Modeling mortality risk effects of cigarettes and smokeless tobacco: results from the National Health Interview Survey Linked Mortality File Data.

Background: Cigarettes and smokeless tobacco (SLT) products are among a wide range of tobacco products that are addictive and pose a significant health risk. In this study, we estimated smoking- and SLT use-related mortality hazard ratios (HRs) among U.S.

Pseudo maximum likelihood approach for the analysis of multivariate left-censored longitudinal data.

The linear mixed effects model based on a full likelihood is one of the few methods available to model longitudinal data subject to left censoring. However, a full likelihood approach is complicated algebraically because of the large dimension of the numeric computations, and maximum likelihood estimation can be computationally prohibitive when the data are heavily censored. Moreover, for mixed models, the complexity of the computation increases as the dimension of the random effects in the model increases.

CBER's Experience With Adaptive Design Clinical Trials.

There is considerable interest among pharmaceutical and other medical product developers in adaptive clinical trials, in which knowledge learned during the course of a trial affects ongoing conduct or analysis of the trial. When the FDA released a draft Guidance document on adaptive design clinical trials in early 2010, expectations were high that it would lead to an increase in regulatory submissions involving adaptive design features, particularly for confirmatory trials. A 6-year (2008-2013) retrospective survey was performed within the Center for Biologics Evaluation and Research (CBER) at the FDA to gather information regarding the submission and evaluation of adaptive design trial proposals.