SEARCH · PubMed Health

Results for “multiple testing”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources

PubMed1988

Investigation of the cause of low sperm motility in asthenozoospermic patients by multiple quantitative tests.

Multiple tests were done on the ejaculates of 10 asthenozoospermic patients and nine healthy normozoospermic volunteers in an attempt to identify individually the cause of low sperm motility in these patients. Possible defects in the sperm plasma membrane and the motility apparatus of sperm, and in epididymal function affecting the development of motility, were investigated. The presence of seminal sperm antibodies or any motility-inhibiting factors in the seminal plasma that could be removed by washing were also tested. Each test was positive in only one or two patients but axonemal dysfunction was identified in nine patients. Removal of seminal plasma from asthenozoospermic samples did not improve sperm motility to any greater extent than with donor ejaculates, and the motile sperm of these patients exhibited characteristics mostly similar to those of donors under various incubation conditions. Selection procedures are, therefore, required to obtain samples of good quality sperm from such asthenozoospermic ejaculates.

Autoantibodies↗

PubMed1994

[Clinical evaluation of whole blood histamine release test simultaneously testing multiple allergens--correlated with bronchial provocation test].

We compared the efficacy of the novel histamine release test (HRT), which allows the determination of many allergens at the same time using a small amount of whole blood, with other conventional allergen diagnostic tests. HRT and RAST were both performed along with bronchial provocation tests (BPT) on 44 bronchial asthma patients in whom the etiologic allergen could not be determined by either intracutaneous tests (ICT) or ophthalmic response tests (ORT). The HRT uses a microtiterplate on which glass fibers have 10 kinds of allergens affixed. The histamine release ability at 6 different concentrations of each kind of allergen was examined. The concordance of HRT with respect to BPT was the highest at 82% in comparison with RAST at 66%, ICT at 55% and ORT at 60%. With each of the allergens, HRT had the highest concordance with BPT. On the other hand, RAST, ICT and ORT showed different results depending on the allergens. The positive predictive value of HRT was the highest at 76% compared with RAST at 59%, ICT at 51% and ORT at 64%. From these results, we concluded that HRT is a more useful diagnostic method for the confirmation of a clinical allergy than other conventional diagnostic methods.

Adolescent↗

PubMed1995

Step-up multiple testing of parameters with unequally correlated estimates.

We consider the problem of simultaneously testing k > or = to 2 hypotheses on parameters theta(1), ..., theta(k) using test statistics t(1), ..., t(k) such that a specified familywise error rate alpha is achieved. Dunnett and Tamhane (1992a) proposed a step-up multiple test procedure, in which testing starts with the hypothesis corresponding to the least significant test statistic and proceeds towards the most significant, stopping the first time a significant test result is obtained (and rejecting the hypotheses corresponding to that and any remaining test statistics). The parameter estimates used in the t statistics were assumed to be normally distributed with a common variance, which was a known multiple of an unknown sigma(2), and known correlations which were equal. In the present article, we show how the procedure can be extended to include unequally correlated parameter estimates. Unequal correlations occur, for example, in experiments involving comparisons among treatment groups with unequal sample sizes. We also compare the step-up and step-down multiple testing approaches and discuss applications to some biopharmaceutical testing problems.

Animals↗

PubMed1975

A novel, convenient, multiple test system for detection of bacteriuria.

A novel, convenient, multiple test system for the detection of bacteriuria is described and evaluated. The system consists of a small plastic strip with three dry reagent areas. One rapidly detects the presence of nitrite in urine and the remaining two quantitate total and gram-negative bacterial urine population after 18 to 24 hours of incubation. Quantitative accuracy was evaluated in two blind studies. In the first, known concentrations of 18 different organisms were compared and in the second, unknown concentrations of 218 randomly collected urine specimens were quantitated by both the calibrated loop streak method the new system. Overall correlation was 96 per cent for growth reagent areas. The nitrite area detected 84 per cent of the urines positive for bacteriuria. The advantages of the system over conventional bacteriuria detection systems are described.

Bacteriuria↗

PubMed2006

Multiple testing methods for ChIP-Chip high density oligonucleotide array data.

Cawley et al. (2004) have recently mapped the locations of binding sites for three transcription factors along human chromosomes 21 and 22 using ChIP-Chip experiments. ChIP-Chip experiments are a new approach to the genomewide identification of transcription factor binding sites and consist of chromatin (Ch) immunoprecipitation (IP) of transcription factor-bound genomic DNA followed by high density oligonucleotide hybridization (Chip) of the IP-enriched DNA. We investigate the ChIP-Chip data structure and propose methods for inferring the location of transcription factor binding sites from these data. The proposed methods involve testing for each probe whether it is part of a bound sequence using a scan statistic that takes into account the spatial structure of the data. Different multiple testing procedures are considered for controlling the familywise error rate and false discovery rate. A nested-Bonferroni adjustment, which is more powerful than the traditional Bonferroni adjustment when the test statistics are dependent, is discussed. Simulation studies show that taking into account the spatial structure of the data substantially improves the sensitivity of the multiple testing procedures. Application of the proposed methods to ChIP-Chip data for transcription factor p53 identified many potential target binding regions along human chromosomes 21 and 22. Among these identified regions, 18% fall within a 3 kb vicinity of the 5'UTR of a known gene or CpG island and 31% fall between the codon start site and the codon end site of a known gene but not inside an exon. More than half of these potential target sequences contain the p53 consensus binding site or very close matches to it. Moreover, these target segments include the 13 experimentally verified p53 binding regions of Cawley et al. (2004), as well as 49 additional regions that show higher hybridization signal than these 13 experimentally verified regions.

5' Untranslated Regions↗

PubMed1999

Extending the p-plot: heuristics for multiple testing. HNRC group.

In the problem of large-scale multiple testing the p-plot is a graphically based competitor to the notoriously weak Bonferroni method. The p-plot is less stringent and more revealing in that it gives a gauge of how many hypotheses are decidedly false. The method is elucidated and extended here: the bootstrap reveals bias and sampling error in the usual point estimates, a bootstrap-based confidence interval for the gauge is given, as well as two acceptably powerful blanket tests of significance. Guidelines for use are given, and interpretational pitfalls pointed out, in the discussion of a case study linking premortem neuropsychological and postmortem neuropathologic data in an HIV cohort study.

Humans↗

PubMed2005

Evaluation of Nyholt's procedure for multiple testing correction.

OBJECTIVE: A simple method for accounting efficiently for multiple testing of many SNPs in an association study was recently proposed by Nyholt, but its performance was not extensively evaluated. The method involves estimating an 'effective number' of independent tests and then adjusting the smallest observed p value using Sidák's formula based on this number of tests. We sought to carry out an empirical and theoretical evaluation of Nyholt's method. METHODS: Nyholt's method was applied to a sample of 31 genes typed at a total of 291 SNPs and permutation used to determine the type-I error rate for each gene. Based on our empirical results, we algebraically investigated the effective number of independent tests for a simple model of haplotype block structure. RESULTS: The nominal 5% type I error rate varied from under 3% to over 7%, and was dependent on linkage disequilibrium. Theoretical considerations show further that the method can be very conservative in the presence of haplotype block structure. CONCLUSION: Although Nyholt's approach may be useful as an exploratory tool, it is not an adequate substitute for permutation tests.

Case-Control Studies↗

PubMed2006

When to combine hypotheses and adjust for multiple tests.

OBJECTIVE: To provide guidelines for identifying composite hypotheses and addressing the probability of false rejection for multiple hypotheses. DATA SOURCES AND STUDY SETTING: Examples from the literature in health services research are used to motivate the discussion of composite hypothesis tests and multiple hypotheses. METHODS: This article is a didactic presentation. PRINCIPAL FINDINGS: It is not rare to find mistaken inferences in health services research because of inattention to appropriate hypothesis generation and multiple hypotheses testing. Guidelines are presented to help researchers identify composite hypotheses and set significance levels to account for multiple tests. CONCLUSIONS: It is important for the quality of scholarship that inferences are valid: properly identifying composite hypotheses and accounting for multiple tests provides some assurance in this regard.

Bias↗

PubMed2004

A powerful strategy to account for multiple testing in the context of haplotype analysis.

Haplotypes--that is, linear arrangements of alleles on the same chromosome that were inherited as a unit--are expected to carry important information in the context of association fine mapping of complex diseases. In consideration of a set of tightly linked markers, there is an enormous number of different marker combinations that can be analyzed. Therefore, a severe multiple-testing problem is introduced. One method to deal with this problem is Bonferroni correction by the number of combinations that are considered. Bonferroni correction is appropriate for independent tests but will result in a loss of power in the presence of linkage disequilibrium in the region. A second method is to perform simulations. It is unfortunate that most methods of haplotype analysis already require simulations to obtain an uncorrected P value for a specific marker combination. Thus, it seems that nested simulations are necessary to obtain P values that are corrected for multiple testing, which, apparently, limits the applicability of this approach because of computer running-time restrictions. Here, an algorithm is described that avoids such nested simulations. We check the validity of our approach under two disease models for haplotype analysis of family data. The true type I error rate of our algorithm corresponds to the nominal significance level. Furthermore, we observe a strong gain in power with our method to obtain the global P value, compared with the Bonferroni procedure to calculate the global P value. The method described here has been implemented in the latest update of our program FAMHAP.

Algorithms↗

PubMed2006

Issues of processing and multiple testing of SELDI-TOF MS proteomic data.

A new data filtering method for SELDI-TOF MS proteomic spectra data is described. We examined technical repeats (2 per subject) of intensity versus m/z (mass/charge) of bone marrow cell lysate for two groups of childhood leukemia patients: acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). As others have noted, the type of data processing as well as experimental variability can have a disproportionate impact on the list of "interesting'' proteins (see Baggerly et al. (2004)). We propose a list of processing and multiple testing techniques to correct for 1) background drift; 2) filtering using smooth regression and cross-validated bandwidth selection; 3) peak finding; and 4) methods to correct for multiple testing (van der Laan et al. (2005)). The result is a list of proteins (indexed by m/z) where average expression is significantly different among disease (or treatment, etc.) groups. The procedures are intended to provide a sensible and statistically driven algorithm, which we argue provides a list of proteins that have a significant difference in expression. Given no sources of unmeasured bias (such as confounding of experimental conditions with disease status), proteins found to be statistically significant using this technique have a low probability of being false positives.

Acute Disease↗

PubMedDate not supplied

Finding the optimal multiple-test strategy using a method analogous to logistic regression: the diagnosis of hepatolenticular degeneration (Wilson's disease).

Finding the optimal strategy among a battery of tests may be cumbersome for decision analytic models. The authors present a method of examining multiple test combinations that is based on a modified Bayes' formula analogous to logistic regression. They examined all 16 combinations of four tests used to diagnose hepatolenticular degeneration. The four tests examined were: serum ceruloplasmin level, 24-hour urinary copper excretion, free serum copper level, and liver biopsy copper concentration. They also simulated the diagnostic workup of the disease for a hypothetical cohort of 15,000 patients at risk. Assuming the disutilities of false positives and false negatives to be equal, and considering sensitivity analysis of test characteristics, the following test combinations were found to be optimal for making the diagnosis at a prior probability of disease equal to 0.05: positive serum ceruloplasmin and 24-hour urinary copper excretion, combined with either positive liver biopsy or free serum copper (or both). The strategies obtained by the modified Bayes' formula were the same as those found using the simulated data set with a standard logistic-regression software package. The logistic model's diagnostic accuracy is 0.98 as measured by the area under the receiver operating characteristic curve. The optimal strategy for diagnosing hepatolenticular degeneration varies with the prior probability of disease. For prior probabilities of 0.05, 0.25, and 0.9, and the optimal strategy, model sensitivities are 0.801, 0.880, and 0.997, and model specificities are 0.991, 0.985, and 0.814, respectively. The new method provides a convenient alternative to decision trees when examining multiple diagnostic tests.

Area Under Curve↗

PubMed2004

Error-rate and decision-theoretic methods of multiple testing: which genes have high objective probabilities of differential expression?

Given a multiple testing situation, the null hypotheses that appear to have sufficiently low probabilities of truth may be rejected using a simple, nonparametric method based on decision theory. This applies not only to posterior levels of belief, but also to conditional probabilities in the sense of relative frequencies, as seen from their equality to local false discovery rates (dFDRs). This approach neither requires the estimation of probability densities, nor of their ratios. Decision theory can also inform the selection of false discovery rate weights. An application to gene expression microarrays is presented with a discussion of the applicability of the assumption of "clumpy dependence."

Journal Article↗

PubMed1992

Strengthening some common multiple test procedures for discrete data.

This paper proposes modification of some commonly used multiple test procedures for testing problems that arise when the underlying distributions are discrete. These procedures have been shown as conservative because the exact nominal levels are unattainable. The amended procedures can achieve actual type I errors much closer to the nominal levels, thus giving rise to more powerful tests.

Animals↗

PubMed1980

HLA--D typing with lymphoblastoid cell lines. VIII. Cut points and gene frequency estimates by multiple testing analysis.

One-way mixed leukocyte culture (MLC) data were analyzed using multiple testing analysis, a new procedure for separating HLA--D typing and non-typing responses. Using the cut points derived by this analysis, HLA--Dw phenotype frequency estimates were computed from a data base which included testing of over 400 Caucasian donors. From these, gene frequency estimates were computed and compared with those of other investigators.

Cell Line↗

PubMed1997

A note on multiple testing procedures in dose finding.

It is shown that, in some recently proposed multiple test procedures for dose finding (Tamhane, Hochberg, and Dunnett, 1996, Biometrics 52, 21-37), strong control of the familywise error is only guaranteed if order relations are assumed to hold among the means. Procedures that can be applied safely without assuming any restrictions on the means can be based on the classical many--one comparisons of doses with the zero dose.

Biometry↗

PubMed2003

Bayesian multiple testing for two-sample multivariate endpoints.

In clinical studies involving multiple variables, simultaneous tests are often considered where both the outcomes and hypotheses are correlated. This article proposes a multivariate mixture prior on treatment effects, that allows positive probability of zero effect for each hypothesis, correlations among effect sizes, correlations among binary outcomes of zero versus nonzero effect, and correlations among the observed test statistics (conditional on the effects). We develop a Bayesian multiple testing procedure, for the multivariate two-sample situation with unknown covariance structure, and obtain the posterior probabilities of no difference between treatment regimens for specific variables. Prior selection methods and robustness issues are discussed in the context of a clinical example.

Bayes Theorem↗

PubMed1997

Methods of correcting for multiple testing: operating characteristics.

We examine the operating characteristics of 17 methods for correcting p-values for multiple testing on synthetic data with known statistical properties. These methods are derived p-values only and not the raw data. With the test cases, we systematically varied the number of p-values, the proportion of false null hypotheses, the probability that a false null hypothesis would result in a p-value less than 5 per cent and the degree of correlation between p-values. We examined the effect of each of these factors on family-wise and false negative error rates and compared the false negative error rates of methods with an acceptable family-wise error. Only four methods were not bettered in this comparison. Unfortunately, however, a uniformly best method of those examined does not exist. A suggested strategy for examining corrections uses a succession of methods that are increasingly lax in family-wise error. A computer program for these corrections is available.

Clinical Trials as Topic↗

PubMed2004

A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other.

In this report, we describe a simple correction for multiple testing of single-nucleotide polymorphisms (SNPs) in linkage disequilibrium (LD) with each other, on the basis of the spectral decomposition (SpD) of matrices of pairwise LD between SNPs. This method provides a useful alternative to more computationally intensive permutation tests. A user-friendly interface (SNPSpD) for performing this correction is available online (http://genepi.qimr.edu.au/general/daleN/SNPSpD/). Additionally, output from SNPSpD includes eigenvalues, principal-component coefficients, and factor "loadings" after varimax rotation, enabling the selection of a subset of SNPs that optimize the information in a genomic region.

Gene Frequency↗