tag:blogger.com,1999:blog-31819641.post7467004149115505110..comments2023-10-06T03:21:26.130-07:00Comments on trust but verify: The 5bA Anchor argumentDBrowerhttp://www.blogger.com/profile/17718913310467614671noreply@blogger.comBlogger78125tag:blogger.com,1999:blog-31819641.post-10657086806365340082007-12-15T22:41:00.000-08:002007-12-15T22:41:00.000-08:00Swim -I'm not trying to make you give up the 5.4.4...Swim -<BR/><BR/>I'm not trying to make you give up the 5.4.4.2.1 argument. I'm trying to get you to see that it's a complicated argument. I personally have NOT given up on the argument, just to let you know.<BR/><BR/>Swim, as a non-lawyer you need to be more patient with the process of legal analysis. It IS a process, and you have to muck your way through it. I drew a distinction between techniques to achieve specificity and techniques to check specificity, to make a point that rule 5.4.4.2.1 is not as simple or straightforward as some here have claimed. But this distinction is not the right way to start the analysis. The right way to start the analysis is to think about what we mean by specificity, and see if we can define what we mean, and then to pose some "egg" cases to see how our definition works in practice to see if we're comfortable with the definition we have.<BR/><BR/>I've started this process over at the "Specificity" discussion, and I suggest we try to work our way through it there. I will move over there to respond to your new posts here -- but probably not tonight.<BR/><BR/>But one last thing: never, NEVER give up on a legal argument when you think you have common sense on your side. You seem to think that when a lab does a CIR analysis, common sense requires the lab to look at the complete mass spectrum. If you're right, and you may well be right, the chances are good that the law is on your side.Larryhttps://www.blogger.com/profile/08976868079076669453noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-81595318380903204882007-12-15T21:51:00.000-08:002007-12-15T21:51:00.000-08:00As for your second, fried egg, challenge: given th...As for your second, fried egg, challenge: given that I now understand that WADA says GC separation is good enough for identification and assuring specificity, I think the second challenge is a moot point. It largely doesn't matter what type of eggs you have, or how much mixing of yolk and white you have. If you have put the egg through the right process, then you get to say you have clearly identified what is yolk and what is white (even if your eyes tell you otherwise).<BR/><BR/>I suppose that there would be some limit to this even for WADA, as if you had the chromatographic equivalent of scrambled eggs. But I guess that's the question we are left with regarding LNDD's work. Do we have the equivalent of chromatographic scrambled eggs or not? Landis and his experts say yes. USADA and their lab directors /experts say no. Two arbs agreed with the latter, so here we are.<BR/><BR/>But two more points: First, it would seem that there is no basis in the WADA documents with which you could prove "scrambled eggs." There is no criteria set up to decide. According to the documents, if you have gone through the process, is it good enough. It is common sense, not WADA documents, which make us think there has to be a limit to how much the eggs can look scrambled and everything still be "good enough."<BR/><BR/>Secondly, common sense, but not WADA documents, would make you think that if there was a question about whether the eggs were scrambled (or merely mixed up fried eggs), then you would require additional evidence to decide the issue. That would be the complete mass spec data. But, alas, that is again, common sense, not the requirement of WADA.<BR/><BR/>Please tell me if you disagree about the egg analogy now being sort of moot.<BR/><BR/>syiMike Solberghttps://www.blogger.com/profile/11784753552166129987noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-75127676766757297572007-12-15T21:30:00.000-08:002007-12-15T21:30:00.000-08:00Larry, I really didn't mean to ignore your challen...Larry, I really didn't mean to ignore your challenge/questions. But you ask so many of them at once! Here goes:<BR/><BR/><I>Here's one challenge for you to think about (and when I describe this challenge, I'm skipping over a bunch of other challenges that we'd have to meet before we ever reach this challenge). Remember, ISL rule 5.4.4.2.1 talks about the ability of the lab's techniques to detect only the substance of interest. What techniques does a lab use to detect only the substances of interest? I think it comes down to sample preparation and setting up the right chromatographic conditions for optimal peak separation. From this perspective, the mass spectrum analysis is not a technique to ACHIEVE specificity, it's a CHECK to see whether you've achieved specificity in a given case.</I><BR/><BR/>Exactly right.<BR/><BR/><I>Does 5.4.4.2.1 require the lab to CONFIRM that its techniques for achieving specificity actually work? Arguably yes, as part of the process of setting up these techniques in the first place and having them reviewed and approved by WADA in the accreditation process. But does rule 5.4.4.2.1 require the lab to REPEAT the confirmation process every time it runs a test?</I><BR/><BR/>No, I don't think so.<BR/><BR/>But specificity is a still an issue, as follows:<BR/><BR/><I>5.4.4.1 Selection of Methods -<BR/>Standard methods are generally not available for Doping Control<BR/>analyses. The Laboratory shall develop, validate, and document<BR/>in-house methods for <B>(I add for clarity - "identification of"</B> compounds present on the Prohibited List and for related substances. The methods shall be selected and<BR/>validated so they are fit for the purpose.</I><BR/>So the lab has to "develop, validate, and document" their own methods for <B>identification of</B> compounds on the Pro. List. Of course, testosterone itself is not on the prohibited list, but rather only exogenous testosterone. So you have to have methods that are fit to identify that exogenous testosterone is present. That is done by measuring the CIR of the metabolites, and comparing that to the ERC. <B>But you don't know that you have found the right CIR unless you know that you are only measuring the metabolite of interest. So your method can't possibly be fit for purpose if you have not guaranteed specificity in the GC/MS step of the GC/C/IRMS test, and clearly maintained that "purity" knowledge into the IRMS by maintaining consistent chromatological conditions.</B><BR/><BR/><I>5.4.4.1.1 ... The Laboratory must develop as part of the method validation process acceptable standards for identification of Prohibited Substances. (See the Technical Document on identification Criteria for Qualitative Assays)</I> That's our TD2003IDCR.<BR/><BR/>Again, the prohibited substance is not testosterone, but exogenous testosterone, so the lab is required to develop acceptable standards for the identification of <B>exogenous</B> testosterone, which they have not done until they have guaranteed the content of the peak for which they are finding the CIR. So certainty of specificity <B>must</B> be part of the method, and the validation of the method.<BR/><BR/><I>We may end up having to argue that you can't rely on sample preparation and good chromatographic conditions to achieve specificity, that these techniques are unreliable to a certain extent, and for this reason we must require an analysis of the mass spectrum in every case.</I><BR/><BR/>You know, this may really be when we say "therein lies the rub." (And, this may be jumping ahead 15 steps, but this point may explain why Landis' legal team approached the hearing the way they did, rather than arguing about whether LNDD produced the mass spec data.) The question does become, "Is sample preparation and (good) chromatographic separation adequate to guarantee specificity?"<BR/><BR/>I think even WADA recognizes that the answer to this question is "Eh, maybe." TD2003IDCR, which is precisely intended to address the question of identification (and thus specificity) allows for identification by chromatographic separation (with a match of retention times to a standard run contemporaneously). But then it also says <B>"A full or partial scan is the preferred approach to identification"</B> !! The limitation of identification by GC separation is recognized in the document. But the "is the preferred approach" language is obviously not mandatory, so the mass spec data can't be required, and the lack of it can't be an ISL violation.<BR/><BR/>That's sad. They recognize the limitation, and acknowledge there is a better way, but don't require the better way. To me, that is just inexcusable. But it doesn't end the case, because the GC/MS is just the first part of the process of identifying exogenous testosterone.<BR/><BR/>If the lab kept the chromatographic conditions the same, then maybe it is case closed. But in our case, they didn't. That breaks the link between GC/MS and IRMS and you have lost your (pseudo) certainty of identification. In that case, there is no way to get back your certainty, other than to rely on the quality of the IRMS chromatography. And again, you have a fight about the quality of the chromatography, and whether it is poor enough to bring doubt as to specificity. And again (frustratingly) here we have a situation where applicable document recognizes the problem, and declares the lower quality acceptable:<BR/><BR/><I>ISL 5.4.4.2.1 - Matrix interferences. The method should avoid interference in the detection of Prohibited Substances or<BR/>their Metabolites or Markers by components of the sample<BR/>matrix.</I><BR/><BR/>And, of course, the arbs let the problem slide because it says "should" rather than "shall" or "must." Again, that's sad.<BR/><BR/>You know, I think for the first time, I see the logic of the arbs majority decision. I think it sucks, but I think I do see it. Previously, I didn't even think their argument was logical. I guess it is, although I think it allows for Landis to be convicted with second tier science, and the sad thing that WADA's own documents recognize it as such. LNDD had better ways available to them (complete mass spec data, and better chromatography), they could have used those better ways (and they may have intentionally erased the data associated with one of those better ways), and they didn't do it. That's disgusting.<BR/><BR/>Given all that, I have a lot more respect for Landis' legal team than I did previously. Given that the WADA documents allow results based on less than ideal science (which they even recognize as less than ideal science), they had to fight for, one, bad chromatography (which would show the GC separation was NOT a "good enough" method of assuring specificity - which they lost because of the permissive language of "matrix interference," and, two, technical ISL violations which would have given them the burden flip, with USADA having no way to meet the burden given the limitations of the science they relied on.<BR/><BR/>So, Larry, yes, the challenge you posed was highly insightful and deserving of greater respect. The answer seems to suck, but let's keep working to find a way to hold their lax rules against them.<BR/><BR/>syiMike Solberghttps://www.blogger.com/profile/11784753552166129987noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-15123269633017438342007-12-14T08:24:00.000-08:002007-12-14T08:24:00.000-08:00syi, thanks for pointing out the link.I left you w...syi, thanks for pointing out the link.<BR/><BR/>I left you with a specificity question the other day, as to whether mass spectrum analysis is a means for a lab to achieve specificity, or is a way for the lab to confirm the other means they use to achieve specificity. I'll raise a second fundamental question for you here, which is: what do you mean by specificity?<BR/><BR/>Let's take the example of an egg. When have we achieved egg specificity? Clearly, if I separate the yolk from the white, and I put the yolk in one bowl and the white in another bowl, then I have egg specificity. This is like a chromatogram with two pure peaks, and good peak separation.<BR/><BR/>The opposite of a separated egg is a scrambled egg. Clearly, there's no specificity in a scrambled egg.<BR/><BR/>How about a hard boiled egg? There is a sense in which we've achieved specificity by hard boiling the egg - in a 3D mapping, we can picture the yolk and the whites as separate. But we live in a 2D world, and many slices of hard boiled egg contain both yolk and white. Also, looking at the egg from the outside, the yolk is hidden, and you don't know for sure it's there. For these reasons, I don't think we've achieved specificity with a hard boiled egg. I think a hard boiled egg is like a chromatogram with a co-eluting peak.<BR/><BR/>Now, the hard question. What about a fried egg? With a fried egg, the yolk is not hidden, you know it's there. However, there are going to be slices of fried egg that contain both yolk and white. With a fried egg, have we achieved egg specificity? I would argue that we have not. <BR/><BR/>The fried egg is like a chromatogram with overlapping peaks. Does ISL 5.4.4.2.1 reject all chromatograms with overlapping peaks, because the area of overlap is not "specific" to a single substance?Larryhttps://www.blogger.com/profile/08976868079076669453noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-35861848471214263012007-12-14T03:57:00.000-08:002007-12-14T03:57:00.000-08:00Larry, go to ArnieBakerCycling.com, and click on "...Larry, go to ArnieBakerCycling.com, and click on "the Wiki Defense" link. The links at the bottom have a link to ISO 17025 or at least a long section of it.<BR/><BR/>syiMike Solberghttps://www.blogger.com/profile/11784753552166129987noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-45248207971958714552007-12-13T22:05:00.000-08:002007-12-13T22:05:00.000-08:00Swim and Ali, the application of ISO 17025 is some...Swim and Ali, the application of ISO 17025 is somewhat complicated. It's a little more complicated for me, because I've never read ISO 17025 and I don't have easy access to it. This is pretty far outside the area where I practice law, but in my copious spare time, I HAVE considered this issue.<BR/><BR/>The general rule governing application of ISO 17025 is ISL Section 5.1. ISL Section 5.1 states that Section 5 of the ISL "is intended as an application as described in Annex B.4<BR/>(Guidelines for establishing applications for specific fields) of ISO/IEC 17025 for the<BR/>field of Doping Control." My understanding of ISO 17025 is that it sets forth general rules applicable to labs, but contemplates that specialty labs will need their own rules, and that Annex B.4 of ISO 17025 addresses the need for these specialty rules. So, at least ISO 17025 seems to contemplate the existence of standards like the ISL, and seems to provide that ISL-like standards would be read together with ISO 17025 standards to provide for comprehensive rules governing WADA labs.<BR/><BR/>ISL Section 5.1 goes on to provide that "[a]ny aspect of testing or management not specifically<BR/>discussed in this document shall be governed by ISO/IEC 17025 and, where applicable, by ISO 9001." So you would think that ISO 17025 would be fully binding on WADA labs, except for those matters expressly addressed by the ISL.<BR/><BR/>Unfortunately, things are possibly more complicated than what is described in ISL 5.1. There is, for example, a very broad and unfortunate statement in ISL 7.1:<BR/><BR/>"References in the International Standard for Laboratories to ISO requirements are for general quality control purposes only and have no applicability to any adjudication of any specific Adverse Analytical Finding."<BR/><BR/>I might argue that this provision of ISL Section 7.1 needs to be read in the broader context of the entire Section, which addresses the contents of the LDP. But the breadth of the quoted language pushes the lawyer in me away from arguments based solely on ISO 17025.Larryhttps://www.blogger.com/profile/08976868079076669453noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-4583250979281505842007-12-13T21:38:00.000-08:002007-12-13T21:38:00.000-08:00Yes, it was ISO 17025 5.4.6.3. The legal status o...Yes, it was ISO 17025 5.4.6.3. The legal status of ISO 17025 with regard to the actions of LNDD is not clear to me.<BR/><BR/>But on that uncertainty issue, Ali, in case you haven't seen it, I've been meaning to point you to a document on Arnie Baker's website:<BR/><BR/>http://www.arniebakercycling.com/<BR/>floyd/other_links/<BR/>2nd%20USADA%20Symp%202003.pdf<BR/><BR/>It's a report of a symposium of people who all work with IRMS, and includes a whole section on uncertainty. The pagination is messed up and frustrating, but you can find what you need.<BR/><BR/>I have no idea how to answer your question about how to apply the ISO 17025 reference to LNDD's tests.<BR/><BR/>syiMike Solberghttps://www.blogger.com/profile/11784753552166129987noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-52662382144033663002007-12-13T18:04:00.000-08:002007-12-13T18:04:00.000-08:00Ali,I'm not 100% certain, but I think that SYI may...Ali,<BR/><BR/>I'm not 100% certain, but I think that SYI may have gotten that quote from one of the ISO standards. Most likely 17025, since that is more specific to medical lab work, but possibly 9001.daniel m (a/k/a Rant)https://www.blogger.com/profile/16126545986721397012noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-47114331286579248102007-12-13T17:36:00.000-08:002007-12-13T17:36:00.000-08:00Larry,Apologies, this is probably my fault. SYI po...Larry,<BR/><BR/>Apologies, this is probably my fault. SYI posted an extract from an international standard some time back (during the quantization error thread). I assumed that was the ISL (important note: ASSUME stands for making an ASS of yoU and ME, as I have so clearly domonstrated).<BR/><BR/>I looked back but couldn't find where it came from. Help, SYI !<BR/><BR/>AliAlihttps://www.blogger.com/profile/00786387057717601356noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-7842240999868172922007-12-13T15:55:00.000-08:002007-12-13T15:55:00.000-08:00Ali, I may be experiencing brain freeze, but where...Ali, I may be experiencing brain freeze, but where is ISL 5.4.6.3? My copy of the ISL has a 5.4.6.2, but no 5.4.6.3.Larryhttps://www.blogger.com/profile/08976868079076669453noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-16078166746012767892007-12-13T14:36:00.001-08:002007-12-13T14:36:00.001-08:00This comment has been removed by the author.Alihttps://www.blogger.com/profile/00786387057717601356noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-60128956635673033142007-12-13T14:36:00.000-08:002007-12-13T14:36:00.000-08:00Larry,This is a "legal" one which I've raised befo...Larry,<BR/><BR/>This is a "legal" one which I've raised before but maybe not highlighted. I was wondering whether you thought it was relevant:<BR/><BR/>ISL rule 5.4.6.3: When estimating the uncertainty of measurement, all uncertainty components which are of importance in the given situation shall be taken into account ...<BR/><BR/>LNDD quote an uncertainty of measurement of +/- 0.8 delta units. They apply that to all situations, even overlapping peak situations. Brenna's paper suggests that additional error is inevitable when peaks overlap.<BR/><BR/>In the presence of peak overlap, is it a violation that they don't account for these additional errors, so that "all uncertainty components which are of importance in the given situation shall be taken into account..."?<BR/><BR/>It strikes me that these are uncertainty components which are relevant and have not been taken into account ?<BR/><BR/>AliAlihttps://www.blogger.com/profile/00786387057717601356noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-8275933290325971912007-12-13T14:26:00.000-08:002007-12-13T14:26:00.000-08:00Ali, I'm not a scientist, but OK. ;^)Ali, I'm not a scientist, but OK. ;^)Larryhttps://www.blogger.com/profile/08976868079076669453noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-71478807480345661922007-12-13T14:18:00.000-08:002007-12-13T14:18:00.000-08:00Everyone,Just for the record, I'd prefer it if peo...Everyone,<BR/><BR/>Just for the record, I'd prefer it if people didn't have to qualify their opinions with their background. I wish I hadn't said that (I was reacting - a weakness). Regardless of the subject matter, I think everyone is capable of making potentially important observations. A lot of the stuff the "lawyers" have posted has already made me think twice about stuff I thought I understood. Most of the science stuff boils down to knowledge and common sense. I assume that it's the same for legal stuff. This isn't a competition, we're exploring theories so anything goes. In summary:<BR/><BR/>Larry, no more "I'm not a scientist ...".<BR/><BR/>M, no more "You're not a scientist ...". <BR/><BR/>Ali, no more "I'm an idiot, an ass and a time waster ..."<BR/><BR/>Let's just buckle down and see what happens.<BR/><BR/>AliAlihttps://www.blogger.com/profile/00786387057717601356noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-22521546189805308462007-12-13T09:25:00.000-08:002007-12-13T09:25:00.000-08:00syi -OK, I'll see what I can do. But specificity ...syi -<BR/><BR/>OK, I'll see what I can do. But specificity is definitely a more challenging legal argument, especially if what you want to prove is that the lab was required to examine the complete mass spectrum for each peak. <BR/><BR/>Here's one challenge for you to think about (and when I describe this challenge, I'm skipping over a bunch of other challenges that we'd have to meet before we ever reach this challenge). Remember, ISL rule 5.4.4.2.1 talks about the ability of the lab's techniques to detect only the substance of interest. What techniques does a lab use to detect only the substances of interest? I think it comes down to sample preparation and setting up the right chromatographic conditions for optimal peak separation. From this perspective, the mass spectrum analysis is not a technique to ACHIEVE specificity, it's a CHECK to see whether you've achieved specificity in a given case. <BR/><BR/>Does 5.4.4.2.1 require the lab to CONFIRM that its techniques for achieving specificity actually work? Arguably yes, as part of the process of setting up these techniques in the first place and having them reviewed and approved by WADA in the accreditation process. But does rule 5.4.4.2.1 require the lab to REPEAT the confirmation process every time it runs a test? <BR/><BR/>We may end up having to argue that you can't rely on sample preparation and good chromatographic conditions to achieve specificity, that these techniques are unreliable to a certain extent, and for this reason we must require an analysis of the mass spectrum in every case. In other words, the lab's technique for achieving specificity would have to include repeating sample preparation and set up of chromatographic conditions (and if necessary, making changes to these techniques) as necessary to produce good mass spectrum results. You can probably see where any such legal argument is going to get messy.<BR/><BR/>Thoughts, comments and reactions?Larryhttps://www.blogger.com/profile/08976868079076669453noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-67263610986098409732007-12-13T07:39:00.000-08:002007-12-13T07:39:00.000-08:00Oh yeah, and to my first paragraph above, add the ...Oh yeah, and to my first paragraph above, add the likely presence of dexamethesone and methylprednisolone.<BR/><BR/>syiMike Solberghttps://www.blogger.com/profile/11784753552166129987noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-85922745780513640322007-12-13T05:49:00.000-08:002007-12-13T05:49:00.000-08:00Larry, I for one would be most interested in seein...Larry, I for one would be most interested in seeing your legal argument about specificity. In my view, this peak identification issue is not Floyd's winner - specificity is. The gapping hole of the missing mass spec data, the different chromatographic conditions, the poor separation of the 5bA and 5aA peaks, and the overall baseline issues, all leave the door wide open to specificity problems.<BR/><BR/>There has to be a way in which LNDD has to prove that they measured only what they say they measured, whether it be ISL 5.4.4.2.1 or something else. It just doesn't make sense to say that they don't have to do that. So if you can show exactly how that is required, I think that would be very interesting.<BR/><BR/>Personally I think paragraph 233 and following of the majority decision is an important place to look. To my reading, they speak of ISL 5.4.4.2.1 as if it is binding to practice not just method, but they focus on the weaker language of "matrix interference" and ignore the stronger language of "specificity."<BR/><BR/>I thought this discussion of 5.4.4.2.1 was one of the weakest sections of the decision (second only to their claim that WMA didn't know what he was talking about).<BR/><BR/>syiMike Solberghttps://www.blogger.com/profile/11784753552166129987noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-88654979908269997352007-12-12T19:33:00.000-08:002007-12-12T19:33:00.000-08:00Just as Georges Clemenceau said about war - That i...Just as Georges Clemenceau said about war - That it is too important to be left to the Generals - so science is too important to be left to scientists and law is too important to be left to lawyers. In the FL case, it is important that "amateurs" understand the issues arising from these esoteric realms and to make comments and suggestions about how law and science can best serve justice. That is what is happening here and I believe that the efforts are laudable.Bill Mchttps://www.blogger.com/profile/13787556081022333034noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-28952481367207491812007-12-12T19:06:00.000-08:002007-12-12T19:06:00.000-08:00Swim, great post.I've stayed away from the legal s...Swim, great post.<BR/><BR/>I've stayed away from the legal side of things, in part because even lawyers have to deal with the facts, but also because I sense a limited interest here in legal argumentation. I think we all hope that somehow, this case can be decided on the basis of the science, as a matter of Truth with a capital "T". If FL is exonerated because, say, LNDD used too much white-out on its lab documentation, my sense is that most of us would feel a sense of dissatisfaction with the result.<BR/><BR/>But you're making a good point, and M in his way is making the same point. The science here is extremely complicated, and we cannot hope to understand it at anything like the level of someone like the top people at LNDD, not to mention people like Brenna and M-A. Every time I try to read the GC operating manual, or one of the science papers published in the journals, I'm reminded that I'm not likely to teach myself chromatography in my spare time on the internet. <BR/><BR/>M, this is addressed to you, too. You're right, I have to have a bucket full of hubris to read the LNDD SOP and say that their specifications are wrong for this kind of testing! But you're doing the same kind of thing when you advance theories like the 5bA anchor theory, that have never been proposed by a scientist, that have never been peer reviewed, etc. Science is a PROCESS. It's not a matter of making logical deductions, particularly when you're making logical deductions from a layperson's knowledge of the science.<BR/><BR/>You ask, would I accept as a matter of science an identification of 5aA based on an IRMS-IRMS comparison of an athlete's sample to a mix cal that contained only 5aA? No, I would not. I cannot accept the scientific validity of a theory unless the theory emerges from the scientific process. I feel differently when you ask if any of these theories might have value to confirm results achived via a primary means that HAS been established by the scientific process. <BR/><BR/>Swim, back to your post. You are making a great point when you say that it IS the responsibility of lay people to understand science well enough to apply rules designed to judge the adequacy of the science. On a certain level, this requires us to trust the rules, and not to regard them as "technicalities" that do not have "Truth" value. My own POV is that, if we can determine that LNDD violated the rules, even technical rules like chain of custody or forensic corrections, then we can feel reasonably certain that we've found "Truth" with greater certainty than any "Truth" we might think we've reached based on our imperfect understanding of the science.<BR/><BR/>And you are absolutely right. As citizens, voters, jurors, we are going to be asked to make decisions of consequence on science matters. Just the issue of global warming alone presents us with a number of difficult decisions we'll all need to make that require us to understand the science as best we can. Are we going to embrace nuclear power to combat global warming, notwithstanding the risks? Are we going to force Detroit to built cars that don't emit greenhouse gases, even if it means that cars get more expensive and some workers may lose their jobs? What about wind, and solar, and drilling in the Alaska Wildlife Preserve? We can't abdicate our responsibility to be part of the decision-making process here, even if we're not scientists.<BR/><BR/>So ... we may be reaching the point where it would be valuable to turn from the science back to the law. IMHO the legal case is even stronger than before that LNDD's peak identification failed to meet ISL standards, that there should have been a "burden flip" under the WADA rules, and that USADA did not (and could not) meet the burden imposed by the burden flip. I don't think it's a close question.<BR/><BR/>If there's interest, I'll stop playing wannabee scientist for a while and be a lawyer instead. <BR/><BR/>The alternative would be to focus on the rules addressing peak specificity. I'm happy to do that too. As I write this, I'm not certain (from a legal point of view) whether those rules were violated in the FL case.<BR/><BR/>If I'm going to return to my role here as a lawyer, I would do it in something like a wiki process. I'd post something, and let people comment and add things to it. I'd try to cajole and educate, I'd let you know which arguments I thought were strong and which were weak. The wiki process can be more collaborative on peak identification. The rules on peak specificity are so difficult to interpret, I might have to do most of the work there.<BR/><BR/>And I'm fine with keeping our focus on the science, which is (I think) a topic of greater interest here.Larryhttps://www.blogger.com/profile/08976868079076669453noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-45381338504333554962007-12-12T17:01:00.000-08:002007-12-12T17:01:00.000-08:00m, your suggestion that we not tread in the detail...m, your suggestion that we not tread in the detailed scientific waters we don't fully understand is all fair and good. I may be more guilty than most in that regard (and I don't even qualify my posts!).<BR/><BR/>However, for quite a while now we have been (intentionally, I believe) staying away from the legal dimension of these arguments. But it is exactly the legal framework of the case that is supposed to make it possible for non-scientific people (like the three arbs who have already ruled, and the three who are yet to rule) to fairly and justly decide the case. We (like the arbs) may not be able to fully comprehend all the arguments about whether the isotope effect could skew the results and lead to an AAF, or whether the 5bA in the mix cal can help with identification of the sample peaks when the chromatographic conditions are not the same. But we can, presumably, look at the specific, scientific requirements of the International Standard for Laboratories and the technical documents, like TD2003IDCR, and decide whether LNDD did things the way they were supposed to.<BR/><BR/>The legal aspects of the case are exactly what is supposed to bridge the gap between the scientists and the rest of us. For that matter, the legal aspects of the case are supposed to bridge the gap between different scientists too, for obviously, they disagree. It is not a matter of giving up the search for "the truth" and debating "technicalities." It is a matter of recognizing the limits of both the science itself, and of our understanding of the science.<BR/><BR/>So I ask again, do you see your "enhanced peak matching" argument as consistent with TD2003IDCR? Do you see your argument as basically a "relaxed retention time" argument, with a little extra support from the matching of the pattern of peak heights between GCMS and IRMS, and a little further extra support from the 5bA anchor?<BR/><BR/>syiMike Solberghttps://www.blogger.com/profile/11784753552166129987noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-65106620496898286392007-12-12T15:16:00.000-08:002007-12-12T15:16:00.000-08:00m,Your suggestion of a piece-wise assessment of IR...m,<BR/><BR/>Your suggestion of a piece-wise assessment of IRMS peak position by injection of known single metabolites, one after the other, would potentially remove any doubts over position. It's a pity they didn't do what you suggest. If they had, we wouldn't be having this conversation.<BR/><BR/>As for being snide, I apolgise if that's how it appeared. I thought it was a reasonable extension to the approach that Larry takes. He qualifies his statements with an indication of his area of expertise in what he's talkng about. I'll happily start adopting a "I'm not a lawyer, but .." approach when it comes to legal matters (if I don't already do that ?)<BR/><BR/>AliAlihttps://www.blogger.com/profile/00786387057717601356noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-52067909475972927112007-12-12T13:10:00.000-08:002007-12-12T13:10:00.000-08:00Larry,By coincidence, it was Dr Davis who responde...Larry,<BR/><BR/>By coincidence, it was Dr Davis who responded (email) to my initial query for info from Mass Spec Solutions. I've explained what we are doing and asked whether he is able to help us with some general technical queries. I'm awaiting a subsequent response.<BR/><BR/>AliAlihttps://www.blogger.com/profile/00786387057717601356noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-12371455427968478622007-12-12T13:04:00.000-08:002007-12-12T13:04:00.000-08:00Ali,"Unless I'm missing something here (entirely p...Ali,<BR/><BR/>"Unless I'm missing something here (entirely possible), why would anyone deny that."<BR/><BR/>It's been like pulling teeth. It seems some people would deny this or hedge this.<BR/><BR/>Here's the caveat. I said that the IRMS reference material contained ONLY the 5A, nothing else. Therefore if there was a match of retention times in the IRMS we would have an identification, even if there was no mass spectra, because there was only 1 analyte in the reference material and there could be no doubt about which one it was.<BR/><BR/>Where the reference material contains multiple analytes as in this case, some folks who want to raise doubt (you know who you are) can claim that we don't know if the 5A in the IRMS reference material is really the 5A because its retention time doesn't match the 5A in the GCMS reference material (that also can be verified by its mass spectra). <BR/><BR/>My response is that the scientists know in which order the analytes are going to elute in the IRMS reference material and approximately the retention time from their reference libraries, previous experience etc. So they are confident that the 5A in the IRMS reference sample really is the 5A. To use one example, we know (from the GCMS and I assume prior experience) that the 5b. elutes long after the IS which elutes at 870 seconds in the IRMS. So we can be confident that the analyte in the reference sample at 1320 seconds is the 5B. To flesh out the example, we know that the IS, etio, 5B, andro elute in that order. So we can match retention times of the IRMS sample with the retention times of the analyte in the IRMS reference material and be confident of the identification. I going to guess that the reason they didn't include the 5A was that it elutes only 20 - 30 seconds after the 5B, and they didn't want to worry about overlap or confusion.<BR/><BR/>One way to get around this uncertainty would be to run a reference sample for each analyte in the IRMS. I assume the lab doesn't do this because it's too costly and cumbersome and thought not necessary since they are not basing their identification on that matching. <BR/><BR/> Nevertheless, one could base an identification on that match, as my question was designed to illustrate.<BR/><BR/>And as to the snide remark, at least I don't hide my qualifications or offer misleading statistical claims when I know better. <BR/><BR/>Larry,<BR/><BR/>What I object to is attempting to find ERROR in the DETAILS of the science, like the inlet pressure, when we don't even understand the basics. Moreover, there has been no expert testimony about this, much less any disagreement of experts. I know I'm not going to stop you guys from doing this, but I can still call attention to it.mhttps://www.blogger.com/profile/11845675234084955737noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-62663586237500769762007-12-12T11:17:00.000-08:002007-12-12T11:17:00.000-08:00M, I will grant you that I have no business questi...M, I will grant you that I have no business questioning the scientific consensus on anything. Unfortunately, we have no scientific consensus on most meaningful points here, we just have a battle of the experts. In such a battle, you have two choices: (1) you can decide that since there is no scientific consensus, there's no firm basis on which to make a decision, in which case the presumption of innocence takes over and FL is not sanctioned, or (2) people with a lower level of scientific expertise (arbitrators, jurors, bloggers) have to decide which expert is wrong and which is right. I'm perfectly happy to make choice (1).<BR/><BR/>Ali, as long as you are trying to open up a line of communication with Dr. Davis, I have another question. Assume for the moment that a lab does CIR testing and does the absolute best job possible of preserving all chromatographic conditions between the MS and the IRMS. Assume also that the IRMS combustion time is known and is the same time for all IRMS peaks. Does this eliminate the need for RRTs? In other words, will the MS RT for each peak always be equal to the IRMS RT minus the combustion time (with some small margin for error)?Larryhttps://www.blogger.com/profile/08976868079076669453noreply@blogger.comtag:blogger.com,1999:blog-31819641.post-51705237556636932122007-12-12T10:32:00.000-08:002007-12-12T10:32:00.000-08:00m,You said: "But if the GC-IRMS Mix Cal Acetate co...m,<BR/><BR/>You said: "But if the GC-IRMS Mix Cal Acetate contained just one substance, the 5A, and it eluted at exactly the same time as the 5A in the GC-IRMS F3 sample, I don't think even he would claim that the 5A in the sample was not the 5A in the Mix Cal. I don't think you can deny that either. Care to try?"<BR/><BR/><BR/>Unless I'm missing something here (entirely possible), why would anyone deny that. You seem to have adopted their arguement - i.e. to provide confidence that the correct peaks are being identified, the mix cal should contain the peaks of interest. <BR/><BR/>Although if they did what you suggest and dropped the 5B from the mix cal and just included the 5a in it, you'd be no better off. It would just mean that you could nail the 5a and be doubtful over the 5B ?<BR/><BR/>Maybe you could use Larry's disclaimer: "I'm no scientist, but ..."<BR/><BR/>AliAlihttps://www.blogger.com/profile/00786387057717601356noreply@blogger.com