A blinded, controlled trial of objective measurement in Parkinson's disease

Abstract

Medical conditions with effective therapies are usually managed with objective measurement and therapeutic targets. Parkinson's disease has effective therapies, but continuous objective measurement has only recently become available. This blinded, controlled study examined whether management of Parkinson's disease was improved when clinical assessment and therapeutic decisions were aided by objective measurement. The primary endpoint was improvement in the Movement Disorder Society-United Parkinson's Disease Rating Scale's (MDS-UPDRS) Total Score. In one arm, objective measurement assisted doctors to alter therapy over successive visits until objective measurement scores were in target. Patients in the other arm were conventionally assessed and therapies were changed until judged optimal. There were 75 subjects in the objective measurement arm and 79 in the arm with conventional assessment and treatment. There were statistically significant improvements in the moderate clinically meaningful range in the MDS-UPDRS Total, III, IV scales in the arm using objective measurement, but not in the conventionally treated arm. These findings show that global motor and non-motor disability is improved when management of Parkinson's disease is assisted by objective measurement.

Fig. 1. Flow chart showing study design.

The first clinical visit and assessment (A) occurs leads to a decision of either “not in target”, treatment change and further clinical assessments or “in target” (B) and clinical scales that constitute the last or final visit. If the subject is still not in target in 5 weeks (C), then the subject exits the study (final visit).

Fig. 2. Change in MDS-UPDRS III from first to final visit against MDS-UPDRS III at first visit.

The difference between the MDS-UPDRS III at the first and final visit against the severity of MDS-UPDRS III at the first visit (X-axis). Plots are box and whiskers (centre line: median, bounds of box:25th and 75th percentile and whisker: 10th and 90th percentile) and white boxes indicating the PKG+ arm and the grey boxes the PGK− arm. P values are from Mann–Whitney test.

Fig. 3. Clinical and PKG scores when “out of target” due to bradykinesia at first visit.

These are box and whiskers plots (centre line: median, bounds of box: 25th and 75th percentile and whisker: 10th and 90th percentile) of MDS-UPDRS III, MDS-UPDRS IV, MDS-UPDRS Total, mBKS, Percent time over target (PTOT) and PDQ39 of the first and last visit in the PKG+ arm (white, first visit and light grey, last visit) and PKG− arm (dark grey, first visit and black, last visit) of cases reported as being out of target because of bradykinesia at the first visit. *, ** and *** indicate P < 0.05, P < 0.01 or P < 0.001, respectively, and n.s. indicates not significant (P > 0.05). The plot shows a significant reduction in all parameters in the PKG+ scores at last visit.

Fig. 4. Change in MDS-UPDRS produced by each doctor.

Panels a, b show the difference between the means (of the 1st and last visit) of the MDS-UPDRS III (a) and MDS-UPDRS total (b) for each doctor (each dot is a doctor and the bar is the SEM). White dots represent PKG+ doctors and black dots indicate PKG− doctors. The grey bands indicate the 95% CI of the whole population (PKG+ and PKG− respectively) with the horizontal line indicating the mean and the darker grey the IQR. Note that the 95% CI and SEM are smaller in the PKG+ arms.

Fig. 5. An example of part of a PKG.

This shows only the smoothed moving median of the DKS over a 6-day period (darker green line) and BKS (darker blue line) plotted against time of day (X-axis). The Y-axis shows the severity of DKS (increasing severity upward from the dark green line adjacent to the zero) and BKS (increasing severity downward from the dark blue line adjacent to the zero). The median BKS and DKS of non-PD subjects is shown with the arrow. The shaded green and blue zones show the target range. BKS in the shaded pink region are usually associated with inactivity. The vertical red lines are the times that reminders were delivered, and the diamonds show the time when consumption of medications was acknowledged. In this example the median BKS is outside of target at the time of the first dose. The response to each dose just reaches target and there is “wearing-OFF” after 2 h (1st dose) and ~3 h (2nd dose). This case was reported as having bradykinesia above target with “Bradykinesia only as Wearing Off” according to the 7-point classification described in the text.