Abstract

OBJETIVO: Evaluar el coste-efectividad de dasatinib 100 mg/día frente a imatinib 600 mg/día, imatinib 800 mg/día y nilotinib 800 mg/día en pacientes con leucemia mieloide crónica (LMC) en fase crónica, resistentes al tratamiento previo con imatinib 400 mg/día desde la perspectiva del Servicio Nacional de Salud portugués.

MÉTODOS: Se desarrolló un modelo de Markov para el tratamiento de la LMC en Portugal. Se consideraron cuatro estados de salud: las tres fases de la LMC (crónica, acelerada y blástica) y el estado de muerte, con ciclos de transición mensuales. El modelo fue elaborado a partir de los datos de eficacia de los ensayos clínicos, el uso de recursos sanitarios según la opinión de los expertos consultados, datos de calidad de vida publicados en el Reino Unido y costes unitarios de las listas de precios oficiales de Portugal del año 2011. Se consideró un horizonte temporal que abarcaba toda la vida del paciente y se obtuvieron resultados determinísticos. También se realizó un análisis de sensibilidad determinístico para evaluar la consistencia de los resultados obtenidos.

RESULTADOS: Los resultados mostraron que los pacientes con LMC en fase crónica con resistencia a imatinib 400 mg/día ganaban en promedio 2,72 años de vida al ser tratados con dasatinib 100 mg/día en comparación con imatinib 600-800 mg/día, y ganaban una media de 0,53 años en comparación con nilotinib 800 mg/día. El coste incremental por año de vida ganado ajustado por calidad asciende a 37.583 € cuando comparamos dasatinib 100 mg/día con imatinib 600 mg/día, hasta 12.111 € en comparación con imatinib 800 mg/día, y 16.988 € en comparación con nilotinib, para un periodo de por vida.

CONCLUSIONES: Los resultados indican que dasatinib presenta unos resultados coste-efectividad razonables en pacientes con LMC resistentes a la dosis estándar de imatinib en comparación con dosis altas de imatinib y nilotinib en Portugal.

Abstract

The objective of this review was to summarize the currently available data describing the sensitivity andspecificity of indicators of unconsciousness and death in the following stun-kill methods and speciescombinations: 1) penetrative captive bolt for bovine animals, 2) head-only electrical stunning for pigs, 3) head-only electrical stunning for sheep and goats, 4) electrical waterbath for poultry (chickens and turkeys), 5) carbondioxide at high concentration for pigs, 6) all authorized gas methods to slaughter chickens and turkeys (carbondioxide at high concentration, carbon dioxide in two phases, carbon dioxide associated with inert gases and inertgases alone), 7) slaughter without stunning for bovine animals, 8) slaughter without stunning for sheep andgoats, 9) slaughter without stunning for chickens and turkeys. The reference tests for unconsciousness and deathwere to have been measured using electroencephalography (EEG). The definition of unconsciousness and deathbased on EEG were not specified, and the definition used by authors was reported. The index tests of interestwere a variety of indicators requested by the funding agency such as no corneal reflex and immediate collapse.The index tests differed by stun-kill methods and species combination. A comprehensive search identified 22publications contained 24 species-stun/kill method combinations. No studies explicitly reported the sensitivityand specificity of the indicators in conscious and unconscious animals. Many studies reported the proportion ofstunned animals with indicators, rather than the proportion of unconscious or conscious animals at a set timepoint with the indicators. Such data could not be translated into sensitivity and specificity. Other studies reportedthe average time to occurrence of an indicator or average time to cessation of the indicators. Such data cannot betranslated into sensitivity and specificity estimates without knowledge of the joint distributions.

Abstract

OBJECTIVE: To assess the likelihood of biased trials contained in 12 recently published meta-analyses.

DESIGN: A review of component randomised controlled trials of systematic reviews with 12 meta analyses.

DATA SOURCES: 12 recently published systematic reviews with 503 component randomised trials, which were published in the BMJ, Lancet, JAMA and The Annals of Internal Medicine up until May 2012.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews were eligible for inclusion if they included only randomised controlled trials (RCTs). We obtained the full text for the component RCTs of the 12 systematic reviews. We excluded RCTs which were not available in English from our review and analysis.

RESULTS: Five of the 12 meta-analyses exhibited heterogeneity (I2 >0.30) in age differences, when there should have been none, with two having significant or substantial heterogeneity (I2 > 0.50). In three meta-analyses we found that the age of intervention group was statistically significantly higher than in the control group. Two meta-analysis had a distribution of p-values that were inconsistent with chance. Meta-regression explained some of the observed heterogeneity in two meta-analyses as a consequence of poor allocation concealment.

CONCLUSIONS: The majority of a sample of recent meta-analyses showed that there were signs of imbalance and or heterogeneity in ages between treatment groups, when there should have been none. Systematic reviewers might consider using the techniques described here to assess the validity of their findings.

Abstract

Postmenopausal women with advanced breast cancer recurring/progressing on or after initial (adjuvant or first-line) endocrine therapy may be treated multiple times with one of several endocrine or combinatorial targeted treatment options before initiating chemotherapy. In the absence of direct head-to-head comparisons of these treatment options, an indirect comparison can inform treatment choice. This network meta-analysis compared the efficacy of everolimus plus exemestane with that of fulvestrant 250 and 500 mg in the advanced breast cancer setting following adjuvant or first-line endocrine therapy. The reported hazard ratios (HRs) for progression-free survival (PFS) or time to progression from six studies that formed a network to compare everolimus plus exemestane (BOLERO-2 trial) with fulvestrant were analyzed by means of a Bayesian network meta-analysis. In the primary comparison (PFS analysis based on the local review of disease progression from BOLERO-2 with the data from the other studies), everolimus plus exemestane appeared to be more efficacious than both fulvestrant 250 mg (HR = 0.47; 95 % credible interval [CrI] 0.38–0.58) and 500 mg (HR = 0.59; 95 % CrI 0.45–0.77). Similar results were obtained in an alternate comparison based on central review of disease progression from BOLERO-2 with the data from the other studies (HR = 0.40; 95 % CrI 0.31–0.51 and HR = 0.50; 95 % CrI 0.37–0.67, respectively), and in a subgroup analysis of patients who had received prior aromatase inhibitor therapy (HR = 0.47; 95 % CrI 0.38–0.58 and HR = 0.55; 95 % CrI 0.40–0.76, respectively). These results suggest that everolimus plus exemestane may be more efficacious than fulvestrant in patients with advanced breast cancer who progress on or after adjuvant or first-line therapy with a nonsteroidal aromatase inhibitor.

Abstract

No abstract available

Abstract

No abstract available

Abstract

PURPOSE: The inclusion of patient-reported outcome (PRO) instruments to record patient health-related quality of life (HRQOL) data has virtually become the norm in oncology randomised controlled trials (RCTs). Despite this fact, recent concerns have focused on the quality of reporting of HRQOL. The primary aim of this study was to evaluate the quality of reporting of HRQOL data from two common instruments in oncology RCTs.

DESIGN: A meta-review was undertaken of systematic reviews reporting HRQOL data collected using PRO instruments in oncology randomised controlled trials (RCTs). English language articles published between 2000 and 2012 were included and evaluated against a methodology checklist.

RESULTS: Four hundred and thirty-five potential articles were identified. Six systematic reviews were included in the analysis. A total of 70,403 patients had completed PROs. The European Organization for Research and Treatment of Cancer QLQ-C30 and Functional Assessment of Cancer Therapy-General questionnaire accounted for 55 % of RCTs. Eighty per cent of RCTs had used psychometrically validated instruments; 70 % reported culturally valid instruments and almost all reported the assessment timing (96 %). Thirty per cent of RCTS reported clinical significance and missing data. In terms of methodological design, only 25 % of RCTs could be categorised as probably robust.

CONCLUSION: The majority of oncology RCTs has shortcomings in terms of reporting HRQOL data when assessed against regulatory and methodology guidelines. These limitations will need to be addressed if HRQOL data are to be used to successfully support clinical decision-making, treatment options and labelling claims in oncology.