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HLA typing and retinitis pigmentosa.

Retinitis pigmentosa is a disease whose pathogenesis remains largely obscure. A lot of evidences support the hypothesis that auto-immunity is involved, but no HLA antigen has ever been associated with retinitis pigmentosa. Ten patients with autosomal recessive retinitis pigmentosa were tissue typed for class I and II HLA antigens. The results of the study show a significant increase in the frequency of the antigens Cw4, Cw6 and DR11. High values of relative risk were found also for some class I antigens, but the size of the group of patients with these loci precluded a meaningful statistical analysis.

Adolescent↗

A review of software for data management, design and analysis of clinical trials.

In clinical trials, subjects are usually entered one at a time, and their responses to treatment monitored sequentially. Regular monitoring of trial progress in the early stages is crucial for accurate reporting of the final results. This paper discusses in detail the principles of quality data management in clinical trials, with specific reference to three clinical data management systems namely, CLINTRIAL, ORACLE CLINICAL and MACRO. All three systems have the essential features for monitoring and processing quality clinical trials data. In terms of functionality, there appears to be no significant advantage of one system over the other. However, to reap the full benefits of sophisticated systems such as these, a good support network and comprehensive training programmes are essential since their day-to-day use demands a high level of technical competence. Basic considerations pertinent to the success of a clinical trial involve not only logistics and data management. Issues relating to the study design are also of primary concern. In this respect, we briefly describe some sample size packages, NQUERY, PEST, POWER, POWER AND PRECISION and SAMPSIZE. Finally, a brief comparison is made with regards to some distinct features of three commonly used statistical packages, namely SPSS, SAS and STATA.

Clinical Trials as Topic↗

Rating scales in psychopharmacology. Statistical aspects.

The scaling problem of measurement of clinical data in psychiatry should be differed from, although connected with, the statistical problem of statistical significance testing in psychopharmacological trials. The scaling levels (ordinal versus interval) of a rating scale as well as the statistical tests (non-parametric versus parametric) are different in Phase II and Phase III trials. Sufficient statistics of improvement curves and of recovery rates are discussed.

Clinical Trials as Topic↗

Reading research critically: results--Part 1.

Nurses in PACUS as well as other areas of nursing are increasingly being asked to incorporate research into their clinical practices. Unfortunately, many nurses have limited formal education in research and are not adequately prepared to critically analyze the quality of the research they are reading. This is especially true when it comes to the statistical analysis section of the published research report. This article lays the foundation for understanding the statistical analysis most commonly seen in results sections of research publications in nursing journals.

Data Interpretation, Statistical↗

[Analysis of correlated data: problems and examples in industrial medicine].

In occupational health we are frequently faced with data that are not independent, but to recognize the lack of such an independence is not yet a common practice. To help researchers in the field to treat correlated data in a proper way this paper has two aims: to highlight practical situations in which the data are not independent and to show the main differences between a statistical analysis which does consider the correlation appropriately and one which doesn't. As to the first aim, four typical examples are discussed: repeated measurements in the same subject (e.g., cells in which the number of sister chromatid exchanges is counted); health effects observed in multiple organs (e.g., visual impairment in both eyes); evaluation of prevention programs (e.g., exposure assessment to styrene before and after environment remediation); longitudinal studies of health effects (e.g., changes over time of pulmonary function parameters). With respect to the second aim a practical exercise is described completely. Measurements of exposure to a toxic substance in two different departments before and after environment remediation are evaluated with statistical tools which both do and do not consider the correlation between such measurements. Differences in the results obtained, with particular reference to indices of variability (e.g., standard errors), point toward the need of analysing correlated data with appropriate statistical tools that take correlation into account.

Analysis of Variance↗

Quantitative analysis of a presence/absence microbiological assay: the hard surface carrier test of disinfectant efficacy.

The Hard Surface Carrier Test (HSCT) is a presence/absence assay for determining the extent to which chemical disinfectants kill bacteria. The disinfectants are marketed for cleaning surfaces in hospitals, restaurants, the home, etc. In the HSCT, a presence response (or equivalently, a positive carrier) is recorded if one or more bacteria survive among M bacteria attached to a glass carrier and exposed to the chemical disinfectant; otherwise, the response is absence. The presence or absence response is observed for each of many (usually 60) glass carriers and the disinfectant is considered effective if few (e.g., < or = 5%) of the carriers are positive. It would be more satisfactory to microbiologists if effectiveness were based on the fraction of bacteria that survive exposure; denote the expected survival fraction by phi. An equivalent parameter commonly used in antimicrobial research is the log-reduction, denoted by psi, where psi = -log10(phi). Although the number M of bacteria on each exposed carrier is not known, this paper shows it is possible to estimate psi. The suggested estimator is based on the assumption that M follows a gamma distribution. The gamma parameters are estimated using counts of bacteria on the HSCT nonexposed (control) carriers. This paper provides a formula for the standard error of the estimate, a computer simulation technique for calculating the lower confidence limit, and a computer simulation study of these statistical methods.

Bacteria↗

Why carve up your continuous data?

Continuous data are commonplace in social, biophysical, and health research. For various reasons, researchers often carve up data into ordered chunks. Such data carving results in less information being carried by the data, a reduction or spurious increase in statistical power, and resultant Type I or Type II errors. We give examples of data carving in selected nursing literature, and illustrate how unnecessary categorization can produce erroneous statistical results. Finally, we propose credible alternatives to data carving.

Analysis of Variance↗

The bootstrap: a technique for data-driven statistics. Using computer-intensive analyses to explore experimental data.

BACKGROUND: The concept of resampling data--more commonly referred to as bootstrapping--has been in use for more than three decades. Bootstrapping has considerable theoretical advantages when it is applied to non-Gaussian data. Most of the published literature is concerned with the mathematical aspects of the bootstrap but increasingly this technique is being utilized in medical and other fields. METHODS: I reviewed the published literature following a 1994 publication assessing the transfer of technology, including the bootstrap, to the biomedical literature. RESULTS: In the ten-year period following that 1994 paper there were 1679 published references to the technique in Medline. In that same time period the following citations were found in the four major medical journals-British Medical Journal (48), JAMA (51), Lancet (52) and the New England Journal of Medicine (45). CONTENT: I introduce the basic theory of the bootstrap, the jackknife, and permutation tests. The bootstrap is used to estimate the accuracy of an estimator such as the standard error, a confidence interval, or the bias of an estimator. The technique may be useful for analysing smallish expensive-to-collect data sets where prior information is sparse, distributional assumptions are unclear, and where further data may be difficult to acquire. Some of the elementary uses of bootstrapping are illustrated by considering the calculation of confidence intervals such as for reference ranges or for experimental data findings, hypothesis testing such as comparing experimental findings, linear regression, and correlation when studying association and prediction of variables, non-linear regression such as used in immunoassay techniques, and ROC curve processing. CONCLUSIONS: These techniques can supplement current nonparametric statistical methods and should be included, where appropriate, in the armamentarium of data processing methodologies.

Computers↗

Gene expression profiling: methodological challenges, results, and prospects for addiction research.

This review describes the current methods used to profile gene expression. These methods include microarrays, spotted arrays, serial analysis of gene expression (SAGE), and massive parallel signature sequencing (MPSS). Methodological and statistical problems in interpreting microarray and spotted array experiments are also discussed. Methods and formats such as minimum information about microarray experiments (MIAME) needed to share gene expression data are described. The last part of the review provides an overview of the application of gene-expression profiling technology to substance abuse research and discusses future directions.

Animals↗

Advanced statistics: statistical methods for analyzing cluster and cluster-randomized data.

Sometimes interventions in randomized clinical trials are not allocated to individual patients, but rather to patients in groups. This is called cluster allocation, or cluster randomization, and is particularly common in health services research. Similarly, in some types of observational studies, patients (or observations) are found in naturally occurring groups, such as neighborhoods. In either situation, observations within a cluster tend to be more alike than observations selected entirely at random. This violates the assumption of independence that is at the heart of common methods of statistical estimation and hypothesis testing. Failure to account for the dependence between individual observations and the cluster to which they belong can have profound implications on the design and analysis of such studies. Their p-values will be too small, confidence intervals too narrow, and sample size estimates too small, sometimes to a dramatic degree. This problem is similar to that caused by the more familiar "unit of analysis error" seen when observations are repeated on the same subjects, but are treated as independent. The purpose of this paper is to provide an introduction to the problem of clustered data in clinical research. It provides guidance and examples of methods for analyzing clustered data and calculating sample sizes when planning studies. The article concludes with some general comments on statistical software for cluster data and principles for planning, analyzing, and presenting such studies.

Cluster Analysis↗

[Preliminary study of an interdisciplinary examination of the body height proportions of Germans in the 19th century and of the influence of living conditions. I. Introductory justification, problems and preliminary studies based on authentic sources from the political districts from northern Germany to Württemburg].

Researches about the influences of the nutritional conditions on body-height need interdisciplinary co-operation of Anthropology, History, and Dietetics. Such a team will be difficult succeed in joining. Especially interesting for human sciences are nutritional-constitutional researches on German populations in the 19th century, because in this century multifarious varieties exist within the German settlement. Author hopes, that preliminary original researches and first trends in results facilitate the joining of such an interdisciplinary team. In part I of this inquiry, the necessity for nutritional-constitutional researches are justified, problems are treated and mustering-statistics, the most important data-material, are collected for the political regions of that time from North to the kingdom Württemberg. The kingdom Württemberg of course is the political region with the most continuous data-series, but the data-material is poor on body-height-means and needs new statistical treatments. Less data are particularly available from the middle of the German settlement.

Anthropometry↗

[REN plot for a graphic expression method of clinical laboratory data statistics].

Laboratory data have been processed statistically on an assumption that they formed a normal distribution curve by themselves or after their transformation. The data of clinical medicine, however, frequently form distributions different from the normal one and thus they are not exactly represented by simple statistics such as mean and standard deviation. We used non-parametric percentiles(pct) as parameters for an improved expression of data distributions. The parameters used in this method are as follows: mean, 50 pct as median, 25 and 75pct as a concentration indicator, 5 and 95pct as a 90 percent central range, 2.5 and 97.5pct as a 95 percent central range, and minimum and maximum data as a distribution range. These indicators were presented on a new form of box-and-whisker plot. This expression was named as REN plot. Our method was compared to the other statistical expression methods using the data of control surveys of Factor IX activity of normal plasmas and prothrombin time of abnormal standard plasmas as well as APTT of abnormal plasma measured for intra-laboratory quality control. It was found that any form of data distribution, normal or abnormal, was precisely expressed in detail and the gradient of data densities were visually plotted by our method. Also neither the median, central range nor distribution range was influenced by extreme values. It was concluded that REN plot was useful expression for the statistical analysis of clinical laboratory data.

Adult↗

Intention-to-treat analyses for incomplete repeated measures data.

In a randomized longitudinal clinical trial designed to evaluate two or more rival treatments, an intent-to-treat analysis requires inclusion of all randomized patients, regardless of whether they remain on protocol for the duration of the study. We propose a piecewise linear random effects model for analyzing longitudinal data where the multivariate outcome can depend upon time spent on treatment. The model assumes that data are available on a random sample of subjects after treatment is terminated, and allows either a pragmatic or explanatory analysis (as defined by Schwartz and Lellouch, 1967, Journal of Chronic Diseases 20, 637-648). Full maximum likelihood estimation of the model parameters is carried out using widely available statistical software for repeated measures with missing data and for nonparametric survival curve estimation. Data from a national, multicenter pediatric AIDS clinical trial are analyzed to illustrate implementation and interpretation of the model.

Acquired Immunodeficiency Syndrome↗

Simple solution to a common statistical problem: interpreting multiple tests.

BACKGROUND: The misinterpretation of the results of multiple statistical tests is an error commonly made in scientific literature. When testing several outcome variables simultaneously, many researchers declare a statistically significant result for each test having a P value of <0.05, for example. This approach ignores the fact that, based on a probability result called the Bonferroni inequality, the risk of incorrectly declaring as significant > or =1 test result increases with the number of tests conducted. The implication of this practice is that many scientific results are presented as statistically significant when the underlying data do not adequately support such a claim (sometimes referred to as false-positive results). Although the sequentially rejective Bonferroni test is well known among statisticians, it is not used routinely in scientific literature. OBJECTIVE: The intent of this article was to increase the awareness and understanding of the sequentially rejective Bonferroni test, thereby expanding its use. METHODS: This article describes the statistical problem and demonstrates how the use of the sequentially rejective Bonferroni test ensures that incorrect declarations of statistical significance for > or =1 test result are bounded by 0.05, for example. CONCLUSION: The sequentially rejective Bonferroni test is an easily applied, versatile statistical tool that enables researchers to make simultaneous inferences from their data without risking an unacceptably high overall type I error rate.

Confidence Intervals↗

Genetic variation at the porcine MYF-5 gene locus. Lack Of association with meat production traits.

The number of muscle fibers at birth appears to determine the maximal lean meat growth capacity in pigs and in cattle. Development of muscle fibers is regulated by the MyoD gene family consisting of MyoD1, myf-5, myf-6, and myogenin. Myf-5 is expressed in proliferating myoblasts. Here we report the genomic sequence of the porcine myf-5 gene with three microsatellites and two RFLPs located close to the coding sequences. Two of the microsatellites are located in the promoter region. The allelic distribution differs between breeds and selection lines. In two GY selection lines, 1216 pigs of two-generation families were genotyped for the HinfI RFLP, which was segregating in the GY breed. The other polymorphic loci are physically linked to this RFLP locus, and therefore the results can be extrapolated to these loci. Statistical analysis revealed no association with birth weight, growth rate, weight at slaughter age, carcass meat weight, and backfat thickness. Thus, in this study myf-5 did not explain genetic variation in meat (muscle) development in pigs.

Animals↗

Statistical heterogeneity in systematic reviews of clinical trials: a critical appraisal of guidelines and practice.

OBJECTIVE: Heterogeneity between study results can be a problem in any systematic review or meta-analysis of clinical trials. Identifying its presence, investigating its cause and correctly accounting for it in analyses all involve difficult decisions for the researcher. Our objectives were: to collate recommendations on the subject of dealing with heterogeneity in systematic reviews of clinical trials; to investigate current practice in addressing heterogeneity in Cochrane reviews; and to compare current practice with recommendations. METHODS: We review guidelines for those undertaking systematic reviews and examine how heterogeneity is addressed in practice in a sample of systematic reviews, and their protocols, from the Cochrane Database of Systematic Reviews. RESULTS: Advice to reviewers is on the whole consistent and sensible. However, examination of a sample of Cochrane protocols and reviews demonstrates that the advice is difficult to follow given the small numbers of studies identified in many systematic reviews, the difficulty of pre-specifying important effect modifiers for subgroup analysis or meta-regression and the unresolved debate concerning fixed versus random effects meta-analyses. There was disagreement between protocols and reviews, often either regarding choice of important potential effect modifiers or due to the review identifying too few studies to perform planned analyses. CONCLUSION: Guidelines that address practical issues are required to reduce the risk of spurious findings from investigations of heterogeneity. This may involve discouraging statistical investigations such as subgroup analyses and meta-regression, rather than simply adopting a cautious approach to their interpretation, unless a large number of studies is available. The notion of a priori specification of potential effect modifiers for a retrospective review of studies is ill-defined, and the appropriateness of using a statistical test for heterogeneity to decide between analysis strategies is suspect.

Clinical Protocols↗

The impact of extreme prematurity and congenital anomalies on the interpretation of international comparisons of infant mortality.

OBJECTIVE: To identify the potential impact that different definitions of live births and practice patterns have on infant mortality rates in England and Wales, France, Japan, and the United States. METHODS: United States data were obtained from the 1986 linked national birth-infant death cohort, and those for the other countries came from either published sources or directly from the Ministries of Health. RESULTS: In 1986 in the United States, infants weighing less than 1 kg accounted for 36% of deaths (32% white and 46% black); 32% resulted from fatal congenital anomalies. These rates were much higher in both categories than in England and Wales in 1990 (24 and 22%, respectively), France in 1990 (15 and 25%, respectively), and Japan in 1991 (9% for infants weighing less than 1 kg, percentage of fatal congenital anomalies unknown). These cases are more likely to be excluded from infant mortality statistics in their countries than in the United States. CONCLUSIONS: In 1990, the United States infant mortality rate was 9.2 per 1000 live births, ranking the United States 19th internationally. However, infant mortality provides a poor comparative measure of reproductive outcome because there are enormous regional and international differences in clinical practices and in the way live births are classified. Future international and state comparisons of reproductive health should standardize the definition of a live birth and fatal congenital anomaly, and use weight-specific fetal-infant mortality ratios and perinatal statistics.

Birth Weight↗