Mapping homicide by 3-D modelling of bloodstain patterns at crime scene.

Background: Three-dimensional (3-D) modelling can be a useful technical aid and we used it to reconstruct a homicide scene to corroborate the statement of an eyewitness. 3-D modelling of the bloodstain was conducted by Micro Smith Poser 11 and Autodesk 3-Ds Max software. The technique was found to be easily understandable by the police and judiciary in the interpretation of the sequence of the events of the crime.

Methods and software tools for design evaluation in population pharmacokinetics-pharmacodynamics studies.

Population pharmacokinetic (PK)-pharmacodynamic (PKPD) models are increasingly used in drug development and in academic research; hence, designing efficient studies is an important task. Following the first theoretical work on optimal design for nonlinear mixed-effects models, this research theme has grown rapidly. There are now several different software tools that implement an evaluation of the Fisher information matrix for population PKPD.

An adaptive optimal design for the E(max) model and its application in clinical trials.

A project team working on a compound to treat Alzheimer's disease is carrying out a first-time-in-human dose-escalation study in patients. The team wished to maximize the efficiency of the study by using doses targeted at maximizing information about the dose-response relationship within certain safety constraints. We have developed an adaptive optimal design tool to recommend doses when the response follows an E(max) model, with functionality for pretrial simulation and in-stream analysis.

Population pharmacokinetic measures, their estimation and selection of sampling times.

In pharmacokinetic (PK) studies, including bioavailability assessment, various population PK measures, such as area under the curve (AUC), maximal concentration (C(max)) and time to maximal concentration (T(max)) are estimated. In this paper we compare a model-based approach, where parameters of a compartmental model are estimated and the explicit formulae for PK measures are used, and a model-independent approach, where numerical integration algorithms are used for AUC and sample estimates for C(max) and T(max). Since regulatory agencies usually require the model-independent estimation of PK measures, we focus on the empirical approach while using the model-based approach and corresponding measures as a benchmark.

Practical usage of O'Brien's OLS and GLS statistics in clinical trials.

Multivariate techniques of O'Brien's OLS and GLS statistics are discussed in the context of their application in clinical trials. We introduce the concept of an operational effect size and illustrate its use to evaluate power. An extension describing how to handle covariates and missing data is developed in the context of Mixed models.

Sample size calculation for the Power Model for dose proportionality studies.

There are several approaches to assess or demonstrate pharmacokinetic dose proportionality. One statistical method is the traditional ANOVA model, where dose proportionality is evaluated using the bioequivalence limits. A more informative method is the mixed effects Power Model, where dose proportionality is assessed using a decision rule for the estimated slope.

Methods of selecting informative variables.

We propose a new method for selection of the most informative variables from the set of variables which can be measured directly. The information is measured by metrics similar to those used in experimental design theory, such as determinant of the dispersion matrix of prediction or various functions of its eigenvalues. The basic model admits both population variability and observational errors, which allows us to introduce algorithms based on ideas of optimal experimental design.

Optimal population designs for PK models with serial sampling.

In various pharmaceutical applications, repeated measurements are taken from each subject, and model parameters are estimated from the collected data. Examples include dose response modeling and PK/PD studies with serial blood sampling, among others. The quality of the information in an experiment is reflected in the precision of estimates of model parameters, which is traditionally measured by their variance-covariance matrix.