Conclusions. The sensitivity and positive predictive value are generally more concerned than the specificity and negative predictive value in assessing and adjusting publication bias in meta-analyses. In this sense, Egger's regression can be recommended for its high sensitivity, while any positive result from Tang's method would suggest a probability of bias that should be taken seriously. Given the different patterns of the accuracy with the OR and the P1-P2 combination, a combination of Egger's regression and Tang's regression would be advisable. Further studies are needed to study the accuracy of methods used in combination. / Due to sampling error and true heterogeneity, a single study cannot provide a comprehensive picture and a precise estimate of, say the effectiveness of a treatment. Systematic reviews that identify and integrate relevant studies have become the most important scientific, quantitative method to summarize scientific research. Meta-analysis is the statistical method used in systematic reviews to combine results from individual studies. / However, due to selective submission and publication, not all relevant studies conducted, especially those unpublished studies with an insignificant negative result, are easily accessible to those who conduct reviews. As a result, the truth, say, the effect of a treatment, would be overestimated. This phenomenon is known as publication bias. A few methods for detecting the bias have been developed and used in meta-analyses. Although their accuracy has been studied, some important issues remain to be answered, such as when would a method be good enough for practical use and is it similarly good for different definitions of the odds ratio? / Methods. We conducted a simulation study to examine the accuracy of four commonly used bias-detection methods with various ORs and P1-P2 combinations. In a simulation study, the true bias status can be predetermined and thus be compared with the results of the bias-detection methods. The four methods are Egger's regression, funnel plot regression, rank correlation regression, and Tang's regression. Realistic sample size was used for simulating individual studies and the numbers of studies in a meta-analysis was also varied. Both the sensitivity and specificity are examined against the magnitude of the OR and the P1-P 2 combination to identify the ORs and P1-P 2 combinations for which a method is sufficiently accurate. Predictive values are also examined for the same reason and in the same manner. / Results. The sensitivity and positive predictive value are generally low and in particular when the OR is close to one for which publication bias is of a particular concern. Egger's regression has the highest sensitivity among the four, in particular when the OR is neither close to one nor exceptionally large or small. Due to the relatively lower specificity, the positive predictive value of Egger's regression is not as high as that for Tang's regression and funnel plot regression. Tang's regression and funnel plot regression are very similar in sensitivity, specificity and predictive values, with the former being slightly better. Rank correlation seems the least accurate method overall. Tang's regression has in general the highest positive predictive value among the four methods in particular when the OR is below one. / Chung Chi-keung. / "June 2006." / Adviser: Tang Jin Ling. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1588. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 116-124). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Note: / Clinical chemistry is a medical discipline whose aim is to diagnose and assess disease by analysis of biological specimens. Modem laboratories can perform several hundred different tests using many different methods developed over the last century. The classical, more traditional assays are typically labour-intensive, not multiplexed (only measure one analyte or disorder per assay), expensive, require a long turnaround time, and may not provide adequate sensitivity and specificity. Developments in mass spectrometry (MS) and related technologies over the last two decades have provided solutions for many if not all of these shortcomings. While MS based applications have not yet been widely implemented in clinical chemistry laboratories, current developments will encourage the replacement of traditional methods as well as the expansion of clinically diagnostic endpoints. Indeed, modem MS can be used to simultaneously analyze and quantitate multiple biomarkers in a single analysis. Currently, no other technique exists that can provide a comparable multiplexed analysis. In this thesis, current MS and related technologies were developed and applied to several important but distinct clinical chemistry applications. [...] / La chimie clinique est une discipline medicale qui a pour but de diagnostiquer la presence et la progression d'une maladie par l'analyse d'echantillons biologiques. Les laboratoires modemes peuvent executer des centaines d'analyses en utilisant plusieurs methodes developpees au courrant des cent demieres annees. Les essaisc1assiques, et plus traditionnels, sont souvent laborieux, non multiplexe (mesurent seulement un analyte par essai), cher, exige un long temps de rotation et risque de ne pas fournir une specificite adequate. Pendant les deux dernieres decennies, les developpements dans Ie domaine de la spectrometrie de masse (MS) et les technologies rattachees ont foumi des solutions a plusieurs, pour ne pas dire tous, manques retrouves dans les methodes d'analyse traditionnelles.

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