Covariate Decomposition Methods for Longitudinal Missing‐at‐Random Data and Predictors Associated with Subject‐Specific Effects

Investigators often gather longitudinal data to assess changes in responses over time within subjects and to relate these changes to within‐subject changes in predictors. Missing data are common in such studies and predictors can be correlated with subject‐specific effects. Maximum likelihood methods for generalized linear mixed models provide consistent estimates when the data are ‘missing at random’ (MAR) but can produce inconsistent estimates in settings where the random effects are correlated with one of the predictors. On the other hand, conditional maximum likelihood methods (and closely related maximum likelihood methods that partition covariates into between‐ and within‐cluster components) provide consistent estimation when random effects are correlated with predictors but can produce inconsistent covariate effect estimates when data are MAR. Using theory, simulation studies, and fits to example data this paper shows that decomposition methods using complete covariate information produce consistent estimates. In some practical cases these methods, that ostensibly require complete covariate information, actually only involve the observed covariates. These results offer an easy‐to‐use approach to simultaneously protect against bias from both cluster‐level confounding and MAR missingness in assessments of change.     

Bias due to Ignoring the Sample Design in Case–Control Studies

Case–control studies allow efficient estimation of the associations of covariates with a binary response in settings where the probability of a positive response is small. It is well known that covariate–response associations can be consistently estimated using a logistic model by acting as if the case–control (retrospective) data were prospective, and that this result does not hold for other binary regression models. However, in practice an investigator may be interested in fitting a non–logistic link binary regression model and this paper examines the magnitude of the bias resulting from ignoring the case–control sample design with such models. The paper presents an approximation to the magnitude of this bias in terms of the sampling rates of cases and controls, as well as simulation results that show that the bias can be substantial.     

Some linear and nonlinear rank tests for competing risks models

Using the methods of asymptotic decision theory asymptotically optimal for translation and scale families as well as for certian nonparmetric families. Moreover, two new classes of nonlinear rank tests are introduced. These tests are designed for detecting either “ omnibus alternatives ” or “ one sided alternatives of trend ”. Under the null hypothesis of randomness all tests are distribution - free. The asymptotic distributions of the test statistics are derived under contiguous alternatives.     

Dependence Estimation for Marginal Models of Multivariate Survival Data

We have previously(Segal and Neuhaus, 1993) devised methods for obtaining marginal regression coefficients and associated variance estimates for multivariate survival data, using a synthesis of the Poisson regression formulation for univariate censored survival analysis and generalized estimating equations (GEE's). The method is parametric in that a baseline survival distribution is specified. Analogous semiparametric models, with unspecified baseline survival, have also been developed (Wei, Lin and Weissfeld, 1989; Lin, 1994).Common to both these approaches is the provision of robust variances for the regression parameters. However, none of this work has addressed the more difficult area of dependence estimation. While GEE approaches ostensibly provide such estimates, we show that there are problems adopting these with multivariate survival data. Further, we demonstrate that these problems can affect estimation of the regression coefficients themselves. An alternate, ad hoc approach to dependence estimation, based on design effects, is proposed and evaluated via simulation and illustrative examples. This revised version was published online in July 2006 with corrections to the Cover Date.     

Repeated chi-square testing

A sequentialized version of the x²; goodness of fit test, called repeated x,²; test, is introduced. The form of the asymptotic distribution of the repeated x² test statistic is given under the null hypothesis as well as under local alternatives. For various numbers of cells Monte Carlo results are given for critical values, power and distribution of stopping time. Finally, the perfor-mance of the repeated and the fixed sample x² test are compared.     

Asymptotically optimal rank tests for the two-sample problem with randomly censored data

Using the methods of asymptotic decision theory asymptotically optimal rank tests are constructed in the two-sample testing problem for translation families and positive scale families under the assumption of equal censoring in both samples. The resulting tests have a simple form extending the known tests for un-censored data in a natural way. Relations to a recent proposal by Albers and Akritas are discussed.     

The inter-rater reliability and validity of self-report of risk factors for cumulative trauma disorders within the hand therapist population - a pilot study

OBJECTIVES: This study examined the validity of hand therapists' self-report of cumulative trauma disorder (CTD) risk factors by comparing the self-report to observations performed by the raters. Inter-rater reliability was also analyzed between the raters who observed the hand therapists. STUDY DESIGN: Two raters simultaneously observed each hand therapist during a splinting task at a therapy facility. Following this task, the raters and the hand therapist independently completed an identical assessment tool. Thirteen therapists were observed and a total of six raters observed the therapists. Responses from two categories of the self-assessment, "posture" and "mechanical stress", were compared. Percentage of agreement was calculated by dividing the number of like responses by the total number of possible responses for each category. RESULTS: Overall inter-rater reliability was 72%, significantly above the accepted minimum standard of 60-70%, and validity was 39%, significantly below the accepted minimum. CONCLUSION: The high percentage of inter-rater reliability established consistency and accuracy among the raters in their observations. However, the low percentage of validity should prompt hand therapists to investigate the accuracy of a patient's self-report before relying on it for treatment.     

Closure of the class of binary generalized linear models in some non-standard settings

This paper considers fitting generalized linear models to binary data in nonstandard settings such as case–control samples, studies with misclassified responses and misspecified models. We develop simple methods for fitting models to case–control data and show that a closure property holds for generalized linear models in the nonstandard settings, i.e. if the responses follow a generalized linear model in the population of interest, then so will the observed response in the non-standard setting, but with a modified link function. These results imply that we can analyse data and study problems in the non-standard settings by using classical generalized linear model methods such as the iteratively reweighted least squares algorithm. Example data illustrate the results.     

Robust estimation for longitudinal data under outcome‐dependent visit processes

In longitudinal data where the timing and frequency of the measurement of outcomes may be associated with the value of the outcome, significant bias can occur. Previous results depended on correct specification of the outcome process and a somewhat unrealistic visit process model. In practice, this will never exactly be the case, so it is important to understand to what degree the results hold when those assumptions are violated in order to guide practical use of the methods. This paper presents theory and the results of simulation studies to extend our previous work to more realistic visit process models, as well as Poisson outcomes. We also assess the effects of several types of model misspecification. The estimated bias in these new settings generally mirrors the theoretical and simulation results of our previous work and provides confidence in using maximum likelihood methods in practice. Even when the assumptions about the outcome process did not hold, mixed effects models fit by maximum likelihood produced at most small bias in estimated regression coefficients, illustrating the robustness of these methods. This contrasts with generalised estimating equations approaches where bias increased in the settings of this paper. The analysis of data from a study of change in neurological outcomes following microsurgery for a brain arteriovenous malformation further illustrate the results.     

Conditions for consistent estimation in mixed-effects models for binary matched-pairs data

Parametric mixed-effects logistic models can provide effective analysis of binary matched-pairs data. Responses are assumed to follow a logistic model within pairs, with an intercept which varies across pairs according to a specified family of probability distributions G. In this paper we give necessary and sufficient conditions for consistent covariate effect estimation and present a geometric view of estimation which shows that when the assumed family of mixture distributions is rich enough, estimates of the effect of the binary covariate are typically consistent. The geometric view also shows that under the conditions for consistent estimation, the mixed-model estimator is identical to the familar conditional-likelihood estimator for matched pairs. We illustrate the findings with some examples.