A toolbox of different approaches to analyze and present PRO-CTCAE data in oncology studies
Menée à partir des données d'un essai clinique de phase II évaluant le bélantamab mafodotine pour traiter un myélome multiple, cette étude examine plusieurs méthodes statistiques et techniques de visualisation pour améliorer la présentation et l'analyse des données concernant les effets indésirables symptomatiques rapportés par les patients à l'aide de critères terminologiques standard
Background : The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is used to assess symptomatic adverse events in oncology trials. Currently, no standard for PRO-CTCAE analysis exists.
Methods : Key methods of descriptive analysis and longitudinal modelling using PRO-CTCAE data from an oncology clinical trial, DREAMM-2, a Phase II trial of belantamab mafodotin in multiple myeloma (NCT03525678), were explored. Descriptive methods included maximum post-baseline ratings, mean change over time, ratings above a predefined cut-off, line graphs, and stacked bar charts to illustrate patient-reported adverse events at one timepoint or dynamics over time. Analysis methods involving modelling over time included toxicity over time (ToxT) (repeated measurement model, time-to-event, area under the curve analyses), generalized estimating equations (GEE), and ordinal log-linear models (OLLM).
Results : Visualizations of PRO-CTCAE data highlighted different aspects of the data. Selection of the appropriate visualization will depend on the audience and message to be conveyed. Consistent results were obtained by all modelling approaches; no difference was found between dose groups of the DREAMM-2 study in any PRO-CTCAE item by the ToxT approach or the more sophisticated GEE and OLLM methods. Interpretation of GEE results was the most challenging. OLLM supported the interval nature of the PRO-CTCAE response scale in the DREAMM-2 study. All modelling approaches account for multiple testing (driven by the number of items).
Conclusions : Descriptive analyses and longitudinal modelling approaches are complementary approaches to presenting PRO-CTCAE data. In modelling, the ToxT approach may be a good compromise compared with more sophisticated analyses.
Journal of the National Cancer Institute , article en libre accès, 2022