I would value a discussion of the usefulness of the MDS-UPDRS (Movement Disorder Society Unified Parkinson's Disease Rating Scale) [1] in measuring the efficacy of a new treatment for PD, especially one for which it is claimed to slow or even to reverse the progression of the disease.

The major claim for the exenatide trial [2] is that the difference between the treated group and the placebo group's MDS-UPDRS Part III score, while small, is statistically significant. (After 60 weeks, off medication scores were 1 point better for the exenatide group, compared to a worsening of 2.1 points for the placebo group). Most other measures, while in favour of exenatide, do not show significance.

The MDS-UPDRS Part III contains 18 questions. Some of which are repeated, for instance, for the left and right side, giving 33 scores in total. Each question is scored 0, 1, 2, 3, 4, where 0 represents normal (no symptoms) and 4 represents severe symptoms. A typical question is 3.17, rest tremor amplitude, where the score of 0 represents no tremor; 1, less than 1 cm maximal amplitude (MA); 2, 1cm<MA<3cm; 3, 3<=MA<=10cm; 4, MA>10. Four scores are given are given, one for each limb.

The individual scores are added together to get a MDS-UPDRS Part III total. Given the way the scoring is done, a low score is good, a high score is bad.

Part III does not measure the underlying disease (perhaps the number of dopaminergic neurons in the substantia nigra, though there are probably more deeply rooted measures). Neither does Part III directly measure the impact of PD on the quality of life of the patient.

The MDS-UPDRS Part III score is a proxy measure. It doesn't measure what we are really interested in (for instance, the quality of life, QOL), but it does usually point in the right direction: as the score decreases the QOL tends to improve.

The billion dollar question is:

Will MDS-UPDRS III give the right answers in discriminating between candidate treatments in a world where the differences in efficacy are small?

References:

[1] http://www.movementdisorders.org/MDS...S7308final.pdf

[2] "Exenatide once weekly versus placebo in Parkinson's Disease: a randomised, double-blind, placebo-controlled trial"
Thomas Foltynie et al.
The Lancet, August 2017.

John