancer (CRC) using CTC with a polyp size threshold. METHODS: The cost-effectiveness ratios of CTC performed at 50, 60 and 70 years old, without (PL strategy) or with (TS strategy) polyp size threshold were compared using a Markov process. Incremental cost-effectiveness ratios (ICER) were calculated per life-years gained (LYG) for a time horizon of 30 years. RESULTS: The ICER of PL and TS strategies were 12 042 and 2765 euro/LYG associated to CRC prevention rates of 37.9 and 36.5%. The ICER of PL and TS strategies dropped to 9687 and 1857 euro/LYG when advanced adenoma (AA) prevalence increased from 6.9 to 8.6% for male participants and 3.8-4.9% for female participants or to 9482 and 2067 euro/LYG when adenoma and AA annual recurrence rates dropped to 3.2 and 0.25%. The ICER for PL and TS strategies decreased to 7947 and 954 euro/LYG or when only two CTC were performed at 50 and 60-years-old. Conversely, the ICER did not significantly change when varying population participation rate or accuracy of CTC. CONCLUSION: CTC with a 6 mm threshold for polypectomy is associated to a substantial cost reduction without significant loss of efficacy. Cost-effectiveness depends more on the AA prevalence or transition rate to CRC than on CTC accuracy or screening compliance.