----- Original Message -----
From: Charles T. Meyer MD
To: Jorge A Romero, MD ; [log in to unmask]
Sent: Sunday, June 04, 2000 7:49 PM
Subject: Re: Re: questions for Charles Murray
Hi Jorge,
I did not get the full article but did get the summary from the NEJM web
site. They set out to discover:
"Background. There is debate about whether the initial
treatment for patients with Parkinson's disease should be levodopa or a
dopamine agonist."
And in my estimation adequately showed it. They conclude:
"Conclusions. Early Parkinson's disease can be managed successfully for up
to five years with a reduced risk of dyskinesia by initiating treatment with
ropinirole alone and supplementing it with levodopa if necessary. (N Engl J
Med 2000;342:1484-91.) "
You are saying the study is fatally flawed because they do not have a group
where they add the ropinerole to the L-DOPA but rather add the L-DOPA to the
ropinerole. While I agree that more information might have been obtained
from the study had the study been done in the way you would have preferred,
they appear IMHO to have proven their hypothesis.They were attempting to
discover whether patients treated with Ropinerole first- prior to l-dopa did
better than those who started with those that started with l-dopa. The end
point was dyskinesia. The study was much simpler to do leaving out the
group you suggest since symptoms were titrated with a known drug known to
improve symptoms- a significant plus for the patients participating in the
study.
I don't think the purpose of the study was to prove that Ropinerole itself
prevents dyskinesia only that its early use can prevent dyskinesias by
making the total needed dose of L-DOPA lower. They are not saying
Ropinerole itself is protective only that early use lowers the dose of
L-DOPA and therefore delays the onset of dyskinetic movements.
What do you think of my interpretation? I think I am correct but I am open
to other ideas.
Charlie
----- Original Message -----
From: "Jorge A Romero, MD" <[log in to unmask]>
To: "Charles T. Meyer, M.D." <[log in to unmask]>
Cc: <[log in to unmask]>
Sent: Sunday, June 04, 2000 3:21 PM
Subject: Re: Re: questions for Charles Murray
> Hi Charles:
>
> I do invite you to read the article in the New England Journal.
>
> It claims to compare the effects of early treatment with ropinorole
against
> early treatment with levodopa. The study design is flawed fatally, in my
> opinion. I do not know how the NEJM reviewers let it pass.
>
> The "standard" way of treating Parkinson's has been to begin with levodopa
> and then, as levodopa has decreasing efficacy and/or increasing side
> effects, to add an agonist.
>
> The NEJM article compares:
>
> 1) Ropinorole first, supplemented with levodopa
> 2) Levodopa first, supplemented with more levodopa.
>
> Of course, the second group ended up with a higher dose of levodopa and
more
> dyskinesias.
>
> Why the investigators omitted the "standard" group from the comparison is
> unexplainable. This would have been a group in which one would use
levodopa
> first, and then supplement with agonist. The interpretation that the
> occurrence of fewer dyskinesias in group 1 has to do with a beneficial
> effect of early ropinorole or a toxic effect of early levodopa is not
proven
> scientifically unless you also have group 3:
>
> 3) Levodopa first, supplemented with agonist.
>
> So long as that group is missing, the same data can be explained by
> observing that the average dose of levodopa in group 2 was greater than in
> group 1 - i.e. a dose dependent effect of levodopa - NOT a protective
effect
> of early ropinorole.
>
> Indeed the study was paid and supported by Smith-Kline. In the same issue
> of the New England Journal there is a powerful editorial by Marcia Angell
> (editor of the NEJM) and a special article on Health Policy that addresses
> the issue of drug company influence on research, publications, and
academic
> efforts, that will be very sobering. Not even the NEJM is protected from
> those influences.
>
>
> Jorge
>
>
> ----- Original Message -----
> From: "Charles T. Meyer, M.D." <[log in to unmask]>
> To: "Jorge A Romero, MD" <[log in to unmask]>;
<[log in to unmask]>
> Sent: Saturday, June 03, 2000 2:36 PM
> Subject: Re: Re: questions for Charles Murray
>
>
> > Jorge and Charles and Jim,
> >
> > I have not read the primary article but if the NEJM holds here to their
> > usual high standards of review it is more than market research that is
> > operative here. While I would not put it beyond the ethics of a drug
> > company to slant data I highly doubt that they put one over on the NEJM
> > editorial staff. but it is possible. I would like to review the article
> if
> > someone has it in an easily transmissible form. The citation is as
> follows:
> >
