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.     

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.     

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.     

Will taxpayers ever like taxes?: Responses to the U.S. Tax Reform Act of 1986

Major policy changes like the 1986 Tax Reform Act (TRA) in the United States provide natural experiments to study attitudinal and behavior responses to law. Surprisingly, public evaluations of the TRA became increasingly negative after passage, while general support for the tax system became more positive in response to the changes. To explain this puzzle, we propose a dynamic model of taxpayer attitudes that is consistent with the observed loose linkage between logically-connected concepts. We briefly review the political context, objectives and impacts of the 1986 Tax Reform Act, and present several studies testing the impact of self-interest, prior beliefs, and social discussion on changes in attitudes and behavior.Results suggest that the complexity of taxes and difficulty in knowing objective impacts weakens the role of self-interest in attitudinal changes, thereby strengthening the role of prior beliefs and discussion. Evaluations of tax laws are most responsive to more politically-oriented influences.     

Effects of Medicaid managed care policies on mental health service use among a national probability sample of children in the child welfare system

Children in the child welfare system are dependent upon Medicaid to finance services for their considerable mental health needs. This study examines the effects of Medicaid policies on mental health service use among a national probability sample of children in the child welfare system. Data for this study came from the National Survey of Child and Adolescent Well-Being, the Caring for Children in Child Welfare study, and the Area Resource File. Weighted multivariate logistic regression analyses were conducted to estimate effects of policy variables on children's use of mental health services, controlling for child-level covariates and county-level health resources. Children in counties with behavioral carve-outs under Medicaid managed care had lower odds of inpatient mental health service use. Medicaid managed care enrollment and variations in type of provider reimbursement did not affect use of mental health services. Older age, greater need for mental health services, and higher levels of caregiver education were associated with increased odds of service use. Restrictions on use of inpatient mental healthcare caused by behavioral carve-outs may disproportionately affect children in the child welfare system who have high rates of such use. Careful adoption of carve-outs is necessary to assure appropriate care for these children.     

Individualised Support and Funding: building blocks for capacity building and inclusion

The paradigm in disability supports is shifting away from institutional services and professional control towards self-determination and community involvement of people with disabilities. The assumption that the best way to provide disability supports is for government to give money to agencies or services, rather than directly to people with disabilities and their support networks, is being challenged. This article reports on findings and themes from a Canadian study that investigated individualised funding projects from different parts of the world. Ten of fifteen of the most 'promising initiatives' were selected for more detailed study and analysis. Projects analysed were from Canada, the US, and Australia. Themes emerging from the study included the fact that values and principles mattered, a policy framework provided coherence and equity, infrastructure supports for individuals were separate from service system, the facilitator-broker role differed from case management, allocation of individualised funds was designed to be equitable and account able to the funder and person, and a 'learn as you go' philosophy maximised positive outcomes. This research project demonstrates that individualised support and funding, when embedded in the new paradigm of disability and community, builds capacity of individuals, families, and communities.     

Integrating Career and Personal Counseling

Career and personal counseling are inextricably intertwined. Career problems have a strong emotional component. Career indecision and procrastination may be better interpreted as zeteophobia, the fear of career exploration. Trait and factor theory pictures career counseling as unrealistically simplistic and leads neophytes to view it as boring. Training all counselors to integrate career and personal counseling would lead to better service for clients.