Alzheimers Dement. 2024 Dec;20 Suppl 6:e083432. doi: 10.1002/alz.083432.
ABSTRACT
An overview is given of surrogate marker evaluation, starting from the original definition of Prentice and his criteria, the estimation framework of Freedman, the meta-analytic framework, and the evaluation of surrogate endpoints from a causal inference point of view. Attention will be given, in particular, to evaluating tau-PET as a reasonably likely surrogate in Alzheimer’s Disease. A meta-analytic surrogate marker evaluation approach will be followed, for a continuous surrogate and a continuous true endpoint. Provisions are made to use both clinical trial data as well as natural history (real world) data. The statistical analysis consists of two steps: (1) a federated step where every site analyzes its own data, according to this protocol and the software provided; (2) a central step where the data hub processes the model outputs from the first step. The federated data analysis is a framework. As such, it can be applied based on a variety of choices made. Such choices pertain to patient population (e.g., early versus later stage), cognitive scale used (or, alternatively, sub-scale or custom-made item set), and particular tau PET measurement used (e.g., with variation over region of interest). A number of possible extensions are discussed too, as well as a single-trial evaluation method to complement the federated meta-analysis.
PMID:39782495 | DOI:10.1002/alz.083432
