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Biomedical subjects

J L Gastwirth

Publications and source records attributed to J L Gastwirth.

10 recordsLinked to original sources

Screening without a "gold standard": the Hui-Walter paradigm revisited.

The authors consider screening populations with two screening tests but where a definitive "gold standard" is not readily available. They discuss a recent article in which a Bayesian approach to this problem is developed based on data that are sampled from a single population. It was subsequently pointed out that such inferences will not necessarily be accurate in the sense that standard errors for parameters may not decrease as n increases. This problem will generally occur when the data are insufficient to estimate all of the parameters as is the case when screening a single population with two tests. If both tests are applied to units sampled from two populations, however, this particular difficulty disappears. In this article the authors further examine this issue and develop an approach based on sampling two populations that yields increasingly accurate inferences as the sample size increases.

Bayes Theorem↗

A weighted test using both extreme discordant and concordant sib pairs for detecting linkage.

Statistical procedures using extremely discordant and concordant sib-pairs have been developed for mapping quantitative trait loci in humans. To improve the power of the existing methods, test statistics placing greater weight on the more discordant or more concordant pairs are proposed. Because the optimum choice of weights would depend on the underlying genetic model, which is not usually known, a test with simple weights is suggested. This test is shown to have greater power than the currently available ones for a variety of genetic models.

Genetic Linkage↗

Latent class analysis of human herpesvirus 8 assay performance and infection prevalence in sub-saharan Africa and Malta.

Human herpesvirus 8 (HHV-8) is thought to be highly prevalent in Mediterranean countries and sub-Saharan Africa, where it causes Kaposi's sarcoma in a small proportion of infected immunocompetent persons. However, the lack of serological tests with established accuracy has hindered our understanding of the prevalence, risk factors and natural history of HHV-8 infection. We tested 837 subjects from Congo, Botswana (mostly young adults) and Malta (elderly adults), using an immunofluorescence assay and 2 enzyme immunoassays (EIAs, to viral proteins K8.1 and orf65). Each assay found HHV-8 seroprevalence to be high (49-87%) in the African populations and generally lower (9-54%) in Malta. However, there was only modest agreement among tests regarding which subjects were seropositive (3-way kappa, 0.05-0.34). We used latent class analysis to model this lack of agreement, estimating each test's sensitivity and specificity and each population's HHV-8 prevalence. Using this approach, the K8.1 EIA had consistently high sensitivity (91-100%) and specificity (92-100%) across populations, suggesting that it might be useful for epidemiological studies. Compared with the K8.1 EIA, both the immunofluorescence assay and the orf65 EIA had more variable sensitivity (80-100% and 58-87%, respectively) and more variable specificity (57-100% and 48-85%, respectively). HHV-8 prevalence was 7% among elderly Maltese adults. Prevalence was much higher (82%) in Congo, consistent with very high Kaposi's sarcoma incidence there. Prevalence was also high in Botswana (87% in Sans, an indigenous group, and 76% in Bantus), though Kaposi's sarcoma is not common, suggesting that additional co-factors besides HHV-8 are needed for development of Kaposi's sarcoma.

Adolescent↗

On power and efficiency robust linkage tests for affected sibs.

For diseases that do not follow a clear Mendelian pattern of inheritance nonparametric tests applied to affected sibs have been shown to be robust to the inherent uncertainty about the precise underlying genetic model. It is known that the weights optimizing the power of tests using IBD alleles shared by affected sib pairs or triples depend on the underlying model. We show how efficiency robustness techniques, used in other areas of statistics, provide a systematic approach for constructing a robust linear combination of the statistics that are optimal for the individual members of a family of plausible genetic models. The method depends on the correlation matrix of the optimal tests as these correlations reflect how different the models are. When the minimal correlation is less than 0.5, an alternate robust procedure is proposed. The methods apply to combining data from sibships of different sizes.

Automation↗

Efficiency robust tests for survival or ordered categorical data.

The selection of a single method of analysis is problematic when the data could have been generated by one of several possible models. We examine the properties of two tests designed to have high power over a range of models. The first one, the maximum efficiency robust test (MERT), uses the linear combination of the optimal statistics for each model that maximizes the minimum efficiency. The second procedure, called the MX, uses the maximum of the optimal statistics. Both approaches yield efficiency robust procedures for survival analysis and ordinal categorical data. Guidelines for choosing between them are provided.

Biometry↗

Efficiency robust tests of independence in contingency tables with ordered classifications.

Ordered categorical data occur frequently in biomedical research. The linear by linear association test for ordered R x C tables permits the investigator to specify row and column scores for analysis. When an investigator believes that there may be more than one set of reasonable scores or when more than one investigator proposes scores, we need a method to decide upon a single procedure to use. We show how to use efficiency robustness principles to combine tests from two or more sets of scores into one robust test for analysis. This test minimizes the worst possible efficiency loss over all the sets of scores. We illustrate the methodology for the R x C case and, in detail, for the important special 2 x C case.

Alcohol Drinking↗

Biostatistical concepts and methods in the legal setting.

Biostatistical concepts and methods apply to various problems arising in actual U.S. legal cases. These involve: measures of association, assessing the potential effect of omitted variables and the Peters-Belson approach to regression. In particular, we present the inapplicability of Fisher's exact test in the case where the process determining the marginal sample sizes is not independent of the hypothesis under study by the 2 x 2 table. We adapt Cornfield's procedure to assess whether the omission of another factor could have contributed to a non-significant finding of the effect of the major factor under investigation. Finally, we demonstrate the relevance and utility of the Peters-Belson regression methodology to equal pay and promotion cases.

Biometry↗

A cautionary note on applying scores in stratified data.

When rank tests are used to analyze stratified data, three methods for assigning scores to the observations have been proposed: (S) independently within each stratum (see Lehmann, 1975, Nonparametrics: Statistical Methods Based on Ranks; San Francisco: Holden-Day); (A) after aligning the observations within each stratum and then pooling the aligned observations (Hodges and Lehmann, 1962, Annals of Mathematical Statistics 33, 482-497); and (P) after pooling the observations across all strata (that is, without alignment) (Mantel, 1963, Journal of the American Statistical Association 58, 690-700; Mantel and Ciminera, 1979, Cancer Research 39, 4308-4315). Test statistics are formed for each method by combining the stratum-specific linear rank tests using the assigned scores. We show that method P is sensitive to the score function used in the case of two moderately sized strata. In general, we recommend methods S and A for use with moderate to large-sized strata.

Biometry↗

On non-parametric and generalized tests for the two-sample problem with location and scale change alternatives.

Various tests have been proposed for the two-sample problem when the alternative is more general than a simple shift in location: non-parametric tests; O'Brien's generalized t and rank sum tests; and other tests related to the t. We show that the generalized tests are directly related to non-parametric tests proposed by Lepage. As a result, we obtain a wider, more flexible class of O'Brien-type procedures which inherit the level robustness property of non-parametric tests. We have also computed the tests' empirical sizes and powers under several models. The non-parametric procedures and the related O'Brien-type tests are valid and yield good power in the settings investigated. They are preferable to the t-test and related procedures whose type I errors differ noticeably from nominal size for skewed and long-tailed distributions.

Clinical Trials as Topic↗