DRUG TESTING ADVISORY BOARD
OPEN SESSION
June 4, 2002

Agenda Item: Welcome

MR. STEPHENSON: Good morning. I would like to welcome you to the open session of the Drug Testing Advisory Board. We are in open session this morning between now and approximately 10:00 o'clock this morning. We have a sign-in sheet outside and ask that anyone who wishes to make public comments to let us know. We will divide the time available for public comments among those who wish to make comments.

We have some interesting things for you this morning. One of those exciting new things that's happened is we have a new member of our Board, Dr. Mahmoud ElSohly. I've got to tell you, in the history of the Drug Testing Advisory Board as long as I've been around here -- and it's just about from the very beginning -- this is the first time that on the first meeting of the Board the new member shows up with an article in the Washington Post on the same day that he arrives. I think we're going to be upstaged on this whole process. This is Dr. ElSohly, as the international expert on marijuana, talking about this is not your dad's marijuana any more. It is in the Health section. I would suggest you go to WashingtonPost.com and look at the article.

Agenda Item: HHS UPDATE

DR. VOGL (HHS): This probably sounds like a broken record, but we have been working on the Federal Register notice to revise the guidelines to include specimen validity testing. Three months ago I gave the impression we were fairly close to publishing the notice. I hate to say that again, but I think this time we are.

Every time we review the document, we find perhaps a slight inconsistency in the current guidelines that needs to be revised so that it accounts for and is consistent with the specimen validity testing policy that we are attempting to incorporate into the guidelines. This time, we are in fact very close to coming up with the final document and the preamble that describes our thinking and how we arrived at our decisions on certain issues.

Assuming that is the case, I would hope to send the package forward to our Administrator for his signature, hopefully by the end of this month. At that point, if he is satisfied with it and it goes downtown to the Secretary's office, there is an additional review which is conducted by the Office of Management and Budget. They have 60 days to review proposed regulations.

We are still talking about potentially the end of August-September time frame for that review to occur at OMB and for the Secretary to sign off on it. We are still in a position to have it published in October. Then we need to select an implementation date, which would not be the date that it's published, but some time several months thereafter to allow all the laboratories to develop the methods and to ensure that they are prepared to do specimen validity testing on all regulated specimens.

That is most likely going to be six months from the time that the notice is published. We are talking about somewhere around May of next year where the actual implementation would occur. That is what I optimistically believe to be the events to take place over the next few months. I think we'll actually be able to accomplish that at this point. We are very close to coming up with the final Federal Register notice.

The next item is on alternative specimens. People who have been here before know we have been working on guidelines to include hair, oral fluid, sweat testing, and on-site testing in our program. We do have a draft Federal Register notice prepared for that. Unfortunately, we cannot move forward on that until we get the SVT policy finalized in the current Federal Register notice. After that, I believe we can quickly move forward with ensuring that the new guidelines for alternative specimens include the specimen validity testing policy and some of the other changes we have made. The notice for the alternative specimen guidelines would have a long public comment period. The minimum would probably be about 120 days.

MR. STEPHENSON: With the status of the specimen validity testing component, realize that that is an important stepping stone towards the new and more inclusive rewrite of the total guidelines with the alternative specimens and new technologies, as well as rewriting all of the guidelines to support all of these other components, too.

As we look at specimen validity, you could say that our whole program has been built on a deterrent system to try to allow individuals subject to drug testing to choose not to use drugs. Over the course of time we have seen a change in human behavior in those industries and environments where testing has been employed as part of a comprehensive program to address substance abuse in workplaces.

What has happened in the last couple of years, we can say that our program has been very successful over the last decade because we have spawned an industry which has brought forth products and mechanisms for people to try to beat the system. All of that being said, we have now gotten the behavior component down to a point where we are dealing with about three-tenths of one percent of the population subject to our regulated testing, which we know through annual examination of the data from the systems, that are still presenting problems and issues.

That is often considered by most to be good enough for anybody's work. 99.97 percent is pretty good. But the important thing here is the message: The rules are important. Since 9-11 the interest in importance of individual accountability, public safety, national security, have been reborn and enhanced in everybody's mind. This program is an integral part of that process.

The message that has to go out is that everybody has to play by the rules and has to abide by the standards or else all of those others that are complying say there's no value, there's no point. Why should I do it?

We look forward to getting the SVT out quickly. When it's done we will be introducing for your consideration and public comment alternative technologies and specimens of and by themselves that will also be able to help decrease the temptation of the folks to try to game the system, to get over on it. Oral fluids, hair, sweat testing, point of collection testing the a collection site, all of these things make it much more difficult for an individual who chooses to continue to use drugs to avoid detection.

That in and of itself is a very important element, because if we can truly get that message out and people understand it then perhaps we can deter drug use in our safety-sensitive and national security environments.

Now, we want to address a couple of areas where we have to do work in order to get to the future we want.

DR. BUSH (HHS): Thanks, Bob.

Months ago, I know we mentioned and asked for some volunteers to participate in medical review officer issues, a group, a working group for medical review officers to help handle the interpretation of any drug test result that a system like the NLCP provides. It will forever be true that analytically we can provide the best value, the best analytical result, the best number, the best quantitation possible, and yet if we don't understand what it means and help with that interpretation then that value, as perfect as it might be and as useful as a good number might be, is really lacks then without the interpretation part of it.

We brought this up a few months ago, asked for volunteers. Again, this was in one of my optimistic modes. I must have been hanging around Walt just too long and I was in a real optimistic mode where, we can do this, we're ready. Actually, we weren't quite ready. We weren't ready at all.

We're not ready yet, because we still have the specimen validity. What intervened was the issues around specimen validity testing and a lot of the interpretation that went with chemicals found in the urine that are aberrant, that are adulterants in and of themselves. We had to spend a good bit of time on looking at those interpretations.

So drug metabolite interpretations and other biological matrices took the second seat and still do. But I have every plan, in an optimistic mode, that September we're going to at our Drug Testing Advisory Board, we'll bring these up and breathe the new breath of life into them and move forward from that point.

That is also going to be true about collection site information, whether it's a manual or directions or whatever. Again, that is going to be partly composed of industry working groups who know the specimens so well, the alternative specimen so well, and all the issues that they have learned through experience to handle and can shed light on for us.

So those couple of groups are going to come back to life again. The third working group is going to be the MS-MS working group. When we start looking at the alternative matrices after the SVT Federal Register notice is published, when we put that on the front burner, we're going to have to look at that alternative confirmation technology or screening technology, using MS-MS as a screening technology. Who knew? Who thought? Maybe that will happen.

We've got to get criteria established for that. That is a very analytically focused working group, but it will be time to reconvene that so that we can best write acceptance criteria for those really good results when we put out our notice for comment on alternative matrices.

So there are three things that are rising back to the surface, but still in the shadow of the specimen validity testing final notice. Walt in his optimism -- and you have to have his optimism to get the final regulation, the final work product done, because to look for consistency among documents that are so complex really takes a mind who can handle that, that kind of thing, and yet keep the optimism: Today we're going to get this done. Then you find a couple more inconsistencies or things that you really want to address to make clearer, and that is also much of the goal, word-smithing to make clear the highly technical details that we have to incorporate into this.

Walt was a little optimistic about getting the specimen validity testing Federal Register notice out. I'm hanging around him too long because I'm optimistic. My goal is to have the alternative specimen and technology Federal Register notice out in draft form in the Federal Register by the end of this calendar year. I'll go on record there and say I'll pick the baton up from Walt and we can chuckle about the procedure and how this is going to go, because today we're going to share with you in a later session about the challenges we're seeing and yet the progress we've made with proficiency testing and for the alternative matrices and new technologies.

You will see how far we have come, but see how far we have to go.

MR. STEPHENSON: Quite honestly, this whole thing is evolving fairly well: the information that we have, the support we're getting from the administration, the additional budget, and we're going to have to create a whole new contract for a national laboratory certification program and have it awarded by next June. We're going to have the tasks embedded in there that are going to carry us through into the new alternative technologies and specimens environment.

The issues around medical review officer and collection site are things that have grown out of what we've done now, but we still need to work with our other federal agencies, with Department of Transportation and NRC, to the degree that it's possible to make sure that we continue that process of harmonizing, reduce the burden if different rules and sets of procedures and training guidance for those who have to review the process.

We are going to commit to doing a lot of work in these areas over the next year. That doesn't mean we have to wait for everything else. We will evolve the PT criteria. We will have more data. There will be more of an ability to interpret the information we are getting. We will pick the brains of those medical review officers and the collection site operators working in the alternative specimens to help establish some standards and guidelines that we can write down and put out to replicate, to spread across the United States as these other procedures come on line.

We actually have a pretty orderly process in play and we do need a good piece of public comment opportunity for everybody who is going to be impacted by these procedures to have an opportunity to read and understand, to ask questions, and then to provide their comments back for our consideration.

Agenda Item: DOT UPDATE

MR. EDGELL (DOT): I'd like to remind you that the Department has established the Electronic Transmission and Storage of Drug Testing Information Federal Advisory Committee. The purpose of this committee is to make recommendations to DOT concerning changes in our regulation that would be necessary to accommodate electronic technology in the reporting of drug testing results.

The committee -- this is a committee that has been selected by the Secretary of Transportation -- will assess the current status of the security technology and will make recommendations consistent with minimum standards for use in the drug testing area. Additionally, the committee will examine and provide advice to DOT related to the format and methodology used in transmitting this type of information, drug testing information going from the laboratory to the medical review officer and subsequently from the medical review officer to the employers.

We have an additional item that the committee will get to pending time and that is the level and procedures used in implementing electronic signature technology. This would not be the primary purpose of the committee, but a secondary or subsequent item. You can find more information on this on our DOT web site, www.dot.gov, and go into the DOT docket section. The docket number is 12148. That has the Federal Register announcement and in that Federal Register announcement it will point you to a meeting that is going to be held here in Washington at the J.W. Marriott on the 17th and 18th of June.

I'd like to advise the Board that DOT has received some funding -- actually, the FAA has received some funding -- from the Senate Appropriations Committee and it's a fairly short notice. For the record, I'll just read the task. The task is:

"A drug and alcohol validity testing study. The Department of Transportation revised its drug and alcohol regulations in December 2000. The regulations address the use of validity testing, which is designed to deter and detect attempts to adulterate or substitute specimens. The committee is concerned over reports that some categories of transportation employees could inadvertently fail to meet the current validity standards due to treatments for certain health-related issues, working conditions, or dietary habits. The committee is aware that the Department of Health and Human Services is in the process of finalizing its rules on validity testing standards. The committee is also aware that once the HHS rule is finalized that the DOT will publish a notice requiring validity testing in the transportation industry. The committee recommendation provides $250,000 for a comprehensive study of validity testing to ensure the highest level of accuracy."

The DOT, our office, and HHS Division of Workplace Programs and the FAA's Civil Aeromedical Institute are in the preliminary stages of developing our approach to addressing this task assigned to us by the Senate Committee.

We have one other item to tell you about today, and I'll let Robert Schoening, the Drug and Alcohol Program Manager for the U.S. Coast Guard, introduce you to the notice of proposed rulemaking and the purpose of that rulemaking on the notice of service agent listing. Bob.

MR. SCHOENING (USCG): At the last DTAB meeting, Donna Bush made mention of the fact of the numerous phone calls that SAMHSA keeps receiving and that I was working on systems to put into place to help relieve that work burden from SAMHSA. On May 3rd, we published in the Federal Register a notice for a listing of service agent providers that could help these mariners throughout the country get a drug test on an individualized type basis.

As of last night we have received close to 60 responses, which I am pleased with. I am expecting by June 15th to have approximately 75 to 100 responses. On June 15th, it is planned to have a database up on the web site so that these mariners can access that, we'll be able to access it, plus the regional exam centers, which are responsible for credentialing these mariners to be able to access and to also assist the mariners, and hopefully take some of this burden off Donna and her wonderful staff, who've been very helpful in referring all these calls to me.

MR. STEPHENSON: People don't understand that when we get calls, we get them from Sydney, Australia, we get them from Chile, we get them from around the world, from some very apprehensive individuals who say: Where do I go to get a drug test? My license is about to expire and I need my medical certificate updated and my drug test done; please, tell me now.

Of course, there is a great gap in time and this guy's spending a lot of money on an international phone call, and we have to tell him to call DOT. This is a very good process for all parties involved. Thank you.

We are looking forward to the work on both the electronic data reporting process, the advisory committee, because we fully intend to use the results from that to help guide us for subsequent regulatory development and procedures adjustment over time. Both of our departments and agencies were charged by the Office of Management and Budget to look at how to proceed into a paperless environment for the laboratory activities and to try to get there by 2003 or explain why we couldn't.

We're fully engaged in that process and it's amazing how much good information and process is going along.

In terms of the CAMI project, that also is an incredibly important piece of work and we fully hope that we will have not only a meeting of high quality, but also proceedings that will come from that and further guidance that will be very helpful to many parties. We were in Oklahoma, what was it, a couple of weeks ago now, and we're going back there again in a couple of weeks to continue to develop this process with DOT and the FAA.

It is an absolute world-class process. I am absolutely amazed by the ability to pull these things together and to have everybody understand what the issues are right off the bat. How we're going to proceed on this I think will please everybody.

Agenda Item: NRC UPDATE

MR. WEST (NRC): Currently the NRC is moving forward with its revision to the fitness for duty rule. This is 10 CFR Part 26 of our regulations. In a nutshell, we are at the stage of -- we make a particular distinction between a draft rule and a proposed rule. So we are a little bit away from a proposed rule.

We have been meeting with stakeholders since about mid-November of last year. We have been meeting on a monthly basis at the NRC headquarters office just up the street here, just across from the White Flint Metro.

Just to give you the big picture, we are expecting to have a proposed rule -- this is not a date for the Federal Register, but shortly thereafter it would be in the Federal Register. But we are hoping to have a proposed rule through our management chain by April 2003, and then another year after that have a final rule out around April 2004.

The next meeting is scheduled for June 26th and we are obliged to have something out on our web site, the NRC web site, about two weeks prior to that. It will be in the White Flint 1 Building. We have two buildings across from the White Flint Metro and it will be in that building.

I want to point out the two key things that we have to do -- I have mentioned one already. We have to take our draft rule that we've been meeting with various stakeholders on since November of last year and convert that, get it to the point where it's a polished proposed rule. I think we're probably about 60 percent where we would like to be.

Around September or so, we should stop. We may not stop completely the meetings, but it should be at pretty close to a point where we then can get it in our management chain and move it forward. Then we have the big items left: a draft regulatory analysis and also a backfit analysis.

So that is somewhat of an overview of where we are and what needs to be done.

If you're interested in looking at our draft language for the rule, you can find it on the NRC's web site and that is nrc.gov. Once you get up there, you then look for -- we have a particular web site for all of our rulemaking, and look specifically for the site for draft rule language. If you can't find your way through the maze, you might just go directly to it via ruleforum -- that is all one word, r-u-l-e-f-o-r-u-m -- .llnl.gov, and that should get you there. But again, the initial way of getting there would just be to go up on the NRC's web site, nrc.gov. Then the other, more direct way would be ruleform.llnl.gov.

Agenda Item: Progress Report on PT Results

MR. STEPHENSON: The next piece we have here is a progress report on PT results and alternative specimens. I want to commend all of the hard work that is gone into developing this presentation. Unfortunately, part of the report card process is we really like it. We really like the way it's been presented. So be gentle with us in your criticism, because we understand we're a little warped. I hope everybody out there who is going to see this will be able to be enthusiastic about it and it will make some sense to you. It makes eminent sense to us and we love the data formatting presentation.

DR. BUSH: Don't mind me if I jump up. We don't have handouts for this. There are no handouts, so everything is going to be from the screen.

DR. MITCHELL (RTI): I would like to tell you that there was a lot of work that has been done in this process, and we are only presenting a very small amount of the work. Two people, especially Dale Hart and Andy McDaniel, have worked with me to get this into a visual presentation, and then Donna and I took their input and worked with it to try to tell a story.

The story we are trying to tell is the process that we are having to go through to develop the guidelines and a performance testing program for the alternative matrices. The story that we are going the tell today will deal only with GC/MS or the confirmation process. We are evaluating the analytical values that we have received over a number of cycles of PT.

In order to tell the story, we need to have a reference. The reference we are going to use today to show the differences is going to be the urine program that we currently have in drug testing. In urine, for your information, the major confirmatory method is gas chromatography-mass spectroscopy. In this program, the levels of analyte that we are looking at are in the parts per billion.

Well, when we get into alternate matrices we find that we are going even further and we are pushing technology beyond what has been established. Now, for hair, for example -- and I want to correct something. In the laboratories, we had two laboratories that were using GC-MS-MS. The rest of the laboratories that participated in this program or in the pilot program were using GC-MS and they were normally using -- some were using EI, electron impact, and others were using chemical ionization.

But here we are looking at quantitations which are in parts per trillion and less than that. We will talk a little bit more about that as we go through the analysis. We are already one-thousandth of the levels that we are looking at in urine.

With oral fluid, the good old spit that we talk about, some people are using GC-MS and others use GC-MS-MS. The quantitations here are in the nanograms per mL. Unfortunately, not many people salivate enough to give 30 or 45 mLs of oral fluid, so now we have an additional problem in that the amount of specimen that is available is much less than urine. Now that in addition lowers the levels that we are looking at below the parts per billion.

In our analysis we are going to look at the variance in the values that we received and we are going to look at this in relationship to the industry agreed-upon cutoffs. When we started this process, we had working groups from industry. They came up with the cutoffs, which changed from time to time. But now we are going to look at what was recommended, or we are looking at what was recommended as the last value that was to be used for the cutoff for each of the analytes.

We are going to look at this in relationship to the means of the values that were reported by the participating laboratories. You know that you cannot get statistics on two values, that is where you only have two. Values that are on three are somewhat iffy and have a lot of variance, as we will see. That is one of the factors that is a problem.

We will be looking at some bar graphs -- this is one of the presentations -- which are going to have histograms and above each histogram we are going to have the mean value that we obtained for each sample that we received three or more values. We are also going to look at variation as what we call percent -- coefficient of variation. Some people call it the relative standard deviation. But this is an expression of a standard deviation, which is a measure of the variance of the values that are reported, that are included in the mean, expressed as a percent. So if you had a value where the percent CV, or coefficient of variation, was 100, that would mean that the variation was equal to the mean, so that is a very high variance, and we'll see some of that.

Another presentation you are going to see is the performance around the cutoffs. Here we are going to have what we call -- we will have some graphs which will be a graph of the reported values from each laboratory versus the mean value. In these presentations we will show the plus and minus 20 percent and plus and minus 50 percent quantitation ranges.

Now, the reason we are showing these is that currently in urine these are the standards. We say that the values must be within plus or minus 20 percent in order for them to be acceptable. If they are outside of plus or minus 20 percent, that means the laboratory needs to look at their system and try to determine why they have values that are outside of 20 percent.

When it's outside of 50 percent, then the program gets involved and requires remediation, and we direct that very closely because there is obviously a problem with the system and it has to be changed and corrected at that point in time.

We will look at the values that were reported by the laboratories during either the pilot or maintenance PT for the urine relative to the cutoff and we'll look at the distribution below the cutoff. One of the things that is necessary is that in order to show that a system is working you need to show accuracy on either side of the critical value, which is the cutoff. That is what we have done in urine and we need to be able to see that in the other matrices.

The source of these analytical values. I have included the most recent two maintenance PT cycles for the urine for the labs that are currently certified within the NLCP. We have had four cycles of hair pilot PT and we took only the six labs, values from the six labs that have competed all four cycles. There were more labs than that initially. A bunch dropped out and we ended up with six labs in the fourth cycle. We will be looking at the values that those labs presented.

We will look at three oral fluid pilot PT cycles and the nine labs that completed all three cycles.

Cannabinoids present some unique problems. They are unique in that the metabolite or the compounds that we are looking at, whether it is the parent compound as we look at that in oral fluid or the metabolite that is produced by the body processing that original compound, which is THC, one of the active ingredients in marijuana, they both have some properties that make them a difficult analyte to work with.

The methods that have been used again are GC-MS in urine, GC-MS-EI and CI, and GC-MS-MS for hair, and then the same type of methodologies for oral fluids.

We will start by looking at urine. This is the histogram or the bar graph that I was talking about. On the left side we have a plot of the coefficient of variation, percent CV. The bar graphs represent the mean concentration, the variance around that mean concentration. For example, this is a variance of about 14 percent around a sample that had a concentration of 11 nanograms per mL. You can see the cutoff, the relative position, the cutoff for THCA, that is the metabolite of THC, tetrahydrocannabinol, is 15 in urine. So it falls between 11 and 19. It's just to give you a reference of where we are and how the variance is on either side.

We try to include with each cycle samples on either side of the cutoff in the maintenance PT program. So occasion 61 was the set of samples, PT samples, we sent to certified laboratories in January; occasion 62 was the samples that we sent in April. We send four cycles a year to our certified laboratories. As you can see, the percent CV runs somewhere around less than 15 percent for this compound. This is -- I might say that the variation we see with THCA is the highest that we see in all of the analytes that we work with in the NLCP.

Another thing that I want to remind you about, the CV is determined by standard deviation and one of the factors in standard deviation, determining standard deviation, is the number of values that you have. So your standard deviation, if the values are good, is going to be real low and is going to get even less as the number of labs increase. So that is one explanation for the very low CVs that we see here. Another explanation is that the laboratories have been doing this for a long time and they've standardized their methods across the system, and so that has provided a unique environment in which we can have a system which has relatively low standard deviations, or CV's.

This is another graph of the reported values for the metabolite from THC from the two cycles. You can see the different samples and the spread of the values within that sample. This is 57 laboratories, by the way, with each sample. You can see that we do have out here -- we did have a lab that had a 50 percent error, which was remediated. I forget which cycle that was in, but it has been remediated and the issue taken care of within the system. You can see that we have values on both sides of the cutoff, as we saw on the previous one. But it's very difficult to see what's going on around the cutoff. On the next slide we have a blow-up of those values.

You can see that we have two samples. I believe one was 9 and one was 11. Then we have another one above the cutoff, which was 18 or 19, something like that. So you can see how in a system that has been standardized, how the values tend to be compressed if the laboratories are doing things the way they should be and systems are in place.

You will occasionally have samples that fall outside, indicating a problem that needs to be corrected. Since this is done every three months, we keep a very close look at the laboratories and on the systems that they have within their laboratory.

DR. SAMPLE (DTAB member): Two quick questions. The dotted lines, is that the 1 and 2 SD?

DR. MITCHELL: The purplish blue lines are the plus or minus 20 percent range and the red, meaning danger, is the plus or minus 50 percent range.

DR. SAMPLE: Do you have an estimate on a percentage basis of the span from minimum to maximum? Did you typically see values ranging, say, as low as 20 percent from the mean at the low end, 30 percent, or 40 percent? Was that constant across different concentration ranges or did you see on a percentage basis larger differences in the full span from minimum to maximum at higher concentrations?

DR. MITCHELL: As a percent, they tend to be within the 20 percent. But you do have values that fall outside of that and that is one of the things that we have to look at with a laboratory. If they are showing with a particular analyte they are constantly giving a high or low 20 percent value for a particular analyte, that means they are off center and need to adjust themselves, remake calibrators or something of this nature to bring them back within the standards.

You will see with THC that this is the worst situation that we have, because we see more variance in the THC. One of the problems, as Dr. ElSohly can give us a dissertation upon the peculiarities of this compound, in aqueous solutions it is very hydrophobic. It tends to glob onto little particles that might be in the urine and things like that. It is going to cause some variation that is very difficult to control for.

But this is the one that we see. You end up with probably not a true solution. You end up with somewhat of a suspension in some cases with this compound, because it doesn't like to be in water. It would be much happier in an organic solvent; it would be much more soluble. Solubility is very low. That is something else, talking about the solubilities and how we get high amounts in urine and things like that. That is another issue, but we are not going to deal with that today.

In the next slide, we are going to talk about hair. I have written the cutoff for hair, which is 0.05 picograms/milligram. If we expressed urine cutoff in picograms, we would say that it was 15,000 picograms/mL of urine. We are talking about a large difference. In reality, it's not exactly comparable, but you could say that the value there is one four hundred thousandth of the value for the cutoff for urine. Just to show that there's a very large difference in the two cutoffs.

In hair, for cycle four we had six labs: lab A, E, G, H, I, and L. You can see that out of that six only four were testing for this metabolite, because this is a hard metabolite to test for. Even the urine, which is looking at much greater amounts, it is difficult. We had four labs, two which were using MS-MS and two which were using the MS and a chemical ionization mode.

Again the histogram with the percent CV; the cycles in which samples were usable, and the reason I say "usable" is that in some of the cycles we had samples that we only got one or two values for the THCA in that sample. Those are not included in this. We will look at those in a minute. These are only samples for which we had three or more values presented.

Secondly, we did not send or have marijuana-spiked samples in every cycle. We are just looking at what is usable in the cycles in which it was included.

Now, in cycle 2 you can see that we had one usable value. The mean for that sample was 3 picograms/mg and the cutoff again is 0.05 picograms. In cycle 2, if you remember going through this process we had in cycle 3, we had the samples analyzed without a wash procedure and with a wash procedure. We are trying to compare what was the effect of washing on the analytical procedures, and we will talk about that in a minute, just trying to explain.

You can see there that in cycle 3 we had some values which were much less than what we saw in cycle 2, the lowest being 0.67 picograms/milligram. We have not found soluble hair yet without some treatments. But 0.67 picograms/milligram was the low. That is still above the cutoff. Also under the wash we had a similar thing, except there the value that was determined on one of the samples was 0.85, was the lowest one.

We can't compare samples in this presentation. We did that previously when we were looking at this. I am not going to compare sample to sample.

DR. JACKSON (DTAB member): The proficiency samples for hair, were these actual user samples or were they spiked samples?

DR. MITCHELL: These were spiked. We have had some from users. I did not intend to present that analysis in this particular one. That is, the results from user hair versus spiked hair. That is a totally different analysis. We will do that as part of the Board's analysis of the PT program at some point in time.

Any more questions before we go on? Because it is important to look at all these issues as far as performance program.

Next slide, please. This is again the graph showing the values, the usable values that we have, and you can see what we saw before, is that the cutoffs down here, the usable values as far as statistics is concerned are all above about 0.6. You can see that we had four labs which provided values. The question is what was happening down in this area (indicating). Let's go to the next slide and let's look at that.

This is a totally different slide. I'm going to have to explain it a little bit. Along the bottom axis we have one or two labs. This is the labs -- the labs provided values for a sample. Now, on the Y axis we have the value that each of the labs provided. So in this case, in this column we have eight points, which means that we had eight different samples for which the laboratories provided -- only one laboratory was able to provide a quantitative value or provided a quantitative value. In the next column, over 2, we see that there are 16 values, which means that again there were 8 samples for which we had 2 labs provided a value on that sample. You can see that we were beginning to approach the cutoff. But the main thing is that when we get down below this 0.6 we had, out of the four labs, only they were able to provide values, and really only two labs were consistently able to provide us values.

Now, that presents a unique situation or challenge to the program, in that how do you determine with just two values and two labs that are able to do the quantitation in this area, how do you provide a performance program for them? So it's going to take some thinking out of the box and we're going to have to address this problem.

Hopefully, though, as we go along then we'll have more labs which it would appear are able to provide the technology that is needed to get down to these levels if we keep the cutoff at this point.

MR. ELSOHLY (DTAB member): On what basis was the cutoff set at 0.05 picograms per milligram?

DR. MITCHELL: That was a value that came out of a meeting in Las Vegas of a group of the laboratories and other people. It was a value that was thought to be attainable. But it is -- in practice at that time, it was thought that it was attainable, but I think now that we're looking at it that it appears to be probably at the end, the lower end of the limit of quantitation and detection. It's probably near the LOD, just from what I'm seen. Unless we have a movement down, we are going to have difficulty in a program, in a PT program, providing values on both sides. That is going to be an issue. In other words, looking at 0.025 is where we would want to be challenging, in that area, picograms, in order to have the same type -- to demonstrate the same type of reliability that we have with the urine matrix.

DR. BUSH: Just a comment on where the cutoffs come from, a little more detail on that since you weren't part of the Board, probably peripherally watching what's going on. But starting in 1997 in April, we had a three-day meeting, then in September a two-day meeting, where when this concept rose to be evaluated, alternative technologies and matrices for use in the drug-free workplace program, specifically drug testing here. We gathered the industry partners together and said: Tell us your story, present your information, your data, to us; show us what you can do. Help us understand where we can take this to the road, on the road show, the NLCP road show? How can we do this, and what can we expect to achieve in a deterrence type program and identification?

It was then established that we would have industry working groups for sweat testing, for oral fluid, for hair testing, for point of collection testing using oral fluid and urine, of laboratory-based urine testing. For all of these we had industry working groups that got together, similar to working groups that I described earlier for medical review officers.

This is what the industry has presented us with what they believe they can do. We are proceeding ahead with that because this is what the industry wants us to incorporate into the guidelines as the cutoffs they can achieve. This is true for all the cutoffs that you see here, whether it's oral fluid or hair, or in another meeting.

Unfortunately for people who thrive on analytical data, I could do this all day long. However, probably not too many other people want to do that, so that is why you're only going to see some of these today. This is why we are trying to marry what's been presented to us and what people believe to their best knowledge they can do and then how are we going to embrace that. That is the bottom line.

DR. MITCHELL: I would like to go back two slides to the histogram because there was a point I missed. Looking at the variation, there are a couple of things that I want to talk about here. You can see that some of the variation was very low, especially in the washed. We had in the range of above a picogram/mg. But again, most of these values dealt with only -- well, most of these means only had three values. That is going to give you high variation. I mean, the CV's are going to go up, standard deviations, with only three values. I want to bring that out at this point in time..

MR. LoDICO (HHS): What about cycle 3, where you have percent CV there well below 10 percent. How do you account for that?

DR. MITCHELL: I can't.

MR. LoDICO: Is that an improvement in the technology?

DR. MITCHELL: I don't know. It may have been.

DR. SAMPLE: Are you saying that there are more labs, though, that tested at that higher level? Because originally you had said that there were six labs that you are basing this data on.

DR. MITCHELL: Well, actually there are only four which were doing THCA.

DR. SAMPLE: There are four labs at the 1.89 and 3.91 means in cycle 3 washed?

DR. MITCHELL: That's correct.

DR. SAMPLE: And at 0.85 there was two labs?

DR. MITCHELL: I can't give you all of that. I have that data with me, Barry. We can look at that later. I just wanted to show that there are at least three in there and no more than four in any of them. Those are the values that we ended up with. But the variance, as we see, can go down. We do see that. There is hope that we can get the CV's down even with three or four labs.

MR. LoDICO: That's only at the higher concentrations.

DR. MITCHELL: That's only with the higher concentration. I would think, since we didn't have any of the THC that we had three values on in cycle 1 and we did have some THC's there, we can see that there has been some signs of improvement throughout the system. This may well be pointed out at the higher levels, but I think that in the lower levels we still have a question of what we can obtain, and we don't have enough data to really assess these fine points at this point in time.

Let's go back to where we were. Next slide.

This is an interesting slide, one of the ones that tells you some things. One of the issues that we have with hair testing is that some of the laboratories will conduct testing on hair that has gone through a wash procedure of some type. Either it's a buffer with some type of alcohol or something of this nature, some type of wash procedure. So just to look a little bit deeper at the effects of that wash upon concentrations, we have presented this type of plot, in which we have the mean of the washed versus the mean of the non-washed. If there is no change in concentration due to wash, then you should see the points going along the theoretical line, which means that the two means were the same. With THC it appears that it's pretty good, there's good agreement, and that would indicate what we would expect, since it's hydrophobic and it does not go into water too well, that the wash mean and the non-wash mean should be about the same. But that is not true for all analytes and we're looking at those issues as we go through.

MR. SLAWSON (DTAB member): Are these the same laboratories that did a washed and an unwashed comparison, or are these from different laboratories?

DR. MITCHELL: There are at least three values for each one, so they would be -- out of that four labs, it would be one of the three.

MR. SLAWSON: But the question is did lab A do an unwashed sample and a washed sample to

get that number?

DR. MITCHELL: Sometimes. There were issues with trying to get -- the instructions were for the labs to analyze it first unwashed or without a wash and then washed, run it through their washing protocol. Some labs were able to do that, some were not. Some only gave me one value, either washed or unwashed. Some labs gave two. These were for various reasons. An issue which I haven't talked about which we will have to consider is the amount of hair that is available, because some labs ran out before they were able -- ran out of hair before they were able to do the second one and things of this nature.

MR. STEPHENSON: What this represents is progress in how to develop the pilot PT program itself. It's not just an analysis of the performance of the labs. It's also an analysis of how we are evolving preparing specimens and getting them out there and then evaluating the responses that come back. That's why with any of these PT programs at the end of the day we have to establish values that the industry says they can achieve, but we also have to demonstrate the ability to perform in an operational environment against those standards. That's where we're working together. It's interesting to see over the last year how much progress has been made. The leading progress has been made in the hair testing environment because that is where we have had the most concentrated work and effort over the longest period of time. But we are having to do the same thing with the other specimens. We have one group that we haven't even really addressed yet and that is the point of collection testing and that is going to have to come later.

The idea is that from our perspective, understand that this is a positive direction, but you can't just look at the data and talk about the performance of the labs, because half of this is about what we're doing.

DR. MITCHELL: That's all I have on the hair. Let's go to oral fluids and look at some of the issues that we have with oral fluids. Again, oral fluids, here we are looking at the parent compound, THC, tetrahydrocannabinol, and the cutoff is 2 nanograms/milliliter of oral fluid. You can see that we have a mixture of -- we have two labs doing MS-MS and four labs doing MS.

Out of the nine labs that were there, we have two that did not test for this analyte.

Looking at the variation, you can see that in cycle 1 the values were all over the place as far as variation is concerned. We had variation all the way up to 120, 130 capability of the mean, which was a problem. That's in cycles 1 and 2. You can see now in cycle 3 that we have, the variation has dropped. In cycle 3 we were looking at the analysis of oral fluid neat -- we call it neat; that is, they were just pipetting the oral fluid in and analyzing it -- and also we asked the laboratories to pipette onto a device the amount that that device theoretically would hold and then to do the analysis as they normally would if they were using a collection device.

We were looking at those issues there. You can see that in this there is still variation. I don't think -- there's a whole series of issues associated with this. But we do have overall the variation has come down to 40, to between 40 and 20 percent. We have seen improvement from early on.

Now, this is the hardest analyte again because it is the hydrophobic analyte. You can see that we were able to have samples on both sides of the cutoff to look at the variation and the ability of the laboratories, we did in cycle 1 and also in cycle 3 in the neat samples.

DR. SAMPLE: Why do we not have on-device for that fourth data point?

DR. MITCHELL: I am not sure. I really don't know that. Again, looking at the values, you can see the wide spread. We have values inside close to and outside the 50 percent. That's why we have the large variation. On one of these there was a value that we left out, which I couldn't plot it on here because it was ten times or more of the mean value. I had a little problem with that. But I left that out of here. You can see the values normally are fairly widely distributed.

Next slide, please.

Now, this is quite different. This is the theoretical, again the mean on the device versus the mean of the neat. You can see that it doesn't follow the theoretical line. The values that we see from the device are less than what we would expect and gives us values which fall below the theoretical line. That's what we would expect if the material was being irreversibly bound to the absorbent material that they use in these collection devices. That is an issue that we do have to face in our review of the oral fluids.

MR. ELSOHLY: Were they instructed to wash the device with a buffer or something, or just to centrifuge it and do whatever comes out? Because it looks like almost exactly 50 percent of what was the theoretical.

DR. MITCHELL: They were asked to process it as they would if they had a device.

MR. ELSOHLY: Which is just centrifuge?

DR. MITCHELL: Well, some of them take the device, they put it into a buffer, and then elute it in that buffer. I'm not sure. I really haven't looked at all the procedures in the device, but they were all lower. It didn't matter.

DR. BUSH: Mahmoud, it was whatever the company would do if they were following their own standard operating procedure with the device as they have it established for performance in their hands.

DR. MITCHELL: One of the things that probably a lot of people here are probably not aware of is that with urine we went through a similar process early on and we found that some of the bottles being used absorbed the THC metabolite, and we had to use a bottle that had minimal absorption and that material is used throughout the industry. It looks like we may have a similar issue here that has to be resolved.

That is my last slide.

DR. BUSH: I hope you can follow this story. What we had intended -- these were all the intentions of what we had when we started out: How do we formulate hair specimens to challenge analytical processes at laboratories who can perform hair testing? The same thing with oral fluids, the same thing with sweat. How could we construct specimens and yet challenge laboratories?

We had to start with confirmatory techniques and technologies. Understand and recall that this is just for confirmation techniques and technologies. We haven't even looked at the screening devices that are paired in the hands of those who do these types of tests. A screen and confirm generally tends to be the process used, and we haven't even looked at those screening devices for presentation here today.

I thought I'd spare you. This is a lot to absorb. I thought we'd start here and then work forward from that. Next time we'll take a look at the screening devices as well as other drugs.

I think the way this data was portrayed and displayed shows you graphically with numbers the issues that we face, looking at the cutoffs, looking at the specimens themselves, looking at the numbers that have been given to us. The reason that we chose cannabinoids for today's presentation is because it is the most challenging molecule in our program to date. It occurs in very low concentrations in whatever biological specimen you want to look at. And it's America's favorite illegal drug. When you look at how many drug test positives we are going to see no matter what specimen we identify, you are going to see a lot of THC's. We better be able to handle this. This actually is our worst case scenario drug, yet the one we need to put most attention on.

You heard John Mitchell mention many times a system, taking a look at the drug testing system. A system in these cases, we need to look at it in two ways. There is the laboratory doing each specific analysis and then there is the system of the program looking at the multiple laboratories participating. When you look at a systems approach you almost have to think on two levels, the operational system at the laboratory as well as how are we going to handle this as a program and the questions that we are going to be asked to address for the credibility of results put out by a nationally implemented, nationally certified drug testing program.

We look at it from our seat, we look at it from the small system within the laboratory, and that includes the collection device and getting it to the lab and getting it off the device, getting it into the analytical instruments to get the result, and then report a systems approach consistency amongst those laboratories, and then how we handle this, looking at the accuracy and reliability of the results.

What comes to mind repeatedly, having befriended DOT for so many years in drug testing, you look at the requirement to have two labs for today's model of an A and a B lab for a split specimen. You look at this always and say we always have to have two labs capable, certified at any one time for this, and you look at the technology that must be brought to bear to do that, as well as us learning how as a program to formulate PT's that reflect the reality of the specimen and the drugs in the specimen. It's no small task, but I see so much progress here since that day. Those of you who were around then, do you remember that April in 1997 when we had the first big meeting?

We have come so far since then, and we do have a way to go. Questions always come up, spiked versus users' hair, it's going to be spiked versus users' oral fluid. It's always those kinds of issues. We must answer some of those questions, because clearly in our urine drug testing program we do not use users' urine in our PT program, and yet we found we can tune the instruments to the analytes of interest quite well without using users' urine.

When you screen, people talk about that, well, you don't have a profile of metabolites, in the case of marijuana you may not have the 50 or 60 metabolites then to light up a screening technology. Do you need that? Where are we going with these technologies, the new technologies? What metabolites do you see versus parent in the oral fluid, in the sweat, in the hair? There are a lot of paired questions and answers that have to be implemented every step we take.

Future plans. I already alluded to it and so did John, to other analytes. We were crunching through those, but out of the goodness of our hearts we decided not to go through all other analytes at this meeting. But you see the issues. This is what we are going to do. This will help us when we visit RTI to take a look at the next round of PT's to formulate. When we at DWP do a site visit, we formulate, evaluate all of this, and look at the next round of PT's, and make a plan for preparing the next round of PT's.

You do not want labs who are doing a lot of work with us and for us to be saddled with a whole lot of work burden that is not going to be productive for both. We constantly evaluate these things.

We are going to use it for that purpose for the next round of PT's that go out. Then, as I said, the immunoassay or the screening tests, whatever they might be, take a look again at the precision and specificity of those, and then have to link that up with the confirmatory information that you saw. That was just for the oral fluid and the hair and we didn't even present the sweat here. Then we have point of collection testing, which is a whole different concept. I've alluded to that earlier. We haven't even gotten to that model yet, and we have to evolve the cutoffs and standards of testing, look at other drugs. MDMA has not fallen off our radar screen. Yet we don't mention it here, yet behind the scenes we still have to pay attention to MDMA and analytical methods with that, as well as other drugs.

Evolve cutoffs and standards of testing. That will continue and has to be broad-based in light of alternative specimens and technologies also.

The goal is to take the word "pilot" out of that title. We want the development, the NLCP PT program for alternative matrices. That is why this evolution and this knowledge helps us with writing that Federal Register notice for the draft for alternative testing technologies.

One thing that does concern us is if we write and accept certain technologies, certain things at a time, we have to know that what we're writing is going to match what we can do, because it would really do no one any good to write to a standard in the future where for a little while we can't achieve. So we try to balance that with our writing. I still want it out by the end of this year.

Agenda Item: Public Comments

MS. JONES: Good morning. It's nice to see everyone here and I appreciate the opportunity to be here and share some very interesting information with you folks today.

My name is Julia Jones and I am a former flight attendant for Frontier Airlines in Denver, Colorado. I have traveled here from Colorado today and I bring each of you gifts. The first gift is a bottle of Visine. The economy size will be for the Department of Transportation from whom I have sought assistance and technical information without success for over two years. This Visine not only gets the red out, it gets the blinders off, especially the type of blinders which may form when principal stakeholders in an industry are charged with setting industry standards. This Visine allows you to see clearly two facts which have already been well documented to DOT and HHS, yet continue to be buried under phrases of statistical improbability.

The first fact is that a normal human being can test below the substitution thresholds. I demonstrated this on a DOT treated back-to-work drug test two years ago, for which I was fired as a flight attendant at Frontier Airlines. Both my employer and the DOT repeatedly said that without a valid medical explanation such as major illness I had to have cheated on the test. But, like Michele Nelson, a healthy flying partner from Delta who told you about testing "substituted" on an observed follow-up drug test, I represent a statistical minority, one that databases have yet to formally recognize and accommodate.

You will see that I have produced five substituted samples in an observed clinically controlled water load study conducted by the University of Colorado just last month.

The Visine will help you to clearly see that: I am not ill; I am human; that I have not used a hidden catheter to produce these samples, as suggested by DOT to explain away Michele Nelson's observed substituted test; and that the submitted studies on my urine are more valid than those conducted or paid for by DOT or HHS.

The Visine will also help with clarity around a second fact. Simply put, the accuracy and reliability of substitution testing merits a Surgeon General's warning on the side of each urine container that says: "Warning: Harmful effects of substitution testing include loss of job, loss of house, and, most predictably, loss of dignity and respect."

I first introduced to you the jeopardous nature of substitution testing after a successful court value to lift the then prohibition of testing my split. Unlike Bottle A, which was declared substituted with values of 4.9 creatinine and 1.001 specific gravity, the test of Bottle B was negative for the presence of any drug and was not substituted, with values of 2.9 creatinine and 1.002 specific gravity.

Unfortunately, even though I have cleared my name, I still do not have my job back and have yet to be successful in getting the test of Bottle A cancelled.

Today I submit to you additional documentation which substantiates that the accuracy and reliability of substitution testing in and between labs continues to be imminently more hazardous to me and others like me than any danger presented by being in a workplace with drug users. No new procedures or directives issued by HHS can fix the 100 percent discrepancy rate in paired creatinine and specific gravity values reported on me for the last two years. No new guidelines or adjustments in values have been established to protect me from another false substituted test result.

As a final gift -- I brought two -- I will give you a card with a very important message I hope you will follow frequently and often as you consider your actions around validity testing: Just do the right thing. For the past two years, I have felt like the sacrificial road kill of a fast-moving alternative drug testing train that wants the validity question quickly settled at all costs.

Doing the right thing means recognizing rather than denying the existence of outliers like myself. It means establishing a new normal which removes the pathology and subsequent employment discipline currently associated with my normal human urine.

I do have packets available and all of my test results are included in that packet of information for you. Thank you very much.

MR. STEPHENSON: Thank you very much. Are there any other public comments? (No response.) At this time, I am going to close the open session of the Drug Testing Advisory Board.

The open session was adjourned at 10:10 a.m..