Thanks for this--I was in a med study earlier, and had some pretty
nasty side effects, but I won't know whether I was on one med, 2 meds,
or placebo until the study completely ends (obviously I wasn't on
placebo).  Towards the end, my sugar returned to the levels it was at
before the study started.

I walk a fine line keeping my sugar in check with diet and exercise,
and I was sick this past week and it was all over the map.  Now it's
back to normal, but I have to analyze the composition of every meal and
snack ahead of time in order to keep it in the safe range.

pc

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G'day G'day David,

Thank you.

 I'm puzzled as to how such a situation could have arisen.  All drug
trials should be run under the watchful eye of an ethics safety
committee to ensure participants are not put at undue risk.  Many will
remember the famous beta-carotene trials on smokers. It had been
observed that smokers who had naturally high levels of beta-carotene
were less likely to get lung cancer.  The study tested the hypothesis
that supplementing with beta-carotene would lower the lung cancer rate
amongst smokers.  The trial took an unexpected turn when the cancer
rate increased in the arm of the trial where participants received a
beta-carotene supplement.  The important point what that the ethical
safeguard committee pulled the plug. The trial was aborted.

To digress for a moment, there followed a period where all sorts of
explanations arose as to why the results were the opposite of what was
expected.  Perhaps someone knows the currently accepted explanation.  

The scientists conducting the experiment used synthetic beta-carotene
which ought to have been a red flag but wasn't.  They did so because
the synthetic beta-carotene was of high purity and well standardised.
What they ignored was that it was the wrong structural isomer.  In
high concentrations it could have blocked the action of natural beta-
carotene.  

Other explanations centred around the idea that beta-carotene isn't
the factor that reduced the cancer rate.  A likely candidate is alpha
carotene.  Alpha carotene is found in foods such as apricots along
with beta-carotene.  Put simply they were barking up the wrong tree
and thankfully the safety committee pulled the plug when things went
pear shaped.

OK, so why didn't it happen here?

Why didn't the safety committee pull the plug and abort the trial?

A serious adverse event rate of FOUR  times that on the placebo arm of
trial should have been enough for the safety committee to have pulled
the plug.  As the writer of the article points out it is not as though
there are no other drugs available for treatment of T2 diabetes.  The
one feature of the drug that perhaps made it different was improving
HDL levels ... which is meant to decrease the heart attack and death
rate.  It is not as though monitoring heart attack and death rate
wouldn't have been top of the agenda in the trial.

Put simply, how on Earth did the trial proceed to the point where ADA
approval was sought and how on Earth did they get it?  

Who was on a mental vacation when it happened?

More importantly, who is going to revue the safety committee
procedures and the ADA approval process?  

Vioxx told us it was time.

Hopefully it won't become a political decision. While deeply
respectful of the right of US citizens to political self
determination, it is worth considering that decisions on drug safety
go way beyond the US political arena and effect the health, life and
death of people around the world.

I say all these things mindful of the possibility that the folks
publishing the warning may have gotten their statistical analysis
wrong ... the point is they may also have gotten it right.  

If they have gotten it wrong then where is the swift rebuttal?

If the various committees had been doing their job someone on those
committees would have had similar concerns at the four to one adverse
event rate and the matter would already have been thrashed out and a
rebuttal prepared.

Best wishes,