Choice of the primary analysis in longitudinal clinical trials

Missing data, and the bias they can cause, are an almost ever‐present concern in clinical trials. The last observation carried forward (LOCF) approach has been frequently utilized to handle missing data in clinical trials, and is often specified in conjunction with analysis of variance (LOCF ANOVA) for the primary analysis. Considerable advances in statistical methodology, and in our ability to implement these methods, have been made in recent years. Likelihood‐based, mixed‐effects model approaches implemented under the missing at random (MAR) framework are now easy to implement, and are commonly used to analyse clinical trial data. Furthermore, such approaches are more robust to the biases from missing data, and provide better control of Type I and Type II errors than LOCF ANOVA. Empirical research and analytic proof have demonstrated that the behaviour of LOCF is uncertain, and in many situations it has not been conservative. Using LOCF as a composite measure of safety, tolerability and efficacy can lead to erroneous conclusions regarding the effectiveness of a drug. This approach also violates the fundamental basis of statistics as it involves testing an outcome that is not a physical parameter of the population, but rather a quantity that can be influenced by investigator behaviour, trial design, etc. Practice should shift away from using LOCF ANOVA as the primary analysis and focus on likelihood‐based, mixed‐effects model approaches developed under the MAR framework, with missing not at random methods used to assess robustness of the primary analysis. Copyright © 2004 John Wiley & Sons, Ltd.     

Health technology assessment between our health care system and our health

In this contribution, I wish to explore the potential of health technology assessment and ethics for increasing our capacity to pre-empt the shortcomings and undesired consequences of modern health care while maintaining its benefits. Central is the presumption that in case of some health problems this cannot be done unless we explicitly reconsider some features of the modern health care system, especially those related to its strong reliance on scientific rationality and the strong role played by medical professionals. So as to both maintain the benefits of advanced health care and ensure that it produces less reason for concern, we need to reconsider our approach to rationality—and maybe even the way in which we build our health care system around that rationality. That is, we need to introduce an element of reflexivity. Two types of circumstances are being explored in which such reflexivity may prove worthwhile: controversies on side effects, and persistent problems encountered in optimising health care. Drawing on brief discussions of typical cases, we explore the potential of reflexive HTA and its methodical prerequisites. We conclude that ethicists may contribute to reflexive HTA, if they combine a hermeneutic—and often also participative—methodology with a solid understanding of the relation between the health problem under scrutiny and more general critique of the health care system. Insights from the areas of science and technology studies, as well as from social philosophy may be critical items in their tool kit.     

Facilitative Aspects of Field Research with Deviant Street Populations*

The authors examine facilitative aspects of field research with deviant street populations. Based on the authors' research with the homeless and with male street prostitutes, the facilitative aspects include access to settings, social relationships, acquisition of information, and the maintenance of researcher interest. The authors argue that in each of these aspects street deviants may in some ways be easier to study than other populations. The paper concludes with suggestions for maximizing the efficiency and quality of fieldwork with specific deviant populations.     

Campus attitudes toward alcohol and drugs in a deep southern university.

In our zeal to deal with alcohol and drug abuse, we may have a distorted picture of what the majority of college students actually think about alcohol and drug use. Students in this study done at a public university located in the Deep South report being generally intolerant of substance abuse.     

A modified random-effect procedure for combining risk difference in sets of 2×2 tables from clinical trials

Summary Meta-analyses of sets of clinical trials often combine risk differences from several 2×2 tables according to a random-effects model. The DerSimonian-Laird random-effects procedure, widely used for estimating the populaton mean risk difference, weights the risk difference from each primary study inversely proportional to an estimate of its variance (the sum of the between-study variance and the conditional within-study variance). Because those weights are not independent of the risk differences, however, the procedure sometimes exhibits bias and unnatural behavior. The present paper proposes a modified weighting scheme that uses the unconditional within-study variance to avoid this source of bias. The modified procedure has variance closer to that available from weighting by ideal weights when such weights are known. We studied the modified procedure in extensive simulation experiments using situations whose parameters resemble those of actual studies in medical research. For comparison we also included two unbiased procedures, the unweighted mean and a sample-size-weighted mean; their relative variability depends on the extent of heterogeneity among the primary studies. An example illustrates the application of the procedures to actual data and the differences among the results. This research was supported by Grant HS 05936 from the Agency for Health Care Policy and Research to Harvard University.     

Ideologies about work: An exploratory study

This paper focuses upon an as yet under-explored factor believed to underlie most managerial and organizational behavior variables—work ideology. Work ideologies are surveyed for several convenience samples of students and managers to show their ability to be studied and that patterned differences may be discovered. In addition, the historical origins and meanings of four major work ideologies are discussed.     

ROBUST METHODS FOR DEPENDENT CELL PEDIGREE DATA

This paper studies a robust approach to the analysis of cell pedigree data, building on the work of Huggins & Marschner (1991) which discussed M-estimation for the so-called bifurcating autoregressive process. The study allows for incomplete observation of the pedigree, and incorporates the possibility of additive effects outliers, as discussed in the time series literature. Some properties of the proposed estimation procedure are studied, including a Monte Carlo investigation of robustness in the presence of contamination.     

Generalized Laplacian approximations in Bayesian inference

This paper presents a new Laplacian approximation to the posterior density of η = g(θ). It has a simpler analytical form than that described by Leonard et al. (1989). The approximation derived by Leonard et al. requires a conditional information matrix R_η to be positive definite for every fixed η. However, in many cases, not all R_η are positive definite. In such cases, the computations of their approximations fail, since the approximation cannot be normalized. However, the new approximation may be modified so that the corresponding conditional information matrix can be made positive definite for every fixed η. In addition, a Bayesian procedure for contingency-table model checking is provided. An example of cross-classification between the educational level of a wife and fertility-planning status of couples is used for explanation. Various Laplacian approximations are computed and compared in this example and in an example of public school expenditures in the context of Bayesian analysis of the multiparameter Fisher-Behrens problem.