Time saved in disease progression for treatments in AD (including 3 monoclonal antibodies and 2 other promising treatments)

Abstract

AbstractBackgroundAlzheimer’s disease progression causes worsening on multiple symptoms of disease which can be measured by cognitive, functional and global scales. These scales can be thought of as surrogate outcomes for the true disease progression. The degenerative and therefore progressive nature of the disease indicates that time is a measurable gold standard against which we can assess all other outcomes. Composite endpoints and global statistical tests have been used to approximate this progression outcome since it is not directly measurable. Using time as the gold standard, one can calculate the alignment of any measure against the gold standard using a signal to noise ratio. A combination of the ADAS‐cog, ADCS‐ADL and CDR‐sb aligns more than 90% with the unmeasurable progression outcome.MethodConverting each of the clinical scales to a time scale allows us to measure progression in “disease progression” time: i.e. months of progression per month of treatment, which should be linear in nature despite any non‐linearity in the clinical scale. A recent meta‐analysis was performed and data from relevant studies have been estimated using an overall progression time metric.ResultResults for five studies of interest (three monoclonal antibodies and two other treatments) Aducanumab, Donanemab, Lecanemab, AD04, and Souvenaid show time savings range from 2 months per year to 7 months per year. Results for these five studies are presented in Table 1.ConclusionMeasuring time savings in a degenerative disease reflects the true goal of disease modifying treatments which is to slow down a progressive disease which will result in slowing of progression on all aspects or symptoms of disease. Progressive diseases would cease to be diseases at all if there was no progression of symptoms. Focusing on the clinical meaningfulness of each separate point on each outcome distracts us from this overall goal. Progression time savings is meaningful to patients, caregivers and all stakeholders and can be calculated from meaningful, clinically acceptable outcomes.