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Potential Surrogate (potential + surrogate)
Selected AbstractsObservations on a vestigial organ: a potential surrogate for enteric neuromesenchymal diseaseNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2008C. H. Knowles Abstract, Abnormalities of enteric nerves, interstitial cells of Cajal (ICC) and smooth muscle are often associated with severe gastrointestinal motility disorders. In this context, full-thickness biopsy of the gut may provide important diagnostic and prognostic clues as well as some possible therapeutic implications. Nonetheless, the unavoidable risk to further worsen prognosis evoked by laparotomy, and the unclear yield of histopathological analysis has hampered full-thickness gut sampling in patients with severe dysmotility. However, recent advances in minimally invasive surgery have refuelled enthusiasm in gastrointestinal neuromuscular pathology. In this issue of Neurogastroenterology and Motility, Miller et al. provide novel and exciting evidence that the appendix might be used as a surrogate tissue to analyse changes to enteric nerves, ICC and smooth muscle cells in patients with diabetic gastroenteropathy. The objective of this short review was to place this very important work in the context of current understanding of enteric neuromuscular dysfunction. [source] Magnetic resonance imaging as a potential surrogate for relapses in multiple sclerosis: A meta-analytic approach,ANNALS OF NEUROLOGY, Issue 3 2009Maria Pia Sormani MscStat Objective The aim of this work was to evaluate whether the treatment effects on magnetic resonance imaging (MRI) markers at the trial level were able to predict the treatment effects on relapse rate in relapsing-remitting multiple sclerosis. Methods We used a pooled analysis of all the published randomized, placebo-controlled clinical trials in relapsing-remitting multiple sclerosis reporting data both on MRI variables and relapses. We extracted data on relapses and on MRI "active" lesions. A regression analysis weighted on trial size and duration was performed to study the relation between the treatment effect on relapses and the treatment effect on MRI lesions. We validated the estimated relation on an independent set of clinical trials satisfying the same inclusion criteria but with a control arm other than placebo. Results A set of 23 randomized, double-blind, placebo-controlled trials in relapsing-remitting multiple sclerosis was identified, for a total of 63 arms, 40 contrasts, and 6,591 patients. A strong correlation was found between the effect on the relapses and the effect on MRI activity. The adjusted R2 value of the weighted regression line was 0.81. The regression equation estimated using the placebo-controlled trials gave a satisfactory prediction of the treatment effect on relapses when applied to the validation set. Interpretation More than 80% of the variance in the effect on relapses between trials is explained by the variance in MRI effects. Smaller and shorter phase II studies based on MRI lesion end points may give indications also on the effect of the treatment on relapse end points. Ann Neurol 2009;65:268,275 [source] Validation of Surrogate Markers in Multiple Randomized Clinical Trials with Repeated MeasurementsBIOMETRICAL JOURNAL, Issue 8 2003Ariel Alonso Abstract Part of the recent literature on the validation of biomarkers as surrogate endpoints proposes to undertake the validation exercise in a multi-trial context which led to a definition of validity in terms of the quality of both trial level and individual level association between the surrogate and the true endpoints (Buyse et al., 2000). These authors concentrated on continuous univariate responses. However, in many randomized clinical studies, repeated measurements are encountered on either or both endpoints. When both the surrogate and true endpoints are measured repeatedly over time, one is confronted with the modelling of bivariate longitudinal data. In this work, we show how such a joint model can be implemented in the context of surrogate marker validation. In addition, another challenge in this setting is the formulation of a simple and meaningful concept of "surrogacy". We propose the use of a new measure, the so-called variance reduction factor, to evaluate surrogacy at the trial and individual level. On the other hand, most of the work published in this area assume that only one potential surrogate is going to be evaluated. We also show that this concept will let us evaluate surrogacy when more than one surrogate variable is available for the analysis. The methodology is illustrated on data from a meta-analysis of five clinical trials comparing antipsychotic agents for the treatment of chronic schizophrenia. [source] Estimating breast cancer-specific and other-cause mortality in clinical trial and population-based cancer registry cohortsCANCER, Issue 22 2009James J. Dignam PhD Abstract BACKGROUND: To compute net cancer-specific survival rates using population data sources (eg, the National Cancer Institute's Surveillance, Epidemiology, and End Results [SEER] Program), 2 approaches primarily are used: relative survival (observed survival adjusted for life expectancy) and cause-specific survival based on death certificates. The authors of this report evaluated the performance of these estimates relative to a third approach based on detailed clinical follow-up history. METHODS: By using data from Cancer Cooperative Group clinical trials in breast cancer, the authors estimated 1) relative survival, 2) breast cancer-specific survival (BCSS) determined from death certificates, and 3) BCSS obtained by attributing cause according to clinical events after diagnosis, which, for this analysis was considered the benchmark "true" estimate. Noncancer life expectancy also was compared between trial participants, SEER registry patients, and the general population. RESULTS: Among trial patients, relative survival overestimated true BCSS in patients with lymph node-negative breast cancer; whereas, in patients with lymph node-positive breast cancer, the 2 estimates were similar. For higher risk patients (younger age, larger tumors), relative survival accurately estimated true BCSS. In lower risk patients, death certificate BCSS was more accurate than relative survival. Noncancer life expectancy was more favorable among trial participants than in the general population and among SEER patients. Tumor size at diagnosis, which is a potential surrogate for screening use, partially accounted for this difference. CONCLUSIONS: In the clinical trials, relative survival accurately estimated BCSS in patients who had higher risk disease despite more favorable other-cause mortality than the population at large. In patients with lower risk disease, the estimate using death certificate information was more accurate. For SEER data and other data sources where detailed postdiagnosis clinical history was unavailable, death certificate-based estimates of cause-specific survival may be a superior choice. Cancer 2009. © 2009 American Cancer Society. [source] Evaluating interactions between soil drainage and seedling performance in a restoration of Pinus sylvestris woodland, ScotlandGLOBAL ECOLOGY, Issue 2 2001M. D. Crowell Abstract 1,This paper evaluates the role of soil drainage in tree seedling performance at a site being restored from Calluna vulgaris moorland to Pinus sylvestris woodland, in Glen Affric, Scotland. The investigation focuses on the relationships between height of planted seedlings, type of ground vegetation and drainage conditions. 2,Slope, aspect, and soil depth were assessed as potential surrogates for direct measures of soil drainage, all of which were derived from digital terrain data. 3,Six variables related to drainage were recorded at 58 seedling locations and used in a factor analysis to understand links between soil moisture conditions, topographic variables and soil depth characteristics. 4,Factor analysis generated two factors that accounted for 70.5% of the variance in the correlation matrix of these variables: Factor 1 correlated strongly with variables that controlled peat accumulation and Factor 2 correlated strongly with topographic controls upon drainage patterns. 5,These two factors explained a significant amount of the variance in height of the Pinus seedlings planted at these locations. Significant differences were found between the factor scores associated with different types of ground vegetation, as well as between the seedling heights observed at locations with different vegetation types. 6,Multiple regressions were developed that indicated that slope, aspect, and soil depth were significant as independent variables in models where soil moisture content and aerobic soil depth were the dependent variables. [source] | ||||||||||