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Iris Pigeot

Publications and source records attributed to Iris Pigeot.

7 recordsLinked to original sources
PubMed2007

Multivariate time-to-event analysis of multiple adverse events of drugs in integrated analyses.

In each clinical trial the statistical evaluation of adverse events (AEs) is a major part of standard safety analyses. However, the analyses of AEs usually lack from adequately accounting for the occurrence of multiple, different AEs. Furthermore, predictive variables other than treatment such as age, sex and concomitant medication are often ignored. These issues can be addressed by the Cox regression as introduced by Andersen and Gill and Wei et al. A further issue arises from the fact that an ordered programme of studies is conducted during clinical testing of pharmaceutical drugs. In this paper, we therefore discuss a stratified multivariate Cox regression model that can be used in integrated summaries of safety. We derive partial maximum likelihood estimators of the model parameters which can be shown to be consistent and asymptotically normally distributed. Mainly based on a sandwich estimator of their covariance matrix several test statistics are proposed that can be used to test various null hypotheses on the underlying parameters. Their asymptotic null distributions are given. The benefit of this survival time approach for analysing AEs is illustrated by evaluating symptoms of common cold from the database of a clinical development project.

Alzheimer Disease↗
PubMed2006

Testing for association in the presence of population stratification: a simulation study comparing the S-TDT, STRAT and the GC.

A novel approach for association testing in the presence of population stratification has been introduced by Pritchard et al. (2000a) and Pritchard et al. (2000b). The structured association approach is a two-tiered procedure that first estimates the population structure and then tests the null hypothesis H0: 'no association within subpopulations' in the second step. A power comparison of the stratified test for association (STRAT) (Pritchard et al., 2000b) and the Transmission-Disequilibrium-Test (TDT) (Spielman and Ewens, 1993a) in a simulation framework showed superiority of STRAT if allele frequencies or associations between allele and disease differ strongly in subpopulations. In more homogeneous situations, the TDT had greater power than STRAT. However, the TDT, based on family trios,that uses population controls, needs 50% more genotyping compared to STRAT. The Sib-Transmission-Disequilibrium-Test (S-TDT) needs the same amount of genotyping since it relays in its minimal configuration on pairs of siblings. This raises the question how the S-TDT (Spielman and Ewens, 1998a) performs compared to the population based methods STRAT and Genomic Controls (GC). In this paper, we present a simulation study accounting for two different models of population stratification in different settings of allele frequencies and under different risk models. The results showed that under a discrete as well as under an admixed population model, STRAT strongly outperformed the S-TDT and the GC when different alleles were associated in different subpopulations. In contrast, the S-TDT had greater power than STRAT when the same allele was associated in both subpopulations. Here, the GC was sometimes even more powerful than the S-TDT, depending on the population model and the allele frequency differences. A general recommendation for the use of one of the tests can therefore not be given.

Algorithms↗
PubMed2005

Establishing efficacy of a new experimental treatment in the 'gold standard' design.

Provided that there are no ethical concerns, the comparison of an active drug with placebo in a randomized two-arm clinical trial provides the most convincing way to demonstrate the efficacy of a new experimental treatment. However, in a placebo-controlled clinical trial it is not sufficient to demonstrate merely a statistically significant treatment difference. Regulatory authorities strongly recommend to assess additionally whether the observed treatment difference is also of clinical relevance. The inherent issue is the necessity of the a priori definition of what constitutes a clinically relevant difference in efficacy. This problem can be solved in a three-arm study by including an active control group. We address the necessary conditions in the gold standard design which allow the claim of efficacy for the new treatment with particular focus on assay sensitivity.

Algorithms↗
PubMed2003

Assessing non-inferiority of a new treatment in a three-arm clinical trial including a placebo.

In non-inferiority trials, where non-inferiority of a new experimental drug compared to an active control has to be shown, it may be advisable to use an additional placebo group for internal validation if ethically justifiable. The focus of this paper is on such designs. Assuming normality and homogeneity of variances we will derive a statistical test procedure which turns out to be equivalent to the assessment based on Fieller's confidence interval. Based on the power function of this test, sample size calculations are carried out to achieve a given power. Additionally, the optimal allocation of the total sample size is derived. As an alternative to this parametric procedure, the bootstrap percentile interval is discussed and finally compared with Fieller's confidence interval in a study on mildly asthmatic patients.

Anti-Asthmatic Agents↗
PubMed2003

Undernutrition in Benin-an analysis based on graphical models.

Undernutrition is one of the most important health problems in developing countries. Examining its determinants implies the investigation of a complex association structure including a large number of potential influence variables and different types of influences. A recently developed statistical technique to cope with such situations are graphical chain models. In this paper, this approach is used to investigate the determinants of undernutrition in Benin (West Africa). Since this method also reveals indirect influences, interesting insight is gained into the association structure of all variables incorporated. The analysis identifies mother's education, socioeconomic status, and religion as three variables with particularly strong direct and indirect linkages to undernutrition.

Anthropometry↗