DRUG TESTING ADVISORY BOARD
OPEN SESSION
September 6, 2000

 

Agenda Item: Welcome

 

MR. STEPHENSON (HHS):  I would like to welcome you to the open session of the Drug Testing Advisory Board.  I'd like to request that everybody who is present take a couple of minutes and make sure that you have signed in, that you give us some information so we can send interesting things to you in the future.

               

Agenda Item:  HHS UPDATE

 

MR. STEPHENSON:  We can start with our HHS updates.  This is our household survey.  It was released for 1999 on August 31st.  The things that are important to us are that the survey has acted as kind of a baseline analysis with which we make public policy decisions and think about the way that we're going to focus public funds and activities.  14.8 million individuals in the United States ages 12 and older, 6.7 percent, were drug users or had used a drug in the past 30 days during 1999.

                The household survey in the age group 12 to 17 has showed a three-year consistent drop in the percent positives.  This is a very important thing.  When we look at what we do in testing, we look at the self-reported estimates from the household survey as part of our guidance that we use to know where we need to focus, to look forward.

                It went from 11.4 percent in 1997 down to 9.9 percent in 1998, down to 9 percent in 1999.  In a parallel survey, the drug abuse warning network -- this is a survey of hospitals and emergency room activities -- we have seen a decrease of 11 percent in emergency room visits for that same age group between 1998 and 1999.

                Unfortunately for us, the work force population that's just preparing to enter the workplace, those 18 to 25, has seen a three-year upswing in current drug use, looking at the 14.7 percent in 1997, 16.1 percent in 1998, and 18.8 percent in 1999.  What that means to us is that we have to pay closer attention to those young people that are preparing for and entering our workforce nationally.

                The tight labor market has made it a very tempting practice to stop doing drug tests, because you do need a labor force and some things you may be willing to forgive or ignore or turn a blind eye towards.  The suggestion is that what's happening.  It is sending a message to our young people at a time when they're at their greatest risk and when they're also at the incidence and prevalence rates we're seeing going up.

                I think we need to hold the line.  I would suggest that we temper the drug testing with even better drug education and that we do an outreach to folks to make sure we have access to adequate counseling and service referrals.  I've said this for several years and this is the first time I'm actually beginning to think it might become a reality.

                This is an echo of a comment that had been made by Mike Walsh some years ago, that in this tight labor market we may well find a day, and that day may be approaching, when even people that have a current drug problem, if there is a significant skill that they offer an employer, we might have a way of identifying them and then offering service, assuring compliance with treatment, abstinence, and then integrating them into a work force at an earlier time.

                Having said that, I think we've got our job cut out for us.  Not only do we have a lifestyle issue of a young population that is going to continue to need our attention and focus as they age.

I think it's important for us to pay attention to the issues of people who want to continue a lifestyle of drug use without the consequence of paying for that with a job or job opportunity.  The issues that we've had to address and have become somewhat controversial about adulteration and substitution has been an issue that we have had to face using the best science we can for some two years now, and I think we'll continue with that. 

                I think you're going to see a portion of this younger population coming into our work force that will try to buy something off the Internet, out of some magazine, that supports that lifestyle, or other sources, from friends, to continue drug use without paying the consequences.  I would hope that that is something that we will continue to focus on and deny as an opportunity for them.  I'd rather have them receive the message that there is no sanctuary, that every day is a day of risk, and if they choose the lifestyle that may not get them a job that they want or keep one that they value.

               

DR. BUSH (HHS):  I'd like to take just a moment to share with you a site, a couple of locations where you can get this document.  It's titled "Summary of Findings from the 1999 National Household Survey on Drug Abuse."  It's got a number on its spine, H-12.  That may be helpful.  There's an 800 number at the National Clearinghouse for Alcohol and Drug Information.  The number is 800-729-6686.  It's also available on our web site, www.samhsa.gov.

                The study format, it has national estimates of substance abuse and use, state estimates of substance abuse and use, and discussion of the trends in the 1999 results.  This may be very helpful to you in your respective businesses and other actions and things that you get into at the state level or a local level.  Maybe this will help with some understanding in making a point about what Bob just said.

 

MR. STEPHENSON:  We have one other thing we'd like to share with you, and this is what's been going on with the Office of Management and Budget.  There have been round table meetings to discuss paperwork elimination.  The idea is to address the issues of the paperless laboratory and electronic signature elements and the trust in archived electronic documents that could meet a stringent standard of forensic acceptability in our kind of work.  We have a prepared summary of this information and it has established the use of the Internet and secured meeting, net meeting, kinds of opportunities to facilitate some of the efforts of the working group to look at documents and to prepare policy statements and to review elements within those records that they're reviewing.

 

MR. LODICO (HHS):   OMB sponsored the initial meeting on August 4^th with industry group members.  From that initial meeting, we had a follow-up meeting several weeks later.  From that meeting several working groups were formed:  one focused on formatting for paperless lab information gathering; another group was for laboratory documentation, and a management group.  From those three groups we have offered a means for those committees to meet and to discuss  these processes through our web site.  I have been participating with one of those groups, which is the HTLM group that was chaired by Ken McCaslen (Quest Diagnostics Group).

                We've had two very successful telephone conferences, and in that conference we focused on what are the data elements to capture from the chain of custody forms, and we have used the Federal custody and control form as the model by which these data elements will be captured and put into a standardized format so that the laboratories as a whole can recognize and say that these are the elements we're going to capture, this is the type of formatting, this is the type of limit of information that's going to be approached, and that we want to have available, as I said, to all the laboratories so that we have a uniform code.

                The first meeting was just telephone conferencing.  The second meeting, which occurred just last week, was a combination of telephone conferencing and a web site that we have available through our office.  I must say it was very successful because the participation was such that each individual had their own PC, they have a password that they entered into that web site.  Then we had our webmaster, our contractor, who controlled the document that would appear on their screens.

                It was interactive in the sense that we were able to discuss verbally through the telephone conferencing, but also visually look at the document that the webmaster was controlling.  As the person was discussing the changes or the recommendation, that was done at real time on the web and on your screen.

                It was very successful.  We also were able to hone in on the subject matter.  We weren't drifting from one end to the other.  We were always focusing on what we wanted to do.

                I encourage the other two groups to contact me and to have that kind of information available so that we can do other telephone conferencing and web presentations, so whatever information that you want to distribute and to discuss, that's the means that we could do this.

                We hope that the industry will come back to us with a final product.  Here are our recommendations for formatting, for management, for laboratory processes.  Then once we get it, then we can critically evaluate it and then bring it back and give it to OMB for recommendation.

 

MR. STEPHENSON:  This is not an invitation for just open membership to anyone in the world who would like to participate, but anyone who is with us today who would express an interest in participating in any of these working groups, please see Charlie or Donna afterwards and we'll take your name and contact numbers down and give it to the working group chairman.

                It'll be their decision how many other people that they want to involve.  I think for the most part the folks that attend this kind of meeting would be the kind that they would welcome.

 

DR. BUSH:  A follow-up on this.  This all comes to fruition and comes to OMB's attention in the context of Paperwork Reduction Act and the short title called "Paperless Lab" for this meeting, taking a look at clearing the custody and control form.  That's very recent.  You know that we've been working on this for quite a while and trying to make changes to it, to change the data field literally on the written form.

                Now we have to define those data fields electronically, because the drive is to collect that information electronically eventually.  Certainly, the laboratories appear to have the smoothest task right now, the easiest task, to go electronically completely within their laboratory.  It's a closed system already, very well defined in the secured limited access area.

                Then we've got communication by the laboratory to the medical review officer concerning results.  We can look at this in three aspects:  the custody and control form and going paperless on that; paperless analytical activities in the laboratory; and then reporting and handling of results by the medical review officer.

                We have three aspects going on this and a perception that because of the limited number of laboratories and the well-defined communication by the lab with the number of MRO's who are out there, they will be the easiest ones to approach first and to model first.  We want to set this up for success.  We want to challenge the technology to meet our needs and to attain the gold standard program capability before we implement it.

                We are moving forward and are willing to take the challenges that come and handle them before they become problems or issues by others questioning our ability to implement this in the laboratory system.  We are full steam ahead, but it's a steamship, so it's kind of going a little slower than a cigarette boat.

 

Agenda Item:  Mandatory Guidelines for Federal Workplace Drug Testing Programs (Draft #1)

 

DR. BUSH:  Our next topic is headed "Alternative Specimens."  I think what we should do at this time is take a look at where we are in the process map update.  We saw this process map at least a year ago.  We've taken a lot of steps forward on that process map and I think it's time we update that for you.

 

DR. CAPLAN (Board member):  As Donna indicated, it must have been about a year since we've actually developed this map to guide the process.  There has been a significant number of changes and a lot of progress.  You have the slides in front of you, so we'll go through it fairly quickly.

                First of all, to recall, there were three stages.  We're going to collect information, which has essentially been completed.  We were going to evaluate this information, most of which is done, but some issues are still outstanding.  As was indicated, there are still some issues surrounding the electronic aspects of the new program.  Finally, the third stage, which is implementation, outcome, which we are generally approaching now.

                We started in 1997 with two large meetings, created these industry working groups.  Those working groups were chaired by individuals noted there and they developed the information that was presented at these introductory meetings and then later continued a follow-up on that, reporting to the Drug Testing Advisory Board beginning in '97 when a matrix was developed to look at the information that was being received.

                The factors, a grid, and many of you were here and you know that we utilized the format of a grid with questions and going both vertically and horizontally eventually along this grid to ensure that we had asked the right questions and captured the information.  These were reported and discussed at various DTAB meetings in '97.

                The working groups began meeting and, as you'll notice, some of the working groups met more frequently than the others.  Some had bigger issues and took longer to resolve.  But each of the groups -- Onsite, Oral Fluids, Sweat, Hair, Lab -- met at least once, some twice and three times, over the period beginning in '98 and '99, attempting to answer the questions that were posed on the grid, generally looking at these vertically within their own framework, within their own specimen type that was to be used, what technical information is available, do we have enough information, and if not where do we get the information, what studies are needed.

                As a result of that, there were a number of studies, particularly in the PT area, that began to happen.

                The working groups reported to the Drug Testing Advisory Board at various dates and those are noted up there.  The information was received.  The Board on various occasions, again noted on the left side on the bottom, evaluated and discussed the status of each of these periodically, and this process occurred pretty much through the end of last year.

                Simultaneously, the literature that was collected was catalogued and is maintained for reference purposes.  These are scientific publications, references, and other things which were collected to support the process.

                The working groups then having presented this information as individual working groups, the Board having looked at these things independently, last year there was a general working group of the Board looked at, created to look at the issues that have come up now essentially horizontally.  How do the various specimen types and the information that was provided by the working groups, how do they fit in amongst each other.

                Beginning in the end of October '99, there have been a series of general Board working group meetings going across the grid, looking at these things horizontally.  Ultimately, through the course of these meetings, a general guideline was developed, and you had already seen Draft 1 of that.

                Draft 1 of the mandatory guidelines was developed as a result of looking across this grid horizontally.  This was presented at the open session in June.  We should probably point out that as part of this process, at least in my view, has been a very successful one, the first draft guideline, which was a fairly rudimentary document, was shared with the relevant community for input prior to actually official rulemaking.

                You'll see that there are going to be three opportunities for input on this, as opposed to one opportunity, which is it's published by the government and it appears.  We've taken extensively from the people that are in the relevant communities and they have provided a lot of information and that will be summarized a little bit later.

                You got Draft 1 in June.  We did receive a number of comments.  Walt's going to talk about them later.  They were, excessively perhaps, evaluated and integrated in what's released today, and you're going to have before you Draft 2 of these guidelines, having been reviewed through these working groups during July, where the informal comments and -- and some of those, although informal, were very, very valuable and very on point and extensive.

                That has been evaluated and you now have as of today, Draft 2 having been distributed and you'll find as you look through it -- and a little bit later we'll talk about it in more detail -- Draft 2 incorporates many of the suggested changes in a very significant manner, and I think most people will be pretty happy.  If you were happy before, you'll be happier, probably be happier now, with the way the process is going.

                But we have not -- this is the critical point of the DTAB working group.  We've not compromised anything.  We've not looked at it because you put it in, but we looked at it realistically from a program point of view, from a scientific point of view.  We were able to do that, quite frankly, because you wrote it down and suggested it.  The fact that someone suggested an idea in this forum before it's this final rulemaking allowed a lot of flexibility.  You'll see some substantial changes in what you have out there.

                That's where we are today.  Simultaneously, PT is being developed at RTI.  I know there will probably be some update on that later, but the results of a second round of alternative matrix PT's were being done coincidentally.  While the technical and operational aspects were being developed, so is the PT program, which is an essential part of eventually getting to the point where entities can be certified.

                After today -- and we want to continue to encourage, take the draft.  Do not assume that anything you wrote before is necessarily going to be re-thought about again.  The way this has to work is that you now are going to have Draft 2, it's sitting in front of you.  If there were things you wrote about before that didn't get incorporated that you still think are important, we need you to say that again.  This is an informal process.  We went through every one of the comments before and, quite frankly, we're probably not going to look at those particularly again.  They were looked at for this purpose and you now have Draft 2, which is the best-integrated thought of what came in plus of the working group.

                If you look at Draft 2, if you were willing to do it the first time, if there's something in there that you still think's an issue, now is the time to look at it because each time you look at this you look at it from a different light.

                You may send us a comment because you're interested in one area, but whenever we get the comment we're saying how does that impact these other areas and can we change this and how do we modify the other areas to make it all uniform.  Those are very, very helpful in that regard and I want to make strong encouragement.  Do it again, even if you have to repeat it, so we can have this process.

                I think you're asked to do that by the end of this month.  We are going to -- we have scheduled in October and November two more of the general Board working group meetings to review these things, and we will then be preparing, revising this to prepare the third draft.  The third draft of this document will essentially be the draft of the document which will kind of leave the Board, go back to HHS, and begin the official process of integrating it for publication and rulemaking in the Federal Register.  Exactly when that will occur, it will be probably after December.  But by December, by the December DTAB meeting, the working group will have finished its work on Draft 3 and essentially put that back onto HHS for publication and redistribution.  You'll notice in each of these working drafts there have been some things omitted that we don't quite have a handle on.  What's probably missing from this one is electronic, information about electronic transmissions and those kinds of things that were just mentioned.  So they'll be integrated.

                Things can continue to change as we get more information through this process.  Particularly cutoffs of things may still be revised.  We're still asking questions.  Some issues came up and we went back and said to the working group:  We may need refinement on this from the industry working group.

                That's where we are today.  The next step in this process after these are finalized in December -- and they will be.  I mean, we're really on good track and this has worked very well, so there's nothing that's going to slow this down.

                Some time between now and probably the end of the year, after this next draft, we will create focus groups and the focus groups will be structured from Board members with industry people.  That hasn't been done yet, but the focus groups will take the same areas and develop the guidance document.  What the guidelines do is give the general rules.  The way the programs have worked in the past is the guidance document.  For those of you who are laboratory-based, you know that there is a guidance document.  There is a checklist for handling this process.  There are some things which might change, which you can change and put in the guidance document.  There are other things that have to be in the regulations, and we've tried to separate them.

                Beginning roughly the end of this year, the beginning of next year, there will be a group of focus groups redeveloping.  It will not be the same group that it was before, which was entirely industry-based.  This will be more selective, with more Board members and a different grouping than before.  But they will be charged with developing the guidance document which will drive each of these processes that are in these regulations.

                If it's hair testing or it's oral fluid testing, there will be an individual document which will say exactly what the details of the requirement are, how the thing would be inspected, and how it would be certified.  This will be done for each of these kinds of specimens.  Then the process -- simultaneously this will be published, and again Donna and Bob can tell you, estimate how long that may take.  The process would be to publish it, then to get official comments.  This will be the last chance.  There will be a time to put official comments in after this working group is done.  I mean, hopefully we will have done it this way and there won't be a lot of differences in the official comments.  There will be an opportunity for official comment and then a final guideline would be published some time next year, hopefully, with various implementation dates.  It will go through the internal review and external publication, as noted on the slide.

                That just indicates what's going to go on.  There's a number of people internally with HHS and OMB and all that have to sign off on things and eventually there will be final publication of this document.

 

DR. SAMPLE (Board member): Is Draft 2 on the web site yet?

 

DR. VOGL (HHS):  I sent it over to the web people yesterday and asked them to put it on the site today but at least by close of business tomorrow.  It should be the very top document listed. 

                There were 28 separate comments submitted by individuals, groups, organizations, etcetera.  In general, they all started off with a supportive comment, how they liked Draft 1.  But naturally everyone had some sort of negative comments to present and they didn't hesitate to do that.   Most of the comments were rather long and not only made a statement with regard to an issue, but gave a reason, gave some sort of justification as to why they didn't like something or suggested what changes should be made.  That was all very helpful to the subgroup that worked on developing Draft 2.

                We didn't put the names of the submitters on the summary.  We just listed 1 through 28.  There's no reason to identify the specific individuals.  We tried to make simple bullet statements as to what the concern was, and then you'll see after each one a word or a phrase or something as to our position on that comment.

                You'll see that many of them, and particularly anything to do with cutoffs, PT samples, anything along that line, those issues are all up for discussion over the next few months, and basically decisions will be made on the results of the pilot PT program that we've been conducting and getting additional input from the industry folks.

                Hopefully by December's Draft 3 we will have in a sense the final cutoffs, analytes, metabolites that would be tested for by the different specimens.  I would say most comments were submitted with regards to the onsite testing area within Draft 1 and the instrumented initial test area.  Yale's going to go over all of the major changes that were made, especially those in response to the comments submitted.  You will see that there are many cases where we disagree with the comment and we'd be more than willing to entertain any questions as to our reasons for disagreeing with some of these comments.

                Every sentence that appears in this document is being looked at carefully.  Many people did recommend word changes and rewording of questions and statements, and it was very helpful.

                In Draft 2 there are several sections dealing with recordkeeping, electronic reporting, things like that, which are going to be ironed out as we go through the OMB process.  Hopefully, that'll be to a point where we have some pretty clear indications what direction we're going.  And that information or comments and requirements will be put into Draft 3 at that time.

                There are a lot of things going on at the same time and hopefully everything's going to come together for this third draft.

                I think the bullets as you go through this sort of speak for themselves.  We tried to keep them as simple as possible with an appropriate sort of comment at the end.  Without spending any more time going over them, I'd be willing to entertain any questions from the Board or the public, if you need any clarification of what somebody was asking about or our position on things.

               

DR. JACOBS (Board member):  Could you clarify for people here what you mean when you said change, disagree?  Who's agreeing to what, disagreeing to what?  What do those mean?

 

DR. VOGL:  Changed, for example, guidelines discouraged use of the point of collection test.  There was obviously in Draft 1 a rather stringent policy with regard to conducting onsite testing and how that was to be set up and the certification, and it was a location thing, certifying a location.  We've changed all of that to look at certifying the person doing the test, not the location.  It's the person doing the test that is certified.

                We feel that we've made significant changes in that policy and that's why we put down the word "disagree."  The next one, for example, "The responsible technician is unnecessary," we disagree with that.  Especially in the instrumented initial test facility, which is a remote initial test site using auto-analyzers doing high volume, there needs to be somebody responsible for the overall operation of that facility.  We disagree that you could do away with an RT or the suggestion that some RP at a laboratory can maintain overall responsibility for a remote site that's doing 3,000 initial tests per day.  There needs to be someone at the site.

                You see, we've changed the whole approach with regards to onsite testing and who's responsible for that.  Agree, for example, oral fluids, same reasons for testing as urine.  We went back and looked at it and we agree.  You know, you could collect oral fluid for the same reasons that you're doing urine at this point.  Now, things may change again as we go to the PT program or we see cutoffs are going to change or analytes.  For now, there was enough comment with justification submitted to say, yes, it makes sense, we need to allow collecting oral fluid for the same reasons as urine.

                The next one, THC oral fluid to 50.  As I stated earlier, any comment related to analytes, metabolites, cutoffs, that's all going to be evaluated as we go through the PT program.

 

MR. LODICO:  I want to state that the decision process is really important as to who said agree, disagree, or change, and that was the collective decision process that included the working group that met in July and our office.  We had the comments already prepared and presented to the working group and we were successful in going through about 75 percent of those comments, and the remaining comments that weren't evaluated, discussed, and thought about, we brought it back to our office and collectively discussed how we're going to approach it.

 

MR. STEPHENSON:  I think it's important for everybody to remember the words that you had said earlier in discussing.  This is a process.  These are informal changes and an informal seeking of input.  This is a process that is facilitating our ability to move forward in this area.  It doesn't lock in any final determination, but it's striving for focus and consensus-building that will help make that formal clearance process less painful, less argumentative, more inclusive when it happens.

                As best we can, we're trying to be accountable and help a generally positive, inclusive group of interested parties to work together.  When we're saying we disagree, we're willing to put that in writing, we're willing to put that out in front of you, and we invite the kinds of opportunities for further input and dialogue.

                None of this is policy-laden bureaucracy.  This is a consensus-driven process within an interested group.  Please, don't look at this as knocking down any of your own positions.  This is simply a way of being accountable for what we have said and what we believe to be our understanding of the issues at this time.  We'll continue with this process informally as long as it's helpful, until we get to a point where we are able in good conscience to step forward and say, this is now the version that is committed to a Federal Register process, and we will go out in the most absolutely inclusive way possible to all parties that need to see this and then to invite and then to address formally all of the comments that come in.

                This is a unique process to us. It's one which has been very rewarding to us so far, but it's not one that takes the place of the formal process.

 

DR. VOGL:  I don't think anyone addressed the urine testing program and any issues there, to be honest with you.  I would encourage anyone here, as they go through Draft 2, do not forget urine.  If there's anything within the urine program that you're concerned with, please bring that up, because we're trying to revise the guidelines and that includes the urine testing program.

                The next area is, if there's any issue you feel has not been addressed, point that out and suggest even a question to be asked with an answer to the question.  We can't say it's a totally complete document, in plain language, that we've asked all of the questions.  If there's anything else that you feel needs to be asked and included, be sure to let us know that.

 

Agenda Item:  Mandatory Guidelines for Federal Workplace Drug Testing Programs (Draft 2)

 

DR. CAPLAN:  I'm going to go through the highlights and I guess we can, if there's a little time after that --  if somebody has some specific thing they want to read and go over the questions.  I'm not going to read and go over each question.  I'm just going to try to go through this and highlight what's changed and what is different and again how we got there.

                If some people, as you read through it, want a little more enunciation on that, I'll be happy to receive the question and direct it to somebody else here who knows more about it probably than me.

                Here are the times that the mandatory guidelines were actually changed.  They were originally published, after Preliminary Rulemaking in '88, and then the only times that the guidelines were ever changed after that was in '94 when we changed the THC cutoff and in '98 when we changed the opiate cutoff.  There was very little movement over a long period of time.

                There are major changes, not only in the alternate specimens, but in the drugs and other elements that are in this document for the urine testing program as well.

                I won't go through these, but these are just a listing, so you have them on your chart, of the subparts that are in the guidelines, and I'll just go through them and tell you where the changes were.

                There are 17.0 elements in the guidelines and that's the way it's broken down.

                Specifically, some of the new areas that were added are definitions, and you can see that we have now defined a confirmatory validity test, and from the validity testing point of view there is some need to begin to recognize in this document and other places, principally for the reasons that validity testing will become mandatory under DOT eventually, as is currently I believe going to be proposed under these guidelines, that there are some distinct differences between the nature of the chemistry and the things that going on in validity testing that have to be recognized in the guidelines.

                Validity tests throughout are more specifically defined as to what they are and how they might differ from the typical drug test.  For example, the selection and drug test of the immunoassay and GC/MS seems to have tied people's hands that that's the only way in the world to ever do any kind of test.  The question is why aren't you doing creatinine by immunoassay with GC/MS confirmation?  Well, it's not necessary.  But these are not easy principles to make people understand, and we need to begin to do that more through these guidelines as well.

                There is something in there now called a certified initial test facility, an IITF, and therefore again these guidelines will permit laboratories to have offsite screening-only laboratories.  Not only will they permit complete laboratories as we know them, they'll permit partial laboratories which are screening-only laboratories and on-site testing.  There's a lot of flexibility.

                An "initial validity test" is defined.  The "POCT" term has been coined for the point of collection test and what constitutes that facility.  That's a new definition, the definition of an "RT," a responsible technician, in addition to the "RP," responsible person at the laboratory.  You'll find now in these guidelines the responsible technician is only applicable to the initial test facility.  It's no longer applicable to onsite testing.  That's changed.  There are definitions about split specimens that have changed.

                The types of specimens.  We throughout have had the four specimen types.  What you will find changed is the circumstances for the use of the specimens.  This is a moving target to some degree.  I will have to say that you'll find the change here where oral fluid and urine have the same uses, hair has pre-employment, random, return to duty, and follow-up, and sweat has only return to duty and follow-up.

                I will probably point out that I'm sure this will continue to be a subject of discussion and we would want input on it.  Mostly, eventually there is going to be some concern as to whether you used the single one throughout or multiple ones and how you mix and match them and how that impacts on the program.  This area was changed, but is one which I think needs more active thought and review.  Think about how they may be used interactively, not necessarily used only one throughout.  That's a change from the original draft.

                The drugs.  Again, there are some changes here from the other draft, major changes.  The benzoylecgonine concentrations have been lowered to screening at 150 and confirmation at 100.  The amphetamine has been lowered to screening at 500 and confirmation at 250, from 1,000 and 500, and that was not in the other draft.  And as was in the other draft, I believe, new analytes are required in the amphetamine category with MDMA, MDA, and MDEA, and focus on d-amphetamine as opposed to amphetamine -- this is an interactive thing.  Don't feed me; just say it.

 

DR. BUSH:  The reason d-amphetamine is listed up there, and actually the point is not just to solely focus on d-amphetamine, but d-isomer.  That's the key here, put "d" in there because we're looking at the psychoactive isomer right now.  There's an awful lot of cross-reactivity.  We continue to evaluate, look for l-methamphetamine and l-amphetamine, and I think we're going to move away from that and focus more on the psychoactive illegal form of the d, the d-isomers of both of those.

 

DR. CAPLAN:  This is providing more specificity.  That was in the original guidelines.  It has stood for many years.  It just said "amphetamines" and it was subject to interpretation whether it was d, l, and which ones.  I remember NRC had a problem early on that laboratories should be able to test equivalently for all four, amphetamine, methamphetamine, each isomer, which is not really physically possible.

                But those questions we're trying to answer and this is another point, try to anticipate for us the questions that might come up as a result of writing anything we write down.  There were things that were missed in the '88 guidelines that we've lived with forever, maybe successfully will live with, but they still became questions.  We want to avoid as many questions of a potential legal nature as we can up front as well.

                There are drug changes.  These drug changes are as big or bigger than any of the two that we made in the other years and therefore the urine program is impacted in a big way.  Even though there have not been a lot of comments about this, these are things that have been felt that would improve the program.  We always knew you can lower the cutoffs to increase the number of people detected, but we feel now that this has been comfortably done, at least with these drugs, at these cutoffs.

                Collector certification is now required.  That is a major change from the previous guidelines.  We will require collectors to be certified.  The document does give training requirements and there would be a process for approving programs that approve or certify collectors, and these programs would need to submit an application, ensure training, audit activities, maintain lists.

                Now that we are in the electronic age, there will be a couple of places in these guidelines you'll see that the agencies that do certification will be required to provide lists and those lists will be available on web sites and it'll be very clear who's approved to do these things on a regular ongoing basis.

                There is a new requirement as well that there would be retraining if an individual makes a mistake that causes a cancelled test.  Mistakes are fixed, but are not going to be tolerated forever.  There will need to be retraining of individuals if they make a mistake that causes a test to be cancelled.  This is a big change.  Many people have said long overdue.

                Collection sites.  The collection sites can be permanent or temporary.  The forms, I don't think there are any substantial changes here to OMB forms.  As we indicated, there will be electronic versions in the future.  But there will need to be forms now developed for each type of specimen.  Whether a universal form can be used or each specimen needs its own form, these will be subjects of those focus working groups.

                Collection device, specimen collection procedure.  There's some discussion in there on the distinction between a collection device which collects only and a collection device that's integrated with a testing device.  If the collection device is only collecting urine or the specimen, then it need not have FDA clearance.  But if the collection device is integrated with a testing device, there would be a requirement that it be FDA-cleared.  Other specimen collection things have not changed.

                The national laboratory certification program.  For the laboratories, there were some additional things in here about the composition of the PT samples, that the concentrations won't exceed ten times the cutoff, that laboratories will be separately inspected for each matrix.  There will be a separate application process.  If you're a laboratory and you want to do urine testing, that's one certification process; if you want to do hair testing, it will be another certification process.  Whether they happen coincidentally or not, you know, with the same team, this all needs to be determined.  There will be a specifically identified process for each one of these analytes.  You could have a lab that does only oral fluid testing and it could be certified for that.  You could have a lab that does urine and oral fluid and it would require two certifications.

                A list of these will be published monthly on the Federal Register and the web site, as they are now.

                Blind samples, no changes in the requirements for blind samples.

                There has been a change in one of the laboratory elements.  Again, this was done principally to make it compatible with other elements and with onsite testing.  But a negative certifying scientist does not require a B.S. degree, as it does today, because we're not going to require a B.S. degree for somebody doing an on-site test.  However, it probably doesn't really impact laboratories as much because, for other reasons, laboratories generally have B.S. people doing these jobs if they operate under various other state licenses.  But there will not be a requirement to have a negative certifying scientist to have a B.S. degree.

                What test is performed on a specimen after a POCT?  This is clearly enunciated here.  The laboratory must test a specimen in the same manner if it comes to the laboratory after a POCT as a regulated specimen that has not been previously tested.  That means it would go back through screening and confirmation.  There would be no assumption when a laboratory test is done following a POCT test that the POCT test counted for the screening-only test or the screening portion.  It would be tested comprehensively just as it is a new test.

                This is not the same as it will be for the instrumented test facility, which is clearly the separation of the laboratory and has the same screening criteria as a laboratory. 

                What test is performed.  The confirmation test in an IITF, which is the screening-only type facility, will be only for the drug identified.  This is because the screening-only facility is now operating exactly under the same conditions as the laboratory that's doing comprehensive testing, except that the confirmation testing's at another site.  Therefore, it will have the same QC and PC requirements and it's the same as a laboratory.  QC would be the same, the confirmation testing for the laboratories will be expanded to use other techniques, and it's not just going to be GC/MS, as it was in the original guidelines.  There will be allowed LC/MS, GC/MS/MS, LC/MS/MS, and therefore other analytical techniques which were essential for certain drugs, say in hair testing, where it couldn't be done with this.  It will have the ability, whether it's a urine lab or whatever, to use a variety of tests.   A confirmatory test will always be on another aliquot from the one that was originally tested.

                QC requirements for confirmation tests.  This is new.  At least one control must be blind.  That does not currently exist.  There is no a requirement for a blind in a confirmatory batch today.

                Electronic storage will be permitted.  This is the part that still has to be worked out.  But as Donna indicated earlier, ultimately these regulations will allow for a paperless type laboratory, again properly documented, properly inspected, when we begin to do away with the paper.

                Lab summaries that are now required to be provided to federal agencies automatically will only be required to be provided on request.  That means that if the laboratories are storing this data electronically they won't have to print them out and send them to everybody every quarter.  Most of this paper seems to -- what seems to have happened is the paper seems to be sent out, then when somebody really gets inspected by DOT they call back the lab and say, I can't find my paper and send me what I need to do this.  Now he won't be required to send out all this excessive paper, but that laboratories in the electronic mode will have to have the ability to generate that when necessary and maintain the records.  There will not be the requirement to send this out quarterly.

                Point of collection testing has been another major track in a lot of the things that are in these regulations.  Point of collection tests are divided into two categories, at least as best we can tell now:  those that are instrumented and those that are non-instrumented. 

                These will need to be cleared by FDA.  There will be a conforming products list developed by HHS.  That means that, as in the model of DOT, which has conforming products lists for breath test devices and things that are used for breath testing, there will be a system to evaluate the products that are available and put them on a list.  Products will have to be on this list in order to be used in this program, and the list will be published periodically.

                The only two types of specimens that currently will be permitted for POCT testing is oral fluid and urine, and those are specifically noted in the guidelines.

                Point of collection testers must be certified.  They can be certified by either a manufacturer or some other organization.  An organization that wants to be a certifier of individuals doing this will have a process to follow which includes an application, ensuring training, being in the position to audit the activities of the testing, of the people that are doing the testing, the certified tester, and maintain a list of those people which is updated on a monthly basis.

                The question which came up a lot -- and this was discussed a great deal, but it is the consensus of the moment -- that the donor should not observe the point of collection test.  There may be comment about that, but again this is to avoid a number of controversies, not necessarily conflicts.  Those of you who have comments on that, that might be a point of discussion.

                This does affect in some regards the handling of the point of collection test and how it's processed, and you'll see that there is a requirement.  It's going to have to be collected separately from the point of collection test.  The individual cannot see the test or have access to the test device, so they'll only have access to the urine.  The urine will have to then be put into the test device by the collector.

                The donor must not have access to testing device.  In the case of an integrated system, as I just said the container-testing device, a separate testing device must be used.  This may impact on some products as they exist today or some configuration of products.

                QA-QC requirements of the point of collection test, again the subject of a lot of discussion, but there will be two QC options:  to do one positive and one negative QC each day the testing is performed; a positive QC, analyzed immediately after donor presumptive positive and in addition to do one QA specimen a day out of 20 negative -- one specimen out of 20 negatives sent to a laboratory.  Either you're doing a positive and negative after each day or you're doing a positive after each positive result and one negative out of 20 each day.

 

DR. SAMPLE:  Aren't they sending in the negative QA specimen in either event?

 

DR. CAPLAN:  Yes.

 

DR. SAMPLE:  Regardless of which QC scenario they use?

 

DR. CAPLAN:  Yes.

 

DR. SAMPLE:  I'm not sure it was clear.  I just wanted to clarify that.

 

DR. CAPLAN:  In addition, one QA specimen in 20 is sent.  You can either run a positive and negative daily or no negatives -- no negatives daily, but a positive after each one, plus one of out 20 negatives.  Now, that may take more than four days, depending on the volume, or it may be one a day.  Those are two QC options, again to try to -- and they may be volume dependent, and the reason for it is if you do the positive after every positive you don't have to do both every day.  You still have to send one out of 20 in as another QC, one out of 20 negatives.

                The concentration of drug in the PT sample doesn't have to be -- these are PT samples now, not control, not daily controls, but a PT sample.  For point of collection testing, the concentration of the drug should be at least 50 percent above cutoff.

                Then probably one of the bigger changes -- and it might not be as clear in the regulations as it will eventually be, but there is no requirement for certification of collection sites, as was in the original, the previous draft.  But there is a requirement for certification of the manufacturer, which includes an inspection.  A manufacturer will be subject to an inspection and the manufacturers will be inspected at least annually.  The exact nature of that will be the subject of one of these guidance documents, how that exactly is to happen.  I think a major change, and it was in part because of suggestions that came in, is the fact that we will not be certifying collection sites as originally proposed; we will be certifying testers.  We will not certify testing sites, as originally suggested.  We will certify the tester and we will monitor the manufacturer on an annual type of on-site inspection.

                Can the POCT tester do validity testing?  Yes.  In fact, that will certainly probably benefit all of this.

                This might not apply to as many people -- probably no one in the room today, unlikely, in the audience, with a lot of on-site or lab people.  But you can have the initial instrument test facility, which is essentially the laboratory as we know it today, separated to a screening-only laboratory.  This was actually a consideration in the 1989 consensus conference.

                In the early days there was a lot of interest in doing this.  This may or may not still exist today.  But this would allow -- a lot of laboratories that were doing workplace testing of a hospital nature or a smaller nature decided not to stay in the business because it is much more costly to maintain confirmation.  This kind of requirement now will allow a moderate sized hospital or a place with multiple sites to do their screening somewhere and then use a central facility for the confirmation testing.

                Along the same lines as the confirmation testing is coming in from point of collection sites.  It will certainly broaden the ability of the program to interact with all sorts of communities which were not as accessible before.

                It may be a remote or a permanent site.  It can be -- it must be supervised -- and here the RT was retained.  There must be a responsible technician who does have a bachelor's degree who is the responsible person for that facility.  Just as a laboratory has the RP responsible for the whole operation, this person has at least a B.S. qualifications and must meet criteria of training and experience to supervise that lab facility.

                They must have a standard operating procedure.  Again, the negative certifying scientist in that facility, just as in the laboratory, need not have a B.S. degree.

                QC requirement is the same as the initial testing in a laboratory, the same concentration of PT sample, and the rest of the guidelines for these are the same as laboratories.

                Also required, and this was not in the first draft -- we didn't get to that; that part was omitted.  There is a requirement that an MRO be certified and that the MRO have specific training, which is documented there -- instruction on the processes, chain of custody, interpretation, regulations.  They must be certified by an approved MRO certification board.

                There is a distinction between training and certification.  You can have many more training organizations if they're interested than certification organizations.  So there's different criteria.  Certification organizations are viewed as the same types of certifying boards that exist today, which are parallel to the certifying boards in other medical specialties in other areas.  We're definitely not looking at people starting new certification boards to meet this rule.  Therefore, the requirements are more rigid than a training program, and there are some elements that might have been initially suggested of having someone have training and certification coincidentally as the same package.  But that's not what we're talking about.  We're talking about certification being required as it exists essentially today, meaning that there are multiple organizations that could do training, but a board reviews or accepts certain training as its own criteria and an examination.  This is now going to be required under this program.

                I know DOT is considering something similar, but maybe not quite as strong.  That's a major change from what you saw last time, because we didn't even address the MRO, we didn't get to that on the first draft.

                Certification board, the process is in there, but the idea is that they would ensure that the people have taken acceptable training.  There's a requirement that the boards audit the activities of these MRO's or 10 percent of the MRO's and maintain a current list.  Individuals who will then seek to find MRO's, organizations that want that, like the questions of church and state separation today, will be a lot easier because they will be published, basically, on the web site:  Here are your MRO's; you can look at them by geographic location or whatever you want.

                There is the continuation of prohibition of MRO's from having financial interest benefit in a laboratory, initial test facility, or point of care product for which they could benefit if they're reviewing those results.  There is still the need for separation.  This again, this may impact some people's business activities because there are some groups that might be mixing that, and that's always been an issue for this program.  The MRO is still viewed as the gatekeeper, the independent party in this, and therefore they should not have a stake in the testing.

                The other thing that is in these guidelines is there is now permission, there will be permission, and the ability to do retesting for adulteration and substitution.

                The same process for drugs.  The donor would initiate this.  They would have 72 hours.  It would be through the MRO, but the MRO would now be authorized to do an adulteration retest, as well as drug retest.

                Split specimens will be retained the same time as the primary specimen.  That means that if they are essentially positive or negative it would be for a year.

                There's a section problems with drug tests.  There's an addition to the fatal flaw.  The fatal flaw now includes no printed collector's name and no collector's signature on the CCF.  The new CCF only has one place for this.  If they're not there, this will become a fatal flaw.  It wasn't a fatal flaw before if you missed one of them and put it somewhere else.  But now that there is no collector and no name and no collector signature, it will be a fatal flaw because there's only one place on the form for it.  The other fatal flaws stay the same.

                There are now rules for the IITF, the POCT, in addition to the laboratories:  suspension, revocation, and changes.  The laboratories have not changed with the other guidelines.

 

MR. McNEIL (Dade Behring):  I just want to clarify the position on the point of collection tests that are integrated, where you have a test and the collection together.  What is the reason for precluding the use of that feature as far as having an integrated device?  There are two major products right now where you have the test strips included in the cup and there are others in the works.

 

DR. CAPLAN:  Well, others may answer this, but it's not precluded from use.  The only thing is you would have to collect the urine and then put it in the device separately.

 

MR. McNEIL:  You are requiring a separate collection unit?

 

DR. CAPLAN:  It's because of the requirement of not having the individual have access to the test.  That person has access -- if they're providing the urine in the test cup which has the device to do the testing, they have access, because there's not an observed collection, they have access to altering potentially the test result by doing something to the test device by having it in their hands.

The position was that they should not have the test device in their hand when they provide the urine.

 

MR. EVANS (NOTA):  I'd like to make clear who NOTA is and who NOTA is not.  At the last DTAB meeting there was some concern about some of the manufacturers having walked away from the process.  NOTA right now, our policy is set by nine manufacturers.  That's Avitar, Biosite, American Biomedica, Roche Diagnostics, Lifepoint Casco, Dade-Bering, Ciba, Drug Check-In, Medtox.  When some manufacturers had walked away or not cooperated with HHS, I think it was very natural for HHS to assume that that was NOTA, but it was not.

                I have three concerns.  On the quality control, section 12.11, we had made a suggestion that we were concerned that the lots get tested.  We think that your either/or approach that you have now developed is a very practical one, but I would suggest that on A.2 it would be possible for someone to have a positive test on one lot and then do a quality control on a different lot.

                I'd like to ask, why wasn't there a focus on lot testing to make sure that the lot was working, as opposed to just doing quality control testing?  Or is that just an oversight and would you amend it to make sure that the lot is tested?  We would like to make sure that when somebody does test positive that a quality control is done on that lot rather than some other lot to make sure that test is accurate.

 

DR. CAPLAN:  There are two ways.  One is -- and others can answer that -- one is that we could put something in here, and that's a good suggestion, that at least the same lot be used for these purposes.  However, it is very likely the intent of the process of manufacturer inspection to ensure lot validation with batch manufacture.  That's not something that's worked out, but that's the way it happens.

                We're not just going to walk in and do an inspection of a manufacturer that day, but they're going to have data on all their lots, the performance of their lots, and that would have to be worked out in the guidance document. 

 

MR. EVANS:  Okay.  The other thing is that we had suggested that, instead of calling this point of collection testing, use the term "onsite," because that is the term now that's used in the industry.  The case law discusses "onsite testing."

                Also, it may be that the onsite test may not be collected -- may not be actually done at the collection site.  It could be done someplace else with some of the tests.  So that was just a question, when you deliberated on that why was that done?

 

DR. CAPLAN:  I think the intent here is that the onsite test not be done somewhere else.

 

MR. EVANS:  Okay.

 

DR. CAPLAN:  If it's an onsite test, that urine's not going to be transported from position A to an onsite test.  It's going to be done there.

 

DR. SAMPLE:  Otherwise it would be an IITF.

 

DR. CAPLAN:  Right.  Although that is theoretically possible, that was not intended, that one would collect urine and take it somewhere else to do an onsite test, but that it be done in a continuous process of collection and testing.

 

MR. EVANS:  I would like to congratulate you on working very hard this summer on this policy, and I think you're really developing a very practical, real world approach to this that's going to have a big impact on fighting drug abuse in the workplace.  I really want to congratulate you for it and for being so open to suggestions and having a very good open process.

 

DR. SAMPLE:  I actually have a question for David.  Back to your question about the QC requirements, is it NOTA's position or your position that it's still recommended to perform control QC checks positive and negative with every new lot when it arrives at the site where tests will be performed?

 

MR. EVANS:  Yes.  I have to look at our comments, but I believe that's the position that we took.

 

DR. SAMPLE:  So you're still recommending that that be done in addition to one of these two?

 

MR. EVANS:  Well, I don't know about in addition.  Again, the board hasn't said.  I'm a creature of the board, so whatever the board instructs me to do, that will be my position.  We wanted to focus on that lot approach.  Again, it's similar to what's done with DOT, is that the products there are monitored, that the expiration date is checked to make sure that the product hasn't expired.  We wanted to focus on the lot, and we urge you to come in and check the manufacturers to make sure that we're doing our job in producing the proper lots, and then they can be checked again, and then monitoring them to make sure they don't expire, because we want good quality products.  We share that goal with you.

 

MR. LINEWEBER (United Transportation Union):  Thank you very much for your hard work.

The question I have is, why wouldn't you allow the donor to witness the result of the POCT, much like the EBT, like the breathalyzer today?  Wouldn't that reduce your paperwork, give them an immediate notification?

 

MR. STEPHENSON:  There's two different sets of issues.  The collection device that was being discussed was in an unobserved collection environment, which means a person goes into a cubicle or enclosure, provides a specimen, looks at it, and can determine if it's positive himself before it is taken out of that facility and handed to someone else.  That's the difference.

                The individual in a breath-testing device does not have control, nor can they manipulate the result once it's been, the breath specimen has been provided.  I think that's the key difference.  We don't know all of the marketing and the new adulterants that might come out that would be manufactured specifically to be used in that kind of event, which creates a whole other layer of almost draconian kind of oversight and invasive strip searches in order to ensure that someone hasn't secreted in a necessary test manipulation chemical.  That's the issue.

                If you allow it, you're creating an opening door in an environment that makes the whole system more problematic.  I think that's the issue and that would be the difference.  I may be off the mark and someone can certainly correct me.

 

MR. LINEWEBER:  I think we're just missing each other.  I'm certainly not an advocate of self-read.  I think we should have learned from Ms. Murdoch's presentation with the Post Office last year where they had the person, the person comes out and gives a sample to the technician, whomever it may be, let that person, that technician, read it, release them.  It stops a layer of paperwork, a layer of management perhaps.

 

MR. STEPHENSON:  I'm not convinced that there's an issue of having an individual see the test results as much as them being in a position to see them and manipulate and change the test results, given the components that are in there.  I think one of the things that I've seen happen in collection site environments in the criminal justice system was that that is a very positive step, that when an onsite test was used that the individual is a part of the process of discovery and of confrontation in the most positive sense, that as long as it's controlled and you don't permit an issue of violence to erupt as an issue of becoming aware, that you have an opportunity to intervene in a positive sense.

 

MR. LINEWEBER:  One more question.  Then when would the individual become notified of either negative or additional testing?

 

MR. STEPHENSON:  I don't think we're there.  We'd be willing to take recommendations, but I think that's one of the issues that is at the crux of what a point of collection test is all about.  I think that a lot of folks have to weigh in on this, I think administratively, procedurally, from collection sites and others.  There should be some discussion and a very informed debate and recommendations made before we go to any final decision.

 

 

DR. CAPLAN:  The issue here is the process -- you may be confusing the lab with the onsite and assuming there's a difference.  The view is that they're the same.  So the results are going to come down the same way through the MRO in the end.  There's going to be uniform reporting.  There's not going to be a different reporting structure for a different specimen type or a different process.

The stages of initial testing, confirmation, MRO reporting are all still intact throughout this program.

 

MR. LINEWEBER:  The time frame will be the same as the existing?

 

DR. CAPLAN:  However, the system gets it back to the MRO.  It could be a pass-through fairly quickly if it's an electronic system.  If it's a paper system, it will take just as long as it does to get the paper to the MRO.

MR. LINEWEBER:  I guess from a naive standpoint I would think that defeats the onsite testing concept, the onsite of course giving you better availability of results quicker.  But perhaps the employee won't know then for a five or six day period.

 

DR. CAPLAN:  It won't be that long, I'm sure.  Nothing is that long.

 

DR. BUSH:  I don't think it's that long.

 

DR. CAPLAN:  It won't be that they know then.  They may know within hours when it gets back to the MRO, but they won't know within minutes.

 

MR. CROUCH:   Do you see a significant advantage for the employee watching the test?  Is that what you're advocating?

 

MR. LINEWEBER:  Yes.  The reason I do so is the greatest fear that the employees have out there is something happening to that sample between the time it leaves them and goes to the laboratory.  Obviously, if they see the results there, boom, it's done.  It stops a layer of paperwork, number one.  Number two, you're not going to have the confrontation that I heard some people talking about.  You don't have confrontations with a person who's positive on a breath alcohol and is confirmed positive.

 

MR. CROUCH:  What would happen if it was a positive result and it went to the laboratory and it was unconfirmed?  Then the employee would think they had a positive result and whatever.

 

MR. LINEWEBER:  Clearly, the employee is going to know that, whatever test result they have there, if indeed it needs additional testing -- I hesitate to call it "positive" -- if indeed it needs additional testing, they'd get that laboratory to confirm or deny that they had that in their system.

 

MR. STEPHENSON:  And probably a split, too.

 

MR. LINEWEBER:  Yes, and we're certainly advocating that.

 

 

MR. BOUCHER (Benzinger DuPont Associates):  If I heard Mr. Stephenson correctly, he said at least in his mind this wasn't an issue of the donor seeing the test result, but it was an issue of the donor not being able to manipulate the test.  Is that a fair reading of what I heard, at least, if not from you specifically, the table?

 

MR. STEPHENSON:  No, I think the issue was broadened rather nicely in the discussion about the intact process of the medical review officer role.  Now, the timing and the event and clearance of an MRO result, especially in a negative test, might be something that can be discussed.  But I don't think this Board in this discussion can preempt that process, and I wouldn't want to say any of my comments should influence that important dialogue through comments that would be made to this draft or the way we would go about looking at the third draft.  I think the role of the medical review officer is critically important and I don't know how to truncate that to make it something that could happen in a site context in an appropriate manner.  Maybe only for negative tests.  I don't know.  I don't want to own that.

 

MR. BOUCHER:  I was really just trying to stay with the issue of the collection of the specimen and how or when the device would be read for the test on that particular specimen.  The rest of it, I have no really response nor really any quarrel to.  I would agree that the process and the test results, if it gets to the lab and goes to the MRO, that's fine.  I'm really just trying to focus on -- and I'm obviously not saying it well -- on this particular issue of what the concern is to have the donor see the test result.  If I heard correctly from at least some on the table, the issue was we didn't want that donor to be able to manipulate the specimen at collection, which would then create a problem in the reading of the device.

 

DR. SAMPLE:  I believe those are two separate issues.

 

DR. CAPLAN:  There are two separate things.  They probably got integrated.  You don't want to have the donor have access while providing the urine with the test device.

 

MR. BOUCHER:  Fine.

 

DR. CAPLAN:  Once the urine is provided to the collector, then the donor is no longer involved and the test will take place afterwards.

 

MR. BOUCHER:  Then I'd like to address the second part, Dr. Caplan, as you've just described it.  That is that once the specimen is collected, why -- it's really the repeat of the previous question -- why don't we want that donor to see?  Why are we so afraid of the donor seeing that result?  I mean, I have no problem with the collection.  Use a separate cup, pour it into a device.  If the device is read immediately, I think then it becomes almost identical, if not identical, to a collection that would occur if I was going to a lab under a normal collection and laboratory process.  Again to echo the previous questioner, one of the concerns that I think a donor might have is to walk away leaving a specimen sitting there uncapped, uncontrolled, in effect, and then expecting that nothing is going to happen.  I mean, this issue of the integrity of the specimen at that point I think is very, very vital.  I still would like to try and get some sense, if I could, from the table as to why we don't want that individual to be able to see the result at that time.

 

DR. CAPLAN:  The process as conceived is that the collection would be independent, this would

be a sealed bottle going.

 

MR. BOUCHER:  Oh, I see, all right.

 

DR. CAPLAN:  Then the tester will not have to contemporaneously do it at that moment.  They can do it five minutes later or within some pre-designated sequence.  But the collection process would be exactly as it is today and documented.  Now, the tester is going to have to certify that they took -- there will have to be a process.  We haven't worked this out yet.  There will be a defined process for chain of custody and determining exactly what happens.  The donor will give up -- he will see it sealed, but he won't see it tested, or she won't see it tested.

 

DR. SAMPLE:  I also believe that these draft guidelines define or delineate that that specimen that would be sent to the laboratory in the event that the POCT test is positive, or at least non-negative is a better phrase, if it's non-negative that original specimen that's sent to the laboratory was sealed in the presence of a donor.  There is no intent to have the tester open the sealed specimen after the donor is gone, perform the test, reseal that specimen, and send that resealed specimen on to the laboratory.

 

MR. BOUCHER: We're going to require a split specimen collection?

 

DR. SAMPLE:  It would still be a split specimen collection.

 

MR. BOUCHER:  You'd have to have a split specimen sealed collection prior to the device being read?

 

DR. SAMPLE:  That is correct.

 

MR. BOUCHER:  I'm sorry, and I don't mean to beat this one.

 

DR. CAPLAN:  No, it's been instructive because we're groping with the sequence of these events, too.

 

MR. BOUCHER:  I move back to my much more narrow question that I'm obviously not doing well on.  That is, why are we afraid of having that individual see the result?  I'm not saying it has to be, but why do you prohibit it?  I think that's the issue.  Let me just make an observation.  The Postal Service now has done over 500,000 what I call on-site tests and in every one of them they've showed the result to the donor right there.  I can tell you that there has not been one problem, one concern raised by any applicant that's been reported anywhere in their system over the last two years.  At least it's the belief of the Postal Service, I think, that this is a source of comfort to them.  It gives them some additional credibility with the applicant as the applicant comes in.  I would just ask the Board to maybe revisit this particular issue on just this narrow point.

 

DR. CAPLAN:  Please put that in your written comments.

 

 

MR. STEPHENSON:  This is the experience that we have, that we see from other similar participants.  I would suggest the NRC from their longstanding experience on onsite testing devices and with the criminal justice system and the Administrative Office of the U.S. Courts, both of whom are in a position to provide us additional insight and instruction, neither of which eliminates the requirement for process and the involvement of the medical review officer, especially in looking at that laboratory confirmation of a non-negative test result that's gone to the lab.

                Those are the issues that are still in front of us and I think this discussion today gives us a set of examples of how complex and multi-system component these issues are and need to be very carefully discussed to make sure that the process is inclusive and ultimately has got the best safeguards for everybody -- the program, an employer, and an individual being tested.

 

MS. BOONE (LabCorps): We've had about four years of experience with the onsite testing products and our program has been designed actually modeling the consensus program of the late eighties.  We do use an MRO with all our testing processes in that review, and we have found that it has been a very critical and important part of the program.

                Now, in terms of sealing and whether the donor is viewing the actual results, I think I mentioned in my comments that I sent in, Oregon right now is the only state that requires that the donor views the result.  Any other state that allows onsite testing does not have that requirement associated with it.  In the 4 years that we've been running the program, we haven't had any complaints, concerns from donors in terms of their not being able to view the results.  One of the things that we do make sure of is that the device is sealed, that the donor has an opportunity to place his or her initials on that product attesting to the fact that it has been sealed.   After the testing product has been sealed, at that time the tester completes the testing process, fills out the chain of custody as it has been filled out all along, etcetera. 

                In terms of how long does it take the MRO to receive the result, we have a requirement that the result has to be forwarded to the MRO either by fax or electronically transmitted within 2 hours.  Now, quite certainly it doesn't take 2 hours to get the result there, but we allow that 2-hour window.  There is a 2-hour window where the MRO gets the result and it's turned around to the employer and then the donor.

                When you have the MRO component, any questions that exist regarding the validity of the test, concerns about the test, that the donor may have can be answered, or the employer may have, can be answered by the MRO, such as it is with the laboratory testing today.

 

MS. NORFOLK (DATIA):  I have two quick questions.  The first is regarding the certification of collectors and MRO's.  I don't know if you can elaborate at this point or if it'll be in a further guidance regarding what you'll be looking for in the 10 percent audits of the certified collectors.

 

DR. BUSH:  That's not been established yet.

 

DR. SAMPLE:  That's part of the focus group process, is it not?

 

DR. BUSH:  Yes.

 

MS. NORFOLK:  My second question, this is more just a clarification on my part for our members.  The majority or a large portion of our members are companies that perform collection services as well as medical review officer and full program administration.  Regarding the point of collection testing and the MRO, the way it's been reworded in Draft 2 it says they cannot be an employee, agent, etcetera, etcetera, for which the MRO is reviewing drug test results.

                Is that to mean that if there's a full service consortium that is providing medical review officer services, if they have a company that wants to do point of collection testing, will they be able to do that if an MRO in a different company is reviewing those results? Or under no circumstances would a collection facility with an MRO be able to do point of collection?  I don't know if I made that very clear.

 

DR. SAMPLE:  I think the intent was that they couldn't MRO their own results, they couldn't review their own results.

 

MS. NORFOLK:  Under no circumstances would they be able to do point of collection testing or they would be able to if those clients that were doing those testings were having the results reviewed by a different MRO in a different company?

 

DR. CAPLAN:  If the MRO owned the point of collection test that would be prohibited.  If the MRO were independent and hired to review tests, that's no different than what we're doing today.  If he's part of the consortium, but doesn't own the consortium, that's fine.  If it's his consortium, then that would be a problem.

 

MR. DeFEO (Avitar): The discussion with regards to the point of care testing and the collection of sample, consideration needs to be taken for the fact that oral fluid testing is going to be handled differently than urine would and therefore there's going to be an issue with how you're actually going to collect that sample and then transport it to the system to test the device.

                I think that the question is are we going to consider the fact that oral fluid is collected differently in an observed fashion and that it will be handled differently.

 

DR. BUSH:  Yes.

 

MR. EVANS:  A question on the conforming products list for the onsite tests.  How is that going to be formulated?  Our position was that, since we all have to be cleared by the FDA for commercial marketing, will you be imposing additional requirements other than FDA clearance for selection on the conforming products list?

 

DR. BUSH:  Yes, and it will follow the NHTSA model on how products are submitted to an independent laboratory, with performance criteria provided by the manufacturer and then performance evaluated by independent laboratory technicians, technologists, chemists, what have you.  There's details to be ironed out later as we become more familiar with those details on the NHTSA model.  But there will be additional testing independent of what's been done by the FDA, what's been done by the manufacturer.

 

MR. STEPHENSON:  I don't want to speak for the FDA and I can't even if I was tempted to try it, but the issue for FDA also is of interest in this process and we'd be looking for a more formal and closer linkage in this process to help everybody at all stages in this evolution as we go through the development of new technologies, the formulation of new products, and then the FDA clearance as a first step in creating a conforming products list.

                If we could do this better, it would ultimately be a shorter process, clearer, and less burdensome to all the participants if we did things consistently, and I think there is an expressed interest from the FDA to do that in a more collegial manner with us and for us in turn to work more constructively with them at earlier stages.  I think everybody in the industry will benefit from this process.

 

MR. REYNOLDS (LifePoint):  I have a question regarding the initial instrumented test locations.  Has the committee given any thought to differentiating between what I would refer to, a CLIA waived product and a non-CLIA waived product with regard to the complexity and the fact that if you have a very, very non-complex use system that is fully automated and the requirements for the supervision of that test, etcetera, as opposed to is there -- I wanted an understanding of what was the model definition for initial instrumented test type of equipment. 

                I know that the guidelines described it as a spectrophotometer.  I guess it really relates more in my mind around what kind of manipulations are required in order to actually do the test.

 

DR. SAMPLE:   I think there may be some misunderstanding about the instrumented part.  You can have an instrumented or a  non-instrumented point of collection test.

 

MR. REYNOLDS:  Correct.

 

DR. SAMPLE:  You could have an instrument which is clear waived or not clear waived as part of a point of collection test.

 

MR. REYNOLDS:  Right.

 

DR. SAMPLE:  The instrumented initial test facility was seen as being a screening-only laboratory, to resuscitate a phrase from the past, that would be really identical to a laboratory in all respects.  But they would only perform the initial test or screening test, and anything that was non-negative on that initial test, just like it was performed in a full service laboratory, would then be forwarded to a certified laboratory for performing the confirmatory test.  In that scenario, the laboratory that it's referred to would only have to perform a confirmatory test.  They would not be required, nor would they be permitted, to perform another initial test when it goes to the laboratory, as they would in a point of collection testing non-negative scenario, where the laboratory would be required to perform both an initial test and, if that's presumptively positive, then a confirmatory test.

 

MR. REYNOLDS:  What I understood was that the requirements for supervision in that were higher than if it was a non-instrumented test; is that correct?

 

DR. SAMPLE:  An instrumented initial test facility in terms of level of supervision, quality control requirements, PT requirements, inspection requirements, is almost identical to a laboratory.

 

MR. REYNOLDS:  That's the way I read that.  I guess my question is that if there is essentially a clear waived product in that situation rather than another type of equipment, would that not perhaps require different levels of training or a lower level of training in order to be able to operate that test?

 

DR. SAMPLE:  For the operator it may require a different level of training, but you'd still have the same quality control requirements, blinds, definition of a batch, running open controls above the cutoff, below the cutoff, and negative, having blinds and having a review by a certifying scientist.

 

DR. BUSH:  We did use a CLIA model, didn't we, when we were evaluating this?  We inquired of laboratory technologists and others who were knowledgeable about the CLIA process and how they were fitting and functioning within that.  We used that as part of our thought process in developing that.

 

DR. SAMPLE:  It's more than just the testing part.

 

MR. STEPHENSON:  Let me not discourage the interest that's been expressed in this environment, but ask you to write your questions down, and we're going to have to move on.  At this point I'll take the last question on this area and then we're going to try to keep on schedule. 

 

MS. McLAREN (Amtrak):  I just want to make sure I'm understanding this correctly.  In the workplace it is believed that this new point of collection testing will give you results analogous to a pregnancy test, that when the test takes place the donor will know on the spot what the results are.  From what I'm hearing, that is not going to take place.  That's the belief right now in the field.

 

DR. BUSH:  The donor will not have access to those results immediately.

 

MS. McLAREN:  It will not be instantaneous?

 

DR. BUSH:  Right.

 

MR. STEPHENSON:  That is the current phase two of this review process.  The issue is we have heard some interesting issues, we need further input from all parties in this environment.  Our thinking has been rather linear and in parallel to what we have done in the past with the collection of a specimen and then testing and the medical review officer.  How that might be modified ultimately over time to address the unique opportunities in point of collection testing is not finished.  It's part of the work that you need to provide additional input on.  Experience from those stakeholders that have experience in that area will be helpful.  I expect it'll be one of those things that we can't predict where it will be right this minute.

 

Agenda Item: PT Results for Alternative Specimens (Cycle 2)

 

DR. MITCHELL (RTI):  Since the last Board meeting, we sent out another round of PT samples to the hair, oral fluid, and sweat testing laboratories that are participating in the pilot PT program.  Today I am presenting the preliminary results from Cycle 2.  The final, once we get in all the results, will be posted on SAMHSA's site (www.health.org/workplace).

                Before I begin, I want to orient you to the package you have been given.  The first four pages consist of the results for the hair, and that's tables 1 and 2, each one of them having two pages.  The third table, table 3, is a brief description of the hair samples that were sent.  The reason we do this is because some of the samples are spiked, some are powdered, some are strands, and some are from drug abusers.  It helps to understand as we go through the results table.  Tables 4 and 5 give the initial test and confirmatory test results for oral fluid.  Table 6, since we only have one participating laboratory on the sweat, gives both the initial and the confirmatory test results.  At the end we are giving you some of the quantitative results for the analytes that were included in the most recent cycle or occasion of maintenance PT, performance testing, for urine.  We will go over that very briefly to give you some idea of what type of variance in the procedures, that is the quantitative procedures, that we see in that program, just as a reference.

                Page 1 of the first part of table 1 is the initial test results the hair samples that were sent out (in referring to table 3).  The analytes which are known to be in the sample are bolded in the case of hair.  The reason we did this in hair is because it appears that we have some issues of cross-reactivity and non-specificity.  We bolded the drug classes that we know are in the samples, and we'll talk about that more as we go through.  The hair we used in preparing when we used powdered hair and we prepared and spiked them were tested initially by an initial test, and then any positives were confirmed.  In some of these samples, we will see later on that there were some very low amounts of some analytes that were not detected in that initial screen which appear in some of the samples.  Specifically, I believe it was the ones that we spiked with methamphetamine.  But we'll go through that.

                We have the total number of initial test positives in this column, the total number of laboratories that conducted tests on that particular analyte or drug class in the second column, and then the results that are obtained for each of the analytes by each of the laboratories, which have been given a random letter rather than random number.  The four X's means that the lab does not have, in this case, an initial test for that particular sample.  In general, it means that a test for that particular analyte was not conducted by the laboratory.

                The first sample that we are dealing with is sample 3.  It was spiked with cocaine, BZE, and CE at the cutoff.  Even though we had the concentration at the cutoff, and we'll talk about the confirmatory results a little bit later, only six out of the ten laboratories found this as positive, that conducted the test.

                With the opiate (sample 10), which was spiked with 400 picograms per milligram of morphine, that's twice the cutoff, and we have 5 out of the 10 laboratories screened that positive. 

                Sample 19 was a sample which had been screened negative and confirmed negative, and you can see that it is negative. 

                These first three samples, which are 3, 10, and 19, were included in Cycle 1 and they were given those particular numbers.  If you go back and reference numbers that we have in this cycle versus any of the others from the previous cycle or the cycle later on, Cycle 3, you'll be able to cross-reference this.  We'll talk a little bit more about those results.  I'm not worried about the initial test results, but we will talk about them when we get to the confirmatory tests.

                Sample 103 was a sample that we spiked with cocaine at 2,500 picograms per milligram, and we put some THC in there at about 1.5, looking at the cross-reactivity about the cutoff for THCA.  You can see that with the cocaine at 2,500 or thereabouts, much above the cutoff, for initial test nine out of the ten laboratories found it positive.  With just the THC at 1, about 1.5 picograms per milligram, no one that conducted the THC assay or screened for marijuana metabolites found that sample positive.

                Sample 104 was at about 5,000 picograms cocaine.  Nine out of the ten laboratories found it positive.

                Sample 113 was spiked with PCP-- actually, 113, 114, and 115 are actually the same spike.  We spiked them at about 300 picograms PCP per milligram of hair, and you can see that there was a good bit of variance in the number of samples that were positive.  There is some variation in the same preparation of hair.  It's just that after it's been homogenized, then it was taken, weighed out into 100 milligram portions under each of these sample numbers.  There is a good bit of variation on the same sample.  We had one lab that did find or appeared to find an amphetamine positive in there, which was not reconfirmed.

                Sample 118 was a sample that we spiked with THCA at about 1.5 picograms per milligram, and at this level only one laboratory screened it positive even though the cutoff is 1 picogram per milligram, and that's pretty close to the cutoff.

                Sample 120 was spiked at 5 picograms THCA per milligram and we only had one lab which found it positive for marijuana.  Again, this is powdered hair that's been spiked artificially with THCA.

                Sample 122 was spiked with 0.05 picograms of THCA per milligram and 10 picograms of THC.   Five out of the six laboratories screened that positive, which would indicate that there is some cross-reactivity with THC, which we didn't see in the sample, I believe it was was sample 103, which only contained 1.5 picograms of THC.  There is some cross-reactivity, it would appear, and it may even be interaction between the two.  Sometimes you see that, like with the Roche amphetamine that we have in the urine immunoassay.  We are not sure exactly what's going on, but it does appear that trying to spike hair with just THCA is going to present some problems for the program.

                Sample 128 was spiked with 1,000 picograms of morphine.  The cutoff for morphine for the initial test is 200.  Eight out of ten of the laboratories found this positive for opiates.

                Sample 130 was spiked with 200 codeine, 200 morphine, and 200 6-AM, and you can see that the performance on the immunoassay with a mixture of analytes was about the same as we saw with the pure compound.

                Next Page.

                I have these divided up in the same manner with the same samples on the page that we have with the confirmatory results.  That's why these tables are not exactly the same size.

                Sample 136 was spiked with methamphetamine at 1,000 picograms per milligram.  Eight out of ten of the laboratories found that positive for methamphetamine.  We also had a couple laboratories that found cocaine in the sample.  In fact, all three of these samples were spiked with the same material and you can see that we did have a consistent result, indicating that cocaine was there in at least a couple of the laboratories.

                That is the sample that I was telling you about that we did not, at the time that we spiked it, we did not know that the cocaine was there.  These samples we obtained from our negative hair.  We normally obtain that from a place that does haircuts for male and female, and evidently the level in this particular hair was pretty low and so it didn't show up in our initial testing.  Of course, there are some, every once in a while, some amphetamines, marijuana and opiates that showed up in this.

                Sample144 was spiked with 5,000 picograms of methamphetamine.  You can see everybody got it positive, which we would expect at that level.

                Going to samples 145, 146, 147, and 148, these are hair samples that were obtained from drug users known to have drug.  I have two samples here, 145 and 146, both of which had marijuana present.  As you can see, with the positive hair, with Sample 145 the levels were somewhere between 1.5 to 2 picograms per milligram of THCA present by analysis.  In the second one, sample 146, we knew that the amount of THCA was approximately 1.5 picograms per milligram.  We also found that we knew that there was a small amount of cocaine in that sample, which is reflected by the positive here.

                Sample 147 was a sample that was positive and it's from a drug user, and it was positive for codeine, morphine, and 6-AM.  The interesting thing about these three samples is that they were all strands of material.  We had taken hair from a drug user, we had cut it into small lengths, and then homogenized it, dried it, and then used that, that is the clipping or the small strands, and sent those to the laboratories to see what type of performance that we could get in that.

                It appears that the performance is pretty good, especially for marijuana.  Even though the levels are very low, we get a much better response than we do with the samples that we spiked with just one or two analytes.  That means we probably do have THC in these samples, which we'll look in the analytical part, which previously shows that there is some cross-reactivity and helps in detecting the marijuana metabolite.

                These are the marijuana, this is the opiate with codeine, morphine, and 6-AM.  The last one is a sample which is a multiple positive.  It actually had, we know that it had the cocaine and BZE, benzoylecgonine.  It also had amphetamine and methamphetamine.  This would indicate that it also had some indication of marijuana by confirmation. 

 

DR. SAMPLE:  I missed the concentrations on the first the first three spikes, 3, 10, and 103.

 

DR. MITCHELL:  Going back to sample 3, sample 3 was spiked with cocaine, benzoylecgonine, and cocaethylene at 500, 100, and 100.  That was the theoretical spike.  We'll see how that comes out in the confirmation.  Sample 10 was spiked with morphine at 400, and sample19 was a negative sample.  Sample 103 was spiked with cocaine at 2500 and THC at 1.5.

 

DR. SAMPLE: You mentioned that samples 136, 139, and 144 were all prepared from the same negative hair pool.  Were there other specimens prepared from the same negative hair pool?

 

DR. MITCHELL:  Not on this slide.

 

MR. CROUCH:  If you applied the current NLCP PT performance criteria for qualitative identification, how many of the laboratories would pass?

 

DR. MITCHELL:  I have not done any of those types of calculations at this time.  I'm not sure it's appropriate at this time, but maybe as we start looking at the final round, maybe we can say something about that.

                Table 2.  The samples are in the same order that we had for the initial test, except this time we list -- with the sample number we have the actual analytes and we have the group mean, the standard deviations.  We have the number, the total number of assays conducted on each analyte, and these n's contain reference values that we have gotten previously on the samples, not just the values from the laboratories.  We have, depending upon the sample, two to three reference assays.  Again, the blank means that we have no value from the laboratory for that particular analyte.  The four X's means that analyte was not tested for by the laboratory.

                I believe that's all I have at this point in time.  These tables are pretty complete.  I think we may have a couple of assays that are still out, directed assays, because the procedure was we sent out the samples, they screened them, they confirmed the positives that they got from the screen, and then we went back and looked and said:  Well, based upon their results, they would have been able to analyze for this analyte even though it was below the screening cutoff.  And so we then directed them to then go ahead and analyze for that analyte.

 

DR. SAMPLE:  Am I understanding these tables correctly that there may be some laboratories that only performed initial tests, but did not perform confirmatory tests?

 

DR. MITCHELL:  That did not perform?  Well, there were some confirmatory tests that were not conducted.  Some laboratories did not do initial tests for some analytes, and there are some analytes that some laboratories did not test for.

 

MR. STEPHENSON:  Remember these are instructive sets of documents.  They're not for scoring purposes.  And because they did or didn't do an initial test, they were directed, if it's not correct, to have done GC/MS confirmation.

 

DR. MITCHELL:  Well, there was a decision point.  If they did the immunoassay and it screened positive, then they were to confirm it.  If it did not screen positive, there was no requirement to do any confirmatory testing at that point in time.  That's in the written instructions.  Now, some laboratories did choose to go ahead. They said, even though they screened below the cutoff, we went ahead and did confirmatory testing, because we were going to go back to them anyway with a directed direction telling them to test this sample.  In the case of a sample that was below the cutoff, the initial test cutoff, we would have gone back and said, we want you to confirm it for this particular class of drugs.  I think we'll see some of those a little bit later as we go through here.

 

MR. LODICO:  You had a "mean."  Are there any outliers that you're not including as part of your mean?

 

DR. MITCHELL:   I'm going to give you the same table.  What I've done is there were some values which appeared to be very erroneous, and I've tried to remove those where it made sense, where I felt that I could really do that, and then change the means to reflect that, the values without that sample.  You have the one with the sample, I mean with all of them.  Up here you can see what the mean will be without that particular sample.

                Beginning with this particular table, sample 3, as I said, was sent out in the previous cycle.  No one would know that because the sample ID's that they get are random numbers.  There would be no way for them to know that they had received this sample.  They might have guessed later on if they looked over their first cycle results after they got the results on this one.

                We had cocaine in it, BZE, benzoylecgonine, and cocaethylene.  The results, as you can see, with a standard deviation is somewhere around 50 percent.  You say that's a little bit high for the cocaine, but the results, uncorrected results, last time the mean was 940 with a plus or minus 1195 for the standard deviation.  There seems to have been, just by one round of PT on this one sample, we can see there has been considerable improvement.

                Actually, the improvement in this particular sample comes about by the laboratory's being aware, it appears, of their procedures in converting cocaine to BE, to benzoylecgonine.  So it seems like they have corrected very well for that, and the values here, there is some, but it appears that the laboratories have made an effort to work on their procedures in the interim and cut down on the conversion of cocaine to benzoylecgonine.

                We only had one of the laboratories which appears to be testing  for cocaethylene.  That's lab G.  None of the laboratories confirmed THCA in that sample.

                Sample 10, we did one spurious result, but when you look at, we remove that, the results look pretty good.  We're down to around a 20 to 25 percent standard deviation for that.  We did not have 6-AM in this, but one lab did find it, and it appears that a couple of laboratories found codeine and there was none spiked in this particular sample.

                In this sample, the previous results for the morphine were 431 plus or minus 639.  Now, we spiked this sample, if I remember correctly, at 400 picograms per milligram of morphine.  These results that I'm seeing across here would indicate to me that there may well be some loss or some degradation of morphine with time in these samples.  We'll have to wait and see how it goes with time.

                These things we look at very carefully to try to make sure that what we produce has the stability that's going to be needed.  I don't know why that didn't take that value out, either.  But we'll do some of these things.

                I didn't get all of the results until we got the final results from the laboratories on Wednesday and we had Thursday and Friday to process all this.  I hope you will realize that this is not the final version that this will be in.  You'll see it on the web site.

                Why we have two laboratories that appeared to have codeine in the sample, which has never been reported, and I don't know at this point in time, but we'll check that out.

                Sample 19, even though we did have several positive screens, for opiates, amphetamines, and THCA, it's still negative, and it was negative the first time it went out.

                Going to sample type 103, again we spiked this sample at about 2500, which is not bad, but we do have considerable variation.  I'm not sure why we get that.  We have some very low values, which could have probably been removed.  They're about a tenth of the mean, which would probably change this.

                The main ones I looked at changing were those whose standard deviations were equal to the mean, equal to or greater than the mean at this point in time. We'll develop a system of looking at that a little bit later.

                Even though we only spiked cocaine in that, we did have some BZE found, and I don't know why that's not reflected from this sample, where we would have seen the cocaine being degraded down to being BZE.   There appears to be, at least in some of the laboratories, a small amount of BZE.  This may be a natural degradation process, so we'll have to watch that in these samples.

                Sample 103 was spiked with 1.5 picograms per milligram of hair and one lab, we had them test it and they found THC at 1.3.  You'll notice that we have THCA.  One of the reference laboratories said that THCA was present.  We'll have to check that value and see what that means.  I haven't gone back to them and asked them if that was really THC rather than THCA, but I will do that.

                Sample 104 was spiked with 5,000 of cocaine and again we're seeing some BZE from some of the laboratories.  Also, we had  some reporting of coca ethylene there.

                Samples 113, 114 and 115 were PCP-spiked at 300.  You can see that the means are fairly consistent, standard deviations are fairly consistent throughout the group.  There appears to be no problem with finding PCP.

                On 118, this is the sample that was spiked with 1.5 picograms per milligram of THCA.  The mean came out to be 1.55 based on the reference values, but it's probably lies somewhere in between in reality.

                Sample 120 was spiked with 5 picograms and it came up with about 4, and we got, 6 laboratories were able to find it confirmed at this level.  Actually, one, two, four of our laboratories were able to confirm at that level.  At below 1 picogram we see that we've got 2 laboratories that appear to be able to confirm at that level, which I think is significant in that it shows us the levels at which the different laboratories are capable of confirming THC in these  samples.

                When we get down to this sample, which we knew had about less than -- well, somewhere around 0.1 or 0.2 picograms of THCA, we find that we only had at that point one laboratory that confirmed at that level.  The lower we get, the fewer laboratories that are able to confirm, which is what we would expect.  We did have one laboratory and a reference lab to give us some values for the THC in that sample.  We spiked it at 10 picograms per milligram, but we ended up with what appears to be more, and I can't explain that at this point in time.

                Sample 128 was spiked with 1,000 of morphine.  One laboratory appeared to find everything -- codeine, morphine, and 6-AM.  And one lab found some codeine.

                Sample 130, was spiked 200, 200, 200 --- you can see that the means are very close and the laboratories appeared to be able to, at least many of the laboratories appear to be able to quantitate in that area of the 200, which is where the cutoff was.

 

DR. ISENSCHMID:  Is there any chance that the lab switched samples?

 

DR. MITCHELL:  We have gone back and asked the laboratories to recheck this and have not received all the information yet.  To be fair, if we see any type of abnormalities like that which could possibly be due to a switch of a sample or even recording the sample incorrectly onto the report forms that we give them, we go back and question them and then wait.  We haven't received any word yet on that one.

                Going to the next page of table 2, sample136 was spiked with methamphetamine at about 1,000 and we are getting some spurious results.  I don't know if this is due to a sample switch right here at these two, which would look like a sample switch to me just from my work with urine.  But we do not know at this time.  We can see that we spiked it with 1,000, the mean is about 900.  We removed this one value that is way out and that is the mean standard deviation.  Some amphetamine was found here by two different laboratories  and the source of that I do not know.

                Remember I was telling you that there were some laboratories, two laboratories, that screened this positive, and also we had two laboratories that confirmed the presence of cocaine and benzoylecgonine in that sample.  Going back and looking at the data, the initial test showed that it wasn't totally negative on initial test when we had the original screening done for the hair that was used.

                Sample 144 was spiked with 5,000 picograms per milligram of methamphetamine.  We had no amphetamine in that sample.  At this time there was a very small amount that was found in the sample at 5,000.

                Sample 145 was a powdered hair that contained THC.  One of the laboratories not only confirmed the THCA, but also THC in the sample, and you can see that these two laboratories -- there are actually three laboratories that were able to confirm fairly consistently at this level.

                Even with the real hair, when we have various sub-picograms amounts we find that there appear to be only two laboratories that can confirm at below the 1 picogram at this time, and I think that is significant.  Again, this sample contained cocaine and BZE, which we confirmed from some of the laboratories.

                Sample 147, we knew that it contained codeine, morphine, and 6-AM.  We removed this value from it.  The mean was about 1,000.  Recently we had thought it was somewhere around 1,500.  The 6-AM values and the codeine values kind of reflect what we see in the morphine as far as the standard deviation, even though we didn't have to remove any values out here. 

                Again, this sample and this sample (indicating) are strands.  This 146 is also.  All three of these are strands that were analyzed by the laboratory.

                Sample 148 contained cocaine, BZE, methamphetamine, and amphetamine.  Again, there was a lot of variation here.  In trying to remove the outlier, because it was anywhere from 12,000 down to 1,000, it made it very difficult to remove any particular value without using some type of outlier program to identify it, rather than trying to do it all myself.  The BZE again was fairly variable, but not quite as much as the cocaine.  Methamphetamine, we had another value which was way out; we removed it and it brought it again into around 40 percent of the mean.  With amphetamine, the amphetamine was very low in this drug user's hair.

                One of the interesting things, one of the limits that we faced with hair in using preparations, whether it be powder or whether it be a strand, is what type of variation are we going to expect from laboratories from the preparation itself.  Hopefully, as we go on and increase the number of samples we'll get a better handle on what type of variation or how much variations from homogenization of a solid matrix and how much is due to laboratory variation.

               

DR. JONES:  Would it be possible to get a list of the spike concentrations for the hair somewhere, just so I can look back at that at some point in time?

 

DR. MITCHELL:  Yes, we will do that.

                I guess next we can go to table 4.  We'll change matrices and we'll change our focus and we'll go to the initial test for the oral fluid samples.

                One of the nice things about the oral fluids is that it does appear that we can fairly consistently spike and get results that we would want.  I hadn't anticipated at the time we made up the samples that we might have some spurious assays or results from the initial tests.  We did not have an indication in Cycle 1 that we had that, but this time we did.

                For example, in sample 22 we did not spike, we did not put any THC in that sample.  But yet we had one laboratory that did find the THC.

 

DR. SAMPLE: If you look at the confirmation results they show a 3.3 for THC on that specimen.

 

DR. MITCHELL:  Right.

 

DR. SAMPLE:   I assume that's why you reviewed that.

 

DR. MITCHELL:  Yes.  Evidently, what the lab did is they did confirmatory results and then went back and did a screening test with immunoassay.

 

MR. STEPHENSON:  Well, that's one way to do it.

 

DR. MITCHELL: They were not able to confirm their confirmatory test by immunoassay.

 

DR. SAMPLE:  It doesn't look like they performed an immunoassay.  It's all X's.

 

DR. MITCHELL:  I think that's wrong.  It was kind of confusing to us at the time, trying to interpret what we get.  But that was the information that I got on that, that it was confirmed by GC/MS and was found by GC/MS, but was not indicated by the initial test, the screening test, whether it was done first or second or whatever.

 

MR. LODICO:  Does this data include reference laboratories also?

 

DR. MITCHELL:  Yes, these means include reference means, or are supposed to.

                Let's go through this real quick.  Sample 21 was spiked with 80 nanograms per mill of methamphetamine.  22, sample 22 was spiked with 240 nanograms per milligram -- per mill, excuse me, per milliliter of oral fluid.  Now, the cutoff for the methamphetamine is 160, so that means that this one was below the cutoff, this is well above, and we did have a couple laboratories that found it at half the cutoff.  Almost all the laboratories found it when it was at about 1, 1.5, is what 240 is.

 

DR. SAMPLE:  That's all d, 100 percent d?

 

DR. MITCHELL:  Yes, that's all d.  We haven't only used the d isomer.  I'll show you in just a minute.

                Sample 4 contained 160 d-amp and 160 d-meth, and so with that combination we were able to get everyone as positive.  It would indicate that this sample right here may have, or at least this lab's immunoassay may have some specificity toward d-amphetamine.  That's what it would appear.

                Sample 24 contained 100 nanograms per milliliter of BE -- yes, of BE -- and 160 nanograms per mill of l-methamphetamine.  That's similar to the sample that I gave, that we gave for the hair where we had the l-meth, and we see that we had one laboratory that did screen that one as positive.

                The coke samples, they all were spiked at 8 nanograms per milliliter and we can see that that is below the 20 cutoff, as it turns out.  As we would expect, there would be very few that would screen it as positive, but there are some that seemed to have -- at least one lab appears to have a much lower cutoff in the presence of BE.

 

DR. SAMPLE:  And those are all the same pool subdivided?

 

 

DR. MITCHELL:  Yes.  Dale Hart (RTI) is our donor.  He has been our major producer of oral fluid over the past 6 months to a year.  He's never seen without his little cup.  It's quite a task.

                Sample 25 was spiked with morphine at 20 picograms per milliliter, which is just below the cutoff for the morphine, and 4 out of the 6 laboratories that screened for it found it positive.  So it's a little bit low.

                Sample 13 -- and there were three sample 13's sent out or sample type 13's -- had 40 of morphine, 4 of 6-AM, and 40 of codeine.  With that mixture, at the cutoffs everybody was able to identify that sample as being positive.

                Sample 26 was spiked with PCP at 2 nanograms per milliliter.  That's half the cutoff and we only had one lab that found that one as positive.  There was no marijuana, even though, as we'll see in confirmatory results, somebody did find marijuana in that particular sample.

                Sample 27 had one nanogram per milliliter of PCP.  We had one lab, this one -- there was a separate sample from 26 which we spiked containing 2 picograms of PCP and a couple of laboratories found that.

                Marijuana, here we're spiking THC and the levels that were spiked in sample 28 was 2 nanograms.  We see 2 out of the 5.  We go up to 6 nanograms, we get 3 out of 5.  We go up to 20 nanograms, we get 5 out of 5.  So I'm not sure where we are on the cutoff of this particular one.  The cutoff for the THC, again, is 4.  That's the one that was agreed upon.

                It makes it a little more reasonable whenever you remove the spurious values.  Not exactly.  There does appear to be a high bias for some reason in the confirmatory tests.  I don't know if that's in these samples.

 

DR. SAMPLE:  That certainly skewed things on the marijuana.

 

DR. MITCHELL:  Yes.  This is confirmatory results on these samples.  A couple things I'd like to point out.  I don't know if we'd want to go through this sample by sample.

 

MR. STEPHENSON:   The biggest value in this is to provide the information to the participating laboratories as to how they had performed if they chose to participate in the tests and, if they did, what could be learned from it, how can you get it.  Some of the issues are still maybe specimen issues.  But others are clearly differences in laboratory abilities, and that may be something that will help move an entire industry group along.

 

DR. MITCHELL:  We did have some samples in this group that's in the blue that went out the first cycle.  Since you don't have your table from Cycle 1 with you, the mean on sample 4, the mean for this sample was 381 plus or minus 404.  So there's been a great deal of change and consistency on the second cycle with the methamphetamine and amphetamine.

                Sample 9 was sent out in the previous cycle and has BE and the mean last time was 8.  Pretty close to the same mean, but the standard deviation there was 4 last time.  So you can see the change in the consistency.

                Sample 13 went out, the morphine was found to be 36 plus or minus 11, the 6-AM was 4.5 plus or minus 1.5.  So they're fairly close.  There hasn't been a lot of change and it was fairly close last time.  The codeine was 41 plus or minus 15, so there has been some small improvements there as far as the consistency between the laboratories as measured by mean and standard deviation.

                Sample 16, which was phencyclidine, was about the same.  It was 2.5 and the standard deviation is plus or minus 0.6.  The negative, which was also sent out, continues to be negative via confirmation.

                These are all spiked into oral fluid, directly into the oral fluid, and have been analyzed by different laboratories in different manners.  I've even gotten some results where the lab, it appeared from what they said they had absorbed it onto the device and then analyzed and back-calculated.  I'm not real sure of all the details on that and I will try to get those details as we get into the phase where we're looking at these issues.

 

DR. BARNSHAW:  You have reference values here, but the total numbers only add up with your lab results, not the reference numbers.

 

DR. MITCHELL:  On some of these samples, no, I do not have all the reference values in here.  That may well be true.  We will be looking at the reference values.

                Sweat testing.  We only had two values.  One will be from the reference lab and one will be from the laboratory which was involved in this testing.

                One issue that has come out of this is the ability to spike THC onto patches and then use them as QA or QC materials.  We are having difficulty.  It appears, even though we went back and spiked samples gain at the end of the last one, that we're still recovering off the sweat patch, or at least the ones that we're using, approximately 10 percent of the material that we're putting there.

                This is my fault.  This is supposed to be "THC", not "THCA", right here down at the bottom.  You can scratch off the "A" on this table.

 

DR. BARNSHAW:  Including 12?

 

DR. MITCHELL:  That should be, yes.  Yes, 12 should also be "THC".

 

MR. LODICO:  Can you give us the fortified values for those?

 

DR. MITCHELL:  No, I do not have those with me at this time.  That's the only one I don't have.   I think that there are a couple of things that are fairly obvious.  For those samples in which we have two values, we can see that the mean from the laboratory and the reference value were very close, which was very comforting.  In fact, in this series of samples with the opiates, the consistency between samples, from sample to sample, that they got, as well as the means from the reference lab, were very close.  It's very interesting that it turned out that way.

                With the PCP you can see that the values again are very close between the reference value, the reference lab, and the participating laboratory.

                I'll go back and check on all these to make sure that all values have been included, and we'll work on the spiked values.  But I do know that these values represent about a tenth of what was put onto the patch.

 

MR. STEPHENSON:  Can you provide us kind of a summary on the laboratory-based PT for urine specimens?

 

DR. MITCHELL:  In tables 7 through 11, you will find the results for cycle or occasion 55.

                The 55 times we have sent out maintenance PT urine samples to urine laboratories, and I have it broken down by drug class, and then with the analytes going from the lowest concentration to the highest concentration that went out. 

                Now, there's something I need to explain to you.  The reason we have so many values is every lab did not receive the same samples in this cycle.  We would have, you can see, we sent out to 65 laboratories -- 64 laboratories, excuse me -- and approximately 30 or so would receive each sample type.

                We only send 15 samples.  In that we try to get at least three confirmation challenges for each analyte in that 15 samples.  This is the pattern.  You can see that the CV's, at least with amphetamines, run somewhere in the 7 range, of 7 to 12.  With benzoylecgonine, we see a similar range for benzoylecgonine, which is the analyte looked for in urine.  Similarly with the opiates, we see 7 to 13 being the range of the CV.  That is, you know what percent CV is, everyone?  I hope.  It's the standard deviation divided by the mean times 100.  It's just an indication of what type of variance you see.

                In PCP, the same type of thing, 7 to 11.  The one that we have the most problem with, as you would expect, and have the highest CV's would be with THCA, the marijuana metabolite.  We have variances anywhere from 9 to 17 percent in the standard deviation of the mean.

                This is the type of thing that we consistently see in urine with this metabolite.  The metabolite's really not that happy in urine as the free acid.

 

MR. STEPHENSON:  Thank you very much for that very thorough presentation.  This is an instructive process where the primary benefit is to the participating laboratories and the individual discussions that they have about their own performance.  I think it's important as a process for everyone who's interested in what we're doing to see this is where we are in creating the reality of taking a concept and focus group discussions into regulatory guidelines.

                This is where we have to perform, and this is the area where if you look in comparison with 55 occasions for performance tests going out to urine laboratories, this is the goal and the direction for development in the alternative specimens in the future.  I'm sure it will occur, and it's happening from one cycle to the next in this environment.  I'm very pleased with what I've seen in terms of movement.  We've been learning as much in the preparation of the specimens as you guys have in the field in actually performing the tests.  This is a good partnership.  Again, nobody's holding folks accountable.  We're not scoring you on them at this point, but you are learning and that's important.

 

MR. LINEWEBER:   The UTU clearly supports onsite testing and the reason we support it is because we feel that it helps all the employers get that positive result or that problem person out of the workplace quicker.  Not only that, we know that there's greater credibility in the testing process if we have an initial screening onsite.

                We are hoping that we get an opportunity to work with one of the DOT regulators, i.e., whether it be Highway or FRA, to form a partnership with one of those employers in the railroad industry or in the trucking industry to start an onsite project.  We don't want a side by side.  We clearly think that the Justice system and the Postal Department have proven that onsite works.  The research that was conducted by Dr. Willette and Dr. Kadigian that shows us that there are adulterants there that oxidize before they get to the laboratory while eating the marijuana metabolite certainly raise concerns for laboratory testing of urine.  I think it makes it a bit antiquated, quite frankly.  What I'm saying to all of you, if you know of an employer out there who's willing to invest in that partnership, certainly encourage it, because onsite testing is the way of the future.

                I commend you for all your good and hard work. 

 

DR. JONES:  When is the next Board meeting?

 

DR. BUSH:  December 5th and 6th.  It won't be here.  Again, it'll be an open and closed session.  We don't know the timing on that.  We won't know until we set up the agenda.  That's why it's important for you to read the Federal Register notice, because that's when we pull it all together, and that's after this meeting.  It's going to be at the Embassy Suites at the Chevy Chase Pavilion. They call it 4300 Military Road.  It's the cross street, but it's Wisconsin Avenue and Military Road.

 

The open session adjourned at 12:18 p.m.