Application of Statistical Methods for Central Statistical Monitoring and Implementations on the German Multiple Sclerosis Registry

authored by: Firas Fneish, David Ellenberger, Niklas Frahm, Alexander Stahmann, Gerhard Fortwengel, Frank Schaarschmidt
Abstract: Monitoring of clinical trials is a fundamental process required by regulatory agencies. It assures the compliance of a center to the required regulations and the trial protocol. Traditionally, monitoring teams relied on extensive on-site visits and source data verification. However, this is costly, and the outcome is limited. Thus, central statistical monitoring (CSM) is an additional approach recently embraced by the International Council for Harmonisation (ICH) to detect problematic or erroneous data by using visualizations and statistical control measures. Existing implementations have been primarily focused on detecting inlier and outlier data. Other approaches include principal component analysis and distribution of the data. Here we focus on the utilization of comparisons of centers to the Grand mean for different model types and assumptions for common data types, such as binomial, ordinal, and continuous response variables. We implement the usage of multiple comparisons of single centers to the Grand mean of all centers. This approach is also available for various non-normal data types that are abundant in clinical trials. Further, using confidence intervals, an assessment of equivalence to the Grand mean can be applied. In a Monte Carlo simulation study, the applied statistical approaches have been investigated for their ability to control type I error and the assessment of their respective power for balanced and unbalanced designs which are common in registry data and clinical trials. Data from the German Multiple Sclerosis Registry (GMSR) including proportions of missing data, adverse events and disease severity scores were used to verify the results on Real-World-Data (RWD).
Organisation(s): Institute of Cell Biology and Biophysics
External Organisation(s): MS Forschungs- und Projektentwicklungs- gGmbH (MSFP)
University of Applied Sciences and Arts Hannover (HsH)
Type: Article
Journal: Therapeutic Innovation and Regulatory Science
Volume: 57
Pages: 1217–1228
No. of pages: 12
ISSN: 2168-4790
Publication date: 11.2023
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Public Health, Environmental and Occupational Health, Pharmacology (medical)
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Electronic version(s): https://doi.org/10.1007/s43441-023-00550-0 (Access: Open)