Sunday, November 04, 2007

Legal Discussion Continues, part II

Continuing the previous discussion, Larry and M are cogitating over the recent document release, and Larry is trying to get at the identification issue one more time.

TBV is hoping to have a major look this week with a new collaborator working over integration issues, including contaminated peaks, so keep that in mind.

Larry wrote (in part):

I think we now have the definitive statement of USADA's final position on how FL's S17 IRMS peaks were identified by LNDD. You and I, and everyone else who is interested, needs to go to p. 46, Section H, at the following link:

USADA's Final Word

This link is to USADA's proposed findings of fact and conclusions of law. I need to read this more carefully, but it appears that:

1. FL's S17 IRMS peaks were identified at LNDD (a) by using RTs or RRTs to identify the IRMS peak representing the internal standard 5aA-AC, (b) then counting large IRMS peaks to the right of the internal standard peak and idenfifying each peak by reference to the large peaks identified in the GC/MS test.

2. So, probably the best way to characterize LNDD's criteria here is not to call it "pattern matching", but "large peak counting".

M, we can go on with this discussion a while longer if you like, but I have another idea. Why don't you and I take this opportunity to "rebrief" our respective positions, using the new material available here and all of the stuff we've learned over the past few weeks. Here's my proposal:

1. You and I would "stipulate" that the method used at LNDD to identify IRMS peaks is the one described in the USADA document cited above. We might agree in advance to a short statement of the facts in the case, so we wouldn't have to repeat that in our briefs.

2. Then each of us would write a relatively short brief setting forth our respective positions. The brief would be limited to whether the LNDD's IRMS identification of FL's S17 sample is an ISL departure sufficient to overturn the FL doping finding. We'd agree in advance to keep our briefs under a specified word limit.

3. I would propose to write my brief here on TBV, in stages, so that everyone could comment. I'd reserve the right to make the final edits.

4. We could limit these briefs to whether there was an ISL violation. This way, we wouldn't have to address the burden shifting kinds of arguments we'd have to make on causation, should the ISL departure be established. We could save THAT argument for later.

5. We'd each write out briefs in as non-formal way as our training will allow. We'd keep the tone friendly and respectful.

M wrote (in the document release comments):

I'm making a vow to take a break from reading all the exhibits.

and TBV is personally giving him permission to take a break, at least for Saturday :-).

Mr. Idiot tweaks us not to belabor this much more:

Two things:

First, M wrote:
"I tend to agree that the blank urine shouldn't be used as a GC-IRMS RT reference material (spiked urine sample) for the same reason I don't think that the Cal Mix Acetate even if it had contained all the metabolites should or could be used as an IRMS reference sample. Since there are no mass spectra, if you include all the metabolites, some of them are so close together that you can't be sure if you've identified them correctly by retention times alone in your Cal Mix."

Sure you can sure, as long as the chromatographic conditions are the same. Isn't that the way it's supposed to be done (or at least one of the ways)?

Second, before you guys do a whole lot more work, can one of you step back and remind me why you are arguing this out? TbV sort of started this discussion by saying that there was a violation of TD2003IDCR. Are you still arguing that fairly narrow (although by no means unimportant) legal issue, trying to decide whether there should have been a burden flip or not?

OR, Larry, in trying to show the unreliability of the IRMS peak identification, are you suggesting the (stronger) point that the peaks themselves really are misidentified? As in, "There is no 5A in the one labeled 5A, or 5B in the one labeled 5B" ?

OR, am I missing something altogether and this is really about the possibility of CONTAMINATION of the peaks.

Ms favorite DP poster, OMJ, has called this peak identification argument a red herring. And although I don't ultimately agree with OMJ, I think he's right about this (unless it is a matter of establishing the burden flip, as TbV originally suggested). The real issue is contamination of the peak(s), isn't it?


Larry said...

To make the record here a bit easier to track, my response to the questions raised above by Mike S. is at the very end of this link: Why Larry Argues

M, we've been talking about Procedural Order No. 2, which restricted the documents available in discovery to those included in the ISL document package, and barred testimony on documents excluded from the arbitration. The new material provided by TBV shines more light on the issues raised by Procedural Order No. 2. First, if there was any doubt that the FL team tried to get LNDD's standard operating procedures (SOP), the doubt is eliminated by this excerpt from the transcript of the February 22, 2007 hearing that led to the issuance of Procedural Order No. 2: Exhibit 101.

But I think you were right when you argued that FL's team were at least partially responsible for the portions of Order No. 2 that restricted testimony at the arbitration. This is clear from additional portions of the February 22, 2007 transcript available on pages 4-7 of the following: Motion To Strike. Based on this limited material, it appears that FL's team pushed for the restrictions on testimony contained in Order No. 2, and that USADA argued against these restrictions.

I quote below from a portion of the February 22 hearing transcript, where Suh sought to close what he called a "loophole". FL's team had tried and failed to get discovery of documents (such as LNDD's SOP). Apparently, Suh was worried that USADA's witnesses might be able to testify concerned the contents of these excluded documents:

"MR. SUH: Which is -- and also, I guess - you know, as we're talking through this, I certainly would be remiss if we were to ignore the loophole that - you know, that the evidence would not come in simply by a witness coming in and saying, "Oh, yes, I've seen a stack of documents. Here's what they say," and, you know, it's not that they would actually have maybe a voice whereby--

ARBITRATOR CAMPBELL: So by either orally or by wrtten, that evidence doesn't come in?

MR. SUH: That evidence doesn't come in."

You may ask, why would the FL team have FIRST fought so hard for discovery of certain documents, and THEN fought to exclude testimony concerning the contents of these same documents? I think the reason is that the FL team was concerned about "cherry-picking": they did not want USADA to solicit testimony about the portions of esxcluded documents that were most favorable to USADA's case. After all, USADA had access to these documents and the FL team did not. The FL team would not have had a similar ability to pick out and ask questions about the portions of these documents that were most favorable to FL's case. So I think that Suh was trying to level the playing field by barring testimony on the contents of excluded documents.

We can question whether this strategy paid dividends for Suh and the FL team, but we can see the reasons for Suh's concern.

Mike Solberg said...

I haven't read too much of all these documents yet, but the last line of paragraph 122 of USADA's Proposed Findings of Fact, says (or claims):

"The GC/MS analysis not only established the three peaks as 5alpha androstanol, 5beta diol and 5alpha diol, it also established that the peaks were pure and that there was no other compound under those peaks."

I don't see anywhere in the document where this claim is supported. Is it there?

Obviously this is important for the contamination question. How exactly did the GC/MS analysis establish that these peaks were pure and there was no other compound under those peaks?

I know they identified that there was some of each metabolite in the peak, but how did they establish that there was nothing else in those peaks?

Note: notice how short paragraph 40 is!

Just like the majority ruling, they talk a lot about matrix interference and not at all about specificity. They are different, as described in ISL

m said...

Mike Solberg,

"Ms favorite DP poster, OMJ, has called this peak identification argument a red herring. And although I don't ultimately agree with OMJ, I think he's right about this (unless it is a matter of establishing the burden flip, as TbV originally suggested)."

OMJ says that regardless whether or not the 1% retention time standard was applicable or violated by the Lab, that the 5A and 5B metabolites were scientifically validly identified because of the visual identification of the 4 peaks only permitted one mapping from the GC-IRMS results to the GCMS results.. I agree with him, and I gather you agree with him wrt to this issue alone.

You say:

"The real issue is contamination of the peak(s), isn't it?"

I don't agree, butI haven't addressed this fully yet.

But as a legal matter even if the identification of metabolites was scientifically valid as OMJ claims, we might still have to set aside the doping finding if some technical standard was violated. That is what Larry and I are arguing about. He is not arguing that the 1% rule applies, as Meier did, but that the Lab used some alternative identification criteria, but did not document it or write it down as they supposedly were required to do by TD2003IDCR. I'm arguing that the lab used TD2003IDCR itself as the identification criteria, although possibly relaxing the 1% standard as was permitted.


You argued in the thread below that USADA did not explain why the 1% standard should be relaxed.

The reason was that stated by Brenna and the Arbs. The 1% standard only applies to retention times measured on the same machine. Two different types of machines were used here. As I noted even Meier testified that under ideal conditions the retention times would be off by 1 to 2 minutes, which implies the RRTs would be off by 2-3% in this case.

With that I'm going off to watch some football.

I hope to be able to take a look at some of the exhibits next week.

Hope you all have a good weekend.

Larry said...

M, we simply disagree at this moment about when and how the TD2003IDCR standards can be relaxed. I think I've made my position clear, maybe we'll re-argue this another day.

Mike, no I don't see much support for USADA's statement that the peaks are pure. Except perhaps their argument that LNDD's chemistry and other procedures were good, which presumably would lead to pure peaks. Of course, there may be support for this statement in the LNDD's document package -- there are graphs and other materials there that I don't completely understand. Could there be some mass spectra data in there? I'm simply not sure.

If you think that USADA may have confused specificity with matrix interference ... that doesn't surprise me, I confuse them too. "Specificity" means (in the context of testing for testosterone) that the graphs you're examining only contain testosterone metabolites? And matrix interference means that the metabolites can be distinguished and measured separately?

One reason I pay more attention to peak identification issues is that the specificity standards are so much more vague. There's certainly nothing I can see that specifically requires mass spectra analysis. And I don't remember the FL team pointing to the absence of mass spectra data. I'm not saying I can't construct a legal argument around specificity - maybe I can. Actually, I was thinking that maybe we're really done with the peak identification issue and we should move on to see what happens if we kick the tires on specificity. Not sure.

Mike Solberg said...

Thanks, Larry and m, for answering my question about why you are doing this. I think the legal issue is real and important, and worth figuring out. I guess it sounds to me like IF the urine blank can be used as an internal standard for all the metabolites, then m wins. If not, Larry wins. I think it cannot according to TD2003IDCR, so I think a burden flip is in order on this point. But, as I implied, I don't think this is the key argument (so, yes, m, I agree with OMJ on that point, as far as the science goes, but not the legality, which OMJ normally avoids).

I will be interested to hear both your thoughts about contamination.

What duckstrap said a while back on DPF is that, no, the ISLs do not specifically state anywhere that the complete mass spectra data must be provided. But he says the ISLs require that you identify everything in the peaks, and the only way to do that is with the complete mass spectra data, so they are required. (duck, I am misrepresenting your view, please chime in - in fact please chime in anyway!)


Mike Solberg said...

Just FYI, the best definition of specificity I can find is this - from an ISO document (99999.2), but not 17025 - I imagine 17025 is probably the same:

"Specificity: The ability of a method to respond exclusively to the target analyte and not to any degradant, impurity, or other component of the matrix. Very few methods are absolutely specific, so the term “selectivity” is often used for this property. This parameter shows that the method can be used to quantitate the analyte without interference."

It also gives this definition:

"Specificity: Ability to assess unequivocally the analyte in the presence of components which may be expected to be present."

So, I think my original layman's summary was right:

Specificity refers to the ability to check for stuff that may happen to elute at the same (or very similar) time as the target.

Matrix interference comes from stuff that "slips through" the GC/MS, not really eluting at it's proper time.

Either matrix interference or a process with insufficient specificity may lead to measuring the wrong stuff in a GCMS peak, and therefore in a IRMS peak.


Larry said...

Mike -

Regarding the use of the blank urine as a reference material ... I think that one is a stretch, at best. It was certainly not the SOP of LNDD to use blank urine as a reference material -- the testimony clearly indicates that blank urine was a control substance, used precisely because it was real-world and not a designed reference material. The idea was to compare current and historic blank urine runs (to see if the machine was operating per usual), not to compare blank urine runs and athlete samples. At best, M might argue that while LNDD did not intentionally use blank urine as a reference material, it might serve that purpose if no other identification technique is available to satisfy TD2003IDCR. (M would then run into the issue of whether LNDD's identification of blank urine IRMS peaks is any better than its identification of athlete sample peaks.) But if M has to stretch this far to make his case, it probably means that we've proved an ISL departure (because LNDD's actual criteria for identifying substances failed to pass muster), and we've had the burden flip.

As a lawyer trying to make a case for FL, I would be concerned about any interpretation of the ISL requirements on specificity that says there's only one scientifically valid way to satisfy the requirements. If that is the case, you'd have to ask why the rules failed to specifically reqire mass spectra. If the labs had no choice (which is, in effect, the argument you're making), then why write a rule that makes it sound like the labs DO have a choice?

If the labs had no choice but to show specificity with the mass spectra, then we should be able to prove that all (or nearly all) labs rely on mass spectra for this purpose. Given the arbitrators' belief that WADA labs don't need to act like other labs, we'd probably need evidence that all (or nearly all) WADA labs rely on mass spectra to achieve specificity. We don't have anything like this evidence in the record, though, which makes our case difficult. Any thoughts on how we'd overcome this obstacle?

I'm still not getting the distinction between specificity and matrix interference. Can you give me an example of how each might have occurred in this case? What is the difference between the unspecific and the interfering material? What might be a source of each type of material?

m said...


Sorry I haven't gotten back to you about your proposal re briefing.

I've read the USADA proposed findings of fact regarding the Brenna retention time testimony. Even though I don't have any real problems with the USADA characterization of that testimony, I think it's better to let Brenna's testimony stand on it's own rather than be boxed in by the lawyer's characterization of that testimony since the issue you are raising with respect to the absence of identification criteria was not raised in the arbitration. I must say though they did a good job explaining scientifically why there couldn't be any real doubt about the identification of the 5A and 5B.

I think I have a little bit more to say about the identification issue and criteria, but I wonder whether you have more issues to raise now and we should move on to those other issues.

Larry said...

M -

I'm less enthusiastic about this legal discussion than I was a few days ago. There are a number of reasons for my loss of enthusiasm. First, I don't think there's much interest in the TBV community at the moment in the law aspects of this case. That may change as the appeal heats up, but for the moment the greater interest is with the science.

Also, I think that some of our more interested on-lookers may have come to the conclusion that we've analyzed this particular issue and that it's time to move on.

Finally, I think we both have stuggled with how difficult it is to deal with the ISL from a legal perspective. We've spent countless hours trying to figure out, what did LNDD do, and is this a criteria, or a procedure that doesn't rise to the level of a criteria, or an absence of procedures and criteria. We've both cycled through a number of positions here. In the final analysis, I'm still not sure what LNDD did, nor can I figure out how to classify what they did under TD2003IDCR. And our discussion kind of stalls without an agreement on these very basic points.

I personally would have liked to argue some of the issues around the "burden flip". If the arbitrators had found that LNDD's method for identifying peaks was an ISL departure, then it would be interesting to see how USADA might have tried to prove that the departure did not cause the adverse finding. What could it have argued? But maybe it's only me (or the both of us) who would find that sort of thing interesting.

At the moment, the interest here at TBV seems to be in specificity, matrix interference, and the stuff being discussed in the so-called "idiot's course". I agree that these are probably more interesting issues from a scientific point of view. I'm just not sure that these issues give us lawyers anything much to discuss.

Even by the fuzzy standards of the ISL, the ISL rules on specificity and matrix interference seem vague to me. In the absence of anything like a clear scientific consensus that the LNDD test results are hopelessly screwed up, I can't figure out a way at the moment to overcome the ISL's presumption that the LNDD's test results are specific enough and free enough of matrix interference. For better or worse, the ISL pushes the lawyers towards more mundane issues, like the use of white-out to make forensic corrections, where the ISL provisions speak more clearly.

If you want to switch gears and argue the legal side of the matrix and specificity issues, I'd be up for that. However, if I was FL's lawyer and was looking for a way to win his case, I probably would not spend much time on these issues.