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There is a paradigm shift underway with more than half a dozen genetically determined PDs known (three of them Finnish alone) with more being searched after. We can probably talk safely about PD in plural and think of it as an evolving concept. Ansa Ojanlatva, PhD, CHES (ret.) Docent, Health and Sexuality Education Sanitas 3rd floor Lemminkäisenkatu 1 20014 University of Turku, Finland mobile +358-400-823 816 tel +358-2-333 8515 fax +358-2-333 8439 Please use the mobile phone number for calling. ----- Original Message ----- From: Greg Wasson <[log in to unmask]> Date: Monday, July 14, 2008 12:10 pm Subject: Re: Spheramine - Another Promising "Failure": Is It Time Reassess Clinical Trial Design? To: [log in to unmask] > Hi Moneesha, > > Thank you for sharing your doctor's thoughts with us. It's good to > know that > some in the medical community are doing some serious rethinking about > what we > have traditionally been satisfied to call "idiopathic Parkinson's disease." > > If the "several variants" hypothesis is correct, it would further > explain why > the big successes are found in small open label Phase I trials, and almost > always fail in subsequent larger phase II and III trials. It's because > the odds > of picking at random five or six people (as in the Spheramine open > label phase > I trial) most or all of whom happen to have the same or a close > disease variant > and therefore would respond similarly to a particular therapeutic application, > are long but not impossible. So occasionally we have what appear to be > "winners" in Phase I. But those "winners" will almost always lose when > the > patient population increases to 40 or 70 people, because of the odds against > randomly picking a 70 patient cohort all of whom have the same or closely > matching disease variants increases enormously, > > For those who are still on a dopamine agonist, let me use a gambling analogy > (sorry, I couldn't resist - I'll offer my 25 cents on that issue some > other > time). Hitting three sevens at a slot machine is hard but it can be done. > Hitting three sevens 10 times in a row must be a near statistical > impossibility. And so researchers occasionally get lucky in the Phase > I "pick > six" portion, but face almost certain failure in the larger trial > phases. And > that is worse than a real waste of time and money, because it's so misleading > clinically. > > Maybe PD research scientists can convince the FDA to accept "adaptive > trial > design." I understand they are considering it. > > Greg > > > > > --- Moneesha Sharma <[log in to unmask]> wrote: > > > Hi all, > > I sent Greg's very interesting mail to our doctor. I am forwarding > his > > response as I thought it might interest some of you. > > Moneesha > > > > > > The arguments are indeed valid. At the end of the day neurological disease > > remains a less explored and understood frontier of medicine. I entirely > > subscribe to the thought that PD is actually a bundle of diseases which > > manifests itself in similar ways. Our current treatments are not > > satisfactory for a large number of the people with the disease. The > lack of > > a clear understanding of the brain's functioning remains an immense > > obstacle. > > > > Actually Parkinsonian disease is perhaps the only neurological > disease for > > which there is any treatment at all. Most other neurological > conditions can > > be diagnosed but not treated. > > > > Interesting perspective > > > > ---------------------------------------------------------------------- > > To sign-off Parkinsn send a message to: mailto:[log in to unmask] > > In the body of the message put: signoff parkinsn > > > > ---------------------------------------------------------------------- > To sign-off Parkinsn send a message to: mailto:[log in to unmask] > In the body of the message put: signoff parkinsn ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn