THE VALIDITY OF BIOMARKERS AS SURROGATE ENDPOINTS IN ALZHEIMER’S DISEASE BY MEANS OF THE QUANTITATIVE SURROGATE VALIDATION LEVEL OF EVIDENCE SCHEME (QSVLES)

Objective: To evaluate the validity of biomarkers that are currently being proposed as potential surrogate endpoints in AD clinical trials with the aid of the “Quantitative Surrogate Validation Level of Evidence Schema” (QSVLES) proposed by Lassere et.al. (1). Procedure: A Pubmed literature search was conducted to identify AD biomarkers with SEP potential, and the QSVLES was applied to determine the extent of the SEP validity. Results: MRI, PET and MRS measures attained a total validity score of 4, NAA/Cre a total score of 5, and cerebral blood flow (SPECT), A , Tau and APP a total score of 2. None of these biomarkers could fall into the rank of Levels 1 or 2, reserved for SEPs, according to the QSVLES criteria. This was mainly attributed to the lack of sufficient evidence that was derived from high ranking studies (RCT, prospective observational studies). Conclusion: Though residing on SEPs as sole determinants of the benefit/risk ratio of AD medications seems to be pretty far, there could be certain cases where the use of SEPs may be beneficial, making efficient therapies available faster when there is a major public health interest involved. However, the potential risks of relying on invalid SEPs should not be underestimated and therefore the research on SEP validation and the development of specific validation guidance should be encouraged. The QSVLES, though not devoid of criticism, may be proposed as a starting point.