Type I error rates from likelihood‐based repeated measures analyses of incomplete longitudinal data

The last observation carried forward (LOCF) approach is commonly utilized to handle missing values in the primary analysis of clinical trials. However, recent evidence suggests that likelihood‐based analyses developed under the missing at random (MAR) framework are sensible alternatives. The objective of this study was to assess the Type I error rates from a likelihood‐based MAR approach – mixed‐model repeated measures (MMRM) – compared with LOCF when estimating treatment contrasts for mean change from baseline to endpoint (Δ). Data emulating neuropsychiatric clinical trials were simulated in a 4 × 4 factorial arrangement of scenarios, using four patterns of mean changes over time and four strategies for deleting data to generate subject dropout via an MAR mechanism. In data with no dropout, estimates of Δ and SE_Δ from MMRM and LOCF were identical. In data with dropout, the Type I error rates (averaged across all scenarios) for MMRM and LOCF were 5.49% and 16.76%, respectively. In 11 of the 16 scenarios, the Type I error rate from MMRM was at least 1.00% closer to the expected rate of 5.00% than the corresponding rate from LOCF. In no scenario did LOCF yield a Type I error rate that was at least 1.00% closer to the expected rate than the corresponding rate from MMRM. The average estimate of SE_Δ from MMRM was greater in data with dropout than in complete data, whereas the average estimate of SE_Δ from LOCF was smaller in data with dropout than in complete data, suggesting that standard errors from MMRM better reflected the uncertainty in the data. The results from this investigation support those from previous studies, which found that MMRM provided reasonable control of Type I error even in the presence of MNAR missingness. No universally best approach to analysis of longitudinal data exists. However, likelihood‐based MAR approaches have been shown to perform well in a variety of situations and are a sensible alternative to the LOCF approach. MNAR methods can be used within a sensitivity analysis framework to test the potential presence and impact of MNAR data, thereby assessing robustness of results from an MAR method. Copyright © 2004 John Wiley & Sons, Ltd.     

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.     

One parent or two? The intertwining of American marriage and fertility patterns

Marriage and fertility in the United States have become less firmly entwined as more women bear children without marrying and more couples with children divorce. Today a sizeable number of children are expected to spend a portion of their childhood in one-parent households. Despite the trends in illegitimacy and divorce, the actual effect of out-of-wedlock childbearing on the living arrangements of children has not been fully explicated. Using the National Survey of Family Growth Cycle III, this paper estimates the probability that children aged 0–13 in 1982 are living in two-parent households, controlling for their mothers' marital statuses at their births. We find that marital status at birth is an important predictor of household structure at later ages for both white and black populations; however, the childhood environment is actually quite elastic as women marry, divorce, remarry, and redivorce.     

Setting operational goals for corporate social responsibility

In this article the author argues that more formality in social responsibility planning efforts is a concept which is extremely pertinent in today's conditions. Rewards will accrue to the organization that can move beyond aesthetic objectives and achieve operationality in social responsibility goal setting. This requires, basically, the application of techniques that have proved to be successful in MBO programs. By translating broadly stated social objectives into goals that are clear, concise, time related and cost related, management will inject an increased measure of integrity into its planning process, improve social responsibility programs, assure future successes in the social performance arena, facilitate the appraisal of management personnel, and enhance the organization's credibility with its multiple publics. Positive benefits will flow to the organization, its immediate publics, and to the society at large as a consequence of operational planning methods as described herein.     

The recruitment and selection of hospital medical consultants

Abstract

The literature on selection has been dominated in recent decades by the ‘prediction’ paradigm. Such an approach requires a substantial number of positions to be filled in order to compute validity coefficients. There are other approaches, using a different paradigm, when concentrated on adjusting the organization and the employee. Here careful analysis of job demands is essential. This article describes such an analysis, taking the medical consultant as an example. The method can be used in an iterative way. It is useful when one has to work with small numbers of positions.     

Methods to assess measurement error in questionnaires of sedentary behavior

Sedentary behavior has already been associated with mortality, cardiovascular disease, and cancer. Questionnaires are an affordable tool for measuring sedentary behavior in large epidemiological studies. Here, we introduce and evaluate two statistical methods for quantifying measurement error in questionnaires. Accurate estimates are needed for assessing questionnaire quality. The two methods would be applied to validation studies that measure a sedentary behavior by both questionnaire and accelerometer on multiple days. The first method fits a reduced model by assuming the accelerometer is without error, while the second method fits a more complete model that allows both measures to have error. Because accelerometers tend to be highly accurate, we show that ignoring the accelerometer's measurement error, can result in more accurate estimates of measurement error in some scenarios. In this article, we derive asymptotic approximations for the mean-squared error of the estimated parameters from both methods, evaluate their dependence on study design and behavior characteristics, and offer an R package so investigators can make an informed choice between the two methods. We demonstrate the difference between the two methods in a recent validation study comparing previous day recalls to an accelerometer-based ActivPal.     

Bayesian variable selection approach to a Bernstein polynomial regression model with stochastic constraints

This paper provides a Bayesian estimation procedure for monotone regression models incorporating the monotone trend constraint subject to uncertainty. For monotone regression modeling with stochastic restrictions, we propose a Bayesian Bernstein polynomial regression model using two-stage hierarchical prior distributions based on a family of rectangle-screened multivariate Gaussian distributions extended from the work of Gurtis and Ghosh [7 S.M. Curtis and S.K. Ghosh, A variable selection approach to monotonic regression with Bernstein polynomials, J. Appl. Stat. 38 (2011), pp. 961–976. doi: 10.1080/02664761003692423[Taylor &; Francis Online], [Web of Science ®] , [Google Scholar]]. This approach reflects the uncertainty about the prior constraint, and thus proposes a regression model subject to monotone restriction with uncertainty. Based on the proposed model, we derive the posterior distributions for unknown parameters and present numerical schemes to generate posterior samples. We show the empirical performance of the proposed model based on synthetic data and real data applications and compare the performance to the Bernstein polynomial regression model of Curtis and Ghosh [7 S.M. Curtis and S.K. Ghosh, A variable selection approach to monotonic regression with Bernstein polynomials, J. Appl. Stat. 38 (2011), pp. 961–976. doi: 10.1080/02664761003692423[Taylor &; Francis Online], [Web of Science ®] , [Google Scholar]] for the shape restriction with certainty. We illustrate the effectiveness of our proposed method that incorporates the uncertainty of the monotone trend and automatically adapts the regression function to the monotonicity, through empirical analysis with synthetic data and real data applications.