I believe that there is a point that both of you are missing.  The  studies
of concern are those where an experimental drug is surgically implanted  into
the brain to treat PD.  To meet the "gold standard" of a double-blind,
placebo-controlled trial, some investigators believe that a sham procedure is
necessary.  Unfortunately, sham surgery is not without risks to the  patient.

The comparison to amputations to prevent the spread of gangrene is
inappropriate.  In that case, amputation is a medical procedure.  We  have to rely upon
the knowledge and experience of the clinical professional as  to whether it
is necessary.  This is the practice of medicine, not  developing an
experimental drug.

It's also not as simple as not telling the clinical evaluator whether the
patient has received surgical treatment or not.  That would be obvious to  him
on a physical examination, as well as to the patient.  Reliance on  "historical
controls" or a "best treatment" group as a control group is  permitted, but
subject to challenge on the grounds that selection is not  randomized.

I agree that the practice of medicine does not require well-designed
experiments.  However, the development of safe and effective drugs does  require
appropriate testing.  There are certainly alternatives to  double-blind,
placebo-controlled trials, but the large pharmaceutical  manufacturers may be reluctant
to use them.  Consider that the cost of  bringing a new drug to market runs
into the hundreds of millions of  dollars.  Do we really want to go back to the
unregulated days of  pharmaceutical marketing that were filled with
unsubstantiated claims of great  benefits?  These led to the quack remedies that were
common in the  early 1900's, and have now largely disappeared from our
pharmacies.

As one of the Pipeliners who developed the survey, I want to encourage
patient participation in clinical trials.  At the same time, I want any  clinical
trial participant to be fully aware of all the risks and ethical  questions
associated with the trial.

To be sure, there are options to sham surgery.  But, if sham surgery  is
truly essential in a clinical trial, we must be aware that it's not like a  sugar
pill placebo, and the patient must demand to know of all the risks.

Wilson DeCamp
Leesburg, VA

In a message dated 9/16/2007 2:03:18 A.M. Eastern Daylight Time,
[log in to unmask] writes:

arnie,  sham surgery is not the only option.   consider  amputations and
gangrene;  do we need to do sham surgery to test  whether amputations
actually prevent the spread of gangrene?

if the  concern is really that investigators have bias, there are much more
ethical  approaches than sham surgery.   for instance, simply don't tell  the
clinician evaluating patient condition which patients have received  surgery
and which haven't.   if the concern is about a placebo  effect on patients,
comparison to historical placebo effects in PD patients  seems like a fairly
good first cut.

statistically speaking, other  approaches may not be as pure, but the whole
point of medicine is to treat  people, not perform elegant experiments.   if
the trials for  something like DBS, just make that information available to
the patients  and physicians considering the treatment with language along
the lines  of  "40% of PD patients showed improvement with DBS surgery, but
there  was no control group for ethical reasons.   historically, 15%  of
patients with similar circumstances have shown improvement without  any
treatment."

On 9/14/07, Arnie Kuzmack <[log in to unmask]>  wrote:
>
> There were several comments made by respondents (most  of whom are
apparently on
> this list), that I would like to  respond to.
>
> Comment:  The statistical proof is not  available in another way.  I am no
expert
> but can't we  demonstrate that something is helpful just by a larger
sample size
> or is a control group always required?  Can't we  pair people as close as
> possible and not have sham?
>
>  Response:  A basic principle in statistics is that a larger sample  size
does not
> correct for bias.  For example, in the classic  case, if the investigators
are
> emotionally committed to showing  that the treatment works, and if they know
> which patients got the  new treatment, they will have an unconscious
> tendency to evaluate  patients in the treated group differently from those
in the
> controls.  This is particularly true with diseases like PD, where the
evaluation  is not
> strictly objective.  It is also a problem using  "historical controls" or
pairing
> patients as suggested by the  commenter, since the evaluations of the
treated
> group would be  subject to evaluation bias.
>
> This is separate from the "placebo  effect", where patients getting a
placebo
> actually do better than  they would otherwise.
>







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