TY - JOUR
T1 - Rasagiline, Parkinson neuroprotection, and delayed-start trials
T2 - Still no satisfaction?
AU - Ahlskog, J. Eric
AU - Uitti, Ryan J.
PY - 2010/4
Y1 - 2010/4
N2 - Rasagiline has been studied as a Parkinson disease (PD) neuroprotective agent in 2 major clinical trials, utilizing the delayed-start design in an attempt to separate symptomatic drug benefits from a disease-modifying effect. The ostensibly positive outcomes of these studies, however, are obscured by potential confounding factors that seem intrinsic to this trial design, including 1) very small changes in clinical outcome measures that could easily be overshadowed by other influences; 2) probable incomplete blinding to study end; 3) subjective components of the Unified ParkinsonÊ's Disease Rating Scale (UPDRS) scoring system; and 4) practice influences from repeated scoring. Interpretation of the recent Attenuation of Disease Progression with Azilect Given Once-daily (ADAGIO) trials is especially problematic given 1) divergent results with the 2 symptomatically beneficial doses and 2) variability in UPDRS scores with active rasagiline, which was twice the magnitude of the major finding of the study. These studies further illustrate the difficulty in documenting a disease-modifying effect when considering a PD drug with symptomatic benefit.
AB - Rasagiline has been studied as a Parkinson disease (PD) neuroprotective agent in 2 major clinical trials, utilizing the delayed-start design in an attempt to separate symptomatic drug benefits from a disease-modifying effect. The ostensibly positive outcomes of these studies, however, are obscured by potential confounding factors that seem intrinsic to this trial design, including 1) very small changes in clinical outcome measures that could easily be overshadowed by other influences; 2) probable incomplete blinding to study end; 3) subjective components of the Unified ParkinsonÊ's Disease Rating Scale (UPDRS) scoring system; and 4) practice influences from repeated scoring. Interpretation of the recent Attenuation of Disease Progression with Azilect Given Once-daily (ADAGIO) trials is especially problematic given 1) divergent results with the 2 symptomatically beneficial doses and 2) variability in UPDRS scores with active rasagiline, which was twice the magnitude of the major finding of the study. These studies further illustrate the difficulty in documenting a disease-modifying effect when considering a PD drug with symptomatic benefit.
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U2 - 10.1212/WNL.0b013e3181d7d8e2
DO - 10.1212/WNL.0b013e3181d7d8e2
M3 - Review article
C2 - 20368634
AN - SCOPUS:77951017105
SN - 0028-3878
VL - 74
SP - 1143
EP - 1148
JO - Neurology
JF - Neurology
IS - 14
ER -