Biomedical subjects

Joachim Hartung

Publications and source records attributed to Joachim Hartung.

4 recordsLinked to original sources

PubMed2006

Assessing the amount of heterogeneity in random-effects meta-analysis.

In a random-effects meta-analysis, a new confidence interval for the heterogeneity parameter is proposed. With this interval, the amount of heterogeneity in a meta-analysis can be assessed so that it can be judged whether the pooling of the estimates is meaningful. Through suitable corrections of the lower bound, based on the treatment effect measure of interest, the resulting interval yields satisfactory results with respect to the predefined confidence coefficient. Lower and upper bound of the interval can be used for one-sided hypothesis testing on the amount of the underlying between-trial variability.

Analysis of Variance↗

PubMed2006

Flexible designs by adaptive plans of generalized Pocock- and O'Brien-Fleming-type and by self-designing clinical trials.

Flexible designs are provided by adaptive planning of sample sizes as well as by introducing the weighted inverse normal combining method and the generalized inverse chi-square combining method in the context of conducting trials consecutively step by step. These general combining methods allow quite different weighting of sequential study parts, also in a completely adaptive way, based on full information from unblinded data in previously performed stages. So, in reviewing some basic developments of flexible designing, we consider a generalizing approach to group sequentially performed clinical trials of Pocock-type, of O'Brien-Fleming-type, and of Self-designing-type. A clinical trial may be originally planned either to show non-inferiority or superiority. The proposed flexible designs, however, allow in each interim analysis to change the planning from showing non-inferiority to showing superiority and vice versa. Several examples of clinical trials with normal and binary outcomes are worked out in detail. We demonstrate the practicable performance of the discussed approaches, confirmed in an extensive simulation study. Our flexible designing is a useful tool, provided that a priori information about parameters involved in the trial is not available or subject to uncertainty.

Clinical Trials as Topic↗

PubMed2006

Repeated confidence intervals in self-designing clinical trials and switching between noninferiority and superiority.

In self-designing clinical trials, repeated confidence intervals are derived for the parameter of interest where the results of the independent study stages are combined using the generalized inverse chi-square-method. The confidence intervals can be calculated at each interim analysis and always hold the predefined overall nominal confidence level. Moreover, the confidence intervals calculated during the course of the trial are nested in the sense that a calculated interval is completely contained in all the previously calculated intervals. During the course of the self-designing trial the sample sizes as well as the number of study stages can be determined simultaneously in a completely adaptive way. The adaptive procedure allows an early stop for significance. The clinical trial may be originally designed either to show noninferiority or superiority. However, in each interim analysis, it is possible to change the planning from showing superiority to showing noninferiority or vice versa. Since the repeated confidence intervals are nested, there is no risk to loose the noninferiority once showed when, after an interim analysis, the trial is continued in an attempt to reach superiority. A simulation study investigates the behavior of the considered confidence intervals. The performance of the derived nested repeated confidence intervals is also demonstrated in examples showing both kinds of switching during an ongoing trial.

Biometry↗

PubMed2003

Improved tests for a random effects meta-regression with a single covariate.

The explanation of heterogeneity plays an important role in meta-analysis. The random effects meta-regression model allows the inclusion of trial-specific covariates which may explain a part of the heterogeneity. We examine the commonly used tests on the parameters in the random effects meta-regression with one covariate and propose some new test statistics based on an improved estimator of the variance of the parameter estimates. The approximation of the distribution of the newly proposed tests is based on some theoretical considerations. Moreover, the newly proposed tests can easily be extended to the case of more than one covariate. In a simulation study, we compare the tests with regard to their actual significance level and we consider the log relative risk as the parameter of interest. Our simulation study reflects the meta-analysis of the efficacy of a vaccine for the prevention of tuberculosis originally discussed in Berkey et al. The simulation study shows that the newly proposed tests are superior to the commonly used test in holding the nominal significance level.

Analysis of Variance↗