Biomedical subjects

Geert Molenberghs

Publications and source records attributed to Geert Molenberghs.

39 records · Page 3Linked to original sources

PubMed2002

Statistical challenges in the evaluation of surrogate endpoints in randomized trials.

The validation of surrogate endpoints has been studied by Prentice, who presented a definition as well as a set of criteria that are equivalent if the surrogate and true endpoints are binary. Freedman et al. supplemented these criteria with the so-called proportion explained. Buyse and Molenberghs proposed to replace the proportion explained by two quantities: (1). the relative effect, linking the effect of treatment on both endpoints, and (2). the adjusted association, an individual-level measure of agreement between both endpoints. In a multiunit setting, these quantities can be generalized to a trial-level measure of surrogacy and an individual-level measure of surrogacy. In this paper, we argue that such a multiunit approach should be adopted because it overcomes difficulties that necessarily surround validation efforts based on a single trial. These difficulties are highlighted.

Endpoint Determination↗

PubMed2002

Investigating the criterion validity of psychiatric symptom scales using surrogate marker validation methodology.

This work investigates whether techniques that are generally used for the validation of surrogate markers in clinical trials can be applied in the validation of psychiatric health measurements (often scales) and more generally to investigate relationships between treatment effects on different measurements. However, the categorical nature of some scales makes these techniques inapplicable in the way they were originally defined. In this work, we show a possible extension of this methodology to the setting in which one of the scales is an ordinal categorical variable. When psychiatric health measurements are either developed or used in a new population, reliability and validity must be investigated. Reliability, more specifically internal consistency, test-retest reliability, and inter-rater reliability, is focused on the reproducibility of the measurement. Validity is defined as the degree to which the scale measures what it purports to measure. This can be performed through the analysis of content, construct, and criterion validity. We argue that recent methodology, in particular developed to study surrogate endpoints, can be used to examine criterion validity, concurrent validity, and predictive validity. In concurrent validity, we correlate the measurement with a criterion measure, both of which are given at the same time. In predictive validity, the criterion will not be available to some point in time in the future. The surrogate methods were applied on pooled data from five trials in schizophrenia.

Clinical Trials as Topic↗

PubMed2002

Strategies to fit pattern-mixture models.

Whereas most models for incomplete longitudinal data are formulated within the selection model framework, pattern-mixture models have gained considerable interest in recent years (Little, 1993, 1994). In this paper, we outline several strategies to fit pattern-mixture models, including the so-called identifying restrictions strategy. Multiple imputation is used to apply this strategy to realistic settings, such as quality-of-life data from a longitudinal study on metastatic breast cancer patients.

Journal Article↗