Quality-adjusted survival as an end point in breast cancer trials

Breast cancer treatment recommendations will often require an appraisal of likely benefits in relation to likely side-effects on survival and quality of life (QoL) endpoints, and possibly also an evaluation of the size of the anticipated net clinical benefit against financial costs. Quality-adjusted survival (QAS) analysis methods provide a formal approach for deriving an estimate of net clinical benefit to facilitate this appraisal process. QAS analysis methods have been applied in trials with breast cancer patients of adjuvant therapies as well as treatments for advanced/metastatic disease. QAS analyses based solely on trial data may fail to capture plausible longer-term benefits; thus methods to explore the possible outcomes of treatment beyond the limits of trial data have been developed. These modelling approaches can help researchers gain insights and identify future research priorities, but do not replace the need for long-term evidence from randomised trials.NHMR

Linking the evidence: intermediate outcomes in medical test assessments

Objectives To review how health technology assessments (HTA) of medical tests incorporate intermediate outcomes in conclusions about the effectiveness of tests on improving health outcomes. Methods Systematic review of English-language test assessments in the HTA database from January 2005 to February 2010, supplemented by a search of the websites of International Network of Agencies for Health Technology Assessment (INAHTA) members. Results 149 HTAs from eight countries were assessed. Half evaluated tests for screening or diagnosis, a third for disease classification (including staging, prognosis, monitoring), and a fifth for multiple purposes. In 71 HTAs (48%) only diagnostic accuracy was reported, while in 17 (11%) evidence of health outcomes was reported in addition to accuracy. Intermediate outcomes, mainly the impact of test results on patient management, were considered in 61 HTAs (41%). Of these, 47 identified randomized trials or observational studies reporting intermediate outcomes. The validity of these intermediate outcomes as a surrogate for health outcomes was not consistently discussed; nor was the quality appraisal of this evidence. Clear conclusions about whether the test was effective were included in about 60% of HTAs. Conclusions Intermediate outcomes are frequently assessed in medical test HTAs, but interpretation of this evidence is inconsistently reported. We recommend that reviewers explain the rationale for using intermediate outcomes, identify the assumptions required to link intermediate outcomes and patient benefits and harms, and assess the quality of included studies

Localization of osteocalcin (BGP) during fish (Sparus aurata) development by in situ hybridization and immunohistochemistry: comparison between gene expression/protein distribution and skeletal mineralization

Osteocalcin (Bone Gla protein, BGP) is a small noncollagenous protein which is synthesized by osteoblasts and odontoblasts and is found exlusively in mineralized bony tissues. Although isolated for the first time in 1978, only recently has a function for this protein been suggested, specifically in controlling hydroxyapatite crystal growth. Appearance of osteocalcin could be linked to the presence of an hydroxyapatite-containing bony skeleton, since the protein was never found in cartilaginous fishes. Furthermore, within its primary sequence the amino acid residues known to be essential for its function are present in fish as well as in mammals, suggesting that function has been conserved over 400 million years of evolution. Taken totgether, these findings prompted us to study in detail the localization of osteocalcin gene expression in fish

The cost effectiveness of bevacizumab when added to capecitabine, with or without mitomycin-C, in first line treatment of metastatic colorectal cancer: results from the Australasian phase III MAX study

Background: Based on the clinical data, bevacizumab has been approved in Australia and globally for the treatment of advanced colorectal cancer. However, limited evidence exists for its cost-effectiveness. The purpose of this study was to evaluate the cost effectiveness of adding bevacizumab to capecitabine monotherapy in patients with metastatic colorectal cancer, using data from the prospective economic evaluation conducted alongside the MAX trial. Methods: Individual patient level data on resource use and progression free survival were prospectively collected in the phase III MAX trial. Resource use data were collected for the period between randomisation and disease progression, and unit costs were assigned from the perspective of the Australian health care funder. Effectiveness was measured in quality adjusted progression free survival years, with utility scores obtained from both the community valued EQ-5D questionnaire and the patient valued UBQ-C questionnaire. Progression free survival was used as a secondary effectiveness measure. Results: The addition of bevacizumab to capecitabine monotherapy cost approximately $192,156 (95$135,619 to $326,894) per quality adjusted progression free survival year gained when using publicly listed pharmaceutical prices and utility values from the EQ-5D questionnaire. This decreased to$149,455 (95% CI, $100,356 to$245,910) when values from the UBQ-C questionnaire were applied. The incremental cost per progression free survival year was $145,059 (95$106,703 to $233,225). Conclusions: Bevacizumab was not found to be cost effective at its listed price, based on results from the MAX trial.Roche Products Pty Lt

The cost effectiveness of bevacizumab when added to capecitabine, with or without mitomycin-C, in first line treatment of metastatic colorectal cancer: results from the Australasian phase III MAX study

Background: Based on the clinical data, bevacizumab has been approved in Australia and globally for the treatment of advanced colorectal cancer. However, limited evidence exists for its cost-effectiveness. The purpose of this study was to evaluate the cost effectiveness of adding bevacizumab to capecitabine monotherapy in patients with metastatic colorectal cancer, using data from the prospective economic evaluation conducted alongside the MAX trial. Methods: Individual patient level data on resource use and progression free survival were prospectively collected in the phase III MAX trial. Resource use data were collected for the period between randomisation and disease progression, and unit costs were assigned from the perspective of the Australian health care funder. Effectiveness was measured in quality adjusted progression free survival years, with utility scores obtained from both the community valued EQ-5D questionnaire and the patient valued UBQ-C questionnaire. Progression free survival was used as a secondary effectiveness measure. Results: The addition of bevacizumab to capecitabine monotherapy cost approximately $192,156 (95$135,619 to $326,894) per quality adjusted progression free survival year gained when using publicly listed pharmaceutical prices and utility values from the EQ-5D questionnaire. This decreased to$149,455 (95% CI, $100,356 to$245,910) when values from the UBQ-C questionnaire were applied. The incremental cost per progression free survival year was $145,059 (95$106,703 to $233,225). Conclusions: Bevacizumab was not found to be cost effective at its listed price, based on results from the MAX trial.Roche Products Pty Lt

Prognostic impact and the relevance of PTEN copy number alterations in patients with advanced colorectal cancer (CRC) receiving bevacizumab

Article first published online: 25 MAR 2013Loss of phosphatase and tensin homologue (PTEN) expression may be prognostic in colorectal cancer (CRC) and may have a correlation with vascular endothelial growth factor (VEGF) expression via hypoxia-inducible factor 1 (HIF-1) alpha, and the PI3K/mTOR pathways. We therefore have explored the prognostic association of PTEN loss and the potential that PTEN loss may be predictive of outcome with bevacizumab. Patients enrolled in the AGITG MAX trial, a randomized Phase III trial of capecitabine (C) +/− bevacizumab (B) (+/− mitomycin C [M]) with available tissues were analyzed for PTEN expression (loss vs. no loss) as assessed using a Taqman® copy number assay (CNA). Of the original 471 patients enrolled, tissues from 302 (64.1%) patients were analyzed. PTEN loss was observed in 38.7% of patients. There was no relationship between PTEN loss and KRAS or BRAF mutation. PTEN status was not prognostic for progression-free survival (PFS) or overall survival (OS) in multivariate analyses adjusting for other baseline factors; loss versus no loss PFS hazard ratio (HR) 0.9 (0.7–1.16), OS HR 1.04 (0.79–1.38). PTEN was not prognostic when assessed by KRAS and BRAF status. By using the comparison of C versus CB+CBM, PTEN status was not significantly predictive of the effectiveness of B for PFS or OS. PTEN status was not prognostic for survival in advanced colorectal cancer, irrespective of KRAS or BRAF status. PTEN status did not significantly predict different benefit with bevacizumb therapy.Timothy J. Price, Jennifer E. Hardingham, Chee K. Lee, Amanda R. Townsend, Joseph W. Wrin, Kate Wilson, Andrew Weickhardt, Robert J. Simes, Carmel Murone & Niall C. Tebbut

High-Frequency Electrooptic Fabry-Perot Modulators

Electrooptic modulators built from GaAs/AlxGa1-xAs Fabry-Perot cavities operating up to 6.5 GHz are reported. The measured frequency response agrees well with the one predicted using an equivalent circuit model derived from high-speed electrical measurements. The parasitic capacitances have been reduced to approximately 30 fF by fabricating the devices on semi-insulating GaAs substrates and integrating them with on-wafer bound pads which have dimensions compatible with microwave coplanar probes

Long-term cardiovascular risks and statin treatment impact on socioeconomic inequalities: microsimulation model

Background: UK cardiovascular disease (CVD) incidence and mortality have declined in recent decades but socioeconomic inequalities persist. Aims: We present a new CVD model and project health outcomes and impact of guideline-recommended statin treatment across quintiles of socioeconomic deprivation in UK. Design and Setting: Lifetime microsimulation model developed using 117,896 participants in 16 statin trials and 501,854 UK Biobank (UKB) participants and quality of life data from national health surveys. Method: We developed a CVD microsimulation model using risk equations for myocardial infarction, stroke, coronary revascularisation, cancer, vascular and nonvascular death, estimated using trial data. We calibrated and further developed this model in the UKB cohort, including further characteristics and a diabetes risk equation, and validated the model in UKB and Whitehall II cohorts. We used the model to predict CVD incidence, life expectancy, quality-adjusted life years (QALYs) and impact of UK guideline-recommended statin treatment across quintiles of socioeconomic deprivation. Results: Age, sex, socioeconomic deprivation, smoking, hypertension, diabetes and cardiovascular events were key CVD risk determinants. Model-predicted event rates corresponded well to observed rates across participant categories. The model projected strong gradients in remaining life expectancy, with 4-to-5 years (5-to-8 QALYs) gaps between the least and most socioeconomically deprived quintiles. Guideline-recommended statin treatment was projected to increase QALYs with larger gains in quintiles of higher deprivation. Conclusions: The study demonstrated the potential of guideline-recommended statin treatment to reduce socioeconomic inequalities. This CVD model is a novel resource for individualised long-term projections of health outcomes and effects of CVD treatments

Gla Rich Protein (GRP) is associated to osteoarthritis being highly accumulated in the joint tissues and synovial fluid

info:eu-repo/semantics/publishedVersio