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.     

UNDERSTANDING THE DECISION TO PARTICIPATE IN A SURVEY

The lack of full participation in sample surveys threatens theinferential value of the survey method. We review a set of conceptualdevelopments and experimental findings that appear to be informativeabout causes of survey participation; offer an integration ofthat work with findings from the more traditional statisticaland survey methodological literature on nonresponse; and, giventhe theoretical structure, deduce potentially promising pathsof research toward the understanding of survey participation.     

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.     

Fast retraction of evidence in a probabilistic expert system

We present and justify a propagation algorithm to facilitate the simultaneous calculation, for every node in a probabilistic exper system of the distribution of the associated random quantity, conditional on all the evidence obtained about the remaining nodes.     

MEASURING LEVELS OF PARTY IDENTIFICATION DOES QUESTION ORDER MATTER?

This article examines whether asking the vote question beforeparty identification alters the strength of partisanship andits relationship to vote choice. It employs the 1992 BritishElection Survey, which included a random split half-sample experiment,and the 1992–93 American Election Study Panel, where thequestion order for party identification and the vote were changed.The results show that altering the question ordering had verylittle effect in Britain and no significant effect in the UnitedStates. These results are consistent with the notion that partyidentification is one of the more enduring and stable componentsof mass political behavior in both presidential and parliamentarysystems.     

Differences in preferred level of arousal in two sub-groups of problem gamblers: A preliminary report

Twelve problem poker machine players and thirteen horse race gamblers (20 males and 5 females; age range 28–69) completed a series of questionnaires which assessed levels of anxiety, their preferred state of arousal and their motivations to gamble. As predicted, problem poker machine gamblers were found to be more anxious and reported avoiding arousal more frequently than the horse race gamblers. Alternately, problem horse race gamblers were found to prefer heightened levels of arousal and appeared to gamble to achieve these optimal levels of arousal. However, there was no difference between the groups on proneness to boredom. The present results provide evidence which is consistent with the Reversal theory and its application to the field of problem gambling.