Thank you all for your replies. Taken in isolation I agree with most of the points made. But, I'm unsure as to the extent to which we agree on the general issue: do you and your doctors wait for regulatory approval before acting, or do you act on incomplete theoretical reasoning, epidemiological data and animal studies?
Especially lacking, in my opinion, is a discussion of the opportunity cost of not moving early.
This is a general issue. But the issue of isradipine is a good one to discuss, because the issues are so clear. NICE (National Institute for Clinical Excellence) in the UK publish clinical guidelines. The one for hypertension recommends:
- Offer people aged under 55 years an ACE inhibitor or a low-cost ARB. If an ACE inhibitor is prescribed and is not tolerated (for example, because of cough), offer a low-cost ARB.
- Offer people aged over 55 years and black people of African or Caribbean family origin of any age a calcium-channel blocker (CCB). If a CCB is not suitable, for example because of oedema or intolerance, or if there is evidence of heart failure or a high risk of heart failure, offer a thiazide-like diuretic.
http://www.nice.org.uk/nicemedia/liv...6015/56015.pdf
This advice is given without taking into account PD. People presenting aged over 55 will get a calcium-channel blocker. People under 55 will normally not. But, in my opinion what is known about isradipine should be enough to lower this threshold age for PwP.
Measuring progression precisely is, indeed, difficult. And may be impossible if there are different subtypes of PD. But, great precision is not required in order to act. An estimate of progression can be made using a proxy measure. For PD this could be finger tapping rate or distance covered on foot in 10 minutes etc.. Do these give an exact measure of PD? No, of course, not. But, that is the wrong question. The right question is: Does using these measures give better results than not using them? Using proxy measures to act on is wrong only if they led to goal incongruent activity. In other words, for harm to be done, a potential therapy would have to show a decrease in the rate of decline of the proxy measure, walking speed say, but increase the true rate of progression. This is certainly possible, but in my opinion it is unlikely.
Finally, someone made the point that using isradipine in the hope that it decelerates the progression of PD is like clutching at straws. To some extent it is: but if you've nothing better to hold on to it makes sense. More positively, I stress that, properly engineered, and in just a few days, clothes, bridges and ocean-going boats can be made out of straw.
John