Statistical analysis for dependent dichotomous data

The analysis of means for attributes data (ANOMAD) is used--when normal approximation applies to binomial distribution--by extending the analysis of means (ANOM) introduced by Ott and Schilling. ANOMAD compares the individual proportions or dependent percentages or set of frequencies of subjects responding to different stimuli, with the grand average of the proportions. It is interesting to see if all temporal values of some risk factors in cardiovascular diseases (CD)--acting as "stimuli"--can provide the same effect on a group of subjects by emphasizing the most important ones.     

Statistical methods for the analysis of tumor multiplicity data

The fit of tumor multiplicity data from 93 mouse skin, lung, and liver carcinogenicity experiments to Poisson, negative binomial, and normal distributions was studied. The data were fitted well by the negative binomial distribution. This distribution has two parameters, the mean tumor multiplicity and an exponent determined by the interanimal homogeneity of tumor response. The value of the latter parameter was related to animal strain and the target tissue studied in the carcinogenicity experiments. The null distribution of the two-sample likelihood ratio test based on the negative binomial with common exponent model for tumor multiplicity data was shown by simulation studies to be approximately chi 2 with 1 d.f. Simulation also indicated that the likelihood ratio test has sufficiently better performance when the negative binomial model is valid to make its use more attractive than the more commonly used Wilcoxon test or Student t test. Charts for estimating the number of animals per group that are required to detect specified differences in tumor multiplicities are provided for several commonly used assays.     

An introduction to survival analysis: Statistical methods for analysis of clinical trial data.

The randomized controlled clinical trial (RCT) is a prospective study using random assignment of subjects to treatment groups to compare the effect and value of a therapeutic intervention against a control. The RCT is the most definitive clinical research tool for evaluating the efficacy of a new therapy in human subjects. Often the outcome of interest in an RCT is the length of time until an event occurs after treatment or intervention. In this article we introduce statistical methods for evaluating differences in the patterns of time to response between two groups of subjects to determine whether one therapy is better than another. The collection of methods for analyzing such data, known as survival data, is called survival analysis. Using data from a hypothetical clinical trial for the prevention of the recurrence of depression, we illustrate two elementary methods for analyzing survival data. We also discuss generalizations of these methods to incorporate covariates and conclude with a general discussion of clinical trials of psychiatric therapies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Statistical analysis of repeated measures data using SAS procedures

Mixed linear models were developed by animal breeders to evaluate genetic potential of bulls. Application of mixed models has recently spread to all areas of research, spurred by availability of advanced computer software. Previously, mixed model analyses were implemented by adapting fixed-effect methods to models with random effects. This imposed limitations on applicability because the covariance structure was not modeled. This is the case with PROC GLM in the SAS System. Recent versions of the SAS System include PROC MIXED. This procedure implements random effects in the statistical model and permits modeling the covariance structure of the data. Thereby, PROC MIXED can compute efficient estimates of fixed effects and valid standard errors of the estimates. Modeling the covariance structure is especially important for analysis of repeated measures data because measurements taken close in time are potentially more highly correlated than those taken far apart in time.     

Dichotomized efficacy end points and global end-point analysis applied to the ECASS intention-to-treat data set: post hoc analysis of ECASS I

BACKGROUND and PURPOSE: It is not yet known which end points are the most suitable for evaluation of the effects of acute stroke intervention. The European Cooperative Acute Stroke Study (ECASS) I study used 2 primary end points. The study was powered to detect a 15% improvement of the median of each primary end point. The study failed to show this effect and was negative in the intention-to-treat analysis. The National Institute of Neurological Disorders and Stroke (NINDS) study used 4 dichotomized end points and applied a global end-point analysis. This study was positive and led to FDA approval of thrombolytic therapy for acute ischemic stroke. This study was undertaken to answer the question of whether a different statistical design may have shown a positive results of the ECASS I trial. METHODS: We performed a retrospective analysis of the ECASS I intention-to-treat data set (615 randomized and treated patients, rtPA treatment versus placebo) and post hoc application of the NINDS trial statistical methodology (global end-point analysis). The scores of the modified Rankin Scale (mRS), Barthel Index (BI), and the National Institutes of Health Stroke Scale (NIHSS) were dichotomized according to the criteria used in the NINDS trial. Favorable outcome was defined as a score of 0 or 1 on mRS, a score of 95 or 100 on BI, and a score of 0 or 1 on NIHSS. RESULTS: The number of patients reaching favorable outcome were higher in all 3 end points in the rtPA-treated group. The effect sizes were 8% for mRS, 6% for BI, and 14% for NIHSS, respectively. The differences are statistically significant for the mRS (P=0.044; odds ratio [OR], 1. 4; 95% confidence interval [CI], 1.0 to 2.0) and the NIHSS (P=0.001; OR, 1.9; 95% CI, 1.4 to 2.8), while for the BI significance was missed (P=0.102; OR, 1.3; 95% CI, 0.9 to 1.8). The global end-point statistics, however, shows a significant increase (P=0.008; OR, 1.5; 95% CI, 1.1 to 2.0) of favorable outcome in the rtPA-treated patient group. CONCLUSIONS: Using the global end-point analysis, ECASS is positive in the intention-to-treat analysis. This may indicate that the time window for thrombolysis may be as long as 6 hours. Looking at the 3 dichotomized end points, the effect sizes for 2 end points, mRS and BI, are smaller in the ECASS 6-hour intention-to-treat population compared with the NINDS trial, whereas the effect size for the NIHSS is larger. While in the NINDS trial all 3 end points reveal statistically significant results, in ECASS only 2 of the 3 corresponding end points, mRS and NIHSS, were statistically significant. This finding underlines an important difference of a global end-point approach: it may show a positive overall result although one of the end points is not positive.     

Statistical analysis of data derived from clinical variables of plaque and gingivitis

BACKGROUND: Historical cohort studies in England have found that impaired fetal growth and lower respiratory tract infections in early childhood are associated with lower levels of lung function in late adult life. These relations are investigated in a similar study in Scotland. METHODS: In 1985-86 a follow up study was carried out of 1070 children who had been born in St Andrew's from 1921 to 1935 and followed from birth to 14 years of age by the Mackenzie Institute for Medical Research. Recorded information included birth weight and respiratory illnesses. The lung function of 239 of these individuals was measured. RESULTS: There was no association between birth weight and lung function. Pneumonia before two years of age was associated with a difference in mean forced expiratory volume in one second (FEV1) of -0.39 litres (95% confidence interval (CI) -0.67, -0.11; p = 0.007) and in mean forced vital capacity (FVC) of -0.60 litres (95% CI -0.92, -0.28; p < 0.001), after controlling for age, sex, height, smoking, type of spirometer, and other illnesses before two years. Similar reductions were seen in men and women. Bronchitis before two years was associated with smaller deficits in FEV1 and FVC. Asthma or wheeze at two years and older and cough after five years were also associated with a reduction in FEV1. CONCLUSIONS: The relation between impaired fetal growth and lower lung function in late adult life seen in previous studies was not confirmed in this cohort. The deficits in FEV1 and FVC associated with pneumonia and bronchitis in the first two years of life are consistent with a causal relation.     

Wrinkles induced by the use of smoothing procedures applied to serial growth data

This paper elucidates the effects of moving average filters when applied to serial growth measurements. This is a question of interest because smoothing procedures are inherently part of a number of analytical methods presently employed in auxological analyses. Particular attention is paid to sequential growth data analysed to identify what has been described as pulsatile, saltation and stasis patterns or mini-growth spurts. When applied to pulsatile, or saltatory, time series data the process of smoothing itself creates artifactual temporal patterns in the time series data similar to previously described mini growth spurts while removing the actual pulsatile characteristics of the data. These observations illustrate that smoothing approaches add noise to time series data while removing meaningful patterns in the original data sequence. Analyses employing such approaches produce results that include waveforms or other fluctuations compatible with an underlying pulsatile driving mechanism, but do not necessarily reflect the temporal characteristics of the original biological process.