Measuring disease progression in early Parkinson disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) experience.
OBJECTIVE
Optimizing assessments of rate of progression in Parkinson disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents.


OBJECTIVE
To examine the value of measures of impairment, disability, and quality of life in assessing progression in early PD.


METHODS
Inception cohort analysis of data from 413 patients with early, untreated PD who were enrolled in 2 multicenter, randomized, double-blind clinical trials.


METHODS
Participants were randomly assigned to 1 of 5 treatments (67 received creatine, 66 received minocycline, 71 received coenzyme Q10, 71 received GPI-1485, and 138 received placebo). We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment.


METHODS
Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression.


RESULTS
After adjusting for baseline confounding variables with regard to the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score, the UPDRS Part III score, the modified Rankin Scale score, level of education, and treatment group, we assessed the rate of change for the following measurements: the UPDRS Part II score; the UPDRS Part III score; the Schwab and England Independence Scale score (which measures activities of daily living); the Total Functional Capacity scale; the 39-item Parkinson's Disease Questionnaire, summary index, and activities of daily living subscale; and version 2 of the 12-item Short Form Health Survey Physical Summary and Mental Summary. Variables reaching the statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid change (ie, worsening) in the UPDRS Part II score (hazard ratio, 1.15 [95% CI, 1.08-1.22] for 1 scale unit change per 6 months), the UPDRS Part III score (hazard ratio, 1.09 [95% CI, 1.06-1.13] for 1 scale unit change per 6 months), and the Schwab and England Independence Scale score (hazard ratio, 1.29 [95% CI, 1.12-1.48] for 5 percentage point change per 6 months) was associated with earlier need for symptomatic therapy.


CONCLUSIONS
AND RELEVANCE In early PD, the UPDRS Part II score and Part III score and the Schwab and England Independence Scale score can be used to measure disease progression, whereas the 39-item Parkinson's Disease Questionnaire and summary index, Total Functional Capacity scale, and the 12-item Short Form Health Survey Physical Summary and Mental Summary are not sensitive to change.


BACKGROUND
clinicaltrials.gov Identifiers: NCT00063193 and NCT00076492.
Struthers Parkinson's Center, Golden Valley, Minnesota.
Sotirios A
SA
Parashos
Division of Biostatistics, University of Texas at Houston.
Sheng
S
Luo
Department of Neurology, University of Rochester, Rochester, New York.
Kevin M
KM
Biglan
State University of New York, Downstate Medical Center, Brooklyn.
Ivan
I
Bodis-Wollner
Division of Biostatistics, University of Texas at Houston.
Bo
B
He
The Parkinson's Institute and Clinical Center, Sunnyvale, California.
Grace S
GS
Liang
VA Pacific Islands Health Care System, Honolulu, Hawaii.
G Webster
GW
Ross
Division of Biostatistics, University of Texas at Houston.
Barbara C
BC
Tilley
Department of Neurology, University of Maryland School of Medicine, Baltimore.
Lisa M
LM
Shulman
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009316:National Institutes of Health (U.S.); D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology*; D011788:Quality of Life; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States
C486238:GPI 1485; D016559:Tacrolimus