RESUMO
BACKGROUND: The new direct-acting anti-virals (DAAs) for hepatitis C virus (HCV) infection offer higher cure rates, but at a much higher cost than the standard interferon-based treatments. AIM: To identify the cost-effective treatment for patients with HCV infection with F3 liver fibrosis who are at high risk of progression to cirrhosis. METHODS: A decision-analytic Markov model compared the health benefits and costs of all currently licensed treatments as single treatments and in sequential therapy of up to three lines. Costs were expressed in pound sterling from the perspective of the UK National Health Service. Health benefits were expressed in quality-adjusted life years. RESULTS: Treatment before progression to cirrhosis always offers the most health benefits for the least costs. Sequential therapy with multiple treatment lines cures over 89% of patients across all HCV genotypes while ensuring a cost-effective use of resources. Cost-effective regimes for HCV genotype 1 patients include first-line oral therapy with sofosbuvir-ledipasvir while peginterferon continues to have a role in other genotypes. CONCLUSIONS: The cost-effective treatment for HCV can be established using decision analytic modelling comparing single and sequential therapies. Sequential therapy with DAAs is effective and cost-effective in HCV patients with F3 fibrosis. This information is of significant benefit to health care providers with budget limitations and provides a sound scientific basis for drug treatment choices.
Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Análise Custo-Benefício , Progressão da Doença , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Acute coronary syndrome (ACS) refers to a spectrum of life-threatening cardiac diseases usually due to coronary artery plaque rupture, subsequent thrombin generation plaque activation and thrombus formation. To date, no economic analyses have been published about the use of fondaparinux in NSTE-ACS patients in Canada. The purpose of our study is to estimate the lifetime cost-effectiveness of fondaparinux compared to enoxaparin for non-ST-elevation acute coronary syndrome (NSTE-ACS) patients in a Canadian hospital setting. METHODS: As an extension of a previous published economic analysis for US patients, an event-based decision analytic model was constructed using clinical and resource use data from OASIS-5, a randomized trial of 20,078 patients from 41 countries. A public payer perspective in the hospital setting was adopted. Resource use data from the trial were valued using Canadian costs. A cost regression model was developed to estimate the mean cost of managing the clinical events over the 180 day period. Annual costs of long-term care for ACS patients were added after 180 days until death. Long-term survival was incorporated using Canadian life tables with further adjustment for additional risks associated with NSTE-ACS. Quality-of-life (utility) decrements from published sources were applied to clinical events. Lifetime costs (2009 CAD$) and quality-adjusted life-years (QALYs), discounted annually at 5 %, were estimated for the typical patient in OASIS-5 (i.e., at mean covariate values). RESULTS: The trial data showed that fondaparinux is protective against all clinical events observed in the trial. The model showed that: over 180 days, fondaparinux dominates enoxaparin, producing similar estimates of QALYs gained and saving $439; over a patient's lifetime, fondaparinux yields an ICER of $4293/QALY. Based on PSA, the probabilities that fondaparinux dominates enoxaparin (less costly and more effective) and that is cost-effective at a $50,000 threshold were 42 % and 96 %, respectively. CONCLUSIONS: In the Canadian hospital setting, fondaparinux is cost-effective when compared to enoxaparin for the treatment of NSTE-ACS. This result holds both in the immediate post-event period and over the lifetimes of patients.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/economia , Anticoagulantes/economia , Anticoagulantes/uso terapêutico , Custos de Medicamentos , Enoxaparina/economia , Enoxaparina/uso terapêutico , Custos Hospitalares , Polissacarídeos/economia , Polissacarídeos/uso terapêutico , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Anticoagulantes/efeitos adversos , Canadá , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Enoxaparina/efeitos adversos , Fondaparinux , Hemorragia/induzido quimicamente , Hemorragia/economia , Hemorragia/terapia , Humanos , Modelos Econômicos , Polissacarídeos/efeitos adversos , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: Comorbid major depression is associated with reduced quality of life and greater use of healthcare resources. A recent randomised trial (SMaRT, Symptom Management Research Trials, Oncology-2) found that a collaborative care treatment programme (Depression Care for People with Cancer, DCPC) was highly effective in treating depression in patients with cancer. This study aims to estimate the cost-effectiveness of DCPC compared with usual care from a health service perspective. METHODS: Costs were estimated using UK national unit cost estimates and health outcomes measured using quality-adjusted life-years (QALYs). Incremental cost-effectiveness of DCPC compared with usual care was calculated and scenario analyses performed to test alternative assumptions on costs and missing data. Uncertainty was characterised using cost-effectiveness acceptability curves. The probability of DCPC being cost-effective was determined using the UK National Institute for Health and Care Excellence's (NICE) cost-effectiveness threshold range of £ 20,000 to £ 30,000 per QALY gained. RESULTS: DCPC cost on average £ 631 more than usual care per patient, and resulted in a mean gain of 0.066 QALYs, yielding an incremental cost-effectiveness ratio of £ 9549 per QALY. The probability of DCPC being cost-effective was 0.9 or greater at cost-effectiveness thresholds above £ 20,000 per QALY for the base case and scenario analyses. CONCLUSIONS: Compared with usual care, DCPC is likely to be cost-effective at the current thresholds used by NICE. This study adds to the weight of evidence that collaborative care treatment models are cost-effective for depression, and provides new evidence regarding their use in specialist medical settings.
Assuntos
Prestação Integrada de Cuidados de Saúde/economia , Depressão/economia , Depressão/terapia , Transtorno Depressivo Maior/economia , Transtorno Depressivo Maior/terapia , Neoplasias/psicologia , Adulto , Idoso , Comorbidade , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de VidaRESUMO
BACKGROUND: Survival rates in lung cancer in England are significantly lower than in many similar countries. A range of Be Clear on Cancer (BCOC) campaigns have been conducted targeting lung cancer and found to improve the proportion of diagnoses at the early stage of disease. This paper considers the cost-effectiveness of such campaigns, evaluating the effect of both the regional and national BCOC campaigns on the stage distribution of non-small-cell lung cancer (NSCLC) at diagnosis. METHODS: A natural history model of NSCLC was developed using incidence data, data elicited from clinical experts and model calibration techniques. This structure is used to consider the lifetime cost and quality-adjusted survival implications of the early awareness campaigns. Incremental cost-effectiveness ratios (ICERs) in terms of additional costs per quality-adjusted life-years (QALYs) gained are presented. Two scenario analyses were conducted to investigate the role of changes in the 'worried-well' population and the route of diagnosis that might occur as a result of the campaigns. RESULTS: The base-case theoretical model found the regional and national early awareness campaigns to be associated with QALY gains of 289 and 178 QALYs and ICERs of £13 660 and £18 173 per QALY gained, respectively. The scenarios found that increases in the 'worried-well' population may impact the cost-effectiveness conclusions. CONCLUSIONS: Subject to the available evidence, the analysis suggests that early awareness campaigns in lung cancer have the potential to be cost-effective. However, significant additional research is required to address many of the limitations of this study. In addition, the estimated natural history model presents previously unavailable estimates of the prevalence and rate of disease progression in the undiagnosed population.
Assuntos
Conscientização , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Análise Custo-Benefício , Neoplasias Pulmonares/diagnóstico , Adulto , Idoso , Diagnóstico Precoce , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Breast, cervical and colorectal cancers are the three most frequent cancers in women, while lung, prostate and colorectal cancers are the most frequent in men. Much attention has been given to the economic evaluation of pharmaceuticals for treatment of cancer by the National Institute for Health and Care Excellence (NICE) in the UK and similar authorities internationally, while economic analysis developed for other types of anti-cancer interventions, including radiotherapy and surgery, are less common. OBJECTIVES: Our objective was to review methods used in published cost-effectiveness studies evaluating radiotherapy for breast, cervical, colorectal, head and neck and prostate cancer, and to compare the economic evaluation methods applied with those defined in the guidelines used by the NICE technology appraisal programme. METHODS: A systematic search of seven databases (MEDLINE, EMBASE, CDSR, NHSEED, HTA, DARE, EconLit) as well as research registers, the NICE website and conference proceedings was conducted in July 2012. Only economic evaluations of radiotherapy interventions in individuals diagnosed with cancer that included quality-adjusted life-years (QALYs) or life-years (LYs) were included. Included studies were appraised on the basis of satisfying essential, preferred and UK-specific methods requirements, building on the NICE Reference Case for economic evaluations and on other methods guidelines. RESULTS: A total of 29 studies satisfied the inclusion criteria (breast 14, colorectal 2, prostate 10, cervical 0, head and neck 3). Only two studies were conducted in the UK (13 in the USA). Among essential methods criteria, the main issue was that only three (10%) of the studies used clinical-effectiveness estimates identified through systematic review of the literature. Similarly, only eight (28%) studies sourced health-related quality-of-life data directly from patients with the condition of interest. Other essential criteria (e.g. clear description of comparators, patient group indication and appropriate time horizon) were generally fulfilled, while most of the UK-specific requirements were not met. CONCLUSION: Based on this review there is a dearth of up-to-date, robust evidence on the cost effectiveness of radiotherapy in cancer suitable to support decision making in the UK. Studies selected did not fully satisfy essential method standards currently recommended by NICE.
Assuntos
Análise Custo-Benefício , Estudos de Avaliação como Assunto , Neoplasias/economia , Neoplasias/radioterapia , Radioterapia/economia , Comitês Consultivos , Neoplasias da Mama/economia , Neoplasias da Mama/radioterapia , Neoplasias Colorretais/economia , Neoplasias Colorretais/radioterapia , Tomada de Decisões , Feminino , Neoplasias de Cabeça e Pescoço/economia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Modelos Econômicos , Neoplasias da Próstata/economia , Neoplasias da Próstata/radioterapia , Anos de Vida Ajustados por Qualidade de Vida , Reino Unido , Estados Unidos , Neoplasias do Colo do Útero/economia , Neoplasias do Colo do Útero/radioterapiaRESUMO
BACKGROUND: A number of published economic evaluations of elective endovascular aneurysm repair (EVAR) versus open repair for abdominal aortic aneurysm (AAA) have come to differing conclusions about whether EVAR is cost-effective. This paper reviews the current evidence base and presents up-to-date cost-effectiveness analyses in the light of results of four randomized clinical trials: EVAR-1, DREAM, OVER and ACE. METHODS: Markov models were used to estimate lifetime costs from a UK perspective and quality-adjusted life-years (QALYs) based on the results of each of the four trials. The outcomes included in the model were: procedure costs, surveillance costs, reintervention costs, health-related quality of life, aneurysm-related mortality and other-cause mortality. Alternative scenarios about complications, reinterventions and deaths beyond the trial were explored. RESULTS: Models based on the results of the EVAR-1, DREAM or ACE trials did not find EVAR to be cost-effective at thresholds used in the UK (up to £30,000 per QALY). EVAR seemed cost-effective according to models based on the OVER trial. These results seemed robust to alternative model scenarios about events beyond the trial intervals. CONCLUSION: These analyses did not find that EVAR is cost-effective compared with open repair in the long term in trials conducted in European centres. EVAR did appear to be cost-effective based on the OVER trial, conducted in the USA. Caution must be exercised when transferring the results of economic evaluations from one country to another.
Assuntos
Aneurisma da Aorta Abdominal/economia , Procedimentos Endovasculares/economia , Idoso , Aneurisma da Aorta Abdominal/mortalidade , Aneurisma da Aorta Abdominal/cirurgia , Análise Custo-Benefício , Procedimentos Endovasculares/mortalidade , Feminino , Custos Hospitalares , Humanos , Masculino , Cadeias de Markov , Cuidados Pós-Operatórios/métodos , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: Ivabradine, a specific heart rate lowering therapy, has been shown in a randomised placebo-controlled study, Systolic HF Treatment with the If Inhibitor Ivabradine Trial (SHIfT), to significantly reduce the composite end point of cardiovascular death and hospitalisation for worsening heart failure (HF) in patients with systolic HF who are in sinus rhythm and with a heart rate ≥70â bpm, when added to optimised medical therapy (HR: 0.82, 95% CI 0.75 to 0.90, p<0.0001). We assessed the cost effectiveness of ivabradine, from a UK National Health Service perspective, based on the results of SHIfT. METHODS: A Markov model estimated the cost effectiveness of ivabradine compared with standard care for two cohorts of patients with HF (heart rate ≥75â bpm in line with the EU labelled indication; and heart rate ≥70â bpm in line with the SHIfT study population). Modelled outcomes included death, hospitalisation, quality of life and New York Heart Association class. Total costs and quality adjusted life years (QALYs) for ivabradine and standard care were estimated over a lifetime horizon. RESULTS: The incremental cost per additional QALY for ivabradine plus standard care versus standard care has been estimated as £8498 for heart rate ≥75â bpm and £13â 764 for heart rate ≥70â bpm. Ivabradine is expected to have a 95% chance of being cost-effective in the EU licensed population using the current National Institute for Health and Care Excellence cost effectiveness threshold of £20â 000 per QALY. These results were robust in sensitivity analyses. CONCLUSIONS: This economic evaluation suggests that the use of ivabradine is likely to be cost-effective in eligible patients with HF from a UK National Health Service perspective.
Assuntos
Antiarrítmicos/economia , Antiarrítmicos/uso terapêutico , Benzazepinas/economia , Benzazepinas/uso terapêutico , Custos de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/economia , Medicina Estatal/economia , Doença Crônica , Análise Custo-Benefício , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Custos Hospitalares , Humanos , Ivabradina , Estimativa de Kaplan-Meier , Cadeias de Markov , Modelos Econômicos , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Tempo , Resultado do Tratamento , Reino UnidoRESUMO
BACKGROUND: Co-morbid major depression occurs in approximately 10% of people suffering from a chronic medical condition such as cancer. Systematic integrated management that includes both identification and treatment has been advocated. However, we lack information on the cost-effectiveness of this combined approach, as published evaluations have focused solely on the systematic (collaborative care) treatment stage. We therefore aimed to use the best available evidence to estimate the cost-effectiveness of systematic integrated management (both identification and treatment) compared with usual practice, for patients attending specialist cancer clinics. METHOD: We conducted a cost-effectiveness analysis using a decision analytic model structured to reflect both the identification and treatment processes. Evidence was taken from reviews of relevant clinical trials and from observational studies, together with data from a large depression screening service. Sensitivity and scenario analyses were undertaken to determine the effects of variations in depression incidence rates, time horizons and patient characteristics. RESULTS: Systematic integrated depression management generated more costs than usual practice, but also more quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) was £11,765 per QALY. This finding was robust to tests of uncertainty and variation in key model parameters. CONCLUSIONS: Systematic integrated management of co-morbid major depression in cancer patients is likely to be cost-effective at widely accepted threshold values and may be a better way of generating QALYs for cancer patients than some existing medical and surgical treatments. It could usefully be applied to other chronic medical conditions.
Assuntos
Doença Crônica/psicologia , Análise Custo-Benefício , Prestação Integrada de Cuidados de Saúde/economia , Transtorno Depressivo Maior/economia , Modelos Econômicos , Neoplasias/psicologia , Doença Crônica/economia , Doença Crônica/epidemiologia , Comorbidade , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/terapia , Humanos , Neoplasias/economia , Neoplasias/epidemiologia , Anos de Vida Ajustados por Qualidade de VidaRESUMO
OBJECTIVE: To assess the long-term cost-effectiveness of 12 months treatment of prasugrel compared to clopidogrel in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the Spanish health care system. METHODS: A Markov state transition model was developed to estimate health outcomes, quality adjusted life years (QALYs), life years (LY), and costs over patients' lifetimes. Clinical inputs were based on an analysis of the TRITON-TIMI 38 clinical trial. Hospital readmissions captured during the trial in a sub-study of patients from eight countries (and subsequent re-hospitalisations modelled to accrue beyond the time horizon of the trial), were assigned to Spanish diagnosis-related group payment schedules to estimate hospitalisation costs. RESULTS: Mean total treatment costs were ?11,427 and ?10,910 for prasugrel and clopidogrel respectively. The mean cost of the study drug was ?538 higher for prasugrel vs. clopidogrel, but rehospitalisation costs at 12 months were ?79 lower for prasugrel due to reduced rates of revascularisation. Hospitalisation costs beyond 12 months were higher with prasugrel by ?55, due to longer life expectancy (+0.071 LY and +0.054 QALYs) associated with the decreased nonfatal myocardial infarction rate in the prasugrel group. The incremental cost per life year and QALY gained with prasugrel was ?7,198, and ?9,489, respectively. CONCLUSION: Considering a willingness-to-pay threshold of ?30,000/QALY gained in the Spanish setting, prasugrel represents a cost-effective option in comparison with clopidogrel among patients with ACS undergoing PCI.
Objetivo: Evaluar a largo plazo el coste-efectividad de 12 meses de tratamiento con prasugrel frente a clopidogrel en pacientes con síndrome coronario agudo (SCA) sometidos a intervención coronaria percutánea (ICP) desde la perspectiva del sistema nacional de salud español. Métodos: Se desarrolló un modelo de Markov de transición entre estados para estimar los resultados en salud, los años de vida ajustados por calidad (AVACs), los años de vida (AV) y los costes a lo largo de la vida de los pacientes. Los datos clínicos fueron obtenidos de un análisis del ensayo clínico TRITON-TIMI 38. Los reingresos hospitalarios registrados durante el ensayo en un subestudio de pacientes provenientes de ocho países, (y las subsiguientes rehospitalizaciones fueron modeladas para acumularse más alla del horizonte temporal del ensayo) fueron asignados a grupos relacionados con el diagnóstico españoles para estimar los costes de hospitalización. Resultados: Los costes medios totales del tratamiento con prasugrel y clopidogrel fueron 11.427 ??y 10.910 ?, respectivamente. El coste medio del fármaco fue 538 ??superior para prasugrel frente a clopidogrel, pero los costes de rehospitalización a los 12 meses fueron 79 ??menores para prasugrel debido a la reducción en las tasas de revascularización. Los costes de hospitalización más allá de los 12 meses fueron 55 ??superiores con prasugrel, debido a la mayor esperanza de vida (+0,071 AV y +0,054 AVACs) asociada a la reducción de la tasa de infartos de miocardio no mortales en el grupo de prasugrel. El coste-efectividad incremental por año de vida y AVAC ganado con prasugrel fue 7.198 ??y 9.489 ?, respectivamente. Conclusión: Considerando el umbral de disponibilidad a pagar de 30.000 ?/ AVAC para España, prasugrel representa una opción coste-efectiva en comparación con clopidogrel en pacientes con SCA sometidos a ICP.
Assuntos
Síndrome Coronariana Aguda/economia , Ensaios Clínicos como Assunto/economia , Estudos Multicêntricos como Assunto/economia , Piperazinas/economia , Inibidores da Agregação Plaquetária/economia , Tiofenos/economia , Ticlopidina/análogos & derivados , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Cateterismo Cardíaco/economia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Ensaios Clínicos como Assunto/estatística & dados numéricos , Clopidogrel , Terapia Combinada , Análise Custo-Benefício , Custos e Análise de Custo , Custos de Medicamentos/estatística & dados numéricos , Custos de Cuidados de Saúde/estatística & dados numéricos , Hemorragia/induzido quimicamente , Hemorragia/economia , Hospitalização/economia , Humanos , Expectativa de Vida , Cadeias de Markov , Modelos Econômicos , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Readmissão do Paciente/economia , Readmissão do Paciente/estatística & dados numéricos , Intervenção Coronária Percutânea/economia , Piperazinas/efeitos adversos , Piperazinas/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel , Anos de Vida Ajustados por Qualidade de Vida , Recidiva , Espanha , Tiofenos/efeitos adversos , Tiofenos/uso terapêutico , Ticlopidina/efeitos adversos , Ticlopidina/economia , Ticlopidina/uso terapêuticoRESUMO
BACKGROUND: Laparoscopic fundoplication surgery has been shown to be a cost-effective alternative to continued medical management over 1 year for patients with gastro-oesophageal reflux disease (GORD). The longer-term cost-effectiveness is, however, uncertain. This study evaluated the long-term health benefits, costs and cost-effectiveness of laparoscopic fundoplication compared with continued medical management in patients with GORD. METHODS: Individual patient data were used from the 5-year follow-up of the REFLUX trial, a large multicentre, pragmatic, randomized trial in which 357 patients with GORD for at least 12 months at trial entry were allocated randomly to early laparoscopic fundoplication or continued medical management. Health outcomes were expressed in quality-adjusted life-years (QALYs). A UK National Health Service perspective was used for costs. RESULTS: The group randomized to surgery experienced better health outcomes in each year of follow-up, but the difference narrowed over time. At 5 years, the surgery group had experienced 0.216 (95 per cent confidence interval 0.021 to 0.412) more QALYs but also accrued 1832 (1214 to 2448) more costs. The incremental cost-effectiveness ratio was 8481 per QALY gained. The probability that surgery is the most cost-effective intervention was 0.932 at a threshold of 24,134/QALY (£20,000/QALY). Results were robust to most sensitivity analyses, except where patients with missing data randomized to surgery were assumed to have worse health outcomes. CONCLUSION: Laparoscopic fundoplication is a cost-effective alternative to continued medical management over 5 years. No evidence was found to suggest that the cost-effectiveness of laparoscopic fundoplication diminishes over time.
Assuntos
Fundoplicatura/economia , Refluxo Gastroesofágico/cirurgia , Laparoscopia/economia , Procedimentos Cirúrgicos Ambulatórios/economia , Análise Custo-Benefício , Fundoplicatura/métodos , Humanos , Laparoscopia/métodos , Tempo de Internação/economia , Anos de Vida Ajustados por Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Despite promising evidence that laparoscopic fundoplication provides better short-term relief of gastro-oesophageal reflux disease (GORD) than continued medical management, uncertainty remains about whether benefits are sustained and outweigh risks. OBJECTIVE: To evaluate the long-term clinical effectiveness, cost-effectiveness and safety of laparoscopic surgery among people with GORD requiring long-term medication and suitable for both surgical and medical management. DESIGN: Five-year follow-up of a randomised trial (with parallel non-randomised preference groups) comparing a laparoscopic surgery-based policy with a continued medical management policy. Cost-effectiveness was assessed alongside the trial using a NHS perspective for costs and expressing health outcomes in terms of quality-adjusted life-years (QALYs). SETTING: Follow-up was by annual postal questionnaire and selective hospital case notes review; initial recruitment in 21 UK hospitals. PARTICIPANTS: Questionnaire responders among the 810 original participants. At entry, all had documented evidence of GORD and symptoms for > 12 months. Questionnaire response rates (years 1-5) were from 89.5% to 68.9%. INTERVENTIONS: Three hundred and fifty-seven participants were recruited to the randomised comparison (178 randomised to surgical management and 179 randomised to continued medical management) and 453 to the preference groups (261 surgical management and 192 medical management). The surgeon chose the type of fundoplication. MAIN OUTCOME MEASURES: Primary: disease-specific outcome measure (the REFLUX questionnaire); secondary: Short Form questionnaire-36 items (SF-36), European Quality of Life-5 Dimensions (EQ-5D), NHS resource use, reflux medication, complications. RESULTS: The randomised groups were well balanced. By 5 years, 63% in the randomised surgical group and 13% in the randomised medical management group had received a total or partial wrap fundoplication (85% and 3% in the preference groups), with few perioperative complications and no associated deaths. At 1 year (and 5 years) after surgery, 36% (41%) in the randomised surgical group - 15% (26%) of those who had surgery - were taking proton pump inhibitor medication compared with 87% (82%) in the randomised medical group. At each year, differences in the REFLUX score significantly favoured the randomised surgical group (a third of a SD; p< 0.01 at 5 years). SF-36 and EQ-5D scores also favoured surgery, but differences attenuated over time and were generally not statistically significant at 5 years. The worse the symptoms at trial entry, the larger the benefit observed after surgery. Those randomised to medical management who subsequently had surgery had low baseline scores that markedly improved after surgery. Following fundoplication, 3% had surgical treatment for a complication and 4% had subsequent reflux-related operations - most often revision of the wrap. Dysphagia, flatulence and inability to vomit were similar in the two randomised groups. The economic analysis indicated that surgery was the more cost-effective option for this patient group. The incremental cost-effectiveness ratio for surgery in the base case was £7028 per additional QALY; these findings were robust to changes in approaches and assumptions. The probability of surgery being cost-effective at a threshold of £20,000 per additional QALY was > 0.80 for all analyses. CONCLUSIONS: After 5 years, laparoscopic fundoplication continues to provide better relief of GORD symptoms with associated improved health-related quality of life. Complications of surgery were uncommon. Despite being initially more costly, a surgical policy is highly likely to be cost-effective. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15517081. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 22. See the HTA programme website for further project information.
Assuntos
Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/cirurgia , Laparoscopia/economia , Laparoscopia/métodos , Inibidores da Bomba de Prótons/economia , Inibidores da Bomba de Prótons/uso terapêutico , Análise Custo-Benefício , Feminino , Seguimentos , Fundoplicatura/efeitos adversos , Fundoplicatura/estatística & dados numéricos , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Complicações Pós-Operatórias/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Medicina Estatal/estatística & dados numéricos , Avaliação da Tecnologia Biomédica , Reino UnidoRESUMO
BACKGROUND: Women in England (aged 25-64 years) are invited for cervical screening every 3-5 years to assess for cervical intraepithelial neoplasia (CIN) or cancer. CIN is a term describing abnormal changes in the cells of the cervix, ranging from CIN1 to CIN3, which is precancerous. Colposcopy is used to visualise the cervix. Three adjunctive colposcopy technologies for examination of the cervix have been included in this assessment: Dynamic Spectral Imaging System (DySIS), the LuViva Advanced Cervical Scan and the Niris Imaging System. OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of adjunctive colposcopy technologies for examination of the uterine cervix for patients referred for colposcopy through the NHS Cervical Screening Programme. DATA SOURCES: Sixteen electronic databases [Allied and Complementary Medicine Database (AMED), BIOSIS Previews, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Database of Abstracts of Reviews of Effects (DARE), EMBASE, Health Management Information Consortium (HMIC), Health Technology Assessment (HTA) database; Inspec, Inside Conferences, MEDLINE, NHS Economic Evaluation Database (NHS EED), PASCAL, Science Citation Index Expanded (SCIE) and Science Citation Index (SCI) - Conference Proceedings], and two clinical trial registries [ClinicalTrials.gov and Current Controlled Trials (CCT)] were searched to September-October 2011. REVIEW METHODS: Studies comparing DySIS, LuViva or Niris with conventional colposcopy were sought; a narrative synthesis was undertaken. A decision-analytic model was developed, which measured outcomes in terms of quality-adjusted life-years (QALYs) and costs were evaluated from the perspective of the NHS and Personal Social Services with a time horizon of 50 years. RESULTS: Six studies were included: two studies of DySIS, one study of LuViva and three studies of Niris. The DySIS studies were well reported and had a low risk of bias; they found higher sensitivity with DySIS (both the DySISmap alone and in combination with colposcopy) than colposcopy alone for identifying CIN2+ disease, although specificity was lower with DySIS. The studies of LuViva and Niris were poorly reported and had limitations, which indicated that their results were subject to a high risk of bias; the results of these studies cannot be considered reliable. The base-case cost-effectiveness analysis suggests that both DySIS treatment options are less costly and more effective than colposcopy alone in the overall weighted population; these results were robust to the ranges tested in the sensitivity analysis. DySISmap alone was more costly and more effective in several of the referral groups but the incremental cost-effectiveness ratio (ICER) was never higher than £1687 per QALY. DySIS plus colposcopy was less costly and more effective in all reasons for referral. Only indicative analyses were carried out on Niris and LuViva and no conclusions could be made on their cost-effectiveness. LIMITATIONS: The assessment is limited by the available evidence on the new technologies, natural history of the disease area and current treatment patterns. CONCLUSIONS: DySIS, particularly in combination with colposcopy, has higher sensitivity than colposcopy alone. There is no reliable evidence on the clinical effectiveness of LuViva and Niris. DySIS plus colposcopy appears to be less costly and more effective than both the DySISmap alone and colposcopy alone; these results were robust to the sensitivity analyses undertaken. Given the lack of reliable evidence on LuViva and Niris, no conclusions on their potential cost-effectiveness can be drawn. There is some uncertainty about how generalisable these findings will be to the population of women referred for colposcopy in the future, owing to the introduction of the human papillomavirus (HPV) triage test and uptake of the HPV vaccine.
Assuntos
Colposcópios/normas , Colposcopia/instrumentação , Avaliação da Tecnologia Biomédica , Displasia do Colo do Útero/diagnóstico , Adulto , Colposcopia/economia , Análise Custo-Benefício , Inglaterra , Feminino , Humanos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Medicina EstatalRESUMO
This study uses a dynamic influenza transmission model to directly compare the cost-effectiveness of various policies of annual paediatric influenza vaccination in England and Wales, varying the target age range and level of coverage. The model accounts for both the protection of those immunised and the indirect protection of the rest of the population via herd immunity. The impact of augmenting current practice with a policy to vaccinate pre-school age children, on their own or with school age children, was assessed in terms of quality adjusted life years and health service costs. Vaccinating 2-18 year olds was estimated to be the most cost-effective policy in an incremental cost-effectiveness analysis, at an assumed annual vaccine uptake rate of 50%. The mean incremental cost-effectiveness ratios for this policy was estimated at £251/QALY relative to current practice. Paediatric vaccination would appear to be a highly cost-effective intervention that directly protects those targeted for vaccination, with indirect protection extending to both the very young and the elderly.
Assuntos
Métodos Epidemiológicos , Vacinas contra Influenza/economia , Vacinas contra Influenza/imunologia , Influenza Humana/economia , Influenza Humana/prevenção & controle , Vacinação/economia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise Custo-Benefício , Inglaterra/epidemiologia , Feminino , Humanos , Lactente , Vacinas contra Influenza/administração & dosagem , Influenza Humana/epidemiologia , Influenza Humana/transmissão , Masculino , Pessoa de Meia-Idade , País de Gales/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To assess the efficacy of endovascular aneurysm repair (EVAR) against standard alternative management in patients with large abdominal aortic aneurysm (AAA). DESIGN: Two national, multicentre randomised trials - EVAR trials 1 and 2. SETTING: Patients were recruited from 38 out of 41 eligible UK hospitals. PARTICIPANTS: Men and women aged at least 60 years, with an AAA measuring at least 5.5 cm on a computerised tomography scan that was regarded as anatomically suitable for EVAR, were assessed for fitness for open repair. Patients considered fit were randomised to EVAR or open repair in EVAR trial 1 and patients considered unfit were randomised to EVAR or no intervention in EVAR trial 2. INTERVENTIONS: EVAR, open repair or no intervention. MAIN OUTCOME MEASURES: The primary outcome was mortality (operative, all-cause and AAA related). Patients were flagged at the UK Office for National Statistics with centrally coded death certificates assessed by an Endpoints Committee. Power calculations based upon mortality indicated that 900 and 280 patients were required for EVAR trials 1 and 2, respectively. Secondary outcomes were graft-related complications and reinterventions, adverse events, renal function, health-related quality of life and costs. Cost-effectiveness analyses were performed for both trials. RESULTS: Recruitment occurred between 1 September 1999 and 31 August 2004, with targets exceeded in both trials: 1252 randomised into EVAR trial 1 (626 to EVAR) and 404 randomised into EVAR trial 2 (197 to EVAR). Follow-up closed in December 2009 with very little loss to follow-up (1%). In EVAR trial 1, 30-day operative mortalities were 1.8% and 4.3% in the EVAR and open-repair groups, respectively: adjusted odds ratio 0.39 [95% confidence interval (CI) 0.18 to 0.87], p = 0.02. During a total of 6904 person-years of follow-up, 524 deaths occurred (76 AAA related). Overall, there was no significant difference between the groups in terms of all-cause mortality: adjusted hazard ratio (HR) 1.03 (95% CI 0.86 to 1.23), p = 0.72. The EVAR group did demonstrate an early advantage in terms of AAA-related mortality, which was sustained for the first few years, but lost by the end of the study, primarily due to fatal endograft ruptures: adjusted HR 0.92 (95% CI 0.57 to 1.49), p = 0.73. The EVAR procedure was more expensive than open repair (mean difference £1177) and not found to be cost-effective, but the model was sensitive to alternative assumptions. In EVAR trial 2, during a total of 1413 person-years of follow-up, a total of 305 deaths occurred (78 AAA related). The 30-day operative mortality was 7.3% in the EVAR group. However, this group later demonstrated a significant advantage in terms of AAA-related mortality, but this became apparent only after 4 years: overall adjusted HR 0.53 (95% CI 0.32 to 0.89), p = 0.02. Sadly, this advantage did not result in any benefit in terms of all-cause mortality: adjusted HR 0.99 (95% CI 0.78 to 1.27), p = 0.97. Overall, EVAR was more expensive than no intervention (mean difference £10,222) and not found to be cost-effective. CONCLUSIONS: EVAR offers a clear operative mortality benefit over open repair in patients fit for both procedures, but this early benefit is not translated into a long-term survival advantage. Among patients unfit for open repair, EVAR is associated with a significant long-term reduction in AAA-related mortality but this does not appear to influence all-cause mortality. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 55703451. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 9. See the HTA programme website for further project information.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Endovasculares/métodos , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/economia , Aneurisma da Aorta Abdominal/mortalidade , Prótese Vascular , Análise Custo-Benefício , Procedimentos Endovasculares/economia , Procedimentos Endovasculares/mortalidade , Feminino , Custos de Cuidados de Saúde , Humanos , Testes de Função Renal , Masculino , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/cirurgia , Modelos de Riscos Proporcionais , Falha de Prótese , Qualidade de Vida , Resultado do Tratamento , Reino Unido , Enxerto Vascular/métodosRESUMO
BACKGROUND: EOS is a biplane X-ray imaging system manufactured by EOS Imaging (formerly Biospace Med, Paris, France). It uses slot-scanning technology to produce a high-quality image with less irradiation than standard imaging techniques. OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of EOS two-dimensional (2D)/three-dimensional (3D) X-ray imaging system for the evaluation and monitoring of scoliosis and other relevant orthopaedic conditions. DATA SOURCES: For the systematic review of EOS, electronic databases (MEDLINE, Allied and Complementary Medicine Database, BIOSIS Previews, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, EMBASE, Health Management Information Consortium, Inspec, ISI Science Citation Index and PASCAL), clinical trials registries and the manufacturer's website were searched from 1993 to November 2010. REVIEW METHODS: A systematic review of studies comparing EOS with standard X-ray [film, computed radiography (CR) or digital radiography] in any orthopaedic condition was performed. A narrative synthesis was undertaken. A decision-analytic model was developed to assess the cost-effectiveness of EOS in the relevant indications compared with standard X-ray and incorporated the clinical effectiveness of EOS and the adverse effects of radiation. The model incorporated a lifetime horizon to estimate outcomes in terms of quality-adjusted life-years (QALYs) and costs from the perspective of the NHS. RESULTS: Three studies met the inclusion criteria for the review. Two studies compared EOS with film X-ray and one study compared EOS with CR. The three included studies were small and of limited quality. One study used an earlier version of the technology, the Charpak system. Both studies comparing EOS with film X-ray found image quality to be comparable or better with EOS overall. Radiation dose was considerably lower with EOS: ratio of means for posteroanterior spine was 5.2 (13.1 for the study using the Charpak system); ratio of means for the lateral spine was 6.2 (15.1 for the study using the Charpak system). The study comparing EOS with CR found image quality to be comparable or better with EOS. Radiation dose was considerably lower with EOS than CR; ratio of means for the centre of the back was 5.9 and for the proximal lateral point 8.8. The lowest ratio of means was at the nape of the neck, which was 2.9. No other outcomes were assessed in the included studies, such as implications for patient management from the nature and quality of the image. Patient throughput is the major determinant of the cost-effectiveness of EOS. The average cost per procedure of EOS decreases with utilisation. Using estimates of patient throughput at national level from Hospital Episode Statistics data suggests that EOS is not cost-effective for the indications considered. Throughput in the region of 15,100 to 26,500 (corresponding to a workload of 60 to 106 patient appointments per working day) for EOS compared with a throughput of only 7530 for CR (30 patient appointments per working day) is needed to achieve an incremental cost-effectiveness ratio of £30,000 per QALY. EOS can be shown to be cost-effective only when compared with CR if the utilisation for EOS is about double the utilisation of CR. LIMITATIONS: The main limitation of the systematic review of the clinical effectiveness of EOS was the limited number and quality of the data available. In particular, there were no studies assessing the potential health benefits arising from the quality and nature of the image, over and above those associated with reduced radiation exposure. Uncertainty in the model inputs was not fully explored owing to a lack of reporting of standard deviations or confidence intervals in the published literature for most of the parameters. As a result, uncertainty in the cost-effectiveness results was not presented. CONCLUSIONS: Radiation dose is considerably lower with EOS than standard X-ray, whereas image quality remains comparable or better with EOS. However, the long-term health benefits from reduced radiation exposure with EOS are very small and there was a lack of data on other potential patient health benefits. The implications of any changes in the quality and nature of the EOS image compared with standard X-ray, for patient health outcomes, needs to be assessed. Given the higher cost of an EOS machine, utilisation is the major determinant of cost-effectiveness. Estimates of patient throughput at national level suggest that EOS is not cost-effective. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Assuntos
Segurança de Equipamentos/estatística & dados numéricos , Imageamento Tridimensional/efeitos adversos , Neoplasias/etiologia , Radiografia/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise Custo-Benefício , Segurança de Equipamentos/instrumentação , Segurança de Equipamentos/métodos , Feminino , Humanos , Doença Iatrogênica , Imageamento Tridimensional/economia , Imageamento Tridimensional/instrumentação , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/diagnóstico por imagem , Assistência ao Paciente/estatística & dados numéricos , Anos de Vida Ajustados por Qualidade de Vida , Radiografia/economia , Radiografia/instrumentação , Medição de Risco , Fatores Sexuais , Avaliação da Tecnologia Biomédica , Fatores de Tempo , Reino Unido , Adulto JovemRESUMO
BACKGROUND: The risk of recurrence following surgery in women with early breast cancer varies, depending upon prognostic factors. Adjuvant chemotherapy reduces this risk; however, increasingly effective regimens are associated with higher costs and toxicity profiles, making it likely that different regimens may be cost-effective for women with differing prognoses. To investigate this we performed a cost-effectiveness analysis of four treatment strategies: (1) no chemotherapy, (2) chemotherapy using cyclophosphamide, methotrexate, and fluorouracil (CMF) (a first generation regimen), (3) chemotherapy using Epirubicin-CMF (E-CMF) or fluorouracil, epirubicin, and cyclophosphamide (FEC60) (a second generation regimens), and (4) chemotherapy with FEC60 followed by docetaxel (FEC-D) (a third generation regimen). These adjuvant chemotherapy regimens were used in three large UK-led randomised controlled trials (RCTs). METHODS: A Markov model was used to simulate the natural progression of early breast cancer and the impact of chemotherapy on modifying this process. The probability of a first recurrent event within the model was estimated for women with different prognostic risk profiles using a parametric regression-based survival model incorporating established prognostic factors. Other probabilities, treatment effects, costs and quality of life weights were estimated primarily using data from the three UK-led RCTs, a meta-analysis of all relevant RCTs, and other published literature. The model predicted the lifetime costs, quality adjusted life years (QALYs) and cost-effectiveness of the four strategies for women with differing prognoses. Sensitivity analyses investigated the impact of uncertain parameters and model assumptions. FINDINGS: For women with an average to high risk of recurrence (based upon prognostic factors and any other adjuvant therapies received), FEC-D appeared most cost-effective assuming a threshold of £20,000 per QALY for the National Health Service (NHS). For younger low risk women, E-CMF/FEC60 tended to be the optimal strategy and, for some older low risk women, the model suggested a policy of no chemotherapy was cost-effective. For no patient group was CMF chemotherapy the preferred option. Sensitivity analyses demonstrated cost-effectiveness results to be particularly sensitive to the treatment effect estimate for FEC-D and the future price of docetaxel. INTERPRETATION: To our knowledge, this analysis is the first cost-effectiveness comparison of no chemotherapy, and first, second, and third generation adjuvant chemotherapy regimens for early breast cancer patients with differing prognoses. The results demonstrate the potential for different treatment strategies to be cost-effective for different types of patients. These findings may prove useful for policy makers attempting to formulate cost-effective treatment guidelines in the field of early breast cancer.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/economia , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/economia , Quimioterapia Adjuvante/economia , Análise Custo-Benefício , Ciclofosfamida/economia , Ciclofosfamida/uso terapêutico , Docetaxel , Epirubicina/economia , Epirubicina/uso terapêutico , Feminino , Fluoruracila/economia , Fluoruracila/uso terapêutico , Custos de Cuidados de Saúde , Humanos , Metotrexato/economia , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prognóstico , Anos de Vida Ajustados por Qualidade de Vida , Taxoides/economia , Taxoides/uso terapêuticoRESUMO
This paper presents a summary of the evidence review group (ERG) report into the use of golimumab for the treatment of psoriatic arthritis (PsA). The main clinical effectiveness data were derived from a single phase III randomised controlled trial (RCT: GO-REVEAL) that compared golimumab with placebo for treating patients with active and progressive PsA who were symptomatic despite the use of previous disease-modifying antirheumatic drugs or non-steroidal anti-inflammatory drugs. The 14-week data showed that, compared with placebo, golimumab 50 mg significantly improved joint disease response as measured by American College of Rheumatology (ACR) 20 [relative risk (RR) 5.73, 95% confidence interval (CI) 3.24 to 10.56] and Psoriatic Arthritis Response Criteria (PsARC) (RR 3.45, 95% CI 2.49 to 4.87), and skin disease response as measured by the Psoriasis Area and Severity Index (PASI) 75 (RR 15.95, 95% CI 4.62 to 59.11). The 24-week absolute data showed that these treatment benefits were maintained. There was a significant improvement in patients' functional status as measured by the Health Assessment Questionnaire (HAQ) change from baseline at 24 weeks (-0.33, p < 0.001). The open-label extension data showed that these beneficial effects were also maintained at 52 and 104 weeks. However, PASI 50 and PASI 90 at 14 weeks, and all of the PASI outcomes at 24 weeks, were not performed on the basis of intention-to-treat analysis. Furthermore, analyses of the 24-week data were less robust, failing to adjust for treatment contamination due to patient crossover at week 16. The manufacturer conducted a mixed treatment comparison (MTC) analysis. The ERG considered the assumption of exchangeability between the trials for the purpose of the MTC analysis to be acceptable, and the statistical approach in the MTC analysis to be reliable. Regarding the safety evaluation of golimumab, the manufacturer failed to provide longer-term data or to consider adverse event data of golimumab from controlled studies in other conditions, such as rheumatoid arthritis and ankylosing spondylitis. Although the adverse effect profile of golimumab appears similar to other anti-tumour necrosis factor (TNF) agents, the longer-term safety profile of golimumab remains uncertain. The manufacturer's submission presented a decision model to compare etanercept, infliximab, golimumab and adalimumab versus palliative care for patients with PsA. In the base-case model, 73% of the cohort of patients were assumed to have significant psoriasis (> 3% of body surface area). Estimates of the effectiveness of anti-TNF agents in terms of PsARC, HAQ change and PASI change were obtained from an MTC analysis of RCT data. The manufacturer failed to calculate incremental cost-effectiveness ratios (ICERs) correctly by comparing golimumab with palliative care instead of the most cost-effective alternative (etanercept). Despite the manufacturer's claim that golimumab is a cost-effective treatment option, the manufacturer's own model showed that golimumab is not cost-effective compared with other biologics when the ICERs are correctly calculated. None of the sensitivity analyses carried out by the manufacturer or the ERG regarding uncertainty in the estimates of clinical effectiveness, the acquisition and administration cost of drugs, the cost of treating psoriasis and the utility functions estimated to generate health outcomes changed this conclusion. However, a key area in determining the cost-effectiveness of anti-TNF agents is whether they should be treated as a class. If all anti-TNF agents are considered equally effective then etanercept, adalimumab and golimumab have very nearly equal costs and equal quality-adjusted life-years (QALYs), and all have an ICER of about £ 15,000 per QALY versus palliative care, whereas infliximab with a higher acquisition cost is dominated by the other biologics.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Anticorpos Monoclonais/economia , Antirreumáticos/economia , Ensaios Clínicos Fase III como Assunto , Análise Custo-Benefício , Humanos , Cuidados Paliativos , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Etanercept, infliximab and adalimumab are licensed in the UK for the treatment of active and progressive psoriatic arthritis (PsA) in adults who have an inadequate response to standard treatment. OBJECTIVE: To determine the clinical effectiveness, safety and cost-effectiveness of these biologic agents in the treatment of active and progressive PsA. DATA SOURCES: Systematic reviews were performed, with data sought from 10 electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index, Conference Proceedings Citation Index - Science, ClinicalTrials.gov, metaRegister of Current Controlled Trials, NHS Economic Evaluation Database, Health Economic Evaluations Database and EconLit) up to June 2009. REVIEW METHODS: Full paper manuscripts of titles/abstracts considered relevant were obtained and assessed for inclusion by two reviewers according to criteria on study design, interventions, participants and outcomes. Data on study and participant characteristics, efficacy outcomes, adverse effects, costs to the health service and cost-effectiveness were extracted, along with baseline data where reported. The primary efficacy outcomes were measures of anti-inflammatory response, skin lesion response and functional status, and the safety outcome was the incidence of serious adverse events. The primary measure of cost-effectiveness was incremental cost per additional quality-adjusted life-year (QALY). Standard meta-analytic techniques were applied to efficacy data. Published cost-effectiveness studies and the economic analyses submitted to the National Institute for Health and Clinical Excellence (NICE) by the biologic manufacturers were reviewed. An economic model was developed by updating the model produced by the York Assessment Group for the previous NICE appraisal of biologics in PsA. RESULTS: Pooled estimates of effect demonstrated a significant improvement in patients with PsA for all joint disease and functional status outcomes at 12-14 weeks' follow-up. The biologic treatment significantly reduced joint symptoms for etanercept [relative risk (RR) 2.60, 95% confidence interval (CI) 1.96 to 3.45], infliximab (RR 3.44, 95% CI 2.53 to 4.69) and adalimumab (RR 2.24, 95% CI 1.74 to 2.88), with 24-week data demonstrating maintained treatment effects. Trial data demonstrated a significant effect of all three biologics on skin disease at 12 or 24 weeks. Evidence synthesis found that infliximab appeared to be most effective across all outcomes of joint and skin disease. The response in joint disease was greater with etanercept than with adalimumab, whereas the response in skin disease was greater with adalimumab than with etanercept, although these differences are not statistically significant. Under base-case assumptions, etanercept was the most likely cost-effective strategy for patients with PsA and mild-to-moderate psoriasis if the threshold for cost-effectiveness was £20,000 or £30,000 per QALY. All biologics had a similar probability of being cost-effective for patients with PsA and moderate-to-severe psoriasis at a threshold of £20,000 per QALY. LIMITATIONS: Limited available efficacy data and difficulty in assessing PsA activity and its response to biologic therapy. CONCLUSIONS: The data indicated that etanercept, infliximab and adalimumab were efficacious in the treatment of PsA compared with placebo, with beneficial effects on joint symptoms, functional status and skin. Short-term data suggested that these biologic agents can delay joint disease progression and evidence to support their use in the treatment of PsA is convincing. Future research would benefit from long-term observational studies with large sample sizes of patients with PsA to demonstrate that beneficial effects are maintained, along with further monitoring of the safety profiles of the biologic agents. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab , Anti-Inflamatórios não Esteroides/economia , Anticorpos Monoclonais/economia , Anticorpos Monoclonais Humanizados , Antirreumáticos/economia , Artrite Psoriásica/economia , Artrite Psoriásica/patologia , Custos e Análise de Custo , Etanercepte , Humanos , Imunoglobulina G/economia , Infliximab , Prognóstico , Anos de Vida Ajustados por Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento , Reino UnidoRESUMO
This paper presents a summary of the evidence review group (ERG) report into capecitabine for advanced gastric cancer (aGC). Capecitabine is an oral prodrug of 5-fluorouracil (5-FU). The decision problem addressed was the use of capecitabine (X) compared to 5-FU (F), in combination regimens with platinum agents [cisplatin (C) or oxaliplatin (O)] with or without epirubicin (E), in patients with inoperable aGC. Approximately 7000 new cases of gastric cancer are diagnosed in England and Wales every year. Of these, 80% are candidates for palliative chemotherapy and around 2900 receive such treatment. The standard UK practice for patients with aGC who are considered fit enough has consisted of a triplet regimen comprising intravenous 5-FU in combination with a platinum agent (capecitabine or oxaliplatin) and epirubicin. The manufacturer's submission (MS) focused on direct evidence from two phase III non-inferiority randomised controlled trials (RCTs), REAL-2 (Randomized ECF for Advanced and Locally advanced oesophagogastric cancer-2; n = 1002) and ML17032 (n = 316). REAL-2 randomised patients to four regimens (ECF, ECX, EOF and EOX) to compare 5-FU with capecitabine and cisplatin with oxaliplatin, whereas ML17032 compared CX with CF. Efficacy outcomes from these trials were pooled in an individual patient data (IPD) meta-analysis. Both RCTs demonstrated statistically significant non-inferiority of capecitabine on the outcome of overall survival (OS) assessed in the per-protocol population; equivalent results were also demonstrated for progression-free survival (PFS). The IPD meta-analysis found a statistically significant benefit in OS for capecitabine compared with 5-FU [unadjusted hazard ratio (HR): 0.87; 95% confidence interval (CI) 0.77 to 0.98, p = 0.027]. There was no evidence of a poorer safety profile for capecitabine overall, nor of any difference in quality of life (QoL) between the two fluoropyrimidines. The MS included a de novo economic evaluation based on a cost-minimisation analysis (CMA), where the costs of capecitabine-based regimens were compared with their equivalent 5-FU-based regimens in aGC. A time horizon of 5.5 cycles (each lasting for 21 days) was used in the base-case analysis, representing the duration of treatment. The results of the manufacturer's base-case analysis showed that capecitabine regimens are associated with mean net cost savings of 1620 pounds (ECX vs ECF), 1572 pounds (EOX vs EOF) and 4210 pounds (CX vs CF). The manufacturer failed to comment explicitly on the uncertainty around the estimates of efficacy and on the fact that the IPD meta-analysis suggests that capecitabine may actually be more effective on average. Further analyses exploring additional costs incurred by the UK NHS from extending survival duration showed that these are unlikely to have a material effect on conclusions. A full probabilistic analysis was not performed; however, the evidence explored by the MS and ERG is consistent in suggesting that capecitabine has a lower mean cost than 5-FU-based regimens. The submission was considered to contain convincing evidence of the non-inferiority of capecitabine to 5-FU on survival; this evidence was considered to be applicable to UK practice. Although some uncertainty remains, the ERG deemed CMA to be an appropriate framework with which to analyse this decision problem. Overall cost estimates for the CMA were generated appropriately and were robust to uncertainties regarding assumptions and sources. At the time of writing, the guidance document issued by NICE on 28 July 2010 states that capecitabine in combination with a platinum-based regimen is recommended for the first-line treatment of inoperable advanced gastric cancer.