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Parametric vs. non-parametric statistics of low resolution electromagnetic tomography (LORETA).

This study compared the relative statistical sensitivity of non-parametric and parametric statistics of 3-dimensional current sources as estimated by the EEG inverse solution Low Resolution Electromagnetic Tomography (LORETA). One would expect approximately 5% false positives (classification of a normal as abnormal) at the P < .025 level of probability (two tailed test) and approximately 1% false positives at the P < .005 level. EEG digital samples (2 second intervals sampled 128 Hz, 1 to 2 minutes eyes closed) from 43 normal adult subjects were imported into the Key Institute's LORETA program. We then used the Key Institute's cross-spectrum and the Key Institute's LORETA output files (*.lor) as the 2,394 gray matter pixel representation of 3-dimensional currents at different frequencies. The mean and standard deviation *.lor files were computed for each of the 2,394 gray matter pixels for each of the 43 subjects. Tests of Gaussianity and different transforms were computed in order to best approximate a normal distribution for each frequency and gray matter pixel. The relative sensitivity of parametric vs. non-parametric statistics were compared using a "leave-one-out" cross validation method in which individual normal subjects were withdrawn and then statistically classified as being either normal or abnormal based on the remaining subjects. Log10 transforms approximated Gaussian distribution in the range of 95% to 99% accuracy. Parametric Z score tests at P < .05 cross-validation demonstrated an average misclassification rate of approximately 4.25%, and range over the 2,394 gray matter pixels was 27.66% to 0.11%. At P < .01 parametric Z score cross-validation false positives were 0.26% and ranged from 6.65% to 0% false positives. The non-parametric Key Institute's t-max statistic at P < .05 had an average misclassification error rate of 7.64% and ranged from 43.37% to 0.04% false positives. The nonparametric t-max at P < .01 had an average misclassification rate of 6.67% and ranged from 41.34% to 0% false positives of the 2,394 gray matter pixels for any cross-validated normal subject. In conclusion, adequate approximation to Gaussian distribution and high cross-validation can be achieved by the Key Institute's LORETA programs by using a log10 transform and parametric statistics, and parametric normative comparisons had lower false positive rates than the non-parametric tests.

Adolescent↗

Parametric modeling of DSC-MRI data with stochastic filtration and optimal input design versus non-parametric modeling.

In the paper MRI measurements are used for assessment of brain tissue perfusion and other features and functions of the brain (cerebral blood flow - CBF, cerebral blood volume - CBV, mean transit time - MTT). Perfusion is an important indicator of tissue viability and functioning as in pathological tissue blood flow, vascular and tissue structure are altered with respect to normal tissue. MRI enables diagnosing diseases at an early stage of their course. The parametric and non-parametric approaches to the identification of MRI models are presented and compared. The non-parametric modeling adopts gamma variate functions. The parametric three-compartmental catenary model, based on the general kinetic model, is also proposed. The parameters of the models are estimated on the basis of experimental data. The goodness of fit of the gamma variate and the three-compartmental models to the data and the accuracy of the parameter estimates are compared. Kalman filtering, smoothing the measurements, was adopted to improve the estimate accuracy of the parametric model. Parametric modeling gives a better fit and better parameter estimates than non-parametric and allows an insight into the functioning of the system. To improve the accuracy optimal experiment design related to the input signal was performed.

Animals↗

Parametric and non-parametric measures in the assessment of knee and hip osteoarthritis: interobserver reliability and correlation with radiology.

The aim of this study was to evaluate the interobserver reliability of parametric and non-parametric variables in the clinical assessment of hip and knee osteoarthritis (OA). Three rheumatologists examined 49 patients with different radiological stages of OA using different assessment tools such as a tape measure, a goniometer, a plurimeter and a hand-held pull gauge. The reliabilities of parametric variables calculated by analysis of variance (ANOVA) showed much higher values than the non-parametric ones calculated by Kendall's tau beta. The highest levels of correlation in hip OA between clinical functional tests and radiological changes were found for hip extension (r = 0.57; P < 0.01) and the Patrick sign (r = 0.54; P < 0.01) while in knee OA the highest correlations were found for knee circumference (r = 0.5; P < 0.01) and knee flexion (r = 0.035; P < 0.02). Knee muscle strength, as measured with a hand-held pull gauge, showed a high level of interobserver agreement (r = 0.79), but correlated poorly with radiological changes. In conclusion parametric variables of joint morphology as knee circumference of parametric variables of function as the Patrick sign should be preferred for assessing secondary endpoints in OA clinical trials.

Aged↗

Segmented regression with errors in predictors: semi-parametric and parametric methods.

We consider the estimation of parameters in a particular segmented generalized linear model with additive measurement error in predictors, with a focus on linear and logistic regression. In epidemiologic studies segmented regression models often occur as threshold models, where it is assumed that the exposure has no influence on the response up to a possibly unknown threshold. Furthermore, in occupational and environmental studies the exposure typically cannot be measured exactly. Ignoring this measurement error leads to asymptotically biased estimators of the threshold. It is shown that this asymptotic bias is different from that observed for estimating standard generalized linear model parameters in the presence of measurement error, being both larger and in different directions than expected. In most cases considered the threshold is asymptotically underestimated. Two standard general methods for correcting for this bias are considered; regression calibration and simulation extrapolation (simex). In ordinary logistic and linear regression these procedures behave similarly, but in the threshold segmented regression model they operate quite differently. The regression calibration estimator usually has more bias but less variance than the simex estimator. Regression calibration and simex are typically thought of as functional methods, also known as semi-parametric methods, because they make no assumptions about the distribution of the unobservable covariate X. The contrasting structural, parametric maximum likelihood estimate assumes a parametric distributional form for X. In ordinary linear regression there is typically little difference between structural and functional methods. One of the major, surprising findings of our study is that in threshold regression, the functional and structural methods differ substantially in their performance. In one of our simulations, approximately consistent functional estimates can be as much as 25 times more variable than the maximum likelihood estimate for a properly specified parametric model. Structural (parametric) modelling ought not be a neglected tool in measurement error models. An example involving dust concentration and bronchitis in a mechanical engineering plant in Munich is used to illustrate the results.

Bias↗

Coverage and precision of confidence intervals for area under the curve using parametric and non-parametric methods in a toxicokinetic experimental design.

PURPOSE: The coverage and precision of parametric Bailer-type confidence intervals (CIs) for area under the curve (AUC) was compared to nonparametric bootstrap confidence intervals. METHODS: Concentration-time data was simulated using Monte Carlo simulation under a toxicokinetic paradigm with sparse (SSC) and dense sampling (DSC) conditions. AUC was calculated using the trapezoidal rule and 95% CIs were computed using various parametric and nonparametric methods. RESULTS: Under SSC, the various parametric CIs contained the true population AUC with coverage probabilities ranging from 0.77 to 0.95 with low inter-subject variation (coefficient of variation (CV) = 15%) and from 0.82 to 0.95 with high inter-subject variation (CV = 50%). The nominal value should be close to 0.95. DSC tended to increase coverage by about 0.05. Bailer's method always produced the lowest coverage of all parametric CIs examined. Under SSC, bootstrap CIs had coverage probabilities ranging from 0.62 (CV = 15%) to 0.68 (CV = 50%). DSC increased coverage to 0.77. Parametric CIs were wider than their nonparametric counterparts, often giving lower CI estimates less than zero. Bailer's method and Bailer's method using the jackknife estimate of the standard error were the worst in this respect. Bootstrap CIs never had lower CI estimates less than zero. However, SSC tends to produce bootstrap distributions that are not continuous which, if used, may produce biased CI estimates. CONCLUSIONS: Bootstrap CI estimates were judged to be the "best". However, the limitations of the bootstrap should be clearly recognized and it should not be used indiscriminately. Examination of the bootstrap distribution for its degree of discreteness must be part of the statistical process.

Area Under Curve↗

Estimating technical efficiency in the hospital sector with panel data: a comparison of parametric and non-parametric techniques.

BACKGROUND: Policy makers are increasingly interested in developing performance indicators that measure hospital efficiency. These indicators may give the purchasers of health services an additional regulatory tool to contain health expenditure. OBJECTIVE: Using panel data, this study compares different parametric (econometric) and non-parametric (linear programming) techniques for the measurement of a hospital's technical efficiency. METHOD: This comparison was made using a sample of 17 Italian hospitals in the years 1996-9. RESULTS: Highest correlations are found in the efficiency scores between the non-parametric data envelopment analysis under the constant returns to scale assumption (DEA-CRS) and several parametric models. Correlation reduces markedly when using more flexible non-parametric specifications such as data envelopment analysis under the variable returns to scale assumption (DEA-VRS) and the free disposal hull (FDH) model. Correlation also generally reduces when moving from one output to two-output specifications. CONCLUSIONS: This analysis suggests that there is scope for developing performance indicators at hospital level using panel data, but it is important that extensive sensitivity analysis is carried out if purchasers wish to make use of these indicators in practice.

Cost Control↗

Comparison of parametric and non-parametric survival methods using simulated clinical data.

We derived three parametric survival models (the log-normal, log logit, and Weibull) from the clinical data of chemotherapy trials for stage II breast cancer. We then used these models to generate simulated survival data, which we analysed using both parametric (log-normal) and non-parametric (logrank, Gray-Tsiatis and Laska-Meisner) methods. With limited follow-up (5 years), the non-parametric tests had greater power than the log-normal model. This advantage diminished, however, with extended follow-up (15 years). Furthermore, only the log-normal model could distinguish reliably a survival advantage due to an increase in cured fraction from an advantage due to an increase in time to failure.

Breast Neoplasms↗

Testing for differences in changes in the presence of censoring: parametric and non-parametric methods.

Some commonly used parametric and non-parametric methods for analysing repeated measures with incomplete observations are briefly reviewed. The performances of these methods in the presence of completely random, as well as informative censoring are compared in simulated experiments generated under the linear random effects model with parameter values derived from realistic examples. The effects of some moderate model deviations are also compared. The results indicate that in the presence of informative censoring, the usual parametric and nonparametric methods derived under the assumption of random censoring could either suffer severe loss of power or provide false positive results. The conditional linear model for informative censoring when used in conjunction with the bootstrap variance estimation procedure performed well under both random and informative censoring mechanisms. The non-parametric procedure obtained by ranking the individual summary statistics, although not as efficient as the conditional linear model with robust variance, also performed relatively well in most situations. Therefore, in situations in which informative censoring is likely to occur it is important to select the proper method of analysis to test for the informativeness of censoring and to account for its effects.

Bias↗

Investigations into parametric analysis of data from in vivo micronucleus assays by comparison with non-parametric methods.

Data from micronucleus assays of 6 compounds were analysed by 3 non-parametric and 3 parametric methods. Two of the latter involved transformation of the data so several transformation strategies were investigated. It was concluded that the non-parametric Kolmogorov-Smirnov two-sample test was the most reliable method of analysis. None of the parametric solutions was entirely satisfactory. The Bayesian solution to the Behrens-Fisher problem of normal distributions with differing variances was an acceptable compromise after the data had been transformed by the inverse hyperbolic sine method applicable to negative binomials.

Animals↗

Parametric and non-parametric statistical analysis of DT-MRI data.

In this work parametric and non-parametric statistical methods are proposed to analyze Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) data. A Multivariate Normal Distribution is proposed as a parametric statistical model of diffusion tensor data when magnitude MR images contain no artifacts other than Johnson noise. We test this model using Monte Carlo (MC) simulations of DT-MRI experiments. The non-parametric approach proposed here is an implementation of bootstrap methodology that we call the DT-MRI bootstrap. It is used to estimate an empirical probability distribution of experimental DT-MRI data, and to perform hypothesis tests on them. The DT-MRI bootstrap is also used to obtain various statistics of DT-MRI parameters within a single voxel, and within a region of interest (ROI); we also use the bootstrap to study the intrinsic variability of these parameters in the ROI, independent of background noise. We evaluate the DT-MRI bootstrap using MC simulations and apply it to DT-MRI data acquired on human brain in vivo, and on a phantom with uniform diffusion properties.

Artifacts↗

Variance in parametric images: direct estimation from parametric projections.

Recent work has shown that it is possible to apply linear kinetic models to dynamic projection data in PET in order to calculate parameter projections. These can subsequently be back-projected to form parametric images--maps of parameters of physiological interest. Critical to the application of these maps, to test for significant changes between normal and pathophysiology, is an assessment of the statistical uncertainty. In this context, parametric images also include simple integral images from, e.g., [O-15]-water used to calculate statistical parametric maps (SPMs). This paper revisits the concept of parameter projections and presents a more general formulation of the parameter projection derivation as well as a method to estimate parameter variance in projection space, showing which analysis methods (models) can be used. Using simulated pharmacokinetic image data we show that a method based on an analysis in projection space inherently calculates the mathematically rigorous pixel variance. This results in an estimation which is as accurate as either estimating variance in image space during model fitting, or estimation by comparison across sets of parametric images--as might be done between individuals in a group pharmacokinetic PET study. The method based on projections has, however, a higher computational efficiency, and is also shown to be more precise, as reflected in smooth variance distribution images when compared to the other methods.

Animals↗

Robust parametric and semi-parametric spot fitting for spot array images.

In this paper we address the problem of reliably fitting parametric and semi-parametric models to spots in high density spot array images obtained in gene expression experiments. The goal is to measure the amount of label bound to an array element. A lot of spots can be modelled accurately by a Gaussian shape. In order to deal with highly overlapping spots we use robust M-estimators. When the parametric method fails (which can be detected automatically) we use a novel, robust semi-parametric method which can handle spots of different shapes accurately. The introduced techniques are evaluated experimentally.

Animals↗

Fully parametric and semi-parametric regression models for common events with covariate measurement error in main study/validation study designs.

The derivation of the likelihood function for binary data from two types of main study/validation study designs where model covariates are measured with error is elaborated. Rather than limiting consideration to a restricted family of models with convenient mathematical properties, we suggest that empirical considerations, customized to the data at hand, should drive model choices. The joint likelihood function for the main study, in which the covariates are measured with error, and the validation study, in which they are not, is maximized, and estimation and inference proceeds using standard theory. Although the choice of the measurement error model is driven by empirical considerations, the relatively small validation study sizes typically seen may lead to misspecification, resulting in bias in estimation and inference about exposure-disease relationships. By using a nonparametric form for the measurement error model, the resulting semi-parametric methods suggested by Robins, Rotnitzky, and Zhao (1994, Journal of the American Statistical Association 89, 864-866) and Robins, Hsieh, and Newey (1995, Journal of the Royal Statistical Society, Series B 57, 409-424) are free from bias due to misspecification of the measurement error model, trading efficiency for robustness as usual. These fully and semi-parametric methods are illustrated with a detailed example from a main study/validation study of the health effects of occupational exposure to chemotherapeutics among pharmacists (Valanis et al., 1993, American Journal of Hospital Pharmacy 50, 455-462). A constant, prevalence ratio model for common binary events, with gamma covariate measurement error, is derived and empirically verified by the available data. A careful reanalysis of the data, taking measurement error fully into account, leads to a threefold increase in the log relative risk and no loss of statistical power. The semi-parametric estimates are consistent with the parametric results, providing reassurance that important bias due to misspecification of the measurement error model is unlikely.

Analysis of Variance↗

Parametric and non-parametric estimation of speech formants: application to infant cry.

The present paper addresses the issue of correctly estimating the peaks in the speech envelope (formants) occurring in newborn infant cry. Clinical studies have shown that the analysis of such spectral characteristics is a helpful noninvasive diagnostic tool. In fact it can be applied to explore brain function at very early stage of child development, for a timely diagnosis of neonatal disease and malformation. The paper focuses on the performance comparison between some classical parametric and non-parametric estimation techniques particularly well suited for the present application, specifically the LP, ARX and cepstrum approaches. It is shown that, if the model order is correctly chosen, parametric methods are in general more reliable and robust against noise, but exhibit a less uniform behaviour than cepstrum. The methods are compared also in terms of tracking capability, since the signals under study are nonstationary. Both simulated and real signals are used in order to outline the relevant features of the proposed approaches.

Computer Simulation↗

Parametric and non-parametric tests for the overall comparison of several treatments to a control when treatment is expected to increase variability.

We consider the problem of making an overall comparison of several treatments to a control where experimental units are randomly assigned to either the 'control' group which receives no treatment or to one of k-1 'treatment' groups. We assume that the effect of the treatments is, if anything, a location shift possibly accompanied by an increase in scale relative to that of the control group. The ANOVA F test loses considerable power in such circumstances. A modification of the ANOVA F test has been proposed which uses the variance estimate from the controls in place of the usual pooled variance estimate. However, this modification has shortcomings when k exceeds two and the variances of the treatment groups are not inflated. We develop a combination procedure to avoid the pitfalls of the modified and usual F tests. We then propose parametric and non-parametric implementations of a likelihood ratio test that more efficiently incorporates the assumptions of this problem, yielding a test with a high power profile over a large range of normal alternatives. We use simulations to compare the power of the competing tests against several alternatives for normal and non-normal data.

Analysis of Variance↗

Constructing confidence intervals for cost-effectiveness ratios: an evaluation of parametric and non-parametric techniques using Monte Carlo simulation.

The statistic of interest in most health economic evaluations is the incremental cost-effectiveness ratio. Since the variance of a ratio estimator is intractable, the health economics literature has suggested a number of alternative approaches to estimating confidence intervals for the cost-effectiveness ratio. In this paper, Monte Carlo simulation techniques are employed to address the question of which of the proposed methods is most appropriate. By repeatedly sampling from a known distribution and applying the different methods of confidence interval estimation, it is possible to calculate the coverage properties of each method to see if these correspond to the chosen confidence level. As the results of a single Monte Carlo experiment would be valid only for that particular set of circumstances, a series of experiments was conducted in order to examine the performance of the different methods under a variety of conditions relating to the sample size, the coefficient of variation of the numerator and denominator of the ratio, and the covariance between costs and effects in the underlying data. Response surface analysis was used to analyse the results and substantial differences between the different methods of confidence interval estimation were identified. The methods, both parametric and non-parametric, which assume a normal sampling distribution performed poorly, as did the approach based on simply combining the separate intervals on costs and effects. The choice of method for confidence interval estimation can lead to large differences in the estimated confidence limits for cost-effectiveness ratios. The importance of such differences is an empirical question and will depend to a large extent on the role of hypothesis testing in economic appraisal. However, where it is suspected that the sampling distribution is skewed, normal approximation methods produce particularly poor results and should be avoided.

Computer Simulation↗

Comparing the areas under two correlated ROC curves: parametric and non-parametric approaches.

In order to compare the discriminatory effectiveness of two diagnostic markers the equality of the areas under the respective Receiver Operating Characteristic Curves is commonly tested. A non-parametric test based on the Mann-Whitney statistic is generally used. Weiand et al. (1989) present a parametric test based on normal distributional assumptions. We extend this test using the Box-Cox power family of transformations to non-normal situations. These three test procedures are compared in terms of significance level and power by means of a large simulation study. Overall we find that transforming to normality is to be preferred. An example of two pancreatic cancer serum biomarkers is used to illustrate the methodology.

Area Under Curve↗

The efficiency of health production: re-estimating the WHO panel data using parametric and non-parametric approaches to provide additional information.

The World Health Report 2000 focuses on the performance of health-care systems around the globe. The report uses efficiency measurement techniques to create a league table of health-care systems, highlighting good and bad performers. Efficiency is measured using panel data methods. This paper suggests that the WHO's estimation procedure is too narrow and that contextual information is hidden by the use of one method. This paper uses and validates a range of parametric and non-parametric empirical methods to measure efficiency using the WHO data. The rankings obtained are compared to the WHO league table and we demonstrate that there are trends and movements of interest within the league tables. We recommend that the WHO broaden its range of techniques in order to reveal this hidden information.

Delivery of Health Care↗