Mad Dog on science

A post this good deserves it's own thread (formerly of "Laff also bad...":

TM says...

I look at this as a classic whistle blower story... and whistle blowers
will
always have their motivations questioned and are open to the argument you
are making.

The tests were done just like any other tests and the only irregularity is
that they were to remain anonymous. Armstrong gave the reporter access to
the documents that linked him to the positives. I don't find the story
very
complicated or sinister so I don't see the dark shadows that would give
cover for your disgruntled guy to operate.

I've done wet chemical method development for analysis of pharmaceuticals in
human bodily fluids, OK? I understand how the process works, from the
chemist's
bench level to the judge's bench level. Some folks have defended the
"research"
that led to EPO analysis results attached to Lance, supposedly proving his
doping guilt. I've got some major problems with the scientific approach and
from GLP or ISO perspectives could point out numerous problems with the
scientific protocol involved, but let's get back to this supposedly being
called
"research". Typically, when one does method development research, there are
critical factors evaluated and optimized, such as sample collection, sample
storage, standards, etc. Thus, if I wanted to say that I was doing research
to
improve the analysis of EPO in urine, I'd pay huge attention to the part of
the
analysis from the sample collection to where the sample is inserted into the
analytical procedure itself.

If I wanted to analyze samples that had been frozen for an extended period
of
time, I'd have to look at the storage procedure in detail. For example, I
may
choose to take an isotopically labelled EPO standard and administer it to a
test
subject, collect urine, analyze an aliquot of it in real time and freeze the
rest. I'd probably freeze numerous subsamples and thaw them sequentially to
see
if any changes occur over time. I'd also collect samples from test subjects
that had no EPO administered to use as one kind of blank and I'd also take
some
blank urine and spike it with known amounts of the isotopically labeled EPO.

Etc., etc., etc. When one does method development research, these kinds of
sub-projects are conducted. It's all standard procedure. Complex
biomolecules
such as EPO are highly influenced by their matrix and under the best of
conditions, such compounds often change over time. If you're going to take
an
unstable biomolecule such as EPO that is collected in a bodily liquid and
then
freeze that liquid, you've made a phase change. Biomolecules are notorious
for
"doing odd things" when subjected to phase changes, such as irreversible
adsorption to sample vessel surfaces, decomposition, etc.

One might look at this and point out that these are processes that would be
expected to LOWER a quantitative result for samples such as those reported
by
Equipe, but it ain't that simple and that's why we play the game of
research.
Often, it's the little things you don't understand about your system that
sneak
up and give you the reality slap. So when I look at what has been done,
namely
breaking WADA protocol by analyzing old frozen samples without following the
procedure of notifying the athlete in advance as is guaranteed, then
analyzing
the thawed samples by a technique that had not been validated for old frozen
samples, I smell a rat, plain and simple.

How could this have been done right? First, a model study to look at aging
effects of EPO in urine samples subjected to freezing should have been
conducted
IN ADVANCE! The validation study should have been done on known samples and
standards and done right. Then, the atheletes should have been notified in
advance, as had been guaranteed. Why is this important? Because the
athlete
has the right to see that the ONLY remaining aliquot is not ADULTERATED
prior to
analysis! Once the sample container was opened, it was too late and the
entire
study was invalidated. Even more importantly, by ignoring the athlete's
guaranteed rights, doubt was cast upon the credibility and integrity of
every
single person involved. If folks like Laffingstockerty can't see the
significance of these issues, consider it evidence of the blinding power of
bias.

The reduction in the specificity of currently accepted EPO in urine analysis
methods has already been brought up in rbr a couple of times over the last
few
of months. That said reduction in specificity was brought about by
non-scientific administrators is not surprising. Anyone with a background
in
analtical biochemistry knows that these are huge steps in the wrong
direction if
your goal is to accurately determine if athletes are doping. As an outsider
with relevant background, when I consider all of the above, I see that once
again: science, politics and money don't mix. If Lance is a doper, I would
like
to see him exposed and if the samples from '99 COULD have proven guilt, then
it's a huge pity that they were not handled appropriately. It's in part a
problem with some decisions made years ago, such as having A and B samples
only.
Had there been a C sample, this would be a whole new ballgame. But this is
expensive stuff, this chain of custody and ultra trace analysis business.
Very
expensive. And the governing bodies have limited budgets, you know...

--
http://spaces.msn.com/members/flomblog/

Jim Flom wrote:
A post this good deserves it's own thread (formerly of "Laff also bad...":

dumbass,

Good call.

Apparently we agree on both the absolutely invalid results from the
testing and the fact that what looks like a duck, smells like a duck
and quacks like a duck is likely to be a Lafferty.

Tom Kunich wrote:
Apparently we agree on both the absolutely invalid results from the
testing and the fact that what looks like a duck, smells like a duck
and quacks like a duck is likely to be a Lafferty.

What's with the ridicule of one of the posters? I don't think BL has
ever said the UCI should act to suspend on the test results, for a
whole bunch of reasons, no b sample, no adoption of the new test by
WADA, etc.

He's just saying, and I am too, if a lab is doing research, and finds
EPO, shouldn't cycling care about that? You critics of BL, and the UCI
suggest that a highly reputable lab doing research has no credibility?
What's with that?

I think an approach like that is what hardens WADA against us, and
ignores the doping issue. We should be saying, (apologies for repeating
another post) let us know when the test is ready, and the lack of b
sample issue is dealt with, and we will implement.

On 6 Oct 2005 15:30:23 -0700, "mtb Dad" wrote:


Tom Kunich wrote:
Apparently we agree on both the absolutely invalid results from the
testing and the fact that what looks like a duck, smells like a duck
and quacks like a duck is likely to be a Lafferty.

What's with the ridicule of one of the posters? I don't think BL has
ever said the UCI should act to suspend on the test results, for a
whole bunch of reasons, no b sample, no adoption of the new test by
WADA, etc.

He's just saying, and I am too, if a lab is doing research, and finds
EPO, shouldn't cycling care about that? You critics of BL, and the UCI
suggest that a highly reputable lab doing research has no credibility?
What's with that?

So your wife goes in for a test for uterine cancer. They call you and say
'sorry, your wife tested positive in her sample that we stored out on the
porch all day in the sun. Oh, and by the way, we didn't bother to run
controls, and the tech that ran them was fired later that day for sloppy
work, because we're a highly reputable lab. Hope that's not a problem.'.

It say it just might be a problem. ;-)

-jet

I think an approach like that is what hardens WADA against us, and
ignores the doping issue. We should be saying, (apologies for repeating
another post) let us know when the test is ready, and the lack of b
sample issue is dealt with, and we will implement.

Huh? Has there been any suggestion of the lab mishandling samples?
All we know is a new test being researched found what they think is
EPO. Where'd this other stuff came from?

On 6 Oct 2005 15:59:19 -0700, "mtb Dad" wrote:

Huh? Has there been any suggestion of the lab mishandling samples?
All we know is a new test being researched found what they think is
EPO. Where'd this other stuff came from?

They tested five year old samples which may have been stored at too high a
temperature (-18C rather than -40C) they apparently did not store controls
to run along with them, and did not follow proper forensics procedures
(chain of custody). Forensics are needed for proving misconduct and though
they were just (apparently) running some old samples on a new test to see
what would happen, there are those that now wish to use them to make
personal allegations. The point is, improperly controlled, improperly
stored samples run on a test not ready for prime time do not produce valid
results that can be interpreted. However it is enough to slander the
individual, unfortunately, and that's all it is, unproven allegations and
slander. Guess they should have waited until the test and controls were
ready, but now they're about out of sample. Too bad for them.

BTW, you might try quoting. I'm just guessing you're replying to me. ;-)

-jet

Not sure I've got the quote thing right, but here goes.

Jet wrote:
They tested five year old samples which may have been stored at too high a
temperature (-18C rather than -40C) they apparently did not store controls
to run along with them, and did not follow proper forensics procedures
(chain of custody). Forensics are needed for proving misconduct and though
they were just (apparently) running some old samples on a new test to see
what would happen,

Exactly. There were no plans to do anything other than research, and
besides, the lab doesn't know which samples are which.

there are those that now wish to use them to make
personal allegations.

But these are different people than the lab. How does that make the
lab less credible?

The point is, improperly controlled, improperly
stored samples run on a test not ready for prime time do not produce valid
results that can be interpreted.

I don't know about this. What source does this come from? But they do
suggest, now that they are out there, that doping is still going on.
Yet the UCI still says, shoot the messanger, instead of, hey, maybe
you're right, let us know when the test etc is ready ...

But they didn't, and Pound is prodding them to do more than shoot the
messenger. Todays announcement suggests that the investigation might
indeed go beyond leaks, or at least they didn't repeat that they were
only looking for leaks.

However it is enough to slander the
individual,

Yes, but that is exagerated by the denials. Why wouldn't Lance and UCI
say, "lets see the test validated". Unfortunately they played the
process card only.

On 6 Oct 2005 17:21:20 -0700, "mtb Dad" wrote:

Not sure I've got the quote thing right, but here goes.

Jet wrote:
They tested five year old samples which may have been stored at too high a
temperature (-18C rather than -40C) they apparently did not store controls
to run along with them, and did not follow proper forensics procedures
(chain of custody). Forensics are needed for proving misconduct and though
they were just (apparently) running some old samples on a new test to see
what would happen,

Exactly. There were no plans to do anything other than research, and
besides, the lab doesn't know which samples are which.

The samples were stored and labeled in the same order as the Tour,
stage-by-stage. It's not difficult to guess which samples belong to whom.

there are those that now wish to use them to make personal allegations.

But these are different people than the lab. How does that make the
lab less credible?

Arguably, the lab ran these without proper safeguards of anonymity. They
should have re-randomized the samples, for one thing.

The point is, improperly controlled, improperly
stored samples run on a test not ready for prime time do not produce valid
results that can be interpreted.

I don't know about this. What source does this come from? But they do
suggest, now that they are out there, that doping is still going on.
Yet the UCI still says, shoot the messanger, instead of, hey, maybe
you're right, let us know when the test etc is ready ...

They suggest nothing. There were no controls run. Again I ask would you
rely on a test with no controls and improperly controlled samples to accept
an unfavorable diagnosis on a loved one? No, you'd ask for a proper test.
Someone tests you for gunpowder residue with out of date reagents - well I
guess you must have shot somebody, the question is when. Fair? Nope.

But they didn't, and Pound is prodding them to do more than shoot the
messenger. Todays announcement suggests that the investigation might
indeed go beyond leaks, or at least they didn't repeat that they were
only looking for leaks.

I didn't read that at all. It said what it said. It's unclear if the
'investigation' by Dutch lawyers will focus on guilt, persons, events or
lab quality.

However it is enough to slander the individual,

Yes, but that is exagerated by the denials. Why wouldn't Lance and UCI
say, "lets see the test validated". Unfortunately they played the
process card only.

Someone alleges you cheated. Would you not deny? After all that lie
detector machine from 1980 probably works ok. ;-)

-jet

Jet wrote:

They suggest nothing.

C'mon. An accredited lab, with a research history in creating the
original test for EPO all of a sudden throws all care and attention out
the window? Even as a completely private effort they wouldn't do that
lest their own employees blow the whistle on the lab leadership. Even
less likely if they planned to leak the results.

It said what it said.

It was the first statement that didn't say they were only looking at
the leak. Can you deny that?

Someone alleges you cheated. Would you not deny?

You're right. Lance would deny. But the UCI should have shown a bit
more interest.

-jet