1,721,071 research outputs found
Meta-analytic-predictive use of historical variance data for the design and analysis of clinical trials
No full textContinuous endpoints are common in clinical trials. The design and analysis of such trials is often based on models assuming normally distributed data, possibly after an appropriate transformation. When planning a new trial, information on the variance of the endpoint is usually available from historical trials. Although the idea to use historical data for a new trial is not new, literature on how to formally summarize and use these data on variances is scarce. The meta-analytic-predictive (MAP) approach consists of a random-effects meta analysis of the historical variance data and a prediction of the variance in the new clinical trial. Two applications that rely on the MAP approach are considered: first, the selection of the sample size in the new trial, guided by the prediction of the variance; and, second, the inclusion of the predicted variance in a Bayesian analysis of the new trial. A clinical trial in patients with wet age-related macular degeneration illustrates the methodology. (C) 2016 Elsevier B.V. All rights reserved
Meta‐analysis of few small studies in orphan diseases
No full textMeta-analyses in orphan diseases and small populations generally face particular problems, including small numbers of studies, small study sizes and heterogeneity of results. However, the heterogeneity is difficult to estimate if only very few studies are included. Motivated by a systematic review in immunosuppression following liver transplantation in children, we investigate the properties of a range of commonly used frequentist and Bayesian procedures in simulation studies. Furthermore, the consequences for interval estimation of the common treatment effect in random-effects meta-analysis are assessed. The Bayesian credibility intervals using weakly informative priors for the between-trial heterogeneity exhibited coverage probabilities in excess of the nominal level for a range of scenarios considered. However, they tended to be shorter than those obtained by the Knapp-Hartung method, which were also conservative. In contrast, methods based on normal quantiles exhibited coverages well below the nominal levels in many scenarios. With very few studies, the performance of the Bayesian credibility intervals is of course sensitive to the specification of the prior for the between-trial heterogeneity. In conclusion, the use of weakly informative priors as exemplified by half-normal priors (with a scale of 0.5 or 1.0) for log odds ratios is recommended for applications in rare diseases. (C) 2016 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd
Using phase II data for the analysis of phase III studies: An application in rare diseases
No full textBackground: Clinical research and drug development in orphan diseases are challenging, since large-scale randomized studies are difficult to conduct. Formally synthesizing the evidence is therefore of great value, yet this is rarely done in the drug-approval process. Phase III designs that make better use of phase II data can facilitate drug development in orphan diseases. Methods: A Bayesian meta-analytic approach is used to inform the phase III study with phase II data. It is particularly attractive, since uncertainty of between-trial heterogeneity can be dealt with probabilistically, which is critical if the number of studies is small. Furthermore, it allows quantifying and discounting the phase II data through the predictive distribution relevant for phase III. A phase III design is proposed which uses the phase II data and considers approval based on a phase III interim analysis. The design is illustrated with a non-inferiority case study from a Food and Drug Administration approval in herpetic keratitis (an orphan disease). Design operating characteristics are compared to those of a traditional design, which ignores the phase II data. Results: An analysis of the phase II data reveals good but insufficient evidence for non-inferiority, highlighting the need for a phase III study. For the phase III study supported by phase II data, the interim analysis is based on half of the patients. For this design, the meta-analytic interim results are conclusive and would justify approval. In contrast, based on the phase III data only, interim results are inconclusive and require further evidence. Conclusion: To accelerate drug development for orphan diseases, innovative study designs and appropriate methodology are needed. Taking advantage of randomized phase II data when analyzing phase III studies looks promising because the evidence from phase II supports informed decision-making. The implementation of the Bayesian design is straightforward with public software such as R. </jats:sec
Meta‐analysis of two studies in the presence of heterogeneity with applications in rare diseases
No full textRandom-effects meta-analyses are used to combine evidence of treatment effects from multiple studies. Since treatment effects may vary across trials due to differences in study characteristics, heterogeneity in treatment effects between studies must be accounted for to achieve valid inference. The standard model for random-effects meta-analysis assumes approximately normal effect estimates and a normal random-effects model. However, standard methods based on this model ignore the uncertainty in estimating the between-trial heterogeneity. In the special setting of only two studies and in the presence of heterogeneity, we investigate here alternatives such as the Hartung-Knapp-Sidik-Jonkman method (HKSJ), the modified Knapp-Hartung method (mKH, a variation of the HKSJ method) and Bayesian random-effects meta-analyses with priors covering plausible heterogeneity values; R code to reproduce the examples is presented in an appendix. The properties of these methods are assessed by applying them to five examples from various rare diseases and by a simulation study. Whereas the standard method based on normal quantiles has poor coverage, the HKSJ and mKH generally lead to very long, and therefore inconclusive, confidence intervals. The Bayesian intervals on the whole show satisfying properties and offer a reasonable compromise between these two extremes
Processing of Industrially Relevant Non Metals with Laser Pulses in the Range Between 10Ps and 50Ps
Full text linkThe interest in ps-laser pulses for industrial applications has significantly increased in the last few years. Today, available ps-lasers are industrially applicable turnkey systems, set up in a MOPA arrangement with rod or disk amplifiers and mostly have pulse durations of about 10ps. The change to fiber based amplifier technologies would help to build more compact systems but with pulse durations between 20ps and 50ps. It has been shown, that the ablation efficiency of a material is mainly given by the threshold fluence and the energy penetration depth. For steel and copper both parameters depend on the number of pulses applied and the pulse duration as well. Unfortunately this influence will lead to a significant drop of the ablation efficiency and quality if the pulse duration rises from 10ps to 50ps. This behavior, also expected for other metals, may reduce the attractiveness of the fiber based systems by having to make use of stretcher power amplifier compressor designs to achieve shorter pulses. However, for industrially relevant non-metals like polycrystalline diamond or ceramic materials the situation is unclear. New results of a systematic study about the influence of the pulse duration onto the ablation efficiency and quality will be presented
Processing of Dielectric Materials and Metals with ps Laserpulses
Full text linkSince industrial suited ps laser systems are available, the cold ablation with ultrashort laser pulses is of huge interest when high requirements concerning accuracy, surface roughness and heat affected zone are demanded. Interesting applications lie within the fields of surface and 3-d structuring of metals, semiconductors (especially flexible solar cells) and dielectric materials with direct and induced processes.
For a profitable industrial use of this technology high process efficiency is required which is confirmed by the development of the corresponding systems towards high average powers up to several 10 W. Beside the pulse duration, which is given by the laser system, the user has a wide variety of parameters, e.g. fluence, repetition rate, wavelength and marking speed, to optimize structuring processes. For a given average power there exist optimal laser parameters to achieve a maximal volume ablation rate. To take benefit of this maximum ablation rate, to simultaneously prevent harmful effects (particle shielding, surface melting) and to achieve the requirements concerning surface quality and accuracy, adapted structuring strategies have to be used. This can lead to equipment needs of the beam guiding system which are often not accomplishable and therefore to the demand for new technologies which have to be developed
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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