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Background: Composite measures, like the Disease Activity Score for 28 joints (DAS28), are key primary outcomes in rheumatoid arthritis (RA) trials. DAS28 combines four different components in a continuous measure. When one or more of these components are missing the overall composite score is also missing at intermediate or trial endpoint assessments. Objectives: This study examined missing data patterns and mechanisms in a longitudinal RA trial to evaluate how best to handle missingness when analysing composite outcomes. Design: The Tumour-Necrosis-Factor Inhibitors against Combination Intensive Therapy (TACIT) trial was an open label, pragmatic randomized multicentre two arm non-inferiority study. Patients were followed up for 12 months, with monthly measurement of the composite outcome and its components. Active RA patients were randomized to conventional disease modifying drugs (cDMARDs) or Tumour Necrosis Factor-α inhibitors (TNFis). Methods: The TACIT trial was used to explore the extent of missing data in the composite outcome, DAS28. Patterns of missing data in components and the composite outcome were examined graphically. Longitudinal multivariable logistic regression analysis assessed missing data mechanisms during follow-up. Results: Two hundred and five patients were randomized: at 12 months 59/205 (29%) had unobserved composite outcome and 146/205 (71%) had an observed DAS28 outcome; however, 34/146 had one or more intermediate assessments missing. We observed mixed missing data patterns, especially for the missing composite outcome due to one component missing rather than patient not attending thier visit. Age and gender predicted missingness components, providing strong evidence the missing observations were unlikely to be Missing Completely at Random (MCAR). Conclusion: Researchers should undertake detailed evaluations of missing data patterns and mechanisms at the final and intermediate time points, whether or not the outcome variable is a composite outcome. In addition, the impact on treatment estimates in patients who only provide data at milestone assessments need to be assessed. Trial Registration ISRCTN Number: 37438295 [ABSTRACT FROM AUTHOR]

Background. Disability questions require older people to report difficulties with everyday activities, using broad categorical responses. Relatively little is known about population group differences in the thresholds for reporting difficulty or inability with medium-distance mobility against tested mobility related performance. We aimed to estimate the thresholds on tested performance at which self-reports change from one category to another, across a range of sociodemographic subgroups. We also aimed to compare reported and tested performance across two national population studies. Methods. The samples were from the third O.S. National Health and Nutrition Examination Study (NHANES III) and the Longitudinal Aging Study Amsterdam (LASA). Measures of gait speed, chair stands, and peak expiratory flow rate in both studies yielded the validated index of mobility-related physical limitations (MOBLI). Latent probit models were used to estimate cutpoints (thresholds) on the index lot reporting difficulty or inability to walk a medium distance. Results. Thresholds for reporting difficulty or inability were studied by age, sex, race, educational level, and income in NHANES III. In models adjusting for the other factors, performance thresholds for reporting disability categories varied by age and income. The younger elderly persons in NHANES III on average reported difficulties or inabilities only when they reached a more severe level of tested limitation compared with older old persons. A similar pattern exists for those on higher incomes. For race, differences in threshold were present only for reporting inability, but not difficulty. Significant differences in thresholds were not present between groups defined by sex or for years of education. Comparisons between the NHANES and LASA studies show that lower reported mobility difficulty or inability prevalence in the Dutch sample is attributable both to reporting at higher levels of limitation and to better functioning. Conclusions. There is evidence of differences in thresholds for reporting mobility disability, especially across age and income groups in older Americans. Further work is needed to understand the perceptual, attitudinal, or environmental factors that cause these reporting differences.

In a number of special cases, it has been shown that categorization of a continuous explanatory variable for use in a regression model can lead to efficiency losses. Nevertheless, categorization remains a popular means of dealing with continuous variables, particularly in medical statistics. Two topics of current interest in medical statistics are subgroup effects in clinical trials and gene-environment interactions in genetic studies. In a regression model setting, these topics involve the examination of interaction effects, often between a binary explanatory variable and a continuous explanatory variable. In this article the efficiency losses associated with dichotomization of a continuous explanatory variable for the testing of such interaction effects are calculated and compared with those associated with the testing of main effects. It is shown that considerable additional efficiency loss can arise because of dichotomization in both a main effect and an interaction. The theoretical development is done in the context of exponential family models, thus also generalizing earlier results on efficiency loss for main effects. Some indication is also given of the losses in efficiency associated with more detailed categorization. The further impact of censoring in time-to-event models is investigated and shown to not alter the qualitative conclusions. The practical importance of the findings is illustrated through the analysis of data from a clinical trial in patients with prostate cancer. KEY WORDS: Categorization; Explanatory variables; Generalized linear model; Interaction; Pitman efficiency., 1. INTRODUCTION Regression models are widely used in many areas of applied statistics. However, there remains a reluctance, notable particularly in medical statistics, to use continuous explanatory variables, especially when [...]

In many studies, interest lies in determining whether members of the study population will undergo a particular event of interest. Such scenarios are often termed 'mover-stayer' scenarios, and interest lies in modelling two sub-populations of 'movers' (those who have a propensity to undergo the event of interest) and 'stayers' (those who do not). In general, mover-stayer scenarios within data sets are accounted for through the use of mixture distributions, and in this paper, we investigate the use of various random effects distributions for this purpose. Using data from the University of Toronto psoriatic arthritis clinic, we present a multi-state model to describe the progression of clinical damage in hand joints of patients with psoriatic arthritis. We consider the use of mover-stayer gamma, inverse Gaussian and compound Poisson distributions to account for both the correlation amongst joint locations and the possible mover-stayer situation with regard to clinical hand joint damage. We compare the fits obtained from these models and discuss the extent to which a mover-stayer scenario exists in these data. Furthermore, we fit a mover-stayer model that allows a dependence of the probability of a patient being a stayer on a patient-level explanatory variable. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Motivated by investigations of factors related to various patient-reported outcome measures in psoriatic arthritis patients, after controlling for the effect of disease activity on these outcomes, we outline an approach for dealing with a rapidly fluctuating explanatory variable in a multistate model. On the basis of a representation of this variable as an ordinal classification, we suggest the use of an expanded multistate model. We examine the bias in estimating effects associated with other variables via simulation for different modelling choices. We present an analysis of a motivating data set on physical functional disability in psoriatic arthritis patients. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Identifies an index of mobility-related limitations composed of physiological measures that are associated with reported mobility disability in elders. Groups of disability in older people; Analysis of the third National Health and Nutrition Examination Survey; Comparison of receiver operating characteristic curves between subsamples in difficulty and inability models.

It is well established that significant numbers of prisoners have psychosis, yet little is known of what happens to them over time. One hundred and forty prisoners with probable psychosis from the National Survey of Psychiatric Morbidity in Prisons were re-interviewed at one-year follow-up. During the follow-up year 10% (95% CI 2-17) were admitted to hospitals, detox or medium secure units. At follow-up, 65% (95% CI 52-77) had ‘caseness’ levels of current psychiatric illness, but less than a quarter had appointments with psychiatric professionals: for violent or sexual offenders, only 41% had such appointments. Three per cent of those released were in supported accommodation at follow-up. [ABSTRACT FROM AUTHOR]