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

verfasst von

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).

Organisationseinheit(en)

Institut für Zellbiologie und Biophysik

Externe Organisation(en)

MS Forschungs- und Projektentwicklungs- gGmbH (MSFP)
Hochschule Hannover (HsH)

Typ

Artikel

Journal

Therapeutic Innovation and Regulatory Science

Band

57

Seiten

1217–1228

Anzahl der Seiten

12

ISSN

2168-4790

Publikationsdatum

11.2023

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Pharmakologie, Toxikologie und Pharmazie (sonstige), Öffentliche Gesundheit, Umwelt- und Arbeitsmedizin, Pharmakologie (medizinische)

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1007/s43441-023-00550-0 (Zugang: Offen)