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This study explores sociocultural differences in alcohol-related impact on quality of life between France and United Kingdom. We included 38 alcohol-dependent patients in France and United Kingdom in 10 focus groups. We used a text-mining approach. Three classes of each corpus regarded identical themes across the countries: (a) core impact on quality of life, (b) drinking habits, (c) sources of help. Core impact was similar between the two countries. Main differences were in drinking habits and referral to sources of help. Despite differences in drinking habits, the domains of life impacted by alcohol were non-country specific.
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Consumo de Bebidas Alcoólicas/epidemiologia , Alcoolismo/epidemiologia , Comparação Transcultural , Qualidade de Vida , Adulto , Idoso , Mineração de Dados , Feminino , Grupos Focais , França , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido , Adulto JovemRESUMO
AIMS: To assess the cost-effectiveness of integrating nalmefene within the treatment pathway for alcohol dependence recommended by the National Institute for Health and Care Excellence in the UK. METHODS: A Markov model, taking a UK NHS perspective, followed a cohort with alcohol dependence and high/very high drinking risk levels (HVHDRLs), who do not require immediate detoxification and who continue at HVHDRLs after initial assessment, for 5 years. Costs and quality-adjusted life years (QALYs) from treatment with nalmefene plus psychosocial support versus psychosocial support alone were modelled. The consequent incidence of alcohol-attributable harmful events and disease progression, with the possibility of requiring other options or recurrent treatment, were captured. RESULTS: Nalmefene plus psychosocial support dominated psychosocial support alone, with lower costs and increased QALYs after 5 years. Savings are driven by the higher response to nalmefene, and the subsequent lower cost accumulation for alternatives. CONCLUSIONS: Nalmefene represents a highly cost-effective treatment option in this population. The analysis shows that integrating nalmefene within the current UK clinical treatment pathway for alcohol dependence could reduce the economic burden on the NHS by limiting harmful events and disease progression.
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Alcoolismo/economia , Alcoolismo/terapia , Terapia Combinada/economia , Análise Custo-Benefício , Naltrexona/análogos & derivados , Psicoterapia/economia , Alcoolismo/tratamento farmacológico , Ensaios Clínicos como Assunto/estatística & dados numéricos , Terapia Combinada/métodos , Custos de Cuidados de Saúde , Humanos , Cadeias de Markov , Modelos Econômicos , Naltrexona/economia , Naltrexona/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: A considerable economic burden has been repeatedly associated with alcohol dependence (AD) - mostly calculated using aggregate data and alcohol-attributable fractions (top-down approach). However, this approach is limited by a number of assumptions, which are hard to test. Thus, cost estimates should ideally be validated with studies using individual data to estimate the same costs (bottom-up approach). However, bottom-up studies on the economic burden associated with AD are lacking. Our study aimed to fill this gap using the bottom-up approach to examine costs for AD, and also stratified the results by the following subgroups: sex, age, diagnostic approach and severity of AD, as relevant variations could be expected by these factors. SAMPLE: 1356 primary health care patients, representative for two German regions. AD was diagnosed by a standardized instrument and treating physicians. Individual costs were calculated by combining resource use and productivity data representing a period of six months prior to the time of interview, with unit costs derived from the literature or official statistics. The economic burden associated with AD was determined via excess costs by comparing utilization of various health care resources and impaired productivity between people with and without AD, controlling for relevant confounders. Additional analyses for several AD characteristics were performed. RESULTS: Mean costs among alcohol dependent patients were 50 % higher compared to the remaining patients, resulting in 1836 excess costs per alcohol dependent patient in 6 months. More than half of these excess costs incurred through increased productivity loss among alcohol dependent patients. Treatment for alcohol problems represents only 6 % of these costs. The economic burden associated with AD incurred mainly among males and among 30 to 49 year old patients. Both diagnostic approaches were significantly related to the economic burden, while costs increased with alcohol use disorder severity but not with other AD severity indicators. CONCLUSIONS: Our study confirms previous studies using top-down approaches to estimate the economic burden associated with AD. Further, we highlight the need for efforts aimed at preventing adverse outcomes for health and occupational situation associated with alcohol dependence based on factors associated with particularly high economic burden.
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Alcoolismo/economia , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Adolescente , Adulto , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Most available pharmacotherapies for alcohol-dependent patients target abstinence; however, reduced alcohol consumption may be a more realistic goal. Using randomized clinical trial (RCT) data, a previous microsimulation model evaluated the clinical relevance of reduced consumption in terms of avoided alcohol-attributable events. Using real-life observational data, the current analysis aimed to adapt the model and confirm previous findings about the clinical relevance of reduced alcohol consumption. METHODS: Based on the prospective observational CONTROL study, evaluating daily alcohol consumption among alcohol-dependent patients, the model predicted the probability of drinking any alcohol during a given day. Predicted daily alcohol consumption was simulated in a hypothetical sample of 200,000 patients observed over a year. Individual total alcohol consumption (TAC) and number of heavy drinking days (HDD) were derived. Using published risk equations, probabilities of alcohol-attributable adverse health events (e.g., hospitalizations or death) corresponding to simulated consumptions were computed, and aggregated for categories of patients defined by HDDs and TAC (expressed per 100,000 patient-years). Sensitivity analyses tested model robustness. RESULTS: Shifting from >220 HDDs per year to 120-140 HDDs and shifting from 36,000-39,000 g TAC per year (120-130 g/day) to 15,000-18,000 g TAC per year (50-60 g/day) impacted substantially on the incidence of events (14,588 and 6148 events avoided per 100,000 patient-years, respectively). Results were robust to sensitivity analyses. CONCLUSIONS: This study corroborates the previous microsimulation modeling approach and, using real-life data, confirms RCT-based findings that reduced alcohol consumption is a relevant objective for consideration in alcohol dependence management to improve public health.
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Consumo de Bebidas Alcoólicas/epidemiologia , Alcoolismo/epidemiologia , Adulto , Abstinência de Álcool/estatística & dados numéricos , Simulação por Computador , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Estudos Prospectivos , Saúde PúblicaRESUMO
BACKGROUND: Alcohol consumption is one of the most important factors for disease and disability in Europe. In clinical trials, nalmefene has resulted in a significant reduction in the number of heavy-drinking days (HDDs) per month and total alcohol consumption (TAC) among alcohol-dependent patients versus placebo. METHODS: A microsimulation model was developed to estimate alcohol-attributable diseases and injuries in patients with alcohol dependence and to explore the clinical relevance of reducing alcohol consumption. RESULTS: For all diseases and injuries considered, the number of events (inpatient episodes) increased with the number of HDDs and TAC per year. The model predicted that a reduction of 20 HDDs per year would result in 941 fewer alcohol-attributable events per 100,000 patients, while a reduction in intake of 3,000 g/year of pure alcohol (ethanol) would result in 1,325 fewer events per 100,000 patients. CONCLUSION: The potential gains of reducing consumption in alcohol-dependent patients were considerable.
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Consumo de Bebidas Alcoólicas/prevenção & controle , Transtornos Relacionados ao Uso de Álcool/prevenção & controle , Alcoolismo/reabilitação , Redução do Dano , Naltrexona/análogos & derivados , Antagonistas de Entorpecentes/uso terapêutico , Ferimentos e Lesões/prevenção & controle , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Transtornos Relacionados ao Uso de Álcool/etiologia , Alcoolismo/complicações , Simulação por Computador , Inglaterra , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Naltrexona/uso terapêutico , Ferimentos e Lesões/etiologiaRESUMO
INTRODUCTION: Health technology assessment (HTA) agencies express a clear preference for randomized controlled trials when assessing the comparative efficacy of two or more treatments. However, an indirect treatment comparison (ITC) is often necessary where a direct comparison is unavailable or, in some cases, not possible. Numerous ITC techniques are described in the literature. A systematic literature review (SLR) was conducted to identify all the relevant literature on existing ITC techniques, provide a comprehensive description of each technique and evaluate their strengths and limitations from an HTA perspective in order to develop guidance on the most appropriate method to use in different scenarios. METHODS: Electronic database searches of Embase and PubMed, as well as grey literature searches, were conducted on 15 November 2021. Eligible articles were peer-reviewed papers that specifically described the methods used for different ITC techniques and were written in English. The review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 73 articles were included in the SLR, reporting on seven different ITC techniques. All reported techniques were forms of adjusted ITC. Network meta-analysis (NMA) was the most frequently described technique (in 79.5% of the included articles), followed by matching-adjusted indirect comparison (MAIC) (30.1%), network meta-regression (24.7%), the Bucher method (23.3%), simulated treatment comparison (STC) (21.9%), propensity score matching (4.1%) and inverse probability of treatment weighting (4.1%). The appropriate choice of ITC technique is critical and should be based on the feasibility of a connected network, the evidence of heterogeneity between and within studies, the overall number of relevant studies and the availability of individual patient-level data (IPD). MAIC and STC were found to be common techniques in the case of single-arm studies, which are increasingly being conducted in oncology and rare diseases, whilst the Bucher method and NMA provide suitable options where no IPD is available. CONCLUSION: ITCs can provide alternative evidence where direct comparative evidence may be missing. ITCs are currently considered by HTA agencies on a case-by-case basis; however, their acceptability remains low. Clearer international consensus and guidance on the methods to use for different ITC techniques is needed to improve the quality of ITCs submitted to HTA agencies. ITC techniques continue to evolve quickly, and more efficient techniques may become available in the future.
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INTRODUCTION: Randomized controlled trials (RCTs) are the gold standard when comparing treatment effectiveness, and Health Technology Assessment (HTA) agencies state a clear preference for such direct comparisons. When these are not available, an indirect treatment comparison (ITC) is an alternative option. The objective of this study was to assess the acceptance of ITC methods by HTA agencies across England, France, Germany, Italy, and Spain, using oncology cases for a homogeneous sample of HTA evaluations. METHODS: The study was conducted on the PrismAccess database in May 2021 to retrieve HTA evaluation reports for oncology treatments for solid tumors, in which an ITC was presented. The analysis was restricted to HTA evaluation reports published between April 2018 and April 2021 in England, France, Germany, Italy, and Spain. Identified HTA evaluation reports were screened and reviewed by two independent reviewers. For each ITC presented, the methodology and its acceptance by the HTA agency were analyzed. RESULTS: Five hundred and forty-three HTA evaluation reports were identified, of which 120 (22%) presented an ITC. This proportion was the highest in England (51%) and lowest in France (6%). The overall acceptance rate of ITC methods was 30%, with the highest in England (47%) and lowest in France (0%). Network meta-analysis (NMA; 23%) was the most commonly used ITC technique, with a 39% acceptance rate overall, followed by Bucher ITC (19%; 43% acceptance rate) and matching-adjusted indirect comparison (13%; 33% acceptance rate). The most common criticisms of the ITC methods from HTA agencies related to data limitations (heterogeneity and lack of data; 48% and 43%, respectively) and the statistical methods used (41%). CONCLUSIONS: The generally low acceptance rate of ITC methods by HTA agencies in oncology suggests that, whilst in the absence of a direct comparison ITCs may provide relevant evidence, this evidence is not widely considered sufficient for the purpose of HTA evaluations. The perception of ITC methods for the purpose of HTA evaluations varies substantially between countries. There is a need for further clarity on the properties of ITC techniques and the assessment of their results as ITC methods continue to evolve quickly and further techniques may become available in the future.
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AIMS: To determine the economic burden pertaining to alcohol dependence in Europe. METHODS: Database searching was combined with grey literature searching to identify costs and resource use in Europe relating to alcohol dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) or the World Health Organisation's International Classification of Diseases (ICD-10). Searches combined MeSH headings for both economic terms and terms pertaining to alcohol dependence. Relevant outcomes included direct healthcare costs and indirect societal costs. Main resource use outcomes included hospitalization and drug costs. RESULTS: Compared with the number of studies of the burden of alcohol use disorders in general, relatively few focussed specifically on alcohol dependence. Twenty-two studies of variable quality were eligible for inclusion. The direct costs of alcohol dependence in Europe were substantial, the treatment costs for a single alcohol-dependent patient lying within the range 1591-7702 per hospitalization and the annual total direct costs accounting for 0.04-0.31% of an individual country's gross domestic product (GDP). These costs were driven primarily by hospitalization; in contrast, the annual drug costs for alcohol dependence were low. The indirect costs were more substantial than the direct costs, accounting for up to 0.64% of GDP per country annually. Alcohol dependence may be more costly in terms of health costs per patient than alcohol abuse. CONCLUSIONS: This review confirms that alcohol dependence represents a significant burden for European healthcare systems and society. Difficulties in comparing across cost-of-illness studies in this disease area, however, prevent specific estimation of the economic burden.
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Alcoolismo/economia , Alcoolismo/epidemiologia , Efeitos Psicossociais da Doença , Custos e Análise de Custo , Bases de Dados Bibliográficas , Europa (Continente)/epidemiologia , Custos de Cuidados de Saúde , Recursos em Saúde/estatística & dados numéricos , Humanos , Tempo de Internação , Resultado do TratamentoRESUMO
OBJECTIVES: This study aimed to compare reimbursement recommendations by the British National Institute for Health and Care Excellence (NICE) and the French National Authority for Health (Haute Autorité de Santé; HAS) for oncology new medicines indicated for the treatment of solid tumors. METHODS: Public assessment reports published on NICE and HAS Web sites between January 1, 2015, and December 31, 2021, describing appraisals for public reimbursement for oncology new medicines indicated for the treatment of solid tumors were searched and systematically reviewed. Biosimilars and generic drugs were excluded from the analysis. RESULTS: Overall, 119 public assessment reports published by NICE and 134 by HAS were identified, with 101 interventions assessed by both agencies. Of 101, 38 (38%) interventions received similar recommendations, 38 (38%) were recommended for different populations, and 25 (25%) were endorsed by one agency but rejected by the other. The main reason NICE would not recommend a drug was due to lack of cost-effectiveness, whereas HAS would primarily reject a drug on the grounds of insufficient clinical evidence. CONCLUSION: The major divergence between agencies is the key criterion used for reimbursement recommendations. NICE mainly considers cost-effectiveness, whereas HAS primarily focuses on the clinical value of interventions. This contributes to the variability in reimbursement recommendations and leads to differential access to oncology new medicines indicated for the treatment of solid tumors among patients in France, and England and Wales. HIGHLIGHTS: Both the National Institute for Health and Care Excellence (NICE) and the National Authority for Health (Haute Autorité de Santé; HAS) have established formal health technology assessment (HTA) processes and offer universal public health care coverage. However, both agencies diverge in the weight given to different elements of evidence during HTA evaluations. NICE uses cost-effectiveness as key criterion for recommendations on drug reimbursement, while HAS mostly limits its assessment to clinical value.For oncology new medicines indicated for treating solid tumors between 2015 and 2021, recommendations differed 62% of the time between NICE and HAS, primarily due to the distinct key decision-making criteria each HTA agency uses.For 4 interventions not endorsed by NICE, HAS saw these drugs as providing a substantial enhancement in clinical value over existing treatments, potentially providing an edge in price negotiations. Conversely, NICE deemed these drugs as not delivering adequate value for money in comparison with current therapies.A key difference between the 2 agencies is HAS's insistence on methodological rigor in efficacy results, compared with NICE's more flexible approach, considering descriptive efficacy results in cost-effectiveness modeling.
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Medicamentos Biossimilares , Neoplasias , Humanos , Análise Custo-Benefício , Neoplasias/tratamento farmacológico , Inglaterra , França , Avaliação da Tecnologia BiomédicaRESUMO
BACKGROUND AND OBJECTIVES: Multiple reforms aimed at improving the Chinese population's health have been introduced in recent years, including several designed to improve access to innovative drugs. We sought to review current factors affecting access to innovative drugs in China and to anticipate future trends. METHODS: Targeted reviews of published literature and statistics on the Chinese healthcare system, medical insurance and reimbursement processes were conducted, as well as interviews with five Chinese experts involved in the reimbursement of innovative drugs. RESULTS: Drug reimbursement in China is becoming increasingly centralized due to the removal of provincial pathways, the establishment of the National Healthcare Security Administration and the implementation of the National Reimbursement Drug List (NRDL), which is now the main route for drug reimbursement in China. There is also an increasing number of other channels via which patients may access innovative treatments, including various types of commercial insurance and special access. Health technology assessment (HTA) and health economic evidence are becoming pivotal elements of the NRDL decision-making process. Alongside the optimization of HTA decision making, innovative risk-sharing agreements are anticipated to be increasingly leveraged in the future to optimize access to highly specialized technologies and encourage innovation while safeguarding limited healthcare funds. CONCLUSIONS: Drug public reimbursement in China continues to align more closely with approaches widely used in Europe in terms of HTA, health economics and pricing. Centralization of decision-making processes for public reimbursement of innovative drugs allows consistency in assessment and access, which optimizes the improvement of the Chinese population's health.
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OBJECTIVE: The objective of this study was to determine the cost-effectiveness of encorafenib with binimetinib (EncoBini) as compared to other targeted double combination therapies, namely dabrafenib with trametinib (DabraTrame) and vemurafenib with cobimetinib (VemuCobi), for the treatment of BRAF V600-mutant unresectable or metastatic melanoma (MM) from the French payer perspective. METHODS: A partitioned survival model was developed considering a lifetime horizon. The model structure simulated the clinical pathway of patients with BRAF V600-mutant MM. Clinical effectiveness and safety inputs were sourced from the COLUMBUS trial, a network meta-analysis and published literature. Costs, resource use, and the quality of life inputs were obtained from the literature and appropriate French sources. RESULTS: Over a lifetime horizon, EncoBini was associated, on average, with reduced costs and increased quality adjusted life years (QALYs), dominating both targeted double combination therapies. For a willingness-to-pay threshold of 90,000 per QALY, the probability of EncoBini being cost-effective against either comparator remained above 80%. The most influential model parameters were the hazard ratios for the overall survival of EncoBini vs DabraTrame and VemuCobi, the pre- and post-progression utility values, as well as treatment dosages and the relative dose intensity of all interventions. CONCLUSION: EncoBini is associated with reduced costs and increased QALYs, dominating other targeted double combination therapies (DabraTrame, VemuCobi) for patients with BRAF V600-mutant MM in France. EncoBini is a highly cost-effective intervention in MM.
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BACKGROUND & AIMS: A randomized trial that compared endoscopic and surgical drainage of the pancreatic duct in patients with advanced chronic pancreatitis reported a significant benefit of surgery after a 2-year follow-up period. We evaluated the long-term outcome of these patients after 5 years. METHODS: Between 2000 and 2004, 39 symptomatic patients were randomly assigned to groups that underwent endoscopic drainage or operative pancreaticojejunostomy. In 2009, information was collected regarding pain, quality of life, morbidity, mortality, length of hospital stay, number of procedures undergone, changes in pancreatic function, and costs. Analysis was performed according to an intention-to-treat principle. RESULTS: During the 79-month follow-up period, one patient was lost and 7 died from unrelated causes. Of the patients treated by endoscopy, 68% required additional drainage compared with 5% in the surgery group (P = .001). Hospital stay and costs were comparable, but overall, patients assigned to endoscopy underwent more procedures (median, 12 vs 4; P = .001). Moreover, 47% of the patients in the endoscopy group eventually underwent surgery. Although the mean difference in Izbicki pain scores was no longer significant (39 vs 22; P = .12), surgery was still superior in terms of pain relief (80% vs 38%; P = .042). Levels of quality of life and pancreatic function were comparable. CONCLUSIONS: In the long term, symptomatic patients with advanced chronic pancreatitis who underwent surgery as the initial treatment for pancreatic duct obstruction had more relief from pain, with fewer procedures, than patients who were treated endoscopically. Importantly, almost half of the patients who were treated with endoscopy eventually underwent surgery.
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Ductos Pancreáticos/fisiopatologia , Pancreaticojejunostomia/métodos , Pancreatite Crônica/terapia , Custos e Análise de Custo , Drenagem/métodos , Endoscopia do Sistema Digestório , Seguimentos , Humanos , Tempo de Internação , Dor/epidemiologia , Ductos Pancreáticos/cirurgia , Pancreatite Crônica/economia , Pancreatite Crônica/fisiopatologia , Prevalência , Qualidade de Vida , Estudos Retrospectivos , Resultado do TratamentoRESUMO
DESCRIPTION: The National Institute for Health and Clinical Excellence released its first clinical guideline on heart failure in 2003. This synopsis describes the update of that guideline, which was released in August 2010 and discusses the diagnosis, treatment, and monitoring of heart failure. METHODS: Guideline developers considered clinical evidence, health economic analyses, clinical expert opinion, and patient views. Systematic literature searches were performed, and an original decision model assessed the cost-effectiveness of serial measurement of serum natriuretic peptide to monitor patients with chronic heart failure. RECOMMENDATIONS: First, this guideline update describes the role of serum natriuretic peptide measurement, echocardiography, and specialist assessment in the diagnosis of heart failure. Second, it presents a pathway for pharmacologic treatment, rehabilitation, and pacing therapy (including implantable cardioverter-defibrillator and cardiac resynchronization therapy) for patients with heart failure and left ventricular systolic dysfunction and patients with heart failure and preserved ejection fraction. Finally, it explains the recommendation to monitor patients with heart failure by using serial measurement of serum natriuretic peptide.
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Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Terapia de Ressincronização Cardíaca , Doença Crônica , Análise Custo-Benefício , Desfibriladores Implantáveis , Ecocardiografia , Terapia por Exercício , Insuficiência Cardíaca/fisiopatologia , Humanos , Monitorização Fisiológica/economia , Monitorização Fisiológica/métodos , Peptídeo Natriurético Encefálico/sangue , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
The National Clinical Guideline Centre (NCGC) develops evidence-based clinical guidelines on behalf of the National Institute for Health and Clinical Excellence (NICE) in the United Kingdom. The U.K. Department of Health has commissioned NICE to make recommendations on the basis of both clinical effectiveness and cost-effectiveness. This article describes how cost-effectiveness is evaluated and accounted for in NCGC guidelines. Six recent case studies are presented, in which consideration of cost-effectiveness has informed recommendations in various ways for clinical guidelines on alcohol use disorders, chronic obstructive pulmonary disease, glaucoma, lower urinary tract symptoms, non-ST-segment elevation myocardial infarction and unstable angina, and venous thromboembolism prophylaxis. Some of the challenges faced in trying to account for cost-effectiveness in clinical guidelines are outlined, as well as some of the difficulties in adapting cost-effectiveness guidelines for other settings.
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Análise Custo-Benefício , Medicina Baseada em Evidências/economia , Medicina Baseada em Evidências/métodos , Guias de Prática Clínica como Assunto , Técnicas de Apoio para a Decisão , Inglaterra , Órgãos Governamentais , Humanos , Irlanda do Norte , Guias de Prática Clínica como Assunto/normas , Controle de Qualidade , Medicina Estatal , País de GalesRESUMO
BACKGROUND: The objective of this study was to estimate the relative efficacy and safety of targeted therapies for the treatment of metastatic melanoma using a network meta-analysis (NMA). METHODS: A systematic literature review (SLR) identified studies in Medline, Embase and Cochrane published until November 2020. Screening used prespecified eligibility criteria. Following a transitivity assessment across included studies, Bayesian NMA was conducted. RESULTS: A total of 43 publications reporting 15 targeted therapy trials and 42 reporting 18 immunotherapy trials were retained from the SLR and considered for the NMA. Due to substantial between-study heterogeneity with immunotherapy trials, the analysis considered a network restricted to targeted therapies. Among combination therapies, encorafenib + binimetinib was superior to dabrafenib + trametinib for overall response rate (OR = 1.86; 95 % credible interval [CrI] 1.10, 3.17), superior to vemurafenib + cobimetinib with fewer serious adverse events (SAEs) (OR = 0.51; 95 % CrI 0.29, 0.91) and fewer discontinuations due to AEs (OR = 0.45; 95 % CrI 0.21, 0.96), and superior to atezolizumab + vemurafenib + cobimetinib with fewer SAEs (OR = 0.41; 95 % CrI 0.21, 0.82). Atezolizumab + vemurafenib + cobimetinib and encorafenib + binimetinib were generally comparable for efficacy endpoints. Among double combination therapies, encorafenib + binimetinib showed high probabilities of being better for all efficacy and safety endpoints. CONCLUSIONS: This NMA confirms that combination therapies are more efficacious than monotherapies. Encorafenib + binimetinib has a favourable efficacy profile compared to other double combination therapies and a favourable safety profile compared to both double and triple combination therapies.
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Melanoma , Segunda Neoplasia Primária , Neoplasias Cutâneas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Teorema de Bayes , Benzimidazóis/efeitos adversos , Carbamatos , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Mutação , Metanálise em Rede , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/tratamento farmacológico , Sulfonamidas , VemurafenibRESUMO
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.
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Neoplasias do Colo , Neoplasias Retais , Adulto , Humanos , Cetuximab/uso terapêutico , Análise Custo-Benefício , Proteínas Proto-Oncogênicas B-raf/genética , Irinotecano , Bevacizumab/uso terapêutico , Inibidores de Proteínas Quinases , FrançaRESUMO
BACKGROUND: Persistent hypotension is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). Midodrine, an orally administered alpha agonist, could potentially reduce intravenous vasopressor use and accelerate ICU discharge of otherwise stable patients. The main objective of this study was to explore the clinical impacts of administering midodrine in patients with persistent hypotension after CPB. Our hypothesis was that midodrine would safely accelerate ICU discharge and be associated with more days free from ICU at 30 days. RESULTS: We performed a retrospective cohort study that included all consecutive patients having received midodrine while being on vasopressor support in the ICU within the first week after cardiac surgery with CPB, between January 2014 and January 2018 at the Montreal Heart Institute. A contemporary propensity score matched control group that included patients who presented similarly prolonged hypotension after cardiac surgery was formed. After matching, 74 pairs of patients (1:1) fulfilled inclusion criteria for the study and control groups. Midodrine use was associated with fewer days free from ICU (25.8 [23.7-27.1] vs 27.2 [25.9-28] days, p = 0.002), higher mortality (10 (13.5%) vs 1 (1.4%), p = 0.036) and longer ICU length of stay (99 [68-146] vs 68 [48-99] hours, p = 0.001). There was no difference in length of intravenous vasopressors (63 [40-87] vs 44 [26-66] hours, p = 0.052), rate of ICU readmission (6 (8.1%) vs 2 (2.7%), p = 0.092) and occurrence of severe kidney injury (11 (14.9%) vs 10 (13.5%) patients, p = 0.462) between groups. CONCLUSION: The administration of midodrine for sustained hypotension after cardiac surgery with CPB was associated with fewer days free from ICU and higher mortality. Routine prescription of midodrine to hasten ICU discharge after cardiac surgery should be used with caution until further prospective studies are conducted.
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OBJECTIVE: A microsimulation model was adapted to evaluate the cost-effectiveness of nalmefene combined with psychosocial support (NMF + PS) versus psychosocial support alone (PS). The economic impact of alcohol reduction using nalmefene treatment was not evaluated. METHOD: The model simulates patient-level alcohol consumption over a 5-year time horizon across different treatment cohorts. Study outcomes included probabilities of alcohol-attributable diseases and injuries as well as deaths from these events. The approach used nalmefene clinical trial data, a time horizon of 1 and 5 years, and a U.K. societal perspective. Extensive deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Compared with the PS strategy, NMF + PS was associated at Year 5 with a gain of 0.047 quality-adjusted life years (QALYs) and an additional £503, leading to an incremental cost-effectiveness ratio (ICER) of £10,613 per QALY gained. When compared with the strategy without treatment, NMF + PS was associated with a gain of 0.228 QALYs and an additional £1,795, leading to an ICER of £1,758 per QALY gained. The NMF + PS strategy dominated both treatment strategies when considering the U.K. societal perspective. Sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: A combination of NMF and PS was better than PS alone, considering a 5-year time horizon and a societal perspective.