Placebo-associated improvements in motor function: comparison of subjective and objective sections of the UPDRS in early Parkinson's disease.
The Unified Parkinson's Disease Rating Scale (UPDRS) is primarily composed of an investigator-derived objective rating of motor function and a patient-derived assessment of activities of daily living (ADL). Using a stringent definition of placebo effect, we examined the frequency, temporal development, and stability of improvements during placebo treatment over 6 months in a large placebo-controlled trial of deprenyl and tocopherol in early Parkinson's disease (DATATOP). One hundred ninety-nine subjects received placebo treatment in the randomized, multicenter, placebo-controlled DATATOP study. We compared the baseline UPDRS motor section scores with follow-up scores at 4, 13, and 26 weeks. Placebo-associated improvement was defined as an improvement over baseline score in motor UPDRS of at least 50% or a change in at least two motor items at any one visit by two or more points. Seventeen percent of the 185 subjects who qualified for analysis met the placebo response criteria. The group prevalence of response was steady (7% to 10%) at any one visit without a marked predominance of an early study effect. Older subjects with more motor impairment at baseline were most likely to show a placebo-associated improvement. ADL scores were low throughout the study, and ADL improvements did not identify the subjects with objectively defined placebo-associated improvement. Prominent improvements in investigator-derived objective measures of Parkinson's disease motor impairment occur during clinical trials, including one that was not aimed at showing improved short-term efficacy. Although the notion of placebo effect often implies patient-based perceptions, we found subjective changes to be infrequent in placebo-treated patients, suggesting that either: (1) the placebo effect was rater-driven; (2) the ADL questionnaire is insensitive to transient but objectively demonstrable motor changes; or (3) that the objective changes, albeit major, are within the realm of natural variation in the UPDRS motor scale from visit to visit.
Goetz
Christopher G
CG
Department of Neurological Sciences Rush University, Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois 60612, USA. cgoetz@rush.edu
Leurgans
Sue
S
Raman
Rema
R
D000203:Activities of Daily Living / Q000145:classification*; D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009048:Motor Skills / Q000187:drug effects*; D009460:Neurologic Examination / Q000187:drug effects*; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy*; D015990:Placebo Effect; D012642:Selegiline / Q000009:adverse effects / Q000627:therapeutic use; D024505:Tocopherols / Q000009:adverse effects / Q000627:therapeutic use
D000978:Antiparkinson Agents; D012642:Selegiline; D024505:Tocopherols