On Mon, 27 Feb 2006 06:43:50 -0800,  Rick Froman wrote:

>>From the last paragraph of: http://www.msnbc.msn.com/id/11532184/ 
>
>"Dr. Mary Jo DiMilia, an integrative medicine physician at Mount 
>Sinai Medical Center, says none of her patients have asked about 
>foregoing calcium, and she's not giving up the glucosamine she's 
>relied on to relieve arthritis pain for the last two years. 'If it works 
>for me,' asks DiMilia, 'why should it matter that the study didn't 
>find benefit for all patients?'"
>
>Dr. Rick Froman

I assume that the above quote was provided to highlight either
the lack of rationality on Dr. DiMilia's part or perhaps the
inability of some physicians to respond adequately to empirical
results (a point I'm willing to concede) or something similar.  
However, I'd like to take this opportunity to provide a "teaching 
moment" by focusing on various issues that we might want to 
keep in mind when we look at medical research, especially if 
we only read media accounts of the original research:

Rely on Primary Sources instead of  Secondary Sources:  
although it is tempting to think that an article in a newspaper
or magazine or a website or a news program might be 
unbiased and comprehensive in its presentation of a subject,
we need to remember how often secondary souces distort,
misrepresent, or just get wrong specific details (Little Albert
anyone?), which is why we tell our students not to rely on
secondary sources but that they should instead go to the 
primary source.  Below is a quote from the New England
Journal of Medicine's abstract for the article described in
the MSNBC article (I reproduce only the last couple of
paragraphs):

|Results The mean age of the patients was 59 years, and 
|64 percent were women. Overall, glucosamine and chondroitin 
|sulfate were not significantly better than placebo in reducing 
|knee pain by 20 percent. As compared with the rate of 
|response to placebo (60.1 percent), the rate of response to 
|glucosamine was 3.9 percentage points higher (P=0.30), 
|the rate of response to chondroitin sulfate was 5.3 percentage 
|points higher (P=0.17), and the rate of response to combined 
|treatment was 6.5 percentage points higher (P=0.09). The 
|rate of response in the celecoxib control group was 10.0 
|percentage points higher than that in the placebo control 
|group (P=0.008). ********For patients with moderate-to-severe 
|pain at baseline, the rate of response was significantly higher 
|with combined therapy than with placebo (79.2 percent vs. 
|54.3 percent, P=0.002)*****. Adverse events were mild, infrequent, 
|and evenly distributed among the groups. 
[Note:  Emphasis added; Also "combined therapy" refers to
the combination of Glucosamine + Chondrotin).

|Conclusions Glucosamine and chondroitin sulfate alone or in 
|combination did not reduce pain effectively in the overall group 
|of patients with osteoarthritis of the knee. Exploratory analyses 
|suggest that the combination of glucosamine and chondroitin 
|sulfate may be effective in the subgroup of patients with 
|moderate-to-severe knee pain. (ClinicalTrials.gov number, 
|NCT00032890 [ClinicalTrials.gov] .) 

And from the last paragraph of the article:

|How should our results affect the treatment of symptomatic 
|osteoarthritis of the knee? Our finding that the combination of 
|glucosamine and chondroitin sulfate may have some efficacy in 
|patients with moderate-to-severe symptoms is interesting but 
|must be confirmed by another trial. 

To be clear, here are a couple of the main results:

(1)  There is a main effect of medication relative to placebo
but this appears to be due to Celebrex's effect (i.e., an 
increase of 10% in people reporting improvement relative
to the 60% reporting benefit due to placebo [which the
authors point out is a huge placebo response rate].  Note
that the combined Glucosamine+Chondritin (G+C) treatment
produced the next largest effect, namely a 6.5% increase
in people reporting benefit relative to placebo.  Is 6.5%
vs 10% that large of a difference?  Apparently for statistical
significance but one might ask what is the statistical power
for this comparison.

(2) There is an interaction of between treatment type
(e.g., placebo, Glucosamine, Chrondritin, G+C, and Celebrex)
and degree of initial degree of knee pain --  G+C appears
to help people with with moderate to severe symptoms as
measured by 20% decrease in WOMAC pain score..
I may have missed it in the MSNBC article but was the
severity of Mr. Milia's ostearthritis identified? (Note:
the p-value for Celebrex for this group was 0.06).

Now, I'm not a big fan of alternative/compementary medicine
(I do admit to a fondness for placebo effects) but it seems
to me that if a person suffers from moderate to severe knee 
osteoarthritis taking a G+C supplement may actually be 
helpful -- which might be the point that Dr. Milia was making 
above (especially since Celebrex doesn't make it to the
"magical 0.05 level" for this group).

Finally there is the issue of cost of taking a G+C supplement,
relative to Celebrex.  Checking Walgreens for their prices:

Celebrex 200mg (dosage used in study):  60 capsules= $189.99
G+C combo (G=250,C=200): 42 tablets=$5.00 (est. 60=$7.15)
(NOTE: above G+C doses are "regular strength", same as in study)

Hmmm, if one has moderate to severe knee osteoarthritis,
would one want to pay $7.15 or $189.99 (that is, if one 
doesn't have a prescription insurance plan for Celebrex plus 
cost of getting a doctor's prescription -- let's ignore the 
potential side-effects of Cox-2 inhibitors like Celebrex until 
after the trial; see, for example:
http://www.miami.com/mld/miamiherald/living/health/13975911.htm

Then again, given that there was a 60% placebo response rate
in the study, maybe we should stock up on those little white pills
with inert substances (not "sugar pills", we have a big enough
problem with obesity in the U.S. ;-).

In general, we should be critical and skeptical of research results
because (a) all research has significant limitations (if not significant
flaws) and (b) scientific knowledge is tentative, subject to revision
or reversal as new results from better research is produced.

Oh yeah, and don't believe everything you read in the newspapers
or see on TV.

-Mike Palij
[EMAIL PROTECTED]
New York University




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