Implementation of the EM Algorithm for Maximum Likelihood Estimation of a Random Effects Model for One Longitudinal Ordinal Outcome

2010 Mathematics Subject Classification: 62J99.Longitudinal data arise when we have repeated measures on subjects over time. The correlated probit model is frequently used for ordered longitudinal data since it allows to seamlessly incorporate different correlation structures. The estimation of the probit model parameters based on direct maximization of the limited information maximum likelihood is a numerically intensive procedure especially when we have repeated measures on subjects. We propose an extension of the EM algorithm for obtaining maximum likelihood estimates for one ordinal longitudinal outcome. The algorithm is implemented in the free software environment for statistical computing and graphics R. We use simulations to examine the performance of the developed algorithm and apply the model to data from the Health and Retirement Study (HRS). We apply a bootstrap approach for standard error approximation. Advantages of the presented algorithm include the potential of dealing with high-dimensional random effects and of extending the algorithm to combinations of ordinal and continuous longitudinal outcomes

Em Algorithm for MLE of a Probit Model for Multiple Ordinal Outcomes

The correlated probit model is frequently used for multiple ordered data since it allows to incorporate seamlessly different correlation structures. The estimation of the probit model parameters based on direct maximization of the limited information maximum likelihood is a numerically intensive procedure. We propose an extension of the EM algorithm for obtaining maximum likelihood estimates for a correlated probit model for multiple ordinal outcomes. The algorithm is implemented in the free software environment for statistical computing and graphics R. We present two simulation studies to examine the performance of the developed algorithm. We apply the model to data on 121 women with cervical or endometrial cancer. Patients developed normal tissue reactions as a result of post-operative external beam pelvic radiotherapy. In this work we focused on modeling the effects of a genetic factor on early skin and early urogenital tissue reactions and on assessing the strength of association between the two types of reactions. We established that there was an association between skin reactions and polymorphism XRCC3 codon 241 (C>T) (rs861539) and that skin and urogenital reactions were positively correlated. ACM Computing Classification System (1998): G.3

Naltrexone and combined behavioral intervention effects on trajectories of drinking in the COMBINE study

Objective—COMBINE is the largest study of pharmacotherapy for alcoholism in the United States to date, designed to answer questions about the benefits of combining behavioral and pharmacological interventions. Trajectory-based analyses of daily drinking data allowed identification of distinct drinking trajectories in smaller studies and demonstrated significant naltrexone effects even when primary analyses on summary drinking measures were unsuccessful. The objective of this study was to replicate and refine trajectory estimation and to assess effects of naltrexone, acamprosate and therapy on the probabilities of following particular trajectories in COMBINE. It was hypothesized that different treatments may affect different trajectories of drinking. Methods—We conducted exploratory analyses of daily indicators of any drinking and heavy drinking using a trajectory-based approach and assessed trajectory membership probabilities and odds ratios for treatment effects. Results—We replicated the trajectories (“abstainer”, “sporadic drinker”, “consistent drinker”) established previously in smaller studies. However, greater numbers of trajectories better described the heterogeneity of drinking over time. Naltrexone reduced the chance to follow a “nearly daily” trajectory and Combined Behavioral Intervention (CBI) reduced the chance to be in an “increasing to nearly daily” trajectory of any drinking. The combination of naltrexone and CBI increased the probability of membership in a trajectory in which the frequency of any drinking declined over time. Trajectory membership was associated with different patterns of treatment compliance. Conclusion—The trajectory-analyses identified specific patterns of drinking that were differentially influenced by each treatment and provided support for hypotheses about the mechanisms by which these treatments work

Baseline Trajectories of Drinking Moderate Acamprosate and Naltrexone Effects in the COMBINE Study: BASELINE TRAJECTORIES OF DRINKING IN COMBINE

The COMBINE Study evaluated the effects of acamprosate, naltrexone and the Combined Behavioral Intervention (CBI). In secondary analyses, our goals were to identify trajectories of any drinking prior to randomization, to characterize subjects in these trajectories, and to assess whether pre-randomization trajectories predict drinking outcomes and moderate treatment response

Baseline trajectories of heavy drinking and their effects on postrandomization drinking in the COMBINE Study: empirically derived predictors of drinking outcomes during treatment

The COMBINE Study sought to answer questions about the benefits of combining behavioral and pharmacological interventions (naltrexone and acamprosate) in alcohol-dependent patients. Our goals were to identify trajectories of heavy drinking prior to randomization in COMBINE, to characterize subjects in these trajectories, and to assess whether pre-randomization trajectories predict drinking outcomes. We analyzed daily indicators of heavy drinking in 90 days prior to randomization using a trajectory-based approach. Each subject was assigned to the most-likely pre-randomization heavy drinking trajectory, and the baseline characteristics of participants in the baseline trajectories were compared. Main and interactive effects of these trajectories and treatment factors (acamprosate, naltrexone or CBI) on summary drinking measures during active treatment (16 weeks) were assessed. We identified five trajectories of heavy drinking pre-randomization: “T1: frequent heavy drinkers”, “T2: very frequent heavy drinkers”, “T3: nearly daily heavy drinkers”, “T4: daily heavy drinkers” and “T5: daily heavy drinkers stopping early” prior to randomization. Trajectory membership was significantly associated with all drinking outcomes. Subjects in “T5: daily heavy drinkers stopping early” had comparable drinking outcomes to the subjects in “T1: frequent heavy drinkers” while the remaining trajectories were associated with significantly worse outcomes. Baseline trajectory did not interact significantly with treatment condition. These exploratory analyses confirmed the hypothesis that baseline trajectories predict post-randomization drinking outcomes. Interestingly, “T5: daily heavy drinkers stopping early” had outcomes that were comparable to the least severe baseline trajectory “T1: frequent heavy drinkers” and baseline trajectories of heavy drinking did not moderate treatment effects

Reducing the duration of untreated psychosis and its impact in the U.S.: the STEP-ED study

Background: Early intervention services for psychotic disorders optimally interlock strategies to deliver: (i) Early Detection (ED) to shorten the time between onset of psychotic symptoms and effective treatment (i.e. Duration of Untreated Psychosis, DUP); and (ii) comprehensive intervention during the subsequent 2 to 5 years. In the latter category, are teams (‘First-episode Services’ or FES) that integrate several empirically supported treatments and adapt their delivery to younger patients and caregivers. There is an urgent need to hasten access to established FES in the U.S. Despite improved outcomes for those in treatment, these FES routinely engage patients a year or more after psychosis onset. The Scandinavian TIPS study was able to effectively reduce DUP in a defined geographic catchment. The guiding questions for this study are: can a U.S. adaptation of the TIPS approach to ED substantially reduce DUP and improve outcomes beyond existing FES? Methods/Design The primary aim is to determine whether ED can reduce DUP in the US, as compared to usual detection. ED will be implemented by one FES (STEP) based in southern Connecticut, and usual detection efforts will continue at a comparable FES (PREPR) serving the greater Boston metropolitan area. The secondary aim is to determine whether DUP reduction can improve presentation, engagement and early outcomes in FES care. A quasi-experimental design will compare the impact of ED on DUP at STEP compared to PREPR over 3 successive campaign years. The campaign will deploy 3 components that seek to transform pathways to care in 8 towns surrounding STEP. Social marketing approaches will inform a public education campaign to enable rapid and effective help-seeking behavior. Professional outreach and detailing to a wide variety of care providers, including those in the healthcare, educational and judicial sectors, will facilitate rapid redirection of appropriate patients to STEP. Finally, performance improvement measures within STEP will hasten engagement upon referral. Discussion STEP-ED will test an ED campaign adapted to heterogeneous U.S. pathways to care while also improving our understanding of these pathways and their impact on early outcomes. Trial registration ClinicalTrials.gov: NCT02069925. Registered 20 February 2014