Budget impact model of Mydrane®, a new intracameral injectable used for intra-operative mydriasis, from a UK hospital perspective.

BACKGROUND: During cataract surgery, maintaining an adequate degree of mydriasis throughout the entire operation is critical to allow for visualisation of the capsulorhexis and the crystalline lens. Good anaesthesia is also essential for safe intraocular surgery. Mydrane® is a new injectable intracameral solution containing two mydriatics (tropicamide 0.02% and phenylephrine 0.31%) and one anaesthetic (lidocaine 1%) that was developed as an alternative to the conventional topical pre-operative mydriatics used in cataract surgery. This study aimed to estimate the budget impact across a one year time frame using Mydrane® instead of topical dilating eye drops, for a UK hospital performing 3,000 cataract operations a year. METHODS: A budget impact model (BIM) was developed to compare the economic outcomes associated with the use of Mydrane® versus topical drops (tropicamide 0.5% and phenylephrine 10%) in patients undergoing cataract surgery in a UK hospital. The outcomes of interest included costs and resource use (e.g. clinician time, mydriasis failures, operating room time, number of patients per vial of therapy etc.) associated with management of mydriasis in patients undergoing cataract surgery. All model inputs considered the UK hospital perspective without social or geographical variables. Deterministic sensitivity analyses were also performed to assess the model uncertainty. RESULTS: Introduction of Mydrane® is associated with a cost saving of £6,251 over 3,000 cataract surgeries in one year. The acquisition costs of the Mydrane® (£18,000 by year vs. £3,330 for eye drops) were balanced by substantial reductions in mainly nurses' costs and time, plus a smaller contribution from savings in surgeons' costs (£20,511) and lower costs associated with auxiliary dilation (£410 due to avoidance of additional dilation methods). Results of the sensitivity analyses confirmed the robustness of the model to the variation of inputs. Except for the duration of one session of eye drop instillation and the cost of Mydrane®, Mydrane® achieved an incremental cost gain compared to tropicamide/phenylephrine eye drops. CONCLUSIONS: Despite a higher acquisition cost of Mydrane®, the budget impact of Mydrane® on hospital budgets is neutral. Mydrane® offers a promising alternative to traditional regimes using eye drops, allowing for a better patient flow and optimisation of the surgery schedule with neutral budget impact.

Assessing the validity of a rapid review against a systematic literature review. A comparison of systematic literature reviews done by Cochrane with rapid reviews and the impact on meta-analyses results.

INTRODUCTION: Rapid reviews (RRs) offer a less rigorous and methodical approach to the process of reviewing literature in comparison to systematic reviews (SRs), which are currently a gold standard. MATERIALS AND METHODS: Three different, expedited strategies of the review process were designed in the different scopes, already reviewed in Cochrane's SRs. Then, the results of our literature searches and the study selection process were compared to the ones from SRs. The final step was assessing the impact of losing some studies on the final results of meta-analyses. RESULTS: In RR1, the initial number of references to be reviewed was reduced by half, and the inclusion list was recreated with 84% efficiency. Three out of 19 studies were missed, all having high risk of bias. Studies missed in RR1 were included in Cochrane's meta-analyses for 23 separate outcomes, and their lack impacted significantly the final results, or the possibility to run meta-analyses, in four cases. In RR2, 89% of trials included in the SR were captured (24/27); missing the three studies did not impact the final results of the meta-analyses. In RR3, the list of included studies overlapped completely with Cochrane's, despite a significantly lower workload. CONCLUSIONS: A prompt and cost-effective methodology may lead to the identification of pertinent evidence in support of healthcare policy; however, it is essential to conscientiously account for potential biases in the analysis.

Cost-Effectiveness Analysis of Innovative Therapies for Patients with Non-Alcoholic Fatty Liver Disease.

OBJECTIVE: Currently there are no disease-specific approved therapies for non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH); however, several treatments are under development. This study aimed to estimate the cost-effectiveness of hypothetical innovative therapies compared with lifestyle intervention alone and combined with pioglitazone, and assess the health economic consequences of their future availability for patients. METHODS: A Markov cohort model was developed, considering fourteen disease health states and one absorbing state representing death. Transition probabilities, costs, utilities, and treatment efficacy were based on published data and assumptions. Four treatment strategies were considered, including two existing therapies (lifestyle intervention, small molecule treatment) and two hypothetical interventions (biological and curative therapy). The analysis was performed from the US third-party payer perspective. RESULTS: The curative treatment with the assumed efficacy of 70% of patients cured and assumed price of $500,000 was the only cost-effective option. Although it incurred higher costs (a difference of $188,771 vs. lifestyle intervention and $197,702 vs. small molecule), it generated more QALYs (a difference of 1.58 and 1.38 QALYs, respectively), resulting in an ICER below the willingness-to-pay threshold of $150,000 per QALY. The sensitivity analyses showed that the results were robust to variations in model parameters. CONCLUSIONS: This study highlighted the potential benefits of therapies aimed at curing a disease rather than stopping its progression. Nonetheless, each of the analyzed therapies could be cost-effective compared with lifestyle intervention at a relatively high price.

A clinical research practice datalink analysis of antidepressant treatment patterns and health care costs in generalized anxiety disorder.

OBJECTIVE: To describe real-life prescription patterns, health care resource use, and costs in adults with generalized anxiety disorder (GAD) initiating antidepressant (AD) treatment in the United Kingdom. METHODS: A retrospective longitudinal cohort study using data from Clinical Research Practice Datalink was conducted. Adults with incident prescription of an AD (index date) between January 1, 2006, and June 30, 2010, and with a diagnosis of GAD within the 2 months preceding or following the index date were included. Patients with a diagnosis of schizophrenia or bipolar disorder were excluded. RESULTS: A total of 29,131 patients with GAD were included in the analysis. Their mean age was 48.5 ± 15.5 years, and two thirds were women. GAD-licensed ADs (i.e., escitalopram, paroxetine, venlafaxine XR, and duloxetine) represented only 12.5% of the index AD prescriptions. At least one anxiolytic was prescribed for 23.5% of the patients. Only 33.2% of the patients continued index AD treatment over the study period. Discontinuation occurred for 46.0% of the patients, after a mean of 3.7 months of treatment. The health care costs were £338.4 per patient in the 6 months before the index date and £984.6 in the 9 months after the index date. Psychiatric hospitalization (relative risk = 4.18; 95% CI 3.53-4.96; P < 0.001) and duloxetine as index treatment (relative risk = 1.85; 95% CI 1.30-2.63; P < 0.001) were the main determinants of increased costs for these patients. CONCLUSIONS: The significant rate of AD discontinuation and associated treatment duration indicate unmet needs among patients with GAD. As described in American studies, substantial health care costs were also observed in this study.

Contribution of prolonged-release melatonin and anti-benzodiazepine campaigns to the reduction of benzodiazepine and Z-drugs consumption in nine European countries.

BACKGROUND: Benzodiazepines (BZD) and benzodiazepine receptor agonists (zolpidem, zaleplon, zopiclone, altogether Z-drugs) are most commonly prescribed for the treatment of insomnia. However, long-term use of BZD/Z-drugs is associated with major adverse events including, but not limited to, falls and fractures, domestic and traffic accidents, confusion, cognitive impairment, Alzheimer's disease and cancer. The prolonged use of these drugs is thought to be related to severe withdrawal symptoms and potential dependency. The chronic and extensive use of BZD/Z drugs has become a public health issue and has led to multiple campaigns to reduce both prescription and consumption of BZD/Z-drugs. Prolonged-release (PR) melatonin is the first of a new class of melatonin receptor agonist drugs that has demonstrated clinically relevant efficacy on improving quality of sleep and morning alertness, with a good safety profile. OBJECTIVE: This study aimed to analyze and evaluate the impact of anti-BZD/Z-drugs campaigns and the availability of alternative pharmacotherapy (PR-melatonin) on the consumption of BZD and Z-drugs in several European countries. METHODS: Annual sales data from nine European countries were extracted from the IMS sales database and analyzed to determine whether trends in use of these treatment options were attributed to campaigns and/or availability and affordability of safer alternatives on the market. RESULTS: Campaigns aiming to reduce the use of BZD/Z-drugs failed when they were not associated with the availability and market uptake of PR-melatonin. The reimbursement of PR-melatonin supports better penetration rates and a higher reduction in sales for BZD/Z-drugs.

Impact of therapy escalation on ambulatory care costs among patients with type 2 diabetes in France.

BACKGROUND: This study compares annual ambulatory care expenditures per patient with type 2 diabetes mellitus (T2DM) in France according to treatment phase and renal function status. METHODS: Records from patients with T2DM were extracted from a health insurance database. Patients were classified in subgroups, by treatment phase: oral/GLP1 monotherapy, double therapy, triple therapy or insulin therapy, and according to renal function status (identified using pharmacy, lab and consultation claims). Annual ambulatory expenditures were estimated from the national insurance perspective by year (from 2005 to 2010) and subgroup. RESULTS: The number of patients ranged from 9,682 to 11,772 between 2005 and 2010. The average annual expenditure per individual in 2010 ranged from €3,017 (standard deviation: €3,829) for monotherapy to €3,609 ± €3,801 for triple therapy, and €7,398 ± €5,487 with insulin (adjusted ratio insulin therapy/monotherapy: 2.36, p < 0.001). Similar differences between treatement stages were found in previous years. Additional costs for insulin were mainly related to nursing care (multiplied by 18.42, p < 0.001), medical devices and pharmacy costs. DM-attributable drug costs were mainly related to antidiabetic drugs (28% for monotherapy to 71% for triple therapy), but also to cardiovascular system drugs (21% for monotherapy to 51% with insulin) and nervous system drugs (up to 8% with insulin). Declining renal function was associated with an increase in expenses by 12% to 53% according to treatment stage. CONCLUSIONS: Overall, ambulatory care expenditures increase with treatment escalation and declining renal function amongst patients with T2DM. Insulin therapy is associated with substantially increased costs, related to pharmacy, nursing care and medical device costs.

Further evidence of reliability and validity of the Huntington's disease quality of life battery for carers: Italian and French translations.

BACKGROUND: Existing research suggests that family caregivers of persons with Huntington's disease (HD) face a distinct series of problems, linked to the complex nature of the disease. Aubeeluck and Buchanan (Clin Genet, 71(5):434-445, 2007) developed and validated a disease-specific measure used to explore caregivers quality of life and assess the efficacy of therapeutic interventions. This current study builds on this research through the validation of French and Italian translations of the Huntington's disease quality of life battery for carers (HDQoL-C). METHOD: A total of 301 family carers completed the HDQoL-C. Participants were recruited through the "Euro-HDB" study which is measuring the burden in HD across Europe and the USA. RESULTS: Factor analysis demonstrated good internal consistency, reliability and congruent validity. Carers who cared for patients with less clinically severe symptoms reported significantly better QoL than carers of patients with more clinically severe symptoms. DISCUSSION: Findings indicate the HDQoL-C is multi-lingual, multi-cultural and easily applicable in other languages.

Systematic literature reviews over the years.

Purpose: Nowadays, systematic literature reviews (SLRs) and meta-analyses are often placed at the top of the study hierarchy of evidence. The main objective of this paper is to evaluate the trends in SLRs of randomized controlled trials (RCTs) throughout the years. Methods: Medline database was searched, using a highly focused search strategy. Each paper was coded according to a specific ICD-10 code; the number of RCTs included in each evaluated SLR was also retrieved. All SLRs analyzing RCTs were included. Protocols, commentaries, or errata were excluded. No restrictions were applied. Results: A total of 7,465 titles and abstracts were analyzed, from which 6,892 were included for further analyses. There was a gradual increase in the number of annual published SLRs, with a significant increase in published articles during the last several years. Overall, the most frequently analyzed areas were diseases of the circulatory system (n = 750) and endocrine, nutritional, and metabolic diseases (n = 734). The majority of SLRs included between 11 and 50 RCTs each. Conclusions: The recognition of SLRs' usefulness is growing at an increasing speed, which is reflected by the growing number of published studies. The most frequently evaluated diseases are in alignment with leading causes of death and disability worldwide.

Rapid literature review: definition and methodology.

Introduction: A rapid literature review (RLR) is an alternative to systematic literature review (SLR) that can speed up the analysis of newly published data. The objective was to identify and summarize available information regarding different approaches to defining RLR and the methodology applied to the conduct of such reviews. Methods: The Medline and EMBASE databases, as well as the grey literature, were searched using the set of keywords and their combination related to the targeted and rapid review, as well as design, approach, and methodology. Of the 3,898 records retrieved, 12 articles were included. Results: Specific definition of RLRs has only been developed in 2021. In terms of methodology, the RLR should be completed within shorter timeframes using simplified procedures in comparison to SLRs, while maintaining a similar level of transparency and minimizing bias. Inherent components of the RLR process should be a clear research question, search protocol, simplified process of study selection, data extraction, and quality assurance. Conclusions: There is a lack of consensus on the formal definition of the RLR and the best approaches to perform it. The evidence-based supporting methods are evolving, and more work is needed to define the most robust approaches.

Economic evaluation of encorafenib with cetuximab in patients with BRAF V600E-mutant metastatic colorectal cancer in France: a cost-effectiveness analysis using data from the BEACON CRC randomised controlled trial.

OBJECTIVE: The BEACON CRC randomised controlled trial (NCT02928224) in BRAF-mutant metastatic colorectal cancer (mCRC) patients showed improved overall survival for the combination treatment of encorafenib (BRAF inhibitor) with cetuximab (EGFR inhibitor) compared with cetuximab with chemotherapy (FOLFIRI (folinic acid, fluorouracil and irinotecan) or irinotecan). We aimed to evaluate the cost-effectiveness of encorafenib with cetuximab in adult patients with BRAF-mutant mCRC after prior systemic therapy, from the perspective of the French healthcare system. DESIGN: A partitioned survival analysis model was developed to assess the cost-effectiveness of encorafenib with cetuximab using data from BEACON CRC (encorafenib with cetuximab and cetuximab with FOLFIRI or irinotecan). For two further comparator treatments (FOLFIRI alone and bevacizumab with FOLFIRI), a systemic literature review identified appropriate clinical trial data for indirect comparison. Piecewise modelling extrapolation was used to fulfil a lifetime horizon in the model. A discount rate of 2.5% was used. Treatment-emergent adverse events ≥grade 3 with an incidence of ≥2% were included, as well as relative dose intensity and utility values. OUTCOME MEASURES: The effectiveness outcomes of the model were expressed in terms of incremental life years gained and incremental quality-adjusted life years (QALY) gained. The cost-effectiveness of encorafenib with cetuximab was assessed using the incremental cost-effectiveness ratio (ICER). Results were presented probabilistically to account for parametric uncertainty. Deterministic and scenario analyses were conducted. RESULTS: The ICER for encorafenib with cetuximab versus cetuximab with FOLFIRI or irinotecan, FOLFIRI alone and bevacizumab with FOLFIRI was €69 823/QALY, €70 421/QALY and €72 336/QALY, respectively. Encorafenib with cetuximab was considered cost-effective compared with the three comparators at a willingness to pay threshold of €90 000/QALY, with probabilities of being cost-effective of 89.8%, 98.2% and 86.4%, respectively. CONCLUSIONS: This analysis showed encorafenib with cetuximab to be a cost-effective treatment in mCRC patients with a BRAF V600E mutation.

Considering potential solutions for limitations and challenges in the health economic evaluation of gene therapies.

INTRODUCTION: The limited evidence in the clinical trials of gene therapies (GTs) posed substantial challenges for a reliable health technology assessment (HTA). This paper provides insights into the relationship between the background of diseases and the health economics assessment of GTs.Areas covered: The impacts of differentiated severity and unmet needs of genetic diseases, on the economic analysis of GTs, were discussed.Expert opinion: GTs offer a potential cure or significant clinical improvement, while limitations in clinical evidence constitute major obstacles for a robust assessment of clinical effectiveness and economic outcomes. This uncertainty may be balanced by the severity of the targeted condition and the associated unmet needs, thus leading to a relatively higher acceptance for GTs. Overtime, HTA agencies will become more demanding on comprehensive evidence of long-term effectiveness. With a growing number of GTs on the horizon, to what extent the unmet needs of previously devastating diseases will be fulfilled remain unclear. Nonetheless, comparative studies, either with a historical control group or existing treatments, will be necessary to demonstrate the additional benefits associated with GTs.

An overview of health technology assessments of gene therapies with the focus on cost-effectiveness models.

BACKGROUND: Gene therapies can treat, prevent, or cure a disease by changing the expression of a person's genes. They are an innovative strategy for treating genetic disorders; however, they are still emerging on the market access and in the healthcare system. Health technology assessment (HTA) agencies have not yet elaborated any standardised approach for assessing gene therapies; therefore, significant differences can be seen during HTAs carried out in various countries. In this review, we focused on submitted economic models of gene therapies approved for use by the US FDA and EMA with the aim to provide a comprehensive summary of how selected HTA bodies assessed the cost-effectiveness of gene therapies. An additional objective was to examine and discuss differences in the methods used in economic models across countries and drugs. METHODS: We identified economic models of gene therapies from six countries (NICE, IQWiG, SMC, HAS, CADTH, ICER) and focused on nine agents (Glybera, Imlygic, Strimvelis, Yescarta, Kymriah, Luxturna, Zynteglo, Zolgensma, Tecartus). Details of cost-utility evaluations and budget impact models were reviewed and extracted. RESULTS: Overall, 983 publications were identified, and 17 studies were included for the analysis. Reviewed evaluations of gene therapies differed in terms of the study perspective, discounting, extrapolation of outcomes based on limited and immature data, time horizon, and adequate estimation of benefits in terms of quality-adjusted life-years. Methods of economic evaluations were in line with the current recommendations; however, long-term follow-up studies are still missing. CONCLUSIONS: Discrepancies in an economic evaluation of gene therapies between different HTA bodies are rooted in a lack of general assessment frameworks specific to gene therapies. Although challenges were resolved by adjustments to the currently used value assessment framework, new methodological approaches would be useful. In addition, to improve the methods and quality of an evaluation, further research would be valuable.

Allocating treatment resources for hepatitis C in the UK: a constrained optimization modelling approach.

Background and objective: Although the treatment of chronic hepatitis C (CHC) has significantly evolved with the introduction of direct-acting antivirals, the treatment uptake rates have been low especially among marginalized groups in the UK, such as people who inject drug (PWID) and men who have sex with men (MSM). Cutting health inequality is a major focus of healthcare agencies. This study aims to identify the optimal allocation of treatment budget for chronic hepatitis CHC among populations and treatments in the UK so that liver-related mortality in patients with CHC is minimized, given the constraint of treatment budget and equity issue. Methods: A constrained optimization modelling of resource allocation for the treatment of CHC was developed in Excel from the perspective of the UK National Health System over a lifetime horizon. The model was designated with the objective function of minimizing liver-related deaths by varying the decision variables, representing the number of patients receiving each treatment (elbasvir-grazoprevir, ombitasvir-paritaprevir-ritonavir-dasabuvir, sofosbuvir-ledipasvir, and pegylated interferon-ribavirin) in each population (the general population, PWID, and MSM). Two main constraints were formulated including treatment budget and the issue of equity. The model was populated with UK local data applying linear programming and underwent internal and external validation. Scenario analyses were performed to assess the robustness of model results. Results: Within the constraints of no additional funding over original spending in status quo and the consideration of the issue of equity among populations, the optimal allocation from the constrained optimization modelling (treating 13,122 PWID, 160 MSM, and 904 general patients with ombitasvir-paritaprevir-ritonavir-dasabuvir) was found to treat 2,430 more patients (relative change: 20.7%) and avert 78 liver-related deaths (relative change: 0.3%) compared with the current allocation. The number of patients receiving treatment increased 4,928 (relative change: 60.1%) among PWID and 42 (relative change: 35.8%) among MSM. Conclusion: The current allocation of treatment budget for CHC is not optimal in the UK. More patients would be treated, and more liver-related deaths would be avoided using a new allocation from a constrained optimization modelling without incurring additional spending and considering the issue of equity.

Efficacy and Safety of Rivaroxaban Compared with Other Therapies Used in Patients with Peripheral Artery Disease Undergoing Peripheral Revascularization: A Systematic Literature Review and Network Meta-Analysis.

BACKGROUND: The guidelines on antithrombotic treatment in patients with symptomatic peripheral artery disease (PAD) undergoing peripheral revascularization of the lower extremities were developed based on heterogeneous trials, assessing various dose regimens and recruiting patients who were subjected to different revascularization procedures. OBJECTIVE: To compare efficacy and safety of treatments used in patients with PAD undergoing peripheral revascularization accounting for between-trial heterogeneity and large dispersion of the quality of evidence. METHODS: A systematic literature review of randomised controlled trials (RCTs) recruiting adult patients with PAD receiving antithrombotics was conducted until January 2020. Hazard ratios (HR) were pooled using Bayesian network meta-analysis. The estimated between-treatment effects were presented as HR together with 95% credible intervals. The base case analysis included studies recruiting patients following recent peripheral revascularization, who received treatment regimens administered within the recommended therapeutic window, while a sensitivity scenario included all identified trials. RESULTS: Thirteen RCTs were identified (8 RCTs enrolled patients following peripheral revascularization and 5 RCTs regardless of the previous revascularization). Five trials, recruiting an overall of 8349 patients, were considered for the base case analysis. Of those, 6564 patients were recruited in the VOYAGER PAD trial comparing rivaroxaban plus aspirin (RIV plus ASA) versus ASA. RIV plus ASA was associated with a lower risk of repeated peripheral revascularization versus ASA monotherapy (HR = 0.88 [0.79, 0.99]), however having a trend towards an increased rate of major bleeding (HR = 1.43 [0.98, 2.11]). There was no evidence for differences between RIV plus ASA and dual antiplatelet therapy and vitamin K antagonists plus ASA. Similar results were observed in sensitivity analyses. CONCLUSIONS: RIV plus ASA is associated with reduced risk of revascularization compared with ASA monotherapy, but the evidence for other comparators, in particular antiplatelet regimens, was insufficient to guide treatment decisions and highlights the challenge in establishing the magnitude of comparative efficacy using existing RCTs.

Real-world cost-effectiveness of rivaroxaban compared with vitamin K antagonists in the context of stroke prevention in atrial fibrillation in France.

OBJECTIVE: The objective was to assess the real-world cost-effectiveness of rivaroxaban, versus vitamin K antagonists (VKAs), for stroke prevention in patients with atrial fibrillation (AF) from a French national health insurance perspective. METHODS: A Markov model was developed with a lifetime horizon and cycle length of 3 months. All inputs were drawn from real-world evidence (RWE) studies: data on baseline patient characteristics at model entry were obtained from a French RWE study, clinical event rates as well as persistence rates for the VKA treatment arm were estimated from a variety of RWE studies, and a meta-analysis provided comparative effectiveness for rivaroxaban compared to VKA. Model outcomes included costs (drug costs, clinical event costs, and VKA monitoring costs), quality-adjusted life-years (QALY) and life-years (LY) gained, incremental cost per QALY, and incremental cost per LY. Sensitivity analyses were performed to test the robustness of the model and to better understand the results drivers. RESULTS: In the base-case analysis, the incremental total cost was €714 and the total incremental QALYs and LYs were 0.12 and 0.16, respectively. The resulting incremental cost/QALY and incremental cost/LY were €6,006 and €4,586, respectively. The results were more sensitive to the inclusion of treatment-specific utility decrements and clinical event rates. CONCLUSIONS: Although there is no official willingness-to-pay threshold in France, these results suggest that rivaroxaban is likely to be cost-effective compared to VKA in French patients with AF from a national insurance perspective.

Economic burden for Alzheimer's disease in China from 2010 to 2050: a modelling study.

Objectives: We aimed to conduct a modelling study to estimate and predict the economic burden of AD to support the healthcare management of AD in China. Methods: The economic burden of AD was estimated with an evaluation of the prevalence of AD patients and a simulation of annual resource use and cost per AD patient in China using a published model. Percentage of AD patients being treated was assumed to be 5% from 2010 to 2050, with three scenarios testing the value of this parameter of 10%, 20% and 40% throughout 2020 to 2050. Results: The costs of AD were estimated to be from around 91 billion RMB in 2010 to 332 billion in 2050. Most of the current burden was related to private caregivers paid by families. With the percentage of patients being treated changing from 5% to 40%, costs were estimated to double. This was related to more hospitalisations and more use of care facilities, while the burden for families would decrease. Conclusion: A high economic burden related to AD is predicted. The burden would be driven mainly by indirect costs related to the social support of the patients. Investment in improving awareness and care of AD patients is needed and worth it.

Cost-effectiveness of pirfenidone compared to all available strategies for the treatment of idiopathic pulmonary fibrosis in France.

Objective: To update the health economic evaluation of pirfenidone in the treatment of idiopathic pulmonary fibrosis (IPF) compared to all available alternatives strategies (Best supportive care - BSC and nintedanib), based on a cost-utility model previously validated by the CEESP's (French Committee for Economic Evaluation) in 2014. Methods: A standard Markov cohort model, adapted to French methodology guidelines, was used to simulate the therapeutic management and the course of IPF patients (including potential adverse events) using the collective perspective. Cost-effectiveness was evaluated regarding life years (LY); quality-adjusted life-years (QALY); average cumulative costs; the incremental cost-effectiveness ratio (ICER) expressed in cost per QALY gained. Data were retrieved from trials, meta-analysis, literature, health insurance and hospitalisation databases, and national tariffs. Results: Over 15 years, total costs accumulated in the pirfenidone strategy were estimated at €99,477 per patient, €104,610 in nintedanib, and €14,177 in Best Supportive Care (BSC). The total number of QALYs accumulated equalled 5.20 (6.91 LYs), 4.52 (5.98 LYs), and 3.79 (4.98 LYs), respectively. Pirfenidone was estimated to be dominant over nintedanib with incremental costs of -€5,133 and 0.67 more QALYs accumulated. Incremental cost versus BSC was €85,300 and 1,404 QALY gained. The cost-effectiveness ratio was estimated at 60,738€/QALY when compared to BSC. Conclusion: Pirfenidone is likely to be a cost-effective strategy compared to BSC and seems more efficient and less costly compared to nintedanib for the treatment of patients with IPF in France.

Cost-effectiveness analyses using real-world data: an overview of the literature.

Objectives: Real-world evidence (RWE) may provide good estimates of absolute event probabilities and costs in patients in actual clinical practice, but their use in decision-analytic models poses many challenges. A literature review based on a systematic search was conducted to summarize the limitations of using RWE in decision-analytic modeling reported in the literature, but also to identify existing recommendations about real-world modeling. Methods: A literature search was performed on Medline and Embase databases, as well as relevant websites. No restrictions in language or geographical scope were imposed. Results: A total of 14 references were included. RWE is recognized as a valuable source of data for market access and reimbursement, and as a complement to clinical trial evidence for treatment pathways, resource use, long-term natural history, and effectiveness. The main limitations identified in the literature were: confounding bias, missing data, lack of accurate data related to drug exposure and outcomes, errors during the record-keeping process, protection of private data, and insufficient numbers of patients. Although most submission guidelines recognized the potential biases associated with RWE, guidance on the appropriate methods to deal with these biases, and approaches to review different relevant evidence to inform model development, were scarce. Several initiatives have attempted to provide guidance on the use of RWE in decision-modeling. Conclusions: RWE is likely to be particularly valuable for informing healthcare policy-makers when formulating appropriate treatment pathways, encouraging the optimal allocation of scarce resources, and improving aggregate patient outcomes. However, little guidance is available on the relative merits of using efficacy and/or effectiveness evidence in Health Technology Appraisal submissions. Further research is needed to better understand these methods and their potential applications in a broader range of scenarios and simulation studies, and their impact on economic modeling.

Cost-effectiveness analysis of pembrolizumab versus standard-of-care chemotherapy for first-line treatment of PD-L1 positive (>50%) metastatic squamous and non-squamous non-small cell lung cancer in France.

INTRODUCTION: In the KEYNOTE-024 trial, pembrolizumab demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS) versus Standard-of-Care (SoC) platinum-based doublets for first-line treatment of PD-L1 -positive (≥50%) metastatic Non-Small-Cell Lung Cancer (NSCLC) patients with no EGFR mutations or ALK translocations. This study aims to assess the cost-effectiveness of pembrolizumab versus SoC platinum-based chemotherapy from the French healthcare system perspective. METHODS: A three-state partitioned-survival model was adapted to project outcomes and costs of squamous and non-squamous NSCLC patients respectively, over a 10-year time horizon. Clinical and utility data were collected from the trial. A network meta-analysis was performed to consider platinum-based triplets also used for non-squamous NSCLC. Direct medical costs were considered based on ressources identified from the trial and literature. Costs and outcomes were discounted at 4% per year. Incremental cost-effectiveness ratios (ICERs) were calculated as cost per Life Year (LY) and cost per Quality-Adjusted Life Year (QALY). Sensitivity and scenario analyses were performed to assess the robustness of results. RESULTS: For squamous NSCLC, pembrolizumab was projected to increase life expectancy of patients by 0.93 LY (11 months), and 0.74 QALY (9 months) for an incremental cost of €62,032 compared with platinum-based doublets. The ICER of pembrolizumab versus platinum-based doublets was €66,825/LY and €84,097/QALY. For non-squamous NSCLC, pembrolizumab was projected to increase life expectancy of patients by 0.85-1.32 LYs (10.2-15.8 months) and 0.64-1.02 QALYs (7.7-12.2 months) for an incremental cost varying from €-14,947-+47,064 depending on the specific comparator. The ICER of pembrolizumab versus platinum-based chemotherapy with paclitaxel plus bevacizumab was €62,846/LY and €78,729/QALY; regimens including pemetrexed were dominated. Results were most sensitive to extrapolations of survival outcomes and assumptions for continued effectiveness and treatment duration of pembrolizumab. CONCLUSIONS: Pembrolizumab appears cost-effective versus SoC chemotherapy for first-line treatment of PD-L1-positive (50%) metastatic NSCLC patients in France, assuming willingness-to-pay under 100,000€/QALY (OECD threshold in the discussion section).

Health related quality of life in patients having schizophrenia negative symptoms - a systematic review.

Background: Schizophrenia negative symptoms (SNS) contribute substantially to poor functional outcomes, loss in productivity and poor quality of life. It is unclear which instruments may be used for assessing quality of life in patients with SNS. Objective: The objective of this review was to identify instruments assessing health-related quality of life (HRQoL) validated in patients with SNS and to assess their level of validation. Data sources: We conducted a systematic literature review in Medline and the ISPOR database in March 2016 to identify studies on the quality of life in patients with SNS published by March 2016. Data extraction: Psychometric properties and validation steps. Data synthesis: After applying inclusion/exclusion criteria, 49 studies were selected for the analysis of HRQoL instruments; however, none of these instruments only addressed patients with SNS. Of these, 19 HRQoL instruments used in patients with schizophrenia or including patients with SNS among others, in the context of instrument validation, were identified (4 generic, 10 non-specific mental health, 5 schizophrenia-specific). Conclusion: No HRQoL instrument has been validated in patients with SNS only; for the remaining instruments identified, it remains unclear whether they were intended to capture HRQoL in patients with SNS.