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.     

Tomb, temple, machine and self: the social construction of the body.

The body is socially constructed; and in this paper we explore the various and ever-changing constructions of the body, and thus of the embodied self, from the Greeks to the present. The one word, body, may therefore signify very different realities and perceptions of reality; and we consider briefly how and why these meanings changed. Plato believed the body was a 'tomb', Paul said it was the 'temple' of the Holy Spirit, the Stoic philosopher Epictetus taught that it was a 'corpse'. Christians believed, and believe, that the body is not only physical, but also spiritual and mystical, and many believed it was an allegory of church, state and family. Some said it was cosmic: one with the planets and the constellations. Descartes wrote that the body is a 'machine', and this definition has underpinned biomedicine to this day; but Sartre said that the body is the self. In sum, the body has no intrinsic meaning. Populations create their own meanings, and thus their own bodies; but how they create, and then change them, and why, reflects the social body.     

BURR CRITICAL VALUE APPROXIMATIONS FOR TESTS OF AUTOCORRELATION AND HETEROSCEDASTICITY

The paper evaluates the accuracy of Burr approximations of critical values and p-values for test a of autocorrelation and heteroscedasticity in the linear regression model.     

The Pyramid Model: A Useful Tool in Career Counseling With University Students

Often university students are faced with career decisions and seek help from the university counseling center. The pyramid model is a useful tool to assist the counselor and the student in the decision-making process. The metaphor enables the student to understand the tasks that lie ahead in the career counseling process. It is holistic. A case study is included to illustrate the three-dimensional model of career counseling of university students.     

Earnings Inequality in the Nonmetropolitan United States: 1967–19901

Abstract Nonmetropolitan (nonmetro) inequality patterns are contrasted with those of metropolitan (metro) areas to assess the utility of neoclassical and restructuring theoretical frameworks. Inequality measures are constructed from March Current Population Surveys for the years 1968–1991. Results indicate that inequality is greater in nonmetro areas than in metro areas. Results of decomposition procedures suggest that the observed inequality is due to a mix of neoclassical and restructuring factors that account for more inequality in metro than nonmetro areas. National policies must take account of metro/nonmetro differences in patterns and sources of inequality.     

Efe fathers: one among many? A comparison of forager children's involvement with fathers and other males

The study reported describes Efe (pygmy) forager one-, two-, and three-year-olds' involvement with males. The Efe of northeastern Zaïre were chosen because their social organization allows us to examine hypotheses based on studies in Western, technologically complex societies about the distinctive role fathers play in the lives of their young children. Behavioral observations of Efe children's day-to-day activities with fathers, men and boys were recorded using a focal subject sampling technique (Altmann, 1974). Two behavioral measures were created to capture the extent to which males were involved with children: Social engagement describes males' involvement with children and social attention describes eavesdropping by children on males' everyday activities. Eight one-year-olds, 7 two-year-olds and 8 three-year-olds were each observed for six, one-hour observation sessions that were distributed evenly over the daylight hours. Data were analyzed using the traditional measure of involvement (e.g., adult males) and using a newly developed measure of the involvement of the average individual (e.g., average adult mate). Comparisons at each of the ages showed that fathers were consistently like other men in the extent to which children participated in social activities with them and watched their activities. Only fathers' level of social engagement declined significantly as children grew older. Boys' role relative to other males became increasingly distinctive as children aged. The findings suggest that Efe fathers may not be unique in the same sense assumed by Western study ideals, and raise questions about the special status given to fathers in Western theory and data. The patterning of mate involvement with children is discussed in terms of Efe community life, and in terms of Efe children's developing understanding of their relationship with fathers and other males.     

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.