Efficiency comparisons of rank and permutation tests.
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Efficiency↗
Biomedical subjects
Markus Neuhäuser
Publications and source records attributed to Markus Neuhäuser.
Two-part permutation tests for DNA methylation and microarray data.
BACKGROUND: One important application of microarray experiments is to identify differentially expressed genes. Often, small and negative expression levels were clipped-off to be equal to an arbitrarily chosen cutoff value before a statistical test is carried out. Then, there are two types of data: truncated values and original observations. The truncated values are not just another point on the continuum of possible values and, therefore, it is appropriate to combine two statistical tests in a two-part model rather than using standard statistical methods. A similar situation occurs when DNA methylation data are investigated. In that case, there are null values (undetectable methylation) and observed positive values. For these data, we propose a two-part permutation test. RESULTS: The proposed permutation test leads to smaller p-values in comparison to the original two-part test. We found this for both DNA methylation data and microarray data. With a simulation study we confirmed this result and could show that the two-part permutation test is, on average, more powerful. The new test also reduces, without any loss of power, to a standard test when there are no null or truncated values. CONCLUSION: The two-part permutation test can be used in routine analyses since it reduces to a standard test when there are positive values only. Further advantages of the new test are that it opens the possibility to use other test statistics to construct the two-part test and that it avoids the use of any asymptotic distribution. The latter advantage is particularly important for the analysis of microarrays since sample sizes are usually small.
Algorithms↗
Risk stratification with cardiac troponin I in patients undergoing elective coronary artery bypass surgery.
OBJECTIVE: Cardiac troponin I (cTnI) is a highly sensitive and specific marker for postoperative prediction of patients outcome after coronary artery bypass surgery (CABG). Whether preoperatively elevated cTnI levels similarly predict the outcome in patients scheduled for elective CABG is currently unknown. METHODS: Therefore, a possible correlation between preoperative cTnI levels and perioperative major adverse events and in-hospital mortality after CABG was investigated. CTnI was measured within 24h before surgery in 1405 out of 3124 consecutive elective CABG patients. Out of these patients, 1178 had a preoperative cTnI level below 0.1ng/ml (group 1), 163 patients had a cTnI level between 0.11 and 1.5ng/ml (group 2), and 64 patients had a cTnI level above 1.5ng/ml (group 3). CTnI levels, electrocardiograms, clinical data, adverse events and in-hospital mortality were recorded prospectively. Patients with ST-elevation myocardial infarction less than 7 days before surgery were excluded from the study. RESULTS: Perioperative myocardial infarction (PMI) occurred in 69/1178 patients (5.9%) in group 1, 14/163 patients (8.6%; odds ratio (OR) 1.5, 95% confidence interval (CI): 0.8-2.8) in group 2, and 11/64 patients (17.2%; OR 3.3, CI: 1.6-7.0) in group 3 (overall: P<0.001, Cochran-Armitage trend test). Low cardiac output syndrome (LCOS) occurred in 19/1178 patients (1.6%), 9/163 (5.5%; OR 3.6, CI: 1.5-8.5), and 7/64 patients (10.9%; OR 7.5, CI: 2.7-19.8) (overall: P<0.001, group 1 vs. group 2: P<0.002), respectively. In-hospital mortality was 1.7% in group 1 and 3.1% in group 2, but 6.3% (OR 3.9, CI: 1.1-12.5) in group 3 (overall: P<0.01, group 1 vs. group 2: P=NS). Intensive care and hospital stay were significantly longer in group 3 compared to groups 1 and 2. Univariate and multivariate logistic regression analysis confirmed the statistically significant relationship between cTnI and PMI, LCOS and in-hospital mortality, respectively (P<0.001). CONCLUSIONS: Risk stratification by measurement of cTnI levels within 24h before elective CABG clearly identifies a subgroup of patients with increased risk for postoperative adverse outcome and in-hospital mortality.
Aged↗
Prognostic value of preoperative cardiac troponin I in patients with non-ST-segment elevation acute coronary syndromes undergoing coronary artery bypass surgery.
STUDY OBJECTIVES: Elevated levels of cardiac troponin I (cTnI) have been associated with adverse short-term and long-term outcomes in acute coronary syndrome (ACS) patients and in patients who underwent coronary artery bypass grafting (CABG); however, the prognostic implications of preoperative cTnI determination have not been investigated so far. DESIGN AND SETTING: Retrospective study in a department of cardiothoracic surgery of a university hospital. PATIENTS AND METHODS: A possible correlation between preoperative cTnI levels and major adverse cardiac events (MACE) and in-hospital mortality in CABG patients with non-ST-segment elevation ACS (NSTE-ACS) was investigated. cTnI was determined in 1,978 of 3,124 consecutive CABG patients. Among these, 1,592 patients had preoperative cTnI levels < 0.1 ng/mL and therefore served as control subjects (group 1), 265 patients had NSTE-ACS with cTnI levels from 0.11 to 1.5 ng/mL (group 2), and 121 patients had NSTE-ACS with cTnI levels > 1.5 ng/mL (group 3). cTnI levels, clinical data, MACE, and in-hospital mortality were recorded prospectively. Logistic regression and receiver operating characteristic analyses were applied to determine prognostic cutoff values of cTnI. RESULTS: Perioperative myocardial infarction was found in 5.8% of the patients in group 1, 8.3% of the patients in group 2 (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.9 to 2.5), and 18.2% patients in group 3 (OR, 3.6; 95% CI, 2.1 to 6.2; p < 0.0001, Cochran-Armitage trend test). Low cardiac output syndrome occurred in 1.5% of patients in group 1, 4.2% of patients in group 2 (OR, 2.8; 95% CI, 1.3 to 6.1), and 10.9% patients in group 3 (OR, 6.5; 95% CI, 2.9 to 14.4; p < 0.0001). In-hospital mortality was 1.5% in group 1, 3.0% in group 2 (OR, 2.0; 95% CI, 0.8 to 4.8), but 6.6% in group 3 (OR, 4.6; 95% CI, 1.9 to 11.1; p < 0.0001). Univariate and multivariate logistic regression analyses identified cTnI as the strongest preoperative predictor for MACE and in-hospital mortality, respectively. CONCLUSIONS: Preoperative cTnI measurement before CABG appears as a powerful and independent determinant of short-term surgical risk in patients with NSTE-ACS.
Aged↗
One-sided nonparametric tests for ordinal data.
Baumgartner, Weiss, and Schindler (1998) introduced a novel non-parametric test for the two-sample comparison that is superior to commonly used tests such as the Wilcoxon rank-sum test. A modification of the novel test statistic can be used for one-sided comparisons based on ordinal data. Such comparisons frequently occur in psychological research, and the Wilcoxon test is often recommended for their analysis. Here, the two tests were compared in a simulation study. According to this study the tests have a similar type I error rate, but the modified Baumgartner-Weiss-Schindler test is more powerful than the Wilcoxon test.
Data Interpretation, Statistical↗
The Baumgartner-Weiss-Schindler test for the detection of differentially expressed genes in replicated microarray experiments.
MOTIVATION: An important application of microarray experiments is to identify differentially expressed genes. Because microarray data are often not distributed according to a normal distribution nonparametric methods were suggested for their statistical analysis. Here, the Baumgartner-Weiss-Schindler test, a novel and powerful test based on ranks, is investigated and compared with the parametric t-test as well as with two other nonparametric tests (Wilcoxon rank sum test, Fisher-Pitman permutation test) recently recommended for the analysis of gene expression data. RESULTS: Simulation studies show that an exact permutation test based on the Baumgartner-Weiss-Schindler statistic B is preferable to the other three tests. It is less conservative than the Wilcoxon test and more powerful, in particular in case of asymmetric or heavily tailed distributions. When the underlying distribution is symmetric the differences in power between the tests are relatively small. Thus, the Baumgartner-Weiss-Schindler is recommended for the usual situation that the underlying distribution is a priori unknown. AVAILABILITY: SAS code available on request from the authors.
Algorithms↗
Comparing parasite numbers between samples of hosts.
The comparison of parasite numbers or intensities between different samples of hosts is a common and important question in most parasitological studies. The main question is whether the values in one sample tend to be higher (or lower) than the values of the other sample. We argue that it is more appropriate to test a null hypothesis about the probability that an individual host from one sample has a higher value than individual hosts from a second sample rather than testing hypotheses about means or medians. We present a recently proposed statistical test especially designed to test hypotheses about that probability. This novel test is more appropriate than other statistical tests, such as Student's t-test, the Mann-Whitney U-test, or a bootstrap test based on Welch's t-statistic, regularly used by parasitologists.
Animals↗
The Fisher-Pitman permutation test when testing for differences in mean and variance.
The Fisher-Pitman permutation test can detect any type of difference between two samples: hence, a significant Fisher-Pitman permutation test does not necessarily provide evidence for a difference in means. It is possible, however, to test separately for differences in means and variances. Here, we present a recently proposed two-stage procedure to decide whether there are differences in means or variances that can be applied when samples may come from nonnormal distributions with possibly unequal variances.
Analysis of Variance↗
Wilcoxon test after Levene's transformation can have an inflated Type I error rate.
It is shown that the procedure of applying the Wilcoxon test after Levene's transformation can have an inflated Type I error rate when distributions are skewed. Thus, when the data may come from an asymmetric distribution, the Wilcoxon test should not be applied as a test for homogeneity of variances after Levene's transformation.
Humans↗
Exact tests for the analysis of case-control studies of genetic markers.
OBJECTIVES: The association of a candidate gene with disease can be evaluated by a case-control study in which the genotype distribution is compared for diseased cases and unaffected controls. Usually, the data are analyzed with Armitage's test using the asymptotic null distribution of the test statistic. Since this test does not generally guarantee a type I error rate less than or equal to the significance level alpha, tests based on exact null distributions have been investigated. METHODS: An algorithm to generate the exact null distribution for both Armitage's test statistic and a recently proposed modification of the Baumgartner-Weiss-Schindler statistic is presented. I have compared the tests in a simulation study. RESULTS: The asymptotic Armitage test is slightly anticonservative whereas the exact tests control the type I error rate. The exact Armitage test is very conservative, but the exact test based on the modification of the Baumgartner-Weiss-Schindler statistic has a type I error rate close to alpha. The exact Armitage test is the least powerful test; the difference in power between the other two tests is often small and the comparison does not show a clear winner. CONCLUSION: Simulation results indicate that an exact test based on the modification of the Baumgartner-Weiss-Schindler statistic is preferable for the analysis of case-control studies of genetic markers.
Algorithms↗
The new phosphodiesterase 4 inhibitor roflumilast is efficacious in exercise-induced asthma and leads to suppression of LPS-stimulated TNF-alpha ex vivo.
Roflumilast is a new phosphodiesterase 4 (PDE4) inhibitor developed by Byk Gulden Pharmaceuticals for the treatment of chronic obstructive pulmonary disease and asthma. A placebo-controlled, randomized, double-blind, two-period crossover study was performed to investigate the safety and efficacy of roflumilast in 16 patients with exercise-induced asthma. The patients received placebo or roflumilast (500 microg/day) for 28 days, each according to the randomly determined treatment sequences roflumilast/placebo and placebo/roflumilast. In both study periods, exercise challenge was performed 1 hour after dosing on days 1, 14, and 28. FEV1 was measured before exercise challenge, immediately after the end of exercise challenge, and then at 1, 3, 5, 7, 9, and 12 minutes after the end of challenge. Blood samples for the determination of lipopolysaccharide (LPS)-stimulated tumor necrosis factor alpha (TNF-alpha) in whole blood ex vivo as a surrogate marker for the inhibition of inflammatory cell activation were taken predose on days 1 and 28. Serial safety measurements were performed during both study periods. Analysis of variance for the crossover design showed a significant superiority of roflumilast over placebo on day 28. The mean percentage fall of FEV1 after exercise was reduced by 41% as compared to placebo (p = 0.021). An improvement of lung function during roflumilast treatment was also observed on days 1 and 14. The median TNF-alpha level decreased by 21% (p = 0.009) during roflumilast treatment but remained essentially constant under placebo. It is concluded that roflumilast is effective in the treatment of exercise-induced asthma. This result was accompanied by a significant reduction of TNF-alpha levels ex vivo. Treatment with roflumilast was safe and well tolerated.
3',5'-Cyclic-AMP Phosphodiesterases↗
The Baumgartner-Weiss-Schindler test in the presence of ties.
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Computer Simulation↗