My interest in this topic is that in the era of personalized medicine I see an advantage in being able to get to any position in the levodopa, carbidopa, entacapone state space. It seems to me that there is a vanishingly low probability that both you and I are optimally treated with a levodopa:carbidopa ratio of exactly 4:1, and an entacapone dose of exactly 200mg per L/C dose.

As far as I understand it, L/C/E has a scaling factor of 1.33 compared to L/C, so roughly speaking a 75mg Stalevo tablet has the same power as 100mg L/C. So, there is good reason to believe that E, taken with L, has a role to play

I'd like to see more attention paid to increasing the half-life of levodopa at a molecular level, rather than at the delivery level, e.g. Rytary, an approach that for some patients gives less consistent results than immediate release L/C.

A short half-life leads to big swings in plasma levodopa concentrations, taking people into dyskinesia territory. So, for instance, for later stage patients with little endogenous dopamine production and reservoirs, to get a continuous "on" with a new dose taken every 3 hours and a levodopa half-life of 90 minutes requires peak levels 4 times higher than those needed just to reach the "on" threshold.

Finally, although I don't think that it well supported, the paper by Hinz et al. [1], which links carbidopa to increased PD death rates, must give a cause for concern.

References:

[1] "The Parkinson’s disease death rate: carbidopa and vitamin B6"
Marty Hinz, Alvin Stein, and Ted Cole
Clinical Pharmacology, 2014
The Parkinson’s disease death rate: carbidopa and vitamin B6

John