Also interesting: https://www.michaeljfox.org/foundation/publication-detail.html?id=83&category=3
So, even though the 1 mg group met all its endpoints, the fact that the 2 mg group did not presents a conundrum. In their last paragraph, the authors of the paper write: “Given the negative findings for the 2 mg dose, we cannot definitively conclude that rasagiline at a dose of 1 mg per day has disease-modifying effects.”
MJFF: It’s difficult to understand why the higher dose would not achieve the same results as the lower dose.
KK: That’s true. There is some speculation that this had something to do with the symptomatic power of the 2 mg dosage. These trial enrollees were very early-stage patients. Perhaps the symptomatic benefit to those who started on the 2 mg dose resulted in such minimal symptoms that by the end you literally couldn’t see a difference between the treated group and the control group.
To test this hypothesis, the researchers separated the data for those participants on both 1 mg and 2 mg whose disability was more severe — a UPDRS score of 25 points or higher, still relatively mild in relation to PD overall but more severe in relation to the enrollees in this trial — and conducted the analysis on these data separately. In this after-the-fact analysis, both the 1 mg and 2 mg groups hit all three endpoints