DRUG TESTING ADVISORY BOARD
OPEN SESSION
June 6, 2000

Agenda Item: Welcome

MR. STEPHENSON (HHS): This is the open session of the Drug Testing Advisory Board meeting. Please sign-in.


Agenda Item: HHS UPDATE

DR. VOGL (HHS): I was hoping to have good news today and to handout the new CCF. Unfortunately, we have not received clearance from OMB. We did send the package to OMB about 2 months ago and on May 1st had a briefing with OMB staff to answer questions and to clarify some of the issues and concerns that they had. We tried to stress the importance of getting clearance by the end of May in order to have the new form available for use by August 1.
In our discussions with OMB, agreement was reached that the current form could be used for at least 12 months. Therefore, two forms would be concurrently used for federally regulated programs. For clarification, the new form can be used beginning 1 August. However, laboratories or third party administrators or anyone who uses the form can choose to delay using the new form for however long they want to. They could start 1 September, 1 October, 1 November, because the current form can be used until next year.
The Federal Register notice will contain an extensive list of acceptable modifications to the form. There is a basic format, but you will be allowed to make some changes. For example, highlighting different fields so that the collector would know what information they need to provide as opposed to what the laboratory would be providing.
We are going to send the information directly to the printers, trade publications, laboratories. We will get the word out as soon as we receive clearance from OMB.
The other issue that's gaining interest is the Government Paperwork Elimination Act, which was put out as a draft document last June or July by OMB. It is a requirement for federal agencies to implement the Paperwork Elimination Act by October 2003. In mid-June, OMB is putting together a roundtable for HHS and DOT with regard to their workplace programs and looking at the form and the laboratories and seeing where changes can be made to eliminate some of the paper.


Agenda Item: DOT UPDATE

MR. EDGELL (DOT): The comment period to our notice of proposed rulemaking, 49 CFR Part 40, for DOT drug and alcohol testing, closed. We received somewhere in the neighborhood of 400, over 400 comments from employers, unions, third party administrators, anyone involved in the DOT testing process. Those comments totaled somewhere in the neighborhood of some 3500-plus comments on issues in the rule. The issues that generated the most comments were a tossup between the collector issues -- and that would include refusals, direct observations, monitored collections -- and the training requirements for collectors, medical review officers, substance abuse professionals, etcetera. Probably the third item of most interest had to do with validity testing, the adulterated and substituted specimens, as well as the paneling of the split specimen with respect to validity testing. Public interest exclusions naturally generated a lot of comment, as did the issue on stand down.
The Department has a goal of getting this rule out by the end of this calendar year. However, that is a huge job and we need to make sure that we do it right. So that emphasis is probably a little higher than the actual date.


Agenda Item: MDMA

DR. BUSH (HHS): You have a handout, but what I'm going to speak about is the slides which are projecting on the front of the room, just for those of you who may not see.
My topic this morning, which you probably heard in the news and have seen in a recent issue of Time magazine, is amphetamines and MDMA. You hear so much about DEA confiscations, local police making pleas to local communities about high schoolers at dances, and monitoring what's happening with youth, and MDMA is always in the same sentence with all of those efforts.
It seems to be a very popular drug and I want to bring this up in open session. Certainly to alert all the Board members about our thoughts as the operational division of drug-free workplace programs for federal agencies and to alert the public as to what we're looking at and ensure the public that we are paying attention to what we are hearing from the media and from other arms of law enforcement.
With that said, I'm going to launch into a couple of mechanical structure reviews here. I'm going to review briefly where we are today in what we look at in our drug-free workplace program and focus on in our analysis and search for and deterrence of methamphetamine and amphetamine misuse and abuse.
(Slide.)
We have our favorite d-methamphetamine psychoactive compound to show you the three-dimensional chemical structure of a dextro optical isomer that happens to be the psychoactive isomer of methamphetamine, as opposed to the l-methamphetamine. That chemical structure is different from the d. You can tell by the way the functional groups are arranged there, and the l-methamphetamine is actually active in the bronchial area, that's in our Vicks inhaler. Vicks has an exemption from DEA to include methamphetamine in that l-isomer form to be included as an active component in their Vicks inhaler. We have two optical isomers of methamphetamine and then the metabolites of those, the d-amphetamine and l-amphetamine, respectively, are the compounds that we are most concerned with in our analysis of the class of drugs amphetamines as the guidelines are currently written.
(Slide.)
We have to look at the other chemical structures of compounds for treatment of allergies, colds, and congestion, and possibly as diet aids in the case of PPA (phenylpropanolamine). You see that the chemical structures are very similar, such that when we do perform a screen, an initial test by immunoassay as described in the guidelines, we may in fact through that antibody-antigen, the drug being the antigen, the immunoassay active component of the analysis being the antibody, we also may have this cross-reactivity with these compounds because they're so similar in chemical structure to the methamphetamine, top left, chemical structure.
(Slide.)
We focus on methamphetamine and amphetamine in our confirmation analysis by GC/MS and can further differentiate the optical isomers, the d's and the l's upon request of the medical review officer for their evaluation of alternative medical explanations for the presence of methamphetamine or amphetamine in a urine specimen.
(Slide.)
MDMA and MDA. Again, a very similar chemical structure except for the ring that is on the far left-hand corner with the two oxygens and the CH-2 group. Similar to the amphetamine and methamphetamine issue.
Today, looking at the immunoassay kits available and used in our certified laboratories, in the clinical arena, and in areas other than federally regulated workplace testing, we have an immunoassay kit that is somewhat, but not very sensitive to detecting the presence of MDA and MDMA in a specimen. Some of the manufacturers have taken a look at what the marketplace is, what the needs of their customers are. What focus is criminal justice, workplace, clinical testing, on needing to know presence, absence, answers about MDMA in a urine specimen. Clearly, a variety of reasons. Because of the lack of sensitivity of the current immunoassay kits, we do have efforts ongoing for a sensitive and specific assay by some manufacturers.
(Slide.)
The background of MDMA. It was patented by Merck in 1914, initially intended as an appetite suppressant. However, the compound also induces psychomotor agitation that can be pleasurably relieved by dancing, and thus it is the ideal party drug. The most profound effect appears to be the experience of intense emotions and perception of experiences of the emotions of others. Psychedelic use of MDMA and LSD flourished amongst Dead Head followers of the Grateful Dead concerts who attempted to achieve a spiritual state, valuing the beauty and love of things. This goes back to the 1980's.
(Slide.)
I have a couple of small pictures of methamphetamine in tablet form, because this drug is ingested orally in tablets. Clearly, this is how it is purveyed and consumed at the rave parties that are currently of issue in our popular press and with law enforcement. The compound MDMA was regulated by DEA as a Schedule 1 drug in 1985 along with other psychedelic drugs.
(Slide.)
MDMA is usually taken as an oral dose, generally 100 to 150 milligrams. It is said that there's an initial amphetamine-like rush which lasts for a short time, 20 to 40 minutes. This may in fact be caused by the serotonin release and a blockage of the reuptake of serotonin. Those of you who know pharmacology understand that this is a common mechanism of action of many of the selective serotonin reuptake inhibitors that are popular today, and tend to level out moods. It is used as a mild antidepressant. Peak effects of "world relatedness" occur with the ingestion of this compound in three or four hours.
(Slide.)
General pharmacokinetics of the compound. MDMA has a duration of general effects of about 4 to 6 hours, with gentler effects and less day after fatigue than other compounds or than MDA. MDA is actually a metabolite of MDMA, but MDA is also synthesized and ingested on its own as a separate drug of abuse, and again in pursuit of the same effects that MDMA is purported to have. MDA has a longer duration of effects, with pronounced day after sluggishness. MDMA is the drug of choice here. After-effects last for 24 hours or more. Again some specifics about that are listed in the slide for your knowledge.
(Slide.)
There's just an awful lot of information on the Internet and that's actually a good source that I have used to update the slides from this presentation that were a few years old. I'm learning more every day with the solid sources on the Internet, and it's also easier to search the peer reviewed literature that way, too.
What I'm hearing and what I'm reading on the Internet is that because this is an oral dosage form people are concerned about ingestion of, shall we say, too much for their desired intended effect. It is a matter of being able to titrate your dose, because once you ingest a compound orally it's yours to keep. It is ingested into your stomach, it's going to be absorbed through the small intestine. For better or for worse, you've got it all, as opposed to other dosage forms, such as smoking, where in fact that allows a user to titrate the dose to get to the desired psychological effect.
With that said about how you own what you eat and then sustain the effects, there's a lot of discussion on the Web about how one should approach ingesting MDMA and the dosage range you should start with so that you have an enjoyable experience with this illegal drug.
I have a list of information there about optimal for most people is 75 to 125 milligrams, and it depends on the size, the body mass, things like this, and experience with the drug. Again, even on the Web -- informational web sites that I didn't expect. A term like "LD-50", lethal dose to 50 percent of the population, that's what I learned in my graduate pharmacology courses. But "LD-50" is listed there and explained to the casual reader. They do try to make sure that people realize you can overdose on this compound, but in fact they're trying to show it takes a lot to do that.
(Slide.)
National Institute on Drug Abuse in their Monitoring the Future survey in 1998 have presented the following information about what they hear from the youth surveyed in 1998. 3.6 percent of twelfth graders have used MDMA in the past year. 3.3 percent of tenth graders have used MDMA in the past year, and 1.8 percent of eighth graders have used MDMA in the past year. Follow-up of a group of previously surveyed high school graduates showed that the number of college students who used MDMA in the past year rose from 0.9 percent in 1991 to 2.4 percent in 1997. And among young adults, annual MDMA use rose from 0.8 percent to 2.1 percent during the same period.
Taking a look at our youth in high school and follow-up to high school graduates is always a priority for us at the Division of Workplace Programs because our youth are working in our workplace. Think about all of our gateway jobs. These young kids who are in high school and holding part-time jobs are certainly going to be our full-time employees in a couple years. It is important to know where kids are today, what their thoughts and feelings are and attitudes, and where we need to look at in our drug-free workplace initiatives.
(Slide.)
I've had some personal communications with several laboratorians who have been reading the same popular press that I have and have been concerned about what's going on in their workplace drug testing programs since they serve clients who have the same questions that we all have. Several workplace populations, as of this morning, 6,000 specimens have been screened for MDMA by immunoassays sensitive and specific for MDMA and MDA. This is not the current off-the-shelf manufacturer immunoassay that I spoke about before that the laboratories use in their drug-free workplace programs that we have today, but rather this is a new product put out by the immunoassay manufacturers to detect specifically MDMA and MDA. The results indicate an extremely low, read zero, positive rate. The specimens that were screened were heavily weighted from the retail industry and thoughtfully were tested for MDMA -- these were urines that were collected on Monday mornings. We are looking at the recent exposure, possibly over a weekend use, either on a Friday night or a Saturday night, trying to optimize the detection of compounds in the urine, MDMA specifically. We have a zero positive rate. Another laboratorian took 200 presumptive positive specimens for amphetamines under the drug-free workplace programs and these specimens were sent on to confirmation for both amphetamines and MDMA and MDA. Results: None of these specimens confirmed positive for MDMA or MDA. Interesting that we're seeing in specimens collected under drug-free workplace programs, not necessarily regulated, but certainly from retail, very low/zero, incidence and prevalence of MDMA.
We are going to leave this, at this time, as a personal communication. The laboratorians and I are planning to prepare a technical note letter to the editor for Journal of Analytical Toxicology so that we can demonstrate our active look into workplace populations and at least state clearly to the world that we're not asleep at the wheel on this issue in drug-free workplace programs and that we're taking a look at what we might have here in our regulated industry program.
(Slide.)
The reason I started with the phone calls and trying to get information from existing laboratorians who share the same concerns that we do from a program level, we all have the goal to maximize the deterrence and the detection of illegal drugs of abuse while managing the costs of such a program. We've taken on the task of determining the availability of MDMA immunoassay kits, what plans manufacturers might have, and application not just to workplace, but certainly criminal justice systems have the same kinds of questions that we have and an awful lot of self-admission in many of their programs of MDMA use and abuse. We need analytical tools out there to help answer some of these questions, and it doesn't appear that the kits and the tools on the shelf right now meet the needs. We are trying to stimulate some discussion amongst the manufacturers and plans of how to approach this serious public health problem. We are taking a look at comprehensive GC/MS procedures for analysis in a single run to include with methamphetamine and amphetamine the analysis of MDA and MDMA.
To include all those drugs in a single run would be very cost effective for the laboratories performing confirmation analysis. John Cody et.al. have published an article in the October issue of the Journal of Analytical Toxicology such an analysis. This is a method that actually focuses on the differentiation of those d and l isomers of methamphetamine and amphetamine and also retain the ability to identify and quantify MDA and MDMA.
Immunoassay kit manufacturers are trying to look at sensitivity and specificity of the kits that they may put out on the market, and there may be a need for a separate kit that would separately screen initial tests for MDA and MDMA or be combined with the existing capability to detect methamphetamine and amphetamine. There are a couple of ways manufacturers are considering going here, and I'm sure laboratories and clients will have a lot of input relative to that cost-benefit analysis.

MR. STEPHENSON: You might wonder why we even bring this up. I want to share with you a couple things. This is like looking into a crystal ball and seeing the future.
To say that we do not have the current experience in the workplace environment with the adult populations that we are currently testing is great news and we should take this with a deep sigh of relief that we don't currently have a hidden problem that we have not seen and responded to. However, that's not the case in other environments. The clinical environment, the criminal justice and juvenile justice testing environments, the treatment environment and others do currently have a problem and are not currently being able to identify it. The same reagents and the same kind of testing protocols and the same laboratory or the same perhaps onsite or alternative specimen testing resources need to begin to get geared up to be able to respond to this, because it is only a matter of time. It is not a question of if.
Donna had referenced things that had come out of the Department of Health and Human Services studies that we do on an annual basis. In the current annual report from ONDCP, the year 2000 annual report on the national drug control strategy, what they quote in there is a sixfold increase in seizures. That's six times more seizures of MDMA in 1999 than in 1998. What we've seen is about a 50 percent increase in the self-admitted use among youth that are identified in the Monitoring the Future study. The conclusion out of that review was that, because MDMA is used with other drugs by youth, we may reasonably expect it to become a gateway drug for youth of the future, that because of that it is anticipated, not to sell stock for those illegal folks manufacturing this, but we expect to see an increase in the use rate. It is not going to go away, it's going to get worse.
The third thing is that right now youth make up a significant new part of our work force population. Today, according to statistics that I've just reviewed, 46 percent of our youth from ages 12 to 17 are already in our workplace in part-time status. That's up 5 percent in just one year. In April of this year, for the first time in 31 years our unemployment rate nationally dropped below 4 percent. It went down to 3.9 percent. We're just now moving into the summer cycle when we're going to have a lot of part-time kids being hired into the workplace. Put all of these things together and count this as a blessing, that at least we have some up front awareness. But we can tell you anecdotal stories about folks who are calling from treatment programs that are saying: We've got 100 self-admitted MDMA users that we put into treatment and when we tested them I only got one positive; why is that? We've got others that say: We've some screening assay results we're getting, looks like problems with our screening assay because we're getting some screening presumptive positives for methamphetamine, but when we send them to GC/MS they're not confirming. In one series of studies that was dealing with criminal justice in traffic areas, the issue was when they went back to those specimens where they have had that anomaly in the screening assay between 70 and 90 percent of those specimens did confirm for MDMA.
The point is that it is out there in selective populations. Whatever we've done to create the kind of armor that seems to still be out there for us in the workplace, don't count on it holding into the indefinite future. We need to build a better deterrent and make sure that the youth who might choose to use this particular drug because of its perceived value to them and their lifestyle and the fact that in the workplace we're not detecting it and they're not in jeopardy of losing a job that they value or getting a job that they want, we need to turn that around and we need to do it as soon as possible.
The more pro-actively we can do that -- we call on each and every one of you through all of your resources and your networking. Share with us your experiences, what you have learned. It will help us to go forward with a strong initiative. Share with us what you think we should be doing in terms of looking at particular assays or groups that you would like to steer us to, and we will follow up on it.

DR. BUSH: Just a final thought. One of the handouts that you were provided this morning is draft number one of the mandatory guidelines. You don't need to do it now necessarily, but when you go through and look at the drugs to be included in the testing you'll see that MDA and MDMA are there with all the alternative matrices included for that analysis. We are taking this very seriously.

MR. CROUCH (DTAB): We had a little different experience for detection of MDMA. It was a study for DOT and we looked at 800, I think it was, arrested drivers, suspected DUI. About 5 percent of them were positive for amphetamines by immunoassay. Half of those were MDA or MDMA. It is a different population than workers, but that's certainly -- at least in that group, half of the positives were for amphetamine, methamphetamine, the other half were MDMA.

DR. ISENSCHMID (DTAB): Just one quick comment with regards to the substituted methamphetamines. Certainly in this country the seizures have been related to MDMA and MDA, but in Europe now MDEA has surpassed MDMA. That may be another forthcoming thing of the future.

MR. STEPHENSON: Thank you very much. I think it was very important to get the message out to you.


Agenda Item: DOT/HHS Laboratory Directors Meeting

MR. LODICO (HHS): I will present a summary of laboratory issues that were discussed at the DOT/HHS laboratory directors meeting. The meeting was a two day closed session on December 13th and 14th of 1999. 59 RP's and Alt-RP's attended from 49 laboratories. This is a 75 percent rate of participation in laboratory attendance that are part of the NLCP program.
I will discuss some of the scientific presentations that were presented at this meeting. Just to do a little backdrop of information and review, the meeting was an effort to bring to the table information that is critical to the laboratories, concerning adulteration, program documents and guidance.
The meeting provided information and updates related to the NLCP program but, more importantly, we wanted to have breakout sessions for specifically related topics, where we get active participation and dialogue from the laboratory directors. I will summarize the comments made and consensus answers to issue questions by laboratory directors that attended this particular meeting.
The first scientific presentations on day one of the meeting began with the issue of what is a substituted specimen. Dr. Caplan provided a detailed description on how DOT and HHS defined a substituted specimen through PD documents 35 and 37 and the reference material used to set the threshold criteria. This was a precursor to the state of the science paper that was released in February of 2000. Dr. Caplan asked the audience if they were aware of a documented situation of individual excessive fluid intake that exceeded this established threshold. No one from the audience knew of any instance were this condition existed.
(Slide.)
The next presentation was an adulterant update given by Ken Davis of RTI. One of the problems that the laboratories are encountering is adulteration. Laboratories are presently testing for adulterants like nitrite and glutaraldehyde. But more importantly, there are new adulterants out on the market that Mr. Davis brought to the attention of the members. He discussed surfactants like Mary Jane, Super Clean 13, Urinaid, and Clear Choice, which are fixatives.
(Slide.)
The next scientific presentation was on MRO issues and laboratory interactions. This was presented by Dr. Joseph Thomasino. He presented issues concerning both the MRO and the laboratory and how to resolve them.
(Slide.)
Continuing on day one with the scientific presentations, we proceeded to the next category of information, which is the advent of data transmission and management security. This was presented by Mark Adams of Lab One. He described the different types of electronic transmission of information, and how you can create a paperless laboratory, which was the next topic. This was presented by Dr. Michael Peat of Lab One. He presented his experience at his laboratory in trying to employ a paperless laboratory with chain of custody forms that are electronic, and with internal laboratory chain of custody forms.
(Slide.)
The final morning scientific presentation was by Jennifer Collins (MedTox). She presented information on the use of an image-based data capture system in the laboratory. How effective it is in capturing the information, timely release of data, and the use in specimen accessioning.
The afternoon scientific sessions were dedicated to Breakout Sessions. The audience was divided into three groups. Each group was given an opportunity to discuss issues on MRO, laboratory operation, and laboratory technologies. In the evening, DOT presented the revised CFR Part 40 and dialogue with Mary Bernstein.
Day two, scientific presentations continued with the new custody and control form. Dr. Vogl, discussed the new custody and control form.
The next scientific presentation was a DOT legal update presented by Robert Ashby, General Counsel for DOT. He provided information to the audience about legal challenges to drug testing program and other issues.
In the afternoon John Mitchell from RTI discussed the NLCP PT program experience with validity testing. Presently all certified laboratories are challenged with specimen validity PT's. He shared performance results with the audience.
Finally, in the afternoon, we had the report of the three breakout sessions and the discussions.
Lastly, we discussed the HHS interactive web site for laboratories.
Let me discuss with you the concept of what is the breakout session on lab-related issues. There are MRO issues, operational issues, and technical issues. Each of the breakout sessions was chaired by two individuals familiar with these topics. The first one was chaired by Paula Chiles and Joseph Thomasina for MRO issues. Operational issues were chaired by Michael Peat and Jennifer Collins, and the technical issues was chaired by Art Zebelman and Barry Sample.
During the course of discussion we had specific questions that we gave to each group, trying to elicit responses and concerns, we took notes after this was completed, the chairpersons rotated when the session was finished. The information was summarized at the end of the day and reported on day two of the meeting. The chairpersons reported the results of the sessions to the total audience.
Under the MRO issues, first question was the use of automatic d-l isomer analysis for methamphetamine. The question is would you rather have a blanket request or individual letter? 45 percent of the respondents indicated that they would rather have an individual letter for a positive methamphetamine, while 35 percent wanted a blanket MRO account. Then 20 percent recommended that all positives for methamphetamine should have an automatic test for d-l isomer.
Another question and concern that the laboratory has is who's going to carry the burden of cost? This was an unresolved issue.
The second question we asked is should reports include a relative percent of d-l methamphetamine, and the majority consensus was for a percent of isomers, not quantitations.
The next category was reporting of specimens unsuitable for analysis, and the question we asked was should this condition require MRO review to determine whether or not an observed specimen is to be collected? The response was that the MRO is best qualified to make that determination. They also recommend that the initial report should contain information on values for creatinine, pH, specific gravity, and reasons for unsuitability. This was unanimous that for the MRO to be effective you need to have this information before they can demand a second collection under observed conditions.
The next question posed to them was, should descriptors to this condition be standardized so that all laboratories report in the same manner? There was unanimous agreement for a uniform code of descriptors, and I might say that this is a result of the new CCF forms, which the new forms have descriptors of what's unsuitable, what's substituted, and what's adulterated. The other comment was that we should provide details in the remarks line of the CCF and not just abbreviations. This is a consensus among all the laboratory directors.
The next category is the MRO regulatory notification. This was chaired by an MRO and he's very concerned about being left out on the information of new regulations and new guidelines. The question was how to promptly inform MRO's of regulatory changes, interpretation, etcetera. The comment back was that the Internet web sites exist and they provide regulatory updates. Some recommended that the MRO's participate through their MRO association and trade publication as a means to update themselves.
The next question is who should administer such a system of updates? There were several different responses. One of them is that the government agencies, DOT or HHS, should take on that responsibility. The other answer is MRO groups, and another recommendation was that RTI, which is contracted by HHS, should perform that function. But by acclamation, not the laboratories.
The next category of question was the central registry and certification of MRO's, and the question is should there be a central registry? Some of the information that was gathered was that approximately 6,000 MRO's are in two existing registries which account for about 80 percent of the tests performed, but there is an additional 15,000 "uncertified" MRO's. The challenge is to rein in those 15,000 into a registry, but they represent only 20 percent. There was no consensus or suggestion of how to get a central registry.
The other question is how should the registry be established, maintained, and updated? They recommended that MRO’s should attend training workshops, pass an exam, do periodic documentary review. They also recommended that HHS should oversee the process.
The other question that we asked is should this be elective or mandatory certification? The majority would like a mandatory certification of MRO's. We asked them how do you verify this and they agreed that, a successful completion of an exam should be part of the skills credentials.
The next breakout session is the laboratory operational issues. The questions concerned laboratory operational issues, current requirement for QA/QC. We're very interested in knowing is there adequate review of quality control by a certifying scientist? Or can a laboratory do without a review of a negative report?
The question we asked them is should the requirement for secondary review by a certifying scientist be dropped for negative screening results? 85 percent are in favor of a negative screening result released from a computer or a LIMS review, provided a full set of open and blind QC's is included. What this is saying is that the laboratories have confidence in their laboratory data and do not need a certifying scientist to review that data prior to releasing it to the MRO.
The next category of questions we asked was the certification signature requirement on negatives and use of electronic signature. The majority favored no signature requirement on copy two of the CCF for screened negative specimens or release of negative reports with electronic signature. Here is a difference of the way the process is working, if the results are negative and the quality controls are reviewed through either the computer or LIMS or a means of reliably knowing that those QC's are within range, then you can go to the next step and have the confidence to release data in this particular manner.
(Slide.)
The next category of questions we asked is electronic transmission of results, use of the Internet and imaged copies. The majority of people favored the use of imaged copies for reporting, because the laboratories receive a hard copy CCF, they are able to scan that into their computer system, it is a copy of the original, it gives them the assurance that they can report this document. But there was a 50-50 split between the participants when it came to the issue of electronic transmission results via the Internet. A major concern was confidentiality of reports. Concerns were related to that security must be assured before it can be used. We need to create that a model has enough firewalls, enough encryption, that the confidentiality of the individual is always maintained. The laboratories look to HHS for guidance and they recommend that until there's program guidance or acceptance criteria that it really shouldn't be used in this manner as a reporting vehicle.
(Slide.)
Another category of questions we asked was use of alternative technology for screening and confirmation. Under immunoassays, there was unanimous consensus that, yes, you should allow alternative screening technologies provided there is adequate validation. We allow, we encourage, new technologies provided there is scientific validity and validation testing.
Under confirmation, the consensus agreement is that LC/MS, GC/MS/MS, and LC/MS/MS instruments can be used in confirmation, provided there is documented performance and it's scientifically defensible. In terms of using these new instruments in identifying the new alternative matrix, in which you're looking at lower concentration, sensitivity is a big issue, GC/MS/MS and LC/MS/MS could to be the new gold standard by which the confirmation will be performed.
There is agreement among the laboratory directors and participants that we should be open to the new technologies coming on board and we should embrace them based on performance and scientific defensibility.
Under the category of question of inter- and intra-laboratory electronic chain of custody, most of the participants are in favor of a paperless laboratory, especially the bigger laboratories, because they are looking for efficiencies, they are looking to reduce their, full-time employees, they're looking for a seamless process. If they have the technology to implement a paperless laboratory, then they're in favor of it.
The other category of questions we asked was relationship between laboratory and collection site. The laboratories are very much in favor of having a close relationship with the collection sites because they believe that it gives them a better form of training the collectors, which results in less collection errors.
The other category of question we asked was inspection frequency and use of self-evaluation? The majority are in favor of the current frequency of inspections and they don't believe that self-reporting really benefits the program.
(Slide.)
The next breakout session is laboratory technical issues. The next category of question we asked was creatinine-corrected thresholds.
Under the question, can we use it in immunoassay screening? A majority are not in favor of such a process because there's a lack of information. They're only currently used for THC quantitations in rehab conditions or follow-up setting, and the concern is problems with establishing cutoffs. If you have a cutoff and you're using a formula to adjust that cutoff, then it could be problematic and it also could be challenged legally. They're not in favor of trying to correct the immunoassay screening or confirmation using creatinine ratios. But they do say that if it's done you should use it for dilute specimens where the creatinine is less than 20 milligrams per deciliter as a determinant for additional testing. Also, under the category of can you use the creatinine-corrected threshold for confirmation? There was very little interest, it cannot be easily accomplished, and it's best applied when testing serial specimens.
In the category of current requirements for batch QC and screening confirmation, surprisingly, 80 percent of the participants wanted to maintain the current 10 percent open quality control. Only 20 percent wanted to decrease it to 5 percent.
The program right now requires that there be 10 percent open controls on both your confirmation and your screening, and we thought that maybe this was overkill. But the majority of participants felt that it was not much of a burden and was a small cost to the laboratories. The majority of the people wanted to maintain a blind program requirement as well, and their comment was that perception was reality.
The other category of question we asked is should QC requirements be the same for instrumented base testing and for non-instrumented base testing? The majority agreed that QC requirements be the same, they wanted to see the same QC applied throughout the program.
(Slide.)
The next category of question, deals with the current urine drug cutoffs, profile, and the type of opiate testing. We asked the question should we lower or eliminate the 200 ng/mL amphetamine requirement in confirmation. 60 percent of the respondents recommended lowering it from 200 to 100 ng/mL for amphetamine. Only 10 percent wanted to eliminate the whole requirement, and the comments made from the participants was that if you reduce or eliminate you may increase the positivity for methamphetamine by about 10 percent.
We also asked the same group about the lowering of benzoylecgonine cutoff from 150 to 100 and, surprisingly, only a third really wanted to lower it. Their comment, is that it might increase the positivity by 10 percent.
(Slide.)
The next question is the use of the 6-acetylmorphine specific screen test? More than half of the participants agreed that it would be useful.
On the issue of amphetamine, MDMA, and MDA, should we include it as part of the drug testing profile? Only 38 percent agreed it should be included in the program, and the concerns were: What is the prevalence rate in the workplace population? As Dr. Bush had already indicated earlier this morning, through her personal correspondence, right now we don't see a prevalence of a positive rate of MDMA or MDA in workplace populations.
(Slide.)
Finally, the laboratory technical issues. We asked them to discuss and to comment on Program Documents 35 and 37. They all agreed that most MRO's don't understand what a substituted specimen is. The ability to explain what is an unsuitable specimen, that's the challenge for the laboratories. We hope to make that clearer with the new CCF and more guidance.
The laboratories concern and questions revolve around the logic or the decision to prohibit the split testing for adulterated or substituted specimen.
Lastly, the biggest comment is that the laboratories run as many adulterant tests as urine tests, and the general feeling is that the laboratories can't keep up with the new adulterants that appear on the Internet web sites.
That is the summary of information from our meeting.

DR. BUSH: I think what you've heard a couple of times this morning of where we are with the custody and control form, a meeting sponsored by the Office of Management and Budget, the laboratory directors meeting and desires concerning paperless specimen collection, paperless laboratory, there is a balance that we have to strike here. It is not just eliminating paper in our case with a document that serves as a custody and control form. There is a forensic underlay. There's a documentation of specific actions that are captured through the use of that form. There are some confidentiality issues here. Recall now that we require a donor's signature stating that this is their specimen, that they understand what is going on with this process. We have to think about how we can do that with a balance of confidentiality and a paperless system throughout a process like this. It is not as simple, necessarily, as eliminating a piece of paper, but rather a totally new concept of how to handle a process of documentation with no paper. I'm real comfortable with little paper right now and we can reduce the paper, but I'm not sure we're going to be able to eliminate it. These are the types of issues that are going to come up at that OMB roundtable to ensure that those who are reviewing this from the government side of things and those that are participating in this streamlining process understand the underlay of that custody and control form.

DR. CAPLAN (DTAB): Charlie didn't mention it, but the laboratories were 85 percent represented. It did serve as a working group scenario for looking at the urine-based program, which has been one of the last elements that have been discussed for general input. This constituted the working group for looking at the urine program, and you'll see that some things that came from that group, like all the others, are in the draft mandatory guidelines in the handout.


Agenda Item: PT Results for Alternative Specimens

MR. STEPHENSON: At this point, we'll move on to the results of the initial pilot program for proficiency testing of alternative specimens. As a general caveat, although we're sharing with you raw data, information about actual specimen values obtained in this PT, no one should use this report or any of the data to make a judgment about any participating laboratory. We have masked and eliminated the ability to identify which laboratory provided which results, but I don't even want you to go there in terms of trying to figure it out. It is of no value to you.
The value is going to be to the individual laboratories who participated. They will get the detailed results back for their own laboratory only, and they will be able to look across the other laboratories unidentified and see how they scored in general. We're looking for improvements in the process. We're looking for better ways to prepare these PT's.
There is no issue here in which HHS or RTI have done this perfectly this time. We intend to keep on learning. Donna assures me and I'm sure that many of you who have been in the laboratory profession for a long time know that the urine program started out with many issues that in general over the years have tightened up enormously.
We will put a copy of the results on our website and we will provide you with a detailed data set looking at the urine-based PT program for comparison. But remember, that's PT's in urine today, not where it was when it first started.
With that general caveat, I'd like to ask the members of the Board how you want to look at the data that you're seeing. It is been proposed that we only look at, for instance, hair and that we discuss every single specimen in hair. But there are other PT's from the oral fluids and the sweat that were also presented and offer us an opportunity to examine those product alternatives, too.

DR. JACOBS (DTAB): I want to look at all of them, but maybe not in the detail of each individual number.

DR. CAPLAN: I think we ought to look at all of them, and obviously as John starts to go through them, I'd say go through them all, but some will be obviously repetitious and just say, okay, this is similar to this one.

MR. STEPHENSON: The purpose of the explanation is to help you understand the dynamics of the document and how to interpret how it's been laid out on the sheet. Once you get it and you understand it, then you can go through and look at the rest of the details yourself without having to do group torture.

Note: The tables of PT results referred to in this presentation are available as a separate document on this website.

DR. MITCHELL (RTI): This is a pilot PT program, and by "pilot" it means we're trying to find out several things. We're trying to find out if it is possible to develop a performance testing program such as we have in urine for the other matrices. That's number one. Number two is, if it is possible, how is that to be done? And three, the reason for the pilot is to assess the state of the technology that is currently available with each of the matrices.
This is a preliminary report. In each of the matrices there are data missing. That means we have not received all the data from all the laboratories. The means, standard deviations, things of this nature, will change on many of the samples that we are looking at today. We felt that we should give you the information that we had as of Thursday of last week. We still have information coming in and I had values actually coming late Friday after I had left. I know that there's a good bit that has not been included in this.
You've been given a packet and I would like to go through this very quickly. The first page is the cover page. Following that is the letter that was sent to the laboratories explaining the program and what we were going to be doing, as well as three tables listing the cutoffs in each of the matrices. Following that we will have tables for each of the matrices, and I have broken it down for the hair and for the oral fluid. We have the initial test result, which is normally immunoassay, and that will be followed by the confirmatory result.
The first one that I would like to go into would be the hair, and I think it's the most complicated for various reasons, one of the major ones being that all of the samples in the hair are not spiked samples or, rather, are not spiked by us. Some were spiked by individuals who took drugs, so it was incorporated into the hair. Overall, it is going to be a little more complicated as we go through and talk about these samples.
(Slide.)
With the hair PT's, let's start with a little background of what we know. We shipped 20 samples of powdered hair to12 participants on April 3rd, and each of the samples contained a total of 100 milligrams. The laboratories were asked to test these samples by their immunoassay and their confirmatory procedures without washing. We received results from 11 of the 12 laboratories that we sent samples to, and some of the results are partial. For example, with the initial testing -- this is a breakdown of the testing that was conducted. Seven laboratories did initial testing for all five drug classes, three did it for four drug classes excluding THCA, the marijuana metabolite. One laboratory tested all samples for three drug classes using their confirmatory methods, they were actually confirming and screening for each of the drug classes at the same time, but they only did it for three. They excluded THCA and PCP, and there was one laboratory that did not have an initial test procedure available, they were directed to test samples by drug class, according to the drug class that was in the particular sample.
(Slide.)
The first table. We have the sample type. We assigned each sample that we sent to the laboratories a sample type number just so that we could keep up with what we had from our major matrix. The analytes that would be expected in that particular sample are bolded on this table. You will see some samples or some analytes which are not bolded. Some analytes are not bolded and they are analytes that might have been found, such as cocaethylene, or analytes, drug classes which screen positive or which were found in those particular samples.
We'll go through this sample by sample. In the first sample, the laboratories have been coded, given a letter at random, so there is no way to decode this.
The mean is the mean of the confirmatory methods. All of these values were from reference testing, as well as the values that we received from laboratories for that particular analyte.
The four X's by a laboratory, by an analyte, means that they did not conduct that test. For example, laboratory A did not test for the marijuana metabolite in the initial testing. Here, the question marks, laboratory K, that's the laboratory that did all of their screening by their confirmatory methods. That was hard. Originally, they told us they did not do initial testing or screening and then when I got the results they had "negative" by each of the analytes. They do not screen by immunoassay as we normally do.
We have a summary, how many were screened positive and the total number of laboratories that tested for that particular analyte or that particular drug class.
Sample 1 was human hair that was found to contain marijuana metabolites. You will note that it also contained cocaine as well as BE with no CE. This sample was limited in amount, so we formulated it to contain cocaine at or about the initial test cutoff of 500. In this sample only three laboratories screened the sample as positive out of a total of seven tests and 70 percent of the laboratories found/identified the sample as containing cocaine.
Sample 2 was a spiked sample. It was hair that had been tested as negative and we spiked it with both cocaine and BE. It was interesting that six out of ten or 40 percent of the laboratories screened this as positive even though the cocaine concentration was over 1,000, which is over twice the initial test cutoff. Also note that two laboratories out of seven laboratories screened it positive for marijuana metabolites.

DR. SAMPLE (DTAB): Are you saying that in the first sample only the marijuana was there naturally and that cocaine was also spiked in the first one?

DR. MITCHELL: It is all natural hair. In these samples, the ones that had analytes that we found to be positive, we used the hair as it was, with the exception of course it was powdered. Let me make one comment about powdering, some laboratories take the hair, cut it up, and then they powder it. Most of the laboratories do not do that procedure. This set of PT's took them out of their normal routine for testing. They had to do some procedures that they normally would not do because they are working with strands of hair or snippets of hair. This did put some additional work on some of the laboratories. I want you to know that, we have to take that into consideration as we look at the data and the consistency of data.
Samples 3, 4, and 5 actually are the same sample. It was sent in triplicate to the laboratories. You note that the rate that the sample screened positive for the cocaine -- we had the cocaine at 500, about 500, and we also had BE and CE in there. Notice that the rate was eight of ten, five of ten, seven of ten. There's a little bit of variation even though this was at the cutoff. That may have been part of the problem, too, is that it was too close to the cutoff.
We can see that, even though this is the same preparation, we had 4 laboratories that screened one of them positive for THCA even though it was the same hair that had been powdered and spiked. One laboratory did for THCA. These are the 4 that did not.
We can look at these three more when we go to the confirmation. I think it would give us more information when we get into the confirmation.
Sample 6 was a real drug positive hair which contained THCA as well as there was indicated some THC. You can see that it screened positive for THC by six of seven laboratories, even though the THCA concentration is about a third of the cutoff, which is one picogram per milligram of hair. It also contained some THC, or appeared to. We have two values on that from some prior testing. You can see that it also screened positive for amphetamines, cocaine, and PCP by a various number of laboratories. Whether or not this individual was truly a multi-drug user we don't know and that represents some residual materials we don't know, or it could just be what we are going to see as variation in the immunoassays.
Sample 7 was spiked with THCA. We spiked it about ten times the initial test cutoff, and you can see that with it spiked only three out of seven laboratories screened that one as positive.
Sample 8 was spiked, it was supposed to be at the cutoff, and you can see that only one sample -- one laboratory screened that positive. Also, one laboratory found the possibility of cocaine in this particular prep. This would indicate that the THCA that we spike is either not readily available to the immunoassay or that the immunoassays are depending a lot on some other compounds. I don't know. Or there's some interference from the hair preps that were used. I do understand that hair can age and can cause some interference. There's been some indications of that from some of the laboratories, that they get better results with freshly cut hair versus hair that has been sitting around for a while. But we'll look at this very closely and see how this pattern develops over time.
Sample 9, the last one on this table, was again a real drug positive hair with opiates. It had morphine, 6-AM, and codeine present, and ten out of the ten laboratories found this one. You would expect that because the concentrations are fairly high. I mean, the cutoff is I believe 200 picograms per milligram, or that's the suggested cutoff that's in the table. But they were able to identify the opiates in that sample?
(Slide.)
This is page 2, sample types 10 through 20. Sample 10 was spiked at about the cutoff. You can see that four out of ten found it positive for opiates. We also had again one laboratory out of seven that found it positive for THCA.
Sample 11 is a real opiate positive sample and contained morphine, 6-AM, and codeine. Most of the laboratories were able to identify or make it a presumptive positive for opiates. We had one laboratory that indicated that it contained cocaine by initial test.
Sample 12 was interesting in that we spiked it not only with morphine, but we also spiked it with l-methamphetamine. Ten out of the ten laboratories, at six times the cutoff, found the sample to be positive for opiates. We had two laboratories that identified amphetamine in the sample -- in this case it was methamphetamine -- indicating that the immunoassay being used is not specific for the d form.
Sample 13 was spiked at around 100 picograms per milligram each of morphine, 6-AM, and codeine. This is below the cutoff, the morphine concentration is below the cutoff, but with the cross-reactivities with other analytes you might expect that there would be some positives, in this case four out of ten.
Sample 14 was a real positive hair, which we powdered and sent out, and you can see that the methamphetamine, which was fairly high, at about twice the cutoff. Nine out of the ten laboratories found it. With the cocaine, which was very high, nine out of ten laboratories identified the presence of cocaine and its metabolites. We had three laboratories that indicated the possible presence of marijuana metabolites and one laboratory found that it was possibly positive for opiates.
Sample 15 was hair spiked with methamphetamine. This is fairly high, and again nine out of ten laboratories identified it. Also 3 laboratories indicated the possible presence of THCA. All of these hair samples had been previously screened to be negative by some immunoassays.

DR. SAMPLE: Were spiked hair samples all from the same pool of hair?

DR. MITCHELL: No. We had, I believe, three separate preps of powdered hair -- each of the samples was, we did about 60 samples and each one was two and a half grams each. You're talking about quite a bit of hair that had to be powdered.

DR. SAMPLE: I think it might be helpful if you could indicate which lot of powdered hair each of the spikes came from.

DR. MITCHELL: We will do that in the final report.

DR. BUSH: I'd like to point out, though, about the homogeneity of each of the lots. John, do you want to pick that up? You used the blender.

DR. MITCHELL: In order to homogenize the hair, first it was powdered and then it was placed into a central container, and then that hair was mixed, not using a blender. There are some problems with trying to use blenders with particles of this density. But they were mixed, put on a roller and were rolled, and then once an hour they were flipped several times in this direction and the other direction to mix. This went on for an eight hour day. We feel that as best we can, from what we're seeing from the samples, that they are fairly homogeneous.
Sample 16 was spiked with methamphetamine below the cutoff and we had none that were found to be positive by that immunoassay. We did have THCA and one laboratory indicated the possible presence of PCP in the sample.
To round out our five drug classes, 17 and 18 are samples containing PCP, and you will note that when the PCP concentration was -- I believe 300 is the cutoff. It was about three times. Then we got ten out of ten laboratories. When we dropped down to the cutoff, we ended up with five out of ten, and that's the normal distribution. That's the type of thing that you might expect to find that close to the cutoff, half on one side, half on the other.
With a sample of negative hair, and this was from one of the batches that we utilized, we had no false indications of the presence of any of the drug classes.
The last negative that I had was in our pre-testing of hair. We had a sample of hair that indicated that it had been screened positive by 2 laboratories that were doing some reference testing for us, and we decided to include it even though it didn't contain detectable amounts of THCA and THC. We had two laboratories that found it positive for THCA and one laboratory each of cocaine and PCP. I like to include these types of samples that will screen positive, but we know they have no analyte present because it allows us to put negatives into the confirmatory process. Exactly how we're going to be able to do that as time goes on, I don't know, but we'll see about that.
(Slide.)
This was the initial testing. Going through confirmatory testing, let's look at how it broke out as far as the testing. We had five laboratories that confirmed for all five drug classes, four for four. One laboratory confirmed for three, one for two, and one of the laboratories that was participated was screening only.
(Slide.)
Confirmatory results. We have gone through the samples, let's look at confirmation and see what we get. With this THCA and this first sample, we had two laboratories that were able to confirm at 0.05 and 0.09 picograms per milligram. That is down near the cutoff, which was I believe 0.05 was the industry suggested cutoff for confirmatory methods.
We are very close to that, and these two laboratories were at least able to meet that criteria. One laboratory also found a small amount of THC. Not all the laboratories test for THC since the THCA is a metabolite and THC is not. Some feel that that gives them a little more assurance as to the identity of the drug and how it got there. We only have two values, as you can see, for the THCA. With the cocaine, the values were fairly consistent. We had a standard deviation of a little less than 20 percent. We had seven laboratories who found, confirmed the cocaine. We had seven laboratories that confirmed the benzoylecgonine. The SD is fairly high with the BE, about 50 percent, actually over 50 percent, and that's because it would appear we didn't do anything, but there were some values which were obviously outliers, which as we get through this process of the data analysis will be taken care of or will be excluded by some type of process. We had five laboratories that gave the concentration very close to one another for the BE, and actually the concentrations are very good. That's interesting in that with the cocaine where we spiked it there was a great deal of variation. We had one laboratory here (indicating) with no cocaine and all BE, and it looks like when we go back and look at this that probably what they're doing is converting the cocaine that's present into BE.
It is more apparent here when we get to this spiked hair. Whether or not -- this sample as I remember -- let me check something real quick. The sample was spiked with only cocaine, but that doesn't mean that with time there's not some conversion, and two laboratories indicated that. That could be either conversion by them or a small amount of conversion in the spiking process. We don't know right now and we'll be looking at that very carefully.
Sample 3 was a spiked sample. We have a little more variation. It is a little more than 20 percent, the standard deviation from the mean. We have another spurious value or what appears to be a spurious value for the BE from one laboratory. We also have a cocaethylene value. One of the things that we found in one of our processes of spiking is that if we had the metabolite, if we had cocaine or BE, actually cocaine in an aqueous or ethanol solution, that we could get some cocaethylene produced in the spiking process. But we were able to minimize that by taking it out of the cocaine.

DR. VOGL: You might want to mention, the n includes some reference laboratory values.

DR. MITCHELL: Yes, the n's may not add up. As I said earlier, the means contain all of the values that we have obtained during testing and in pre-testing of these samples. It doesn't just include the mean from the laboratories that were participants in the PT program. The reason for that was to try to increase the n and to give us a better standard deviation and mean from which to compare.
These three samples are replicates, and presented under different identification numbers and everything to the laboratory. The means are fairly constant. With time as we develop the statistics, I think that this will do very well, and with the cocaine.
Sample 6. We had two laboratories that were able to detect the THCA present. One laboratory gave us a THC concentration, and we have at this point in time no reference values on this particular sample. Our reference laboratories are having trouble, as you can see with some of the other laboratories that were participants, in getting the sensitivity down to these levels. We also had one laboratory that found -- had screened it positive for cocaine and found 290 picograms per milligram of cocaine present. We have not verified that yet and we will have that verified by our reference laboratories.

DR. SAMPLE: Did the laboratories do the screening and confirmation regardless of the screening results?

DR. MITCHELL: No.

DR. SAMPLE: I notice as I look at laboratory D for 3, 4, and 5, they always screened it positive on the initial test for sample 3, whereas on the confirmation method, confirmation results, they have no results for cocaine for 3, but they do for 4 and 5.

DR. MITCHELL: Okay, a very simple answer. Once a laboratory has screened a sample negative, we are going back and directing them to analyze that sample for a particular drug class. All those values are included in here. In fact, our letter addresses that point, the letter of introduction to laboratories, and I'm sorry that I left that out at the very beginning. As I said, it contains everything that we've gotten from the laboratory. That's why some of the information in here, the data is incomplete, because we don't have the results of all directed assays. It gets kind of confusing at times, but we thought it was best to get all the data that we have out to laboratories.
Sample 6 was a real sample. Sample 7 was spiked to contain THCA -- our target on this one was 10 and you see we had one laboratory that gave us a 48, which is a little high. Again, we're not sure. We haven't talked to the laboratories. That could be 4.8.
We will be sending these tables with the values to the laboratory and say, please look at this and ensure that this is what your data reflects, make sure that there were no misunderstandings, such as we don't screen, which is laboratory K, I believe it was, we do no screening tests, but actually they are screening by GC/MS.
With the sample which was down about the cutoff, actually this one was spiked to contain THC below the cutoff at about 0.05, which is a phenomenon that I've seen several times in the spiking process, is that when I go very low the concentration appears to be higher than what we expected. The value that was given by the laboratories was 1.9. We'll watch that carefully and see if there appears to be at the lower end some type of positive bias or higher bias; I won't say it's positive, but a higher bias.
Sample 9 again was a real hair with codeine, morphine, and THC -- I mean, codeine, morphine, 6-AM. The values were somewhat varied. One of the things that we're going to have to look carefully according to the type of confirmatory method -- whether you do an extraction or a digestion -- you will see differences in the level of the compound that is obtained. I believe that the digested gives a higher value than the extracted preparations. That's been reported. We'll be looking at that also, and how is that affected by natural hair versus the hair that we spike?
This one laboratory found MDMA in this sample also. That's the only prep and I'll have to see if we can confirm this.
(Slide.)
The morphine at around the cutoff, you can see a mean of 210, a 20 percent SD. That appears to be the type of SD that we may see at least in this initial phase of the program. Hopefully, that SD will go down as the laboratories are aware of what's going on. We've seen that phenomenon in urine testing.
Sample 11, if I remember correctly, was also a real positive hair, and you can see that we had the morphine, 6-AM, and codeine found in the sample. Like I said, the standard deviation here for the 6-AM was a little high, was about a third, was about 30 percent, but for the most part was around 20 percent except for this, and that's the phenomenon that I was talking about earlier.
We had one laboratory that had what appeared to be an erroneous value. It was about almost ten times what everyone else had. The spiked hair with morphine and l-methamphetamine, we did have one laboratory that reported the presence of 6-AM in this sample. I'm not sure.
One thing that we do know from testing for 6-AM is that if you're not careful, if you don't design your methods properly, you can't generate 6-AM in the extraction process. This mainly is when you're using acetate buffers or material which has come in contact with acetate. I don't know if that's the case. We'll be asking the laboratories additional questions as we go along. But the fact that they know that this happened would allow them to look for that type of thing and gaining from the experience that we've gotten from the urine matrices at this point in time.
Again, the opiate that was spiked by RTI with codeine, morphine, and 6-AM at about 100 each and the means come out in that general area from the reference laboratories as well as the laboratories. This is getting down below the 200 cutoff. In urine testing, the laboratories are required to demonstrate their ability to accurately quantitate and identify at 40 percent of the cutoff. So we were just trying to look and see that with these cutoffs with some of these samples if this particular matrix -- and we did it, will do it, we have done it or will do it with all the matrices -- are able to quantitate and identify down about half to 40 percent of the cutoff.
Sample 14 contained amphetamine, methamphetamine, cocaine, and BE. We had some values which were rather high coming out of this laboratory compared to the rest of the laboratories that were participating, but they all identified it and did quantitate it. There's just some question as to the quantitation. You can see that the standard deviations are abnormally high. The sample spiked only with methamphetamine was fairly consistent. We had one -- well, actually it's not fairly consistent. It looks like we almost have two groups. There's the 2,000 and the 1,000 group, and I'm not sure why this type of variation existed. We'll follow this very closely in future cycles.
The methamphetamine, this is reference values, the 80. PCP, again there was some variation, about 30 percent. I'm not sure that any type of statistical is going to reduce that, but down around the cutoff they seem to be fairly consistent. Again, we're back down to about the 20 percent or so standard deviation.
Again, in the samples, this one of course did not go through confirmation, but this one did go through confirmation in some laboratories for THCA, cocaine, PCP, and there were no indications of false positives.
Overall I would say it was very encouraging. We're seeing laboratories starting to standardize their procedures. They're becoming consistent. There is the question how many false positives are we generating or false presumptive positives, should I say, generating in the initial test, and I'm not sure that it's any more than what we would generate in urine in some cases.
The nice thing is that none of them appear to be, with the exception of possibly the cocaine, and we'll look at that -- we'll verify that one. None of them possibly appear to be generating false positives in the confirmatory process, that is, with the cocaine, but possibly 6-AM out of morphine.

MR. STEPHENSON: Before we go on, one of the things that I'd like to try to get out of this presentation for the group would be what would be helpful to the members of the Board in terms of the display of the data that you've seen in a format that might be shared with others that would be helpful?

DR. SAMPLE: I think an additional form indicating each specimen, the specimen type, whether it's a user, fortified, what it was fortified with, if it is a fortified what the original lot or pool of negative hair that was used, so that you could have that as a quick reference as you're looking at both the initial testing results and the confirmation results.

DR. MITCHELL: I think there's a lot that we can do, but we don't have enough information at this point in time. Once we get all the data from all the cycles, we can look at the full picture, the full range of concentrations and standard deviations. I think there's a lot more that we can do.

DR. BUSH: I want to take us all back to what the purpose of this first cycle of a pilot PT program was. We had to start somewhere with something. That's what it comes down to, and you've got to sit down and figure out what's the best something to start with.
After evaluating a whole bunch of different possibilities, we have to come back to powdered hair because we had to try to ensure homogeneity of the matrix. I guess that's why I was so sensitive when John was mentioning this before. I put my hand right up: Tell them about the blender, tell them about all the other things that we tried in this effort to try to ensure homogeneity of these samples as they went out to all the laboratories, so that we made sure we had to have our best effort at a level playing field for what those specimens were, what we really knew they were. And we knew they were powdered hair, and we knew they were either from in vivo real live drug users who provided us the specimens or RTI has spent an awful lot of labor hours and brainpower in trying to get spiking schemes and technologies and methods together to do this well.
We felt that powdered hair would be our best approach specifically to go to the GC/MS level at the concentrations, the very low concentrations that the industry provided, suggested to us, that were their functioning capability range. We had to figure out how we could get those concentrations homogeneous at such low levels and take a look at what we could count on the laboratories extracting, what the capability was to extract, and then derivatize and confirm, all the things that we know into the analysis of these particular drugs of interest.
We didn't have any washing -- differences in the approach to washing or how to handle that matrix, whether it was a snippet or whether it was a strand or whether it was a powder. We had to call it even, and so we did it with powder. That was the intent and the drive here.
We're not sure how all the immunoassay tests and kits and initial screening methods reacted to this powdered hair, but we were fairly confident and comfortable with the approach, our approach to evaluating the confirmation range and seeing where we were with that.
That's not to say that's going to remain the drive. We're going to change with what we learned and as we keep talking to the laboratories and getting more information back from them. This is a learning process. We drove this to see what confirmation capabilities we did have with the hair matrix.

MR. STEPHENSON: One other comment, remember the levels that we are testing for, that we are trying to identify, are those that have been identified by the members of the industry working groups over the last two years in the submissions that they had made to the Drug Testing Advisory Board. These were not arbitrary values developed either for this matrix or for the others that we're examining. These are informed issues coming to us from the industry.
The second thing, we took advantage of lessons that had been learned and things that had been attempted by others in trying to create a proficiency challenge type program. The State of Florida had attempted to do this as a basis of what they had done, so we were able to benefit from the richness of experience that they've gone through over the last couple of years. We actually brought the experts in and sat down with them and talked to them at RTI to go through this.
Third, this initiative as it currently is configured, is being paid for by HHS funding. This is not a distributed cost item to the laboratories. In the future, when we get this thing resolved to a point that it is a functioning component, there will be a cost that will be ascribed to the individual laboratories for participating.
Everything we can learn now on our funds is going to save the laboratories money in the future. But you've got to realize, this stuff is very expensive. It's labor hours, it's resources, it's doing this instead of something else. We've chosen to focus on this and we greatly appreciate the participation of the laboratories and the donation of your resources and your learning exercises with us. We probably are going to need to get some of these industry working groups back together, either by conferencing techniques that we can use over the Internet or by phone or by maybe actual working groups to go through some of this data, so that you maximize what it is you're learning out of this.

DR. MITCHELL: I'd like to acknowledge the help that we got from Bruce Goldberger initially in working with these PT samples, Donna Wilkins from the Center for Human Toxicology. Also, Dr. Pascal Kintz in France is working with us, and also two of the laboratories early on -- they were put into some screening tests of samples that we obtained, Psychemedics and John Irving and Mike Schaefer have worked with us on this, as well as Jim Borland from APL. Without the help of them, we would not have done it.
Again, my staff has worked very hard. They've put all this on top of all the other urine duties that they have. Without a concerted effort and a cooperative effort by the laboratories and staff and HHS, this wouldn't have happened.
Oral fluid. Oral fluid has turned out to be quite an interesting matrix. Probably the biggest thing is getting the material to work with. I have two people on our staff that sit around with a bottle on their desks giving us oral fluid. We had tried some unique things. We tried a collection device. We got some of those supposedly that would collect from the parotid only. Those didn't work too well, very limited. It came down that this is definitely a mixture. It's really saliva versus just from one gland, as you might expect. But we haven't figured out how to cannulate one of the glands yet.
The oral fluid samples were shipped to ten laboratories on the 24th of April. Each sample consisted of 2 mLs of oral fluid which had been spiked by RTI with drug analytes. Out of the ones sent, we got results back from nine.
On the initial testing, we had five laboratories that conducted initial testing for all the drug classes -- one laboratory for four classes, one for one -- and two laboratories did not have initial test procedures available or methods available.
(Slide.)
The first table we have, and I just put it up here for us to kind of familiarize ourselves. I don't know how much in depth we want to go into this, but this table gives us, just as the previous ones for hair, the performance of the laboratories on the various analytes in the screening process.
Again, we have the amphetamines. BE is the directed analyte that they have there, according to the industry group, morphine in the opiates, and PCP. Here, instead of THCA, they're looking at THC.
We were fairly successful in our spiking routine for the opiates and benzoylecgonine. Morphine and PCP we did okay. THC presented us with a problem. THC always presents a problem whenever you're spiking THC and so you just have to work out the routine.
The problem with oral fluids in developing the specimens or the PT's was that we did not have the quick response on the oral fluid reference assays. We did not set up a liaison with the laboratories as we had with the hair. The hair was going to be a bigger problem and we spent a little more effort on it. But we will be working on the THC. That's the only one that we appeared to have any major difficulty in spiking at the level that we want.
(Slide.)
Let's go through the samples. We have a total of 20 samples. The first sample up here was spiked with both methamphetamine and codeine. 20 is the cutoff, I believe 20 is for the opiates on confirmation.

DR. SAMPLE: 40.

DR. MITCHELL: 40, that's right. So this is right at the cutoff. You can see that. Five of the seven laboratories found the codeine, identified it as an opiate; six out of six for the methamphetamine, the methamphetamine cutoff being160. So this is about twice. That's what we spiked it at. They did not have any problem, it appeared, with the methamphetamine as long as it was above the cutoff. But when it went below the cutoff, you can see that the number of initial test positives dropped.
With benzoylecgonine, the cutoff is 20. All the ones who were over 20 were positive. The one that was 10, only one laboratory found it as positive. That's at half. We did very well with these: two-thirds, 50 percent.
But we actually had to go up quite a bit in order for all the laboratories to find initial test positives for BE. It went up to almost 200, which is ten times. We saw a similar phenomenon with some of the analytes, I believe, with hair.
With the morphine -- and I'm just trying to give general rather than go through it sample by sample, because what you see is what you get. It's spiked and what we're going to get -- with the morphine, the cutoff for morphine is 40 for the screening and 40 for the confirmation. With the morphine the laboratories did very well. This is just above the cutoff.
Whenever we dropped down below the 40 with a mixed group of analytes, that is codeine, morphine, and 6-AM, we still had some positives and they appeared to do all right. This was right about the cutoff with the -- we were spiking at approximately the cutoff of 40. We would expect less than 100 percent right at the cutoff because of the distribution in immunoassay.
PCP, the cutoff is 4 nanograms per mL. The laboratories at twice the cutoff, four out of five; at ten times the cutoff, five out of five; at half the cutoff, I only had one positive, very reminiscent of what we saw up here. The response or the performance with PCP appeared to be pretty good.
THC, again we had what appears to be some spiking problems, but we're still waiting on reference assays on the THC. We had I believe one value for the THC of about one nanogram per mL. We had two laboratories that screened it positive. The cutoff for THC for initial test is 4, so it makes us wonder where we are in that respect.
The THC at 30, we got five out of six laboratories. That's almost ten times the cutoff. With the THC, we appear to have not quite the response that we would expect, but we're still working very limited data here. On the next set we'll be able to look at it a little bit more.

VOICE: How many different technologies are there?

DR. MITCHELL: The question is what types of immunoassays were used, and I don't have that right in front of me at this point in time. I'm pretty sure that there were things other than the ELISA that were used. I'm just trying to remember the matrix in which that was recorded and presented to me. We'll look at that type of information when we get into a more detailed analysis of the data.
In the confirmation of the oral fluids, we had five laboratories that confirmed for five drug classes, one for two, one for one, and two laboratories were screening-only laboratories.
(Slide.)
Now for the real data. Again, this data is incomplete. We have not received all the responses from the directed assays, so we'll be waiting on that.
The methamphetamine, let's look at the standard deviations in the analysis of these samples. Here it's about a third, here it's a little less than a third, about 25 percent. As we go down in concentration, the standard deviation goes up a little bit. This is around 10, these are a little over, between 10 and 15 percent, which is not too bad with the amphetamines. This one, around a third, and again about a 25 percent.
We saw quite a bit of variation in the standard deviations of the confirmatory method, but they're still within about the 20 to 30 percent range is what we're looking at this point in time with amphetamines.
With BE as a group, and again we're talking of laboratories as a group, I'm sure that some values like this will drop out, where it's almost twice that of the values of the other laboratories. But where we have the mean, this is about not quite 50 percent, it's over 40 percent. Here it's about 25 percent, 25 percent, and this is only three values. It doesn't have a lot of meaning here. We're again in the 20 to 30 percent with a high of somewhere between 40 and 50 percent standard deviation in BE quantitation.
With the morphine, a third,10 percent. If this holds up, it would appear that the lower concentration in this group has -- the standard deviation appears to go down some. Granted we are dealing with smaller numbers, and probably there are a couple laboratories that are driving it, where the standard deviation is going. There is some consistency at the lower levels.
With PCP, 25 percent, this one happened to be about a third, and that was all the values that we had for PCP at a higher concentration.
THC, the one good value, the one good sample that we have, actually it looks like it's somewhere around between 10 and 15 nanograms per mL. We had one spurious value here of 85, which drove the mean way up beyond what it should be or what the other laboratories would indicate that it would be. But we'll learn more about this, as I said, the THC, as we go along.

MR. REYNOLDS (Life Point): The question is why did you choose just BE and not cocaethylene and BE?

DR. MITCHELL: The industry is the one that has driven these analytes that are to be used or to be identified. We were just trying to see the practicality of analytes that the industry has given us. That doesn't mean that the industry will not be given samples that contain other analytes. The oral fluid industry has somewhat limited the analytes that are to be looked at.

DR. WELCH (DTAB): John, how close are these numbers to what you think you spiked them with?

DR. MITCHELL: Morphine ended up being somewhere around 60 percent of what we expected and the THC was much less, somewhere about 40 percent of what we expected. The others were within 20 percent, 25 percent of what we expected in spiking. That's just a general rule.
MR. ANDERSON (Ansys Diagnostics): Looking through the literature, I saw an interesting article from 1995 in JAT that looks at smoked as well as ingested cocaine and that monitored the saliva content of cocaine and BE. In my review of that, it looks like there is about a sixfold improvement in detection of drug use if you screen for both cocaine and BE. I would recommend that we go back and consider which method we have to be looking at in the laboratory.

DR. MITCHELL: I'm sure that that is one of the things that the Board will be looking at, as well as the industry, is a single analyte for what we need in the workplace programs. One of the reasons that I know for the oral fluid for this particular portion of the program that cocaine was not chosen was because the cocaine tends -- has some stability problems according to pH in aqueous solutions and can cause some problems. I was present at the oral fluid, some of the oral fluid meetings in which that decision was made because of that stability problem with cocaine.

MR. PORTER (Life Sign): I was curious about the cutoffs that were established. The cutoffs that you used, are they industry standard or have these now been incorporated as SAMHSA standards? Did the laboratories agree to these same cutoff levels? Were their tests run at the same cutoffs?

DR. MITCHELL: In the first one, there were a group of individuals who met from industry and laboratories, who met to talk about cutoffs and what was possible and what wasn't. At that point in time, there was very little data available as to the types of concentrations you could expect to find for the various analytes and things of this nature that had, say, a significant number of samples. I know that some of the work that has been done at STC as well as some work that Mike Peat at Lab One did in the analysis of samples that he received, I think that is a large part of the data that was used in what was possible. Whether or not these are the cutoffs that's going to be done, to be finalized, that is what part of this process is, to see, are those cutoffs, are they reasonable and can they be met? That is our job.
Then eventually the DTAB will look at whether or not the cutoffs, what they mean, and should they be utilized, changed, or whatever.

MR. STEPHENSON: The short answer is no, they're not the final cutoffs. Number two, do all the laboratories agree on the values that were used at this time? I would say probably not, but it was an issue of a rolling revision that was going on even as they were preparing the specimens to come out for testing. It is an issue where a lot of the data was coming in late and was being revised right up to the time that those specimens went out, so those things will change. This is an issue of laboratory ability to detect and to figure out what we can do to manufacture specimens that are subject to reasonable testing amongst a group of laboratories.

MR. CROUCH: I have a couple of comments along this line. I actually have three sets of the cutoffs here, one from September, one from 5/18, and one from today, and they're all different.

DR. SAMPLE: Average them.

MR. CROUCH: In fact, there's a sixteenfold difference in the cutoff for stimulants from last September. I think it's probably a good suggestion that we maybe get all these in a table and look at them and see which ones are real and which ones are not, because in a month some of them have changed by a factor of two.

DR. BUSH: That's a very good point. What was happening as the industries realized that our time had come and we needed input on the final proposed concentrations for us to formulate this set, the first cycle of PT's to go out, last call was issued to all the industries. We reflected back on where the DTAB had been, we went through all the meetings and all the cutoff tables that we had gathered, going over it to make sure that these tables were where we needed to be with the industry's understanding and knowledge and the go-ahead to do this first PT cycle.
The intention is with Sam Niedbala being the industry coordinator for the oral fluid and John Kippenberger with the hair, and Neal Fortner with the sweat, and Bob Willette and Yale Caplan, after the onsite drug testing meeting in October, we're going to be taking a look again at developing the industry focus group, take this back to the industry working group, figure out where we all need to go from here with this knowledge. We're very open to suggestions.

MR. CROUCH: There's more to it than this. If a laboratory did the screening based on the cutoffs that were set in September, they would have very different results than they would based on the cutoffs today. What cutoffs were used by the laboratories when they did this testing? Do you see what I'm saying? I mean, it's in constant motion, but you're going to identify or determine whether it's a potential false positive or false negative based on the cutoffs.

DR. BUSH: Actually, that's why the tables were included with the introductory letter back in March that were sent to the industry. This is what the industry had agreed to and these were the tables that were sent with the letter, to let the laboratories know where we were going to be working at, above and below those cutoffs is fair game for spiking schemes to see where we are.

DR. MITCHELL: And we tried to talk to each laboratory. It was before the samples were ever sent. We did talk to the laboratories. We had asked them to send us certain pieces of information and asked them that they try to adhere to these cutoffs. In other words, we had laboratories say, well, how do you want us to do that, and things like that. We did make an attempt to make that common, and in this, in our letter that will be going out, we will include that as an issue, as to -- I've had one laboratory from the hair group that contacted me and I'm not sure, but they wanted to tell me what the cutoff was. Obviously, they didn't use the same cutoff as we had asked, and so they were going to give me information pertaining to that cutoff.
How accurate these are, is going to depend upon what the laboratory has done, and hopefully we can get that information, which will help us in our evaluation. We'll have to go back to them. If they are as slow in getting the information to us the second time as they were the first, we may have it by the end of the study.

MR. REYNOLDS: Where will I find the actual cutoffs that were used?

DR. MITCHELL: There in that packet. Go back to the fourth page.
These are the ones, the samples that we have. The thing that -- one of the questions I have on oral fluids is whether or not any of the laboratories introduced their devices into the testing. I know that one laboratory actually spiked their device with a known volume and then gave us that analysis as well as just an analysis of the solution that we gave.
That data is not presented here. I just thought it would confuse things a little bit more. When that came to me, the question then was, exactly how did you do this, and this was one of the questions that we're going to have to ask the oral fluid people as we go through.

MR. ANDERSON: I have one more comment about passive inhalation and the very low cutoff levels that the industry is recommending at this point in time. That is, that there is an article from 1985 from UCLA that shows that passive inhalation by nonsmokers at four and a half times the cutoff that's being proposed for screening, so having an average of 18 nanograms per mL 15 minutes after smoking. I think we want to look at the cutoff.

DR. MITCHELL: What are they smoking?

DR. BUSH: What specimen?

MR. ANDERSON: THC in cigarettes.

DR. MITCHELL: Okay.

DR. BUSH: Is this oral fluid?

MR. ANDERSON: Yes, oral fluid, and that's Gross et al.,1985.

MR. STEPHENSON: Realize that what we're doing right now is a combined effort of mechanical process, a learning curve of basic research in how to create a product that can be tested and then the group dynamic issues in which there are individuals as well as groups working together sometimes to come up with some consensus document. All this will be put forward in the way that we set regulation in place via notice of proposed rulemaking-like environment with a Federal Register notice inviting public comment, and we will address it. We're not at this point in time setting these standards and you'll have further opportunity to make public comments.
Right now this is a group dynamic, trying to work together to figure out how to make it, how to test it, what does it mean when we've got the results, and go back and figure it out. This is a combined effort of HHS, RTI, and the participating laboratories.

DR. MITCHELL: The one thing about the oral fluid is that, even right up to the time we were going to make the samples, there was still some question about cutoffs. We had some conferences with the industry. Our idea is just to see what can be done, what is the industry capable of. I think that they are very capable. There are other issues that have to be associated with cutoffs: the significance of the cutoff, what does it mean.
(Slide.)
Sweat patches. We shipped to three laboratories on the 24th, the same day we shipped oral fluids. We spiked the sweat patches, which were provided to us by PharmChem, with various analytes. It turned out we only got a response from one laboratory.
(Slide.)

MR. STEPHENSON: Before we presented this in "public" we did ask laboratory A whether or not they minded not being adequately masked as part of a group. It was fine.

DR. MITCHELL: I put the target value as well as the mean of laboratory A's value and the reference values that we have. I was trying to get every piece of information look at. It points out that in most cases laboratory A, when they confirm, they came very close to the mean, which means that their values were very good. At least two laboratories seemed to agree. There is the reference laboratory and laboratory A.
The cutoff, if you look at the cutoffs on these, the information as nanograms per patch. The cutoff in table 2 is on per mL of fluid, which is, I believe, two and a half mLs. You have to multiply two and a half times what they have there to get the actual cutoff that we were looking at on a patch basis.
For methamphetamine the cutoff listed here was 10, so that translates to a 25. You see where at twice and ten times the cutoff they were positive with the methamphetamine. When we drop down to about the cutoff, which was 25, you can see that they did not screen positive, but as a result we do not have the confirmation results.
I do have the directed assays from PharmChem. That was what was laying on my desk when I walked in Monday morning. So they don't have the answer before they go back and re-analyze. We do have that. It's just not included on this chart. I didn't have the time to do it.
The cutoff for the BE again was 25. We appear to be fairly close in our spike because the means are 43. We're somewhere around 15 to 20 percent low, so this very well could have been just above the cutoff, and when you get to cutoff it's a 50-50 chance in that respect.
With morphine the cutoff again is 25, positive at twice, here it was positive where we had it 10 times. Now, you'll notice that I threw in cocaethylene on this one, the sample, and it did not screen positive for BE or for cocaine. It was just cocaethylene. I'm trying to look at some of the specificities in the immunoassays that are being used. The people know that I do these things just so that we can learn a little bit about the immunoassays.
The opiates appear to be pretty good. It appears to be probably a higher cross-reactivity with opiates because these did screen positive for morphine when I had a mixture of codeine, morphine, 6-AM, and heroin. The same thing here; we're at the cutoff, but we did get a positive.
PCP, there appears to be no problem. THC, our concentrations, as you'll see, were somewhat similar to oral fluid. They were much lower than what we expected, somewhere about 40 percent or even 25 percent of what we expected. We have to work on the spiking of THC onto the sweat patches and we're not sure whether that's a stability problem or whether it's a problem of trying to get it off the patch, whether it's irreversibly bound. I'm sure we'll find that out here in the not too distant future.


Agenda Item: Draft Guidelines for Alternative Specimens

MR. STEPHENSON: At this time, I'd like to initiate a discussion of the guidelines for alternative specimens. This is an initial draft. This is part of a promise that we had made that where we could frame the issues we would, with the expectation that in collaboration with others, we would look for areas where we don't have the data included yet, where there are issues of additional guidance or questions or clarifications that you upon reading can help inform us.
This is a mutual exchange. This is not the regulatory process. This is a sharing with a group of experts and interested parties as a preliminary document. We don't expect to have anybody run out and say: This is what they're going to do; how could they possibly do this; look how stupid they are. Come back and tell us that. You can tell us how stupid we are and where we've got to fix in, and that's okay. That's what we want you to do. But from this point on we are going to have focused input. We are going to continue to press to get clarification, resolution on the issues, and the material that you were given this morning on the PT cycle is part of the essential process that must accompany simultaneously the development of the drug testing guidelines.

DR. CAPLAN: As Bob had indicated, this is an ongoing process and, for a variety of reasons, you may remember that we outlined sort of a process map in the last several meetings of things that need to be happening in order to go forward with the development of guidelines and the fact that we were going to develop guidelines that covered the entire gamut of testing as we know it today, rather than doing the thing piecemeal, which will include an evaluation of each of these things. Prior to today there has been a lot of -- and you heard the last report this morning from what is the working group at the DOT laboratory directors meeting. We have had significant input now in different ways, by formal meetings, by working group meetings, for each of the modalities and parameters that are going to be included. The preliminary base has been completed.
Earlier this year a subgroup of the Board met. I think there have already been three meetings plus some working time at the actual DTAB meetings in order to redraft a basic guideline, including maximized input from all these other sources which we have today. To reiterate what Bob had said, there's that note on here. This is probably unusual for government in that the guideline is not being held until it's been scrutinized to death internally, but it has been drafted in cooperation with the working groups and there are a couple of notable things. One is there are some sections which are still not complete. Mostly those deal with electronic transmissions and electronic use of data and electronic signatures and things like that. They need to be added and they will be in the next round.
We also are working with the input that we are getting from meetings like today and the data on the PT program to refine numbers. There are numbers in there, there are things in there, and I guess to the best of the group's combined ability at a point in time last week or last month this is where the thinking is going. Input is definitely sought and I think there's a note in here that the input needs to be in writing. It doesn't do a lot to call people, but if you have specific things that you think were missed -- there are some things we haven't gotten to yet to add. But certainly, if there are things or issues that should be addressed, you need to tell us that.
There is a major change and this document is following the outline of the question and answer format that was introduced by DOT. In doing that there's always the risk that something didn't get transferred from a written guidelines concept into a question, and if anybody notices any of those -- we'll be continuing to do this, but we want to be sure that the guidelines are easy to read and that they cover all of the topics and ask all of the questions that we were asked originally when the program started in the late eighties and the things that were also reiterated or restructured through the use of the working groups.
I believe, and we put a sort of a timetable when we last talked about the guidelines, that we expect to have a first publishable type draft of this by the end of the year, and I think we definitely are on that track and there's no reason why from the technical point of view and the input from the Board and the industry we can't have that all done.
We will be having a group of at least two other meetings between the Board meetings. There's another one scheduled in July for a sub-working group of the Board, there's the DTAB meetings again in September and in December, and in between there'll be another one. I'm saying again that by the end of the year, maybe by the December DTAB meeting, we would have this in reasonably final form, which will then have to go through the other scrutiny processes within the regulatory agencies and get published and all that, which, as Bob has said, our promise was to get this conceptually done, to get it shared with as many people as possible, to make this a comprehensive interactive program.
There are a couple major areas I want to point out. First, there are a lot of new definitions. Barry Sample is going to review the ones that are new. You have to start by saying, what are the elements and how do we define those elements. If there are elements not defined or you can think of better definitions, that's a key thing, because once you've written down a definition then you can go about documenting what it means, how it's to operate. We need to define it in clear language, and there are a number of new definitions in here.
A couple of other conceptual things. There are now 3 facility types. We have the laboratory as before. We have authorized here something that has been discussed at least since the first consensus conference, which is a screening-only laboratory, and we have the point of collection testing element. In these guidelines, there are 3 places where drug testing can take place. We have to assure that they have similar levels of quality control, quality assurance, proficiency testing. When you look at these, think about it that way, that there are three facilities and each of these facilities can operate independently, but you can't have one with low control and another heavily controlled. There has to be some equal semblance of control.
Anything that's in a laboratory as we know a laboratory today will be very similar to what it was before and the issues are what constitutes a screening-only laboratory that does the front end of the process and how does that differ and work if there's a point of collection.
We also have defined in here in addition an individual known as an RT. We have an RP for the laboratories and we have a responsibility technician for the non-laboratory functions. We are designating an individual who would have oversight responsibility for point of collection testing who is functionally similar to a responsible person, and there are a number of very distinct points about what that person needs to be able to do and how that operates. That's another major change.
A significant portion of what's in here, some of the things we talked about this morning, which will undoubtedly undergo revision, is that ultimately final cutoffs will be enunciated in the document. The cutoffs will be finalized eventually and therefore there is still a lot of time as science and the information will allow a tweaking of this to adjust the numbers, to adjust the drugs. You'll notice also that for the laboratory an expansion of the amphetamine class into MDA and MDMA is proposed. We're looking at the guidelines as an opportunity to look at the whole program, what drugs should the program include, cutoffs, specimens, and how they interact.
Another new area, again subject to modification, is the use of each specimen. There are now different specimen types which are going to be permissible and, unlike urine, which was used for all components -- pre-employment, random, post-accident, etcetera -- there are some suggestions in these guidelines about different specimens being available for different uses.
We ask the people, the industry, if those need to be expanded, then we need to have the information that allows the database to include that. That will grow, and we have definitely seen an explosion of information in the last 2 years, and I know by the end of this year the onsite oral fluid products -- there were none a year ago and there's going to be at least four or so by the end of this year and into next year. There's an explosion of technology and resource going on and we're going to try to make these guidelines reflect that, and that's where we need everybody's help.
Another element is collector certification. We've always had the greatest difficulty in that end of the process and the least control over it, and there are some new requirements suggested for collector certification and there are certainly requirements for testers and testing.
The few areas, as I said, to be determined, I think they're noted in there. These areas are things which are still being worked on by the Board. At our next meeting we'll probably get through those and, as I said before, they focus mostly on electronic signatures, electronic transmissions of materials, paperless. It's probably very timely since that seems to be dynamically being looked at by a variety of other parties. We did look at that issue beginning with the meeting of the laboratory directors last December. As was indicated, OMB is involved in it and the government is involved and there will be a movement in this direction.
I think you should find that there are a lot of modifications and refinements, which include some new restrictions on the laboratories, such as perhaps releasing results on negatives directly, and there is questions about how to include all the other specimens with equal quality control.
That is an overview of where we are, and everybody should have gotten a document this morning. We wanted to get this to the people as quickly as possible. What you have has just been finished within a week or so, so there was no time to distribute it.
Maybe there really isn't ample time to discuss it today, but we want to see whatever interactions we can get back from you today, and certainly encourage people to look at the things that are relevant to your expertise and get something back in one of the written formats that is suggested there as soon as possible.
If that information is back by the date -- July 12th -- we are having another working group meeting later in July, and anything that's in by July 12th, any of the kind of concerns -- I mean, but things that are conceptual or you deem as very important, we will want to hear them as we finish the document in July. Shortly after that, prior to the next Board meeting, there should be an updated, a new revised one, and we'll do this one or two more times towards the end of the year.
I think the next part of this is, Barry, if you're ready -- Barry was going to go through some of the definitions and where we got to them and maybe go through some other elements in the document to explain how those were arrived at. We're not going to try to go through the whole document today and I don't think -- we're not going to leaf through it page by page or section by section. But if anyone wants to do that later on, we can look at other issues as you might identify them after Barry goes through a little bit of a litany and explanation of some of the things that the group has discussed.
Generally, this was a subgroup of the Board. It was whichever members. It always was about half the Board or more who were able to get together in between and work on this in between Board meetings. The people that generally participated in that were myself, Barry Sample, Prentiss Jones, Mike Baylor, Dan Isenschmid. Donna and Charlie LoDico.
There's six or seven of us trying to assimilate the information that's out there into the document you have today. As indicated, it's not been reviewed by the whole Board. Today's the first time the whole Board, along with everybody else here, has an opportunity to look at this, and the feedback starts now.

DR. SAMPLE: I want to try to keep this informal if I can. I'm going to try and go through really new definitions or significant changes and try and talk about some of the rationales for some of the key items as we go through the whole document here. If anyone has any questions, don't wait until we're done, or if there's a burning issue that you have, go ahead and raise it while we're in that area of the document, and I'm sure one of the members of the Board would love to talk to you about it.
If we could start on page 9. One of the changes really had to do with the type of test, the definition of a confirmatory test, and then initial test. If you look at this definition as opposed to some of the previous definitions, it's a little more generic, and as we get into the individual testing modalities we'll flesh that out a little bit more.
But a confirmatory test is now just an analytical procedure that's performed on a separate aliquot of a specimen to identify the presence of the specific drug or metabolite. Where we're going in methodology, which we can hit on as well later, is we're really opening it up to any type of combined procedure involving chromatographic separation and mass spectrometric identification. That would open it up to GC/MS, GC/MS/MS, LC/MS, LC/MS. There's a whole wide variety so long as you're using the combined analytical procedures involving chromatographic separation and a mass spectrometric identification.
There's also definitions now of what a dilute, or an attempt at a definition of what a dilute specimen is. You see it says that actually needs to be determined for each specimen. That has not been done yet in this document. We certainly welcome feedback from those working groups that have experience with the different types of specimens and what would be considered an adequate specimen or an inadequate specimen.
On the definition of the initial test, greatly simplified again, it's just a test that is used to differentiate a negative specimen from one that requires further testing. We've also added definitions of negative results, invalid results, non-negative results, and positive results, expanding that out; a variety of reasons for test modeling after the proposed Part 40.
As Yale mentioned earlier, two brand new concepts. One is the HHS-certified instrumented initial test facility, and that's defined as a location where initial testing, reporting of results, and recordkeeping is performed under the supervision of a responsible technician. Conceptually, this is the screening-only facility that does not do any confirmation. They're doing only screening in a manner analogous to what would occur in a laboratory.
There's also the HHS-certified point of collection test facility, in other words more of an on-site testing scenario, and that's a location where specimen collection, the initial testing, reporting of results, and recordkeeping again is performed under the supervision of a responsible technician.

MR. ANDERSON: Barry, how is that different from the provider? There's also the term "provider," "DOT provider."

DR. SAMPLE: The question is how does the certified point of collection test facility differ from the point of collection test provider. That's a good point. I'm not sure there's much difference between those two. The provider is the person, is the location where that test is being performed, and I appreciate your mentioning that. The word "provider" is new in here.

DR. BUSH: Did we define that? Because we have that later.

MR. LODICO: A test provider can be an entity, a service company that provides the service.

DR. SAMPLE: The manufacturer?

MR. LODICO: Not the manufacturer. It could be a manufacturer, but, more importantly, the provider is the one that oversees the responsible technician. They're the ones that contract out with the clients and sets whatever relationship that they have between the client and the testing facility. The facility itself is the actual place where the test is performed.

MR. ANDERSON: There should be a definition for it.

DR. SAMPLE: I agree, that's a good point.

MR. ANDERSON: Barry, what are the qualifications of the responsible technician?

DR. SAMPLE: We will get to that. I think there will be some defined -- backing up just a second, the definitions tried not to put in the criteria. The definition is just the definition and then in the body of the document it goes into more specifics about requirements. There could be additional guidance documents, just as there is now, even on the traditional laboratory-based side, where it may further expand what the educational background of certain individuals would be.
The concept is essentially for the RT, we will using like CLIA, thinking in terms of a CLIA model, where you have somebody who's qualified from a CLIA standpoint as a supervisor of analysts or a general supervisor in CLIA terms, although obviously CLIA doesn't apply per se to drug testing, but it provides a model. It would be somebody of that level, that type of educational background and experience.

DR. CAPLAN: Later on in the document it says what the responsibilities of the RT are, but not exactly the qualifications. Just like qualifications could vary, and that may come up in the other guidance document. It's not clearly defined in here, but it would be similar to the RP. It's a person who would have -- and you already mentioned it -- the equivalent of a CLIA supervisor, but would then be reviewed by the program and have to be approved for that position. Much like the laboratory program approves the RP's today, there would be a process to approve RT's in the future, and their exact flexibilities of their qualifications will be somewhat defined later.

DR. ISENSCHMID: It's in article 12.6.

DR. SAMPLE: Just responsibilities, that's correct.

VOICE: On the definition of "additional tests," is the door being opened again for non-immunoassay type (inaudible).

DR. SAMPLE: The question is is the door being opened for non-immunoassay initial tests. The answer to that is yes, and we will talk about that in more detail when we get to that section in the document.
On subpart B, there is a proposal of recommended reasons for different specimen types being collected, and we certainly welcome feedback from the industry on some of those suggested or recommended reasons, but by no means are they exclusively suggesting that specimens would be tested in these scenarios exclusively.
Subpart C talking about the drugs, you notice that under the urine-based model there is a proposed change in cocaine metabolites for the initial test to 150 and for amphetamines to 500, and that that initial test should significantly cross-react with MDMA, giving roughly equal but not necessarily identical, but roughly equivalent, cross-reactivity.

MR. EVANS (NOTA): On the issue for which drugs can a specimen be tested, the first sentence ends with "as otherwise authorized by law." Does that include state law? There are some states now that authorize the use of marijuana. You ought to say "federal law."

DR. BUSH: We will clarify that it will be under federal law. This is what's going to apply to the federally regulated. It will be consistent with federal laws and federal interpretation of what's appropriate in safety sensitive, health sensitive positions.

MR. STEPHENSON: There has already been clarification that has been put out, I think, over two years ago that spells out the issues related to federal agency personnel, and I think also a similar effort that was put out through Department of Transportation in their regulated industries. It will be federal law and federal regulations affecting positions either in the federal government or regulated by federal laws, not state laws.

MR. McNEIL(Dade Behring): On the two drugs where the cutoffs are changing, what is the rationale for lowering the cutoff? Particularly with amphetamines, it seems like that may create more confirmation work for the laboratory.

DR. BUSH: I'll take the one on benzoylecgonine first, and cocaine. Actually, Ed Cohn in Journal of Analytical Toxicology quite a while back published an article taking a look at the passive exposure to cocaine vapors from smoking that drug, and we looked at that in terms of interpretation: Would passive exposure to cocaine vapors then confuse or confound the interpretation of a urine drug test positive using our existing cutoffs and how low could we go actually then, based on the research study that he did? We can go lower, based on that JAT article. We just have not done that in the past. We have taken a look at what laboratories, what experienced laboratories, have using lower cutoffs for both screening and confirmation. Quite frankly, since our rulemaking and changing the cutoffs is such an arduous procedure, we were not sure that it was worth the drive to make that change. However, in the context of a whole new document, we believe it's time to approach that issue again. The same thing with the amphetamines. We can go lower. The technology is there today. When the guidelines were first written with cutoffs of 1,000 nanograms per mL for initial tests back in 1987, clearly that was then and this is now where it comes down to the antibody technology.
We're very easily able to go down and focus, not just on amphetamines, but then in the confirmation we really want to take a drive toward the d-isomers of those drugs, the psychoactive isomers. It's just a matter of -- laboratories agree they can do it. We've had some experience with that already in private sector drug testing programs, and it's time to put it out there to see.

DR. SAMPLE: As Yale mentioned, we'd certainly like the industry working groups that are intimately familiar with the other specimen types to carefully review these cutoffs that are in this draft document to ensure that they are in alignment with what they are proposing and to make sure that their ideas in terms of what the cutoffs need to be have not changed since those were first suggested.

DR. MOORE (USDTL): Could I ask why cocaethylene is not in the hair confirms? Is that supposed to be?

DR. SAMPLE: Aaron, do you know why? I'm sorry, the question was why is cocaethylene not in the list of analytes for confirmation testing purposes with hair. That may have been an oversight. As we are moving from -- but again, thank you for bringing that to our attention.

DR. BUSH: Taking a look at the table that we have from this morning's expedition through our entrance into the pilot PT program, it's not in our table at this time.

DR. MITCHELL: I think in one of the previous versions it was suggested and we were just looking to see if perhaps we could do it in the PT program.

DR. BUSH: We're going to be revisiting this. Point well taken. We'll put it in there, but it was not intentionally a specific analyte in our first advent with the PT. We'll go back to the tables.

MR. STEPHENSON: One of the things that I remember anecdotally was told to me was that sometimes people who use cocaine may choose to enhance or extend the effect by using alcohol to produce a cocaethylene type environment, which will give them a significant longer window of buzz. Good scientific phrase here. If that's the case, then as one of these learned experiences cocaethylene may be a very valid target analyte for us to examine. I don't think there was any deliberate intent to exclude it at this point.

VOICE: The working group documents for the hair group also had nor-cocaine.
DR. SAMPLE: The comment was that the working group documents with hair also included nor-cocaine.

MR. REYNOLDS: Back to cocaine again with oral fluids. The answer I thought I heard was that the reason it was excluded from the PT was particularly some chemical issues as far as stability was concerned. Could you explain to me again why cocaine is excluded from the cutoffs as far as screening is concerned? You've got benzoylecgonine or its metabolites, but cocaine is not there.

DR. MITCHELL: Again, cocaine was not excluded as an analyte. It is excluded from the cutoff, and the reason for that is the cocaine is unstable in aqueous solution. This is dealing with oral fluids, not necessarily with hair but with oral fluids, it's unstable. It's very difficult to set up a solution which is going to give you, have a long lifetime, without degradation of the cocaine. That's the reasoning that the oral fluid group chose BE. The cocaine, if it hydrolyzes in solution, it's going to go to BE. If you have cocaine in there, you're going to have a problem for quantitation of cocaine and quantitation of BE if you have degradation, if you get degradation. S

DR. SAMPLE: I also believe that the original working group for oral fluid specified just BE, not cocaine, and that's really a working group question. That was an industry working group that came together to suggest analytes and cutoffs.

DR. CAPLAN: Right, that's where it came from. It had to do with stability. But as of this time, the working group decided only to leave the metabolite in. There was some concern again about stability and whether uniformly cocaine could be determined. To make it a minimum amount -- a minimum criteria is what's in here now -- everybody agreed that cocaine metabolite could be assayed by all the techniques reliably and that cocaine might not be. It was a working group recommendation.

DR. SAMPLE: On subpart D, one of the new items is the requirement that collectors be trained or certified to collect specimens and that the collectors attain certification through a recognized collector certification program for the type or types of specimen or specimens that they are going to collect, and that they be recertified once every two years. That certainly raises the question of who will perform that certification, train and certify the collectors, and that's an item that's still to be determined.

MR. EVANS: Barry, was any thought given to automatically permitting certain professions to do this, like nurses or physicians? I know there are some states that address this issue by saying that a specimen can be collected by a physician or by a licensed nurse, something like that, without having to get special certification, like we do with MRO's. The DOT just says you have to be a physician; it doesn't require a special certification.

DR. CAPLAN: The answer is no -- it's mostly for blood. A nurse or a doctor is generally allowed to draw blood because that's generally a medically invasive procedure. I would still guess that most of the doctors and nurses for this program, if they're not trained in the rules, would have a hard time in collecting an adequate correct specimen. It wasn't considered that anybody would be exempted.

DR. SAMPLE: Plus there's also a wider variety of specimen types now under these proposed guidelines that physicians and nurses are not in the habit of collecting.

MR. STEPHENSON: One of the things that was presented this morning that Charlie LoDico had referenced was that in the laboratory directors meeting there was a sense that we needed to address an issue of regulation and certification, mandatorily certifying medical review officers, that overwhelmingly there was a feeling that we probably should and that there are existing registries that covered 6,000 of the MRO's that are currently out there performing these services. There are still another 15,000 out there that are not. Why would we want to extend that to other specimens, where we've already by experience said that we're not having great success in the most controlled environment with the most feedback to date as we extend into these other areas?
I think one of the things that we will look to the Department of Transportation to help inform us in is in their experience as they set up Part 40 with the issues of certification, and a piece that goes with that is public exclusion because, as we have a regulatory oversight and an authority that deals with the testing laboratories, there are elements that will have to be equivalent in these other areas. I would suggest that we not do it alone, that we do this as a part of a responsible approach.

DR. SAMPLE: Subpart E, how is a specimen collected at the collection site?

MS. BOONE (LabCorp): Just to mention that several states do indicate that laboratories be responsible for the training of collectors.

DR. SAMPLE: Like Florida.

MS. BOONE: Yes. I was just going to bring it out for today's meeting.

DR. SAMPLE: That is a good point. There are some states that actually hold the laboratories accountable for all collections that are performed for specimens sent to their laboratories.
Subpart E, the collection sites, how is a specimen collected at the collection site? Here there's really no change for those requirements. There is the addition of hair, sweat, and oral fluid. For hair, it says that head hair should be collected unless it's not available. The collection of hair from other areas of the body has to be done in accordance with agency guidelines, also ensuring appropriate privacy. For the sweat patch, it should be applied to the donor's upper arm, chest, or back, and the donor must be allowed privacy during the application and removal of the patch by the collector. For oral fluid, the collection device must be inserted into and removed by the donor in the presence of the collector, and as such the donor will be observed by the collector during the entire process.
The collection device, subpart G: Must a collection device be cleared by the FDA? The answer to that question is that if the collection device is a unique and integral part of a collection procedure and the analytical testing, then it must be cleared by the FDA as a medical device. If it's a single use, disposable item like plastic bottles, plastic bags, foil in the case of hair collection, those are not unique collection devices and therefore would not be required to be cleared by the FDA. But aspirators for oral fluid or pads or applicators or the sweat patch itself, those are unique and integral to collecting a valid specimen and would need to be FDA-cleared.
Subpart I refers to the national laboratory certification program. No changes there.
Subpart J has to do with blind samples submitted by the agency, by an agency, and again really no change there, although there was some discussion for the new specimen types if more frequent blind specimens might be required, analogous to what occurred when urine first came about. But for the time being, the recommendation is to leave it as is.
Subpart K are the laboratory requirements. There are very few changes there, but if we can go to page 32, section 11.8, what is an initial test, and this gets to one of the questions that came up earlier. The definition is repeated that an initial test is a test used to differentiate a negative specimen from those that require further testing. It goes on to say that an initial test may include, but is not limited to, the following techniques: immunoassay or chromatographic separation coupled with an appropriate detector. The requirement for immunoassay only is lifted as we're looking at perhaps different specimen types, potentially different drugs, different sensitivity levels. The field is opened up a little bit. Obviously, the test must still be validated by the laboratory before it's used to test donor specimens.

VOICE: The initial test again has to be approved by the FDA, I am assuming; is that correct?

DR. SAMPLE: The question is must the initial test be approved or cleared by the FDA, and the answer is not necessarily, depending upon the type of test. The FDA does not clear GC/MS's for performing screening tests. There are FDA-cleared kits for the point of collection testing device for some of the immunoassay screens. But there's also a thin layer chromatography kit from the early days which do have a 510k clearance.
As long as they have the requisite sensitivity, specificity, and linearity of the cutoff and everything else that's required for one of those tests, yes, and an appropriate detector.

DR. MOORE: How can you confirm and screen on the same thing? You do a chromatographic screen like a GC/MS screen and a GC/MS confirmation; surely that can't be acceptable?

DR. SAMPLE: The question is how can you screen by GC/MS and confirm by GC/MS. The feeling is that those are already two separate analytical techniques. There's a chromatographic separation followed by a mass spectrometric identification. You would still be required to perform testing on two separate aliquots of that specimen in order to report something as positive.

DR. MOORE: You're actually saying you could do that? You could screen and confirm in the exact same way?

DR. SAMPLE: If you chose to use GC/MS for the screen and chose to use GC/MS for the confirmation.

DR. MOORE: You could do that?

DR. SAMPLE: You could do that. But that would probably not be very cost effective in most of the specimens.

DR. CAPLAN: This is an issue that comes up in other parts of this program like adulterants. The fact that you have to have immunoassay, the fact that you have to have GC/MS, that has never been a forensic principle. That has been application, which we derived from the general forensic principle, which is to do a test on two aliquots by two methods. You can't limit it to specific techniques totally, but we sort of got hung into that, probably inadvertently now, and there really isn't that requirement. It doesn't have to be GC/MS. We don't do GC/MS for most of the adulterants and most of them you don't do GC/MS for metals. But very good forensic work is done on a lot of other areas, and it does require some redefinition now. The answer would be yes, you could do it twice.

MR. EVANS: NOTA's position is that we only advocate using FDA-cleared onsite assay tests. We'd like to make you aware of the difficulty if you change this. You may open it up to more litigation. The U.S. Supreme Court in NTEU versus Robb specifically held that the current process of using an FDA-approved immunoassay combined with GC/MS meets all the legal requirements, and if you get into something other than that we're going to open up some other areas of legal inquiry. Just making you aware of that potential problem. Why couldn't you, with the urine onsite tests alone, require FDA clearance there? That's certainly something I think we would support, because the FDA clearance guarantees a whole host of qualities about it.

DR. SAMPLE: When we get to the point of collection test device, I think we'll answer that question.

MR. PORTER: What is an appropriate detector?

DR. CAPLAN: What you have to remember is that these documents are going to be followed by more specific documents that outline each of these things. To get guidelines that cover all things, you can't sit there and list them all. As a result of these guidelines there's going to be the operational document, the checklist, etcetera, for each sub-discipline, and that's where you're going to find out what's acceptable.

MR. PORTER: My only issue is this implies instrumentation, a detector system. Are we saying that digitally read is not appropriate?

DR. SAMPLE: Now, that is not necessarily true as we're talking about the point of collection test device. When we get to the non-instrumented point of collection testing devices we will be discussing that.

DR. CAPLAN: Remember this is the laboratory section. There is a point of collection section. We have these three new distinct things. We made an effort to try to separate them and talk about them independently where they do overlap.

DR. SAMPLE: That's a very good point. This is just for the laboratory. These are the laboratory requirements, and a laboratory is a facility, location, that performs both initial tests and confirmatory testing at the same location, at the same site.
The confirmatory test in a laboratory, has to be performed on a separate aliquot of the specimen to identify the presence of a specific drug or metabolite, and that procedure must combine chromatographic separation and mass spectrometric identification in the same procedure. We would then permit GC/MS, LC/MS, GC/MS/MS, LC/MS/MS, LC/MS to the nth, GC/MS to the nth.
As long as you're using chromatographic separation and mass spectrometric identification for the confirmation of that specific drug or metabolite, you'd be in compliance with the guidelines.
I think the last change in the laboratory section is 11.21. It has to do with statistical reporting and for the statistical reporting it talks about the summary report listing the total number of specimens reported, as opposed to received. That's in compliance with the proposed Part 40. If you would also take a look at the note underneath the proposed statistical report, it is that we are currently evaluating the need for this report.

DR. BUSH: To the greatest extent possible, we are trying to harmonize with what DOT proceeds with as far as the comments that they've got back. If the comments have been made, we need to consider them, too, as part of this developmental process.

MR. STEPHENSON: We recently held a meeting of the inter-agency coordinating group which looks at the federal agency workplace program. We asked this question to that assembled group of 85 or 90 people. When we asked the question, do you get your semi-annual report, do you have your submission, I think there were two hands that went up and they were kind of lingering.
The issue is that this may be an event that is past its time, but we're not going to prejudge that. There may be a way to make this of more value operationally, and if it is we don't want to eliminate it either in the public sector or in the private sector. From our experience, it's probably not being used very much right now by people who would be receiving it.

DR. SAMPLE: Subpart L of these draft guidelines really begins the new cheese section. We've been fond of saying "new cheese." Subpart L deals with the point of collection test or POCT, taking the model of point of care. We're talking about a test that's performed at the point of collection, not at the bed side. Point of collection test is defined as an initial test conducted at the collection site from either the presence of drugs or to determine specimen validity. We're testing for drugs, we're testing for specimen validity at the point of specimen collection.
What types of initial test devices are there? There are two types. There's the non-instrumented initial test device. The end point result from this device is obtained by visual evaluation. In other words, it's read by the human eye. There is also an instrumented initial test device, where the end point from that device is obtained by instrumental evaluation -- densitometer, spectrophotometer, something of that nature.
What are the requirements for the point of collection test? The point of collection test device must be cleared by the FDA. Validation studies must be completed prior to placing a new lot in service and the point of collection device must be included on the SAMHSA HHS conforming products list. This is consistent with the NHTSA model. We're really using, where models existed, to piggyback on those and try and adopt them to these tests as well.

MS. MURDOCH (Benzinger DuPont): Does that mean, Barry, that, like the conforming products for the breath collection devices, you're going to be doing testing validation for the devices?

DR. SAMPLE: That was the idea, yes.

MS. MURDOCH: Are the standards going to be in these guidelines for the devices?

DR. BUSH: It will be in a separate document, but we will write the standards and the procedure using the NHTSA model. That is going to be our first cut with how to proceed with this.

MR. EVANS: When you say in 12.3 "Validation studies must be completed prior to placing a new lot in service," does that mean before it leaves the manufacturer? The manufacturer does that?

DR. SAMPLE: No, this refers to it being placed into service at the point of collection testing facility.

DR. SAMPLE: Who may conduct the point of collection test? A certified collector must collect the specimen. The specimen may then be transferred under chain of custody if the specimen is going to be tested by the individual -- by another individual. But it does not necessarily have to be tested by a different individual, recognizing that some collection facilities may only have one person. The trained tester, under the supervision of a responsible technician, must perform the test.

MR. EVANS: Barry, you have a contradiction in here, in that you talk about it being tested by another individual and then also in another section you talk about the test having been conducted in front of the employee.

DR. SAMPLE: In section 12.9, jumping ahead a little bit, the question is "May the donor observe the point of collection test being performed?" "No. The donor must leave prior to performing the test." What are the qualifications for the person who performs a point of collection test? The individual performing that test must also be a certified collector, in addition to being a trained tester. Obviously, then, they have to be trained in the use of that specific device or system and that training must be documented.

MR. REYNOLDS: I don't see the definition of what "validation studies" is.

DR. SAMPLE: The question is is there a definition of what "validation studies" are. As Yale mentioned earlier, there are guidance documents that are part of the program that would specify that, just as there are guidance documents for traditional laboratory urine-based testing right now on how to validate the initial test or how to validate that confirmatory test.
What are the qualifications of a responsible technician? It really has to do more with responsibilities than qualifications, and I think that's a good note that somebody really brought out earlier. Like the RP, the responsible person, the RT or responsible technician has analogous duties. They manage the day to day operations of that point of collection testing facility. They ensure that there are adequate personnel with training and experience, maintain a complete and current SOP, maintain a quality assurance program, implement any remedial actions that may be necessary in order to maintain satisfactory operation. They must also qualify as a certified collector and tester for the point of collection devices used at that testing facility.
Which specimen types may be tested under a point of collection test? Currently only envisioning urine or oral fluid would be tested at the point of collection.
We talked about the fact that donors are not able to observe that point of collection test before performed.
Section 12.11, what are the quality control requirements when conducting a point of collection test? Slightly modified from your traditional laboratory-based or screening-only, instrument-based screening test. In this case, each day testing is performed one control certified to contain no drug or metabolite and one control that has a concentration of the drug or metabolite at 25 percent above the cutoff must be analyzed. In addition, as a quality assurance mechanism, one out of every 20 negative specimens, or 5 percent of the negatives, must be submitted to an HHS-certified laboratory as part of an overall quality assurance program.

VOICE: Back to 12.1 for a moment, item B says: "The point of collection test is performed after the specimen is sealed." I could envision that the collection of the specimen could be completed, but the specimen itself not be sealed. Is there a specific intention that a specimen would need to be sealed or just that the collection is complete and the donor not be witnessing the performance of the test itself?

DR. SAMPLE: I think the question relates to 12.10, what are the requirements for conducting a point of collection test, on the bottom of page 38, and number B under that item. Or actually, let me just read through all three. A is that "The point of collection test is performed on an aliquot of the specimen that has been separated from the specimen: B, that point of collection test is performed after the specimen is sealed" -- in other words, after that original bottle or foil -- well, not foil pouch -- or applicator or oral fluid collection device has been sealed, as it normally would in a test that's being screened and confirmed at a laboratory. The idea is that you sealed the specimen in the same manner as you would a specimen that is going to the laboratory. This specimen ultimately may or may not go to the laboratory depending upon the result of that point of collection test. Then you must maintain chain of custody and it has to be documented.
Does that answer your question?

VOICE: It does answer the question, although it is viewed then as being required that the initial specimen container would need to be sealed and not handled as part of a collection validation. It seems like the security of that specimen could be verified by the collection procedure itself and not have to do it in a time-dependent manner.

MR. LODICO: I might answer that question. There are a variety of point of collection test devices. There are the integrated collection and testing devices and you have those dip and reads. This will dictate what part of the document that will be supporting this regulation as to how to proceed in the actual testing procedures. We like to try to limit the initial specimen to test the aliquot. While the sample is sealed, if it is presumptive positive, it goes to the laboratory; if it's negative, then it's discarded.

MR. EVANS: Barry, I think I was correct about that contradiction. In 8.2.G you say: "If an onsite test is to be conducted"

DR. SAMPLE: What page are you on?

MR. EVANS: Page 23, 8.2.G. It says: "If an onsite test is to be conducted, it is conducted before sealing the specimen and the donor watches the collector conduct the onsite test."

DR. SAMPLE: Thank you. We appreciate your finding that inconsistency because G is not supposed to say that. It's supposed to be compliant with what's in 12.9.

MR. EVANS: I remember reading that.

DR. SAMPLE: Thank you.

MS. MURDOCH: One of the problems that we ran into looking at the devices was that many of them are temperature-sensitive to the temperature of the urine specimen. If you have to wait until the donor leaves and this chain of custody stuff and what-not goes on, will there be provision for raising the temperature of the urine back to body temperature?
Yes, it affects the outcome of the test, Denny. It does. We saw a high degree of false negatives with cooler specimens in our evaluations and that's just a fact of life. So will there be a provision for raising the specimen temperature back to body temperature so that you don't get false negatives?
Two, why not leave it agency option as to whether or not the donor is absent or leaves if they don't feel like having to make a chain of custody form for each and every specimen when 98 percent of them are going to be negative and get thrown in the trash?

DR. BUSH: I'm not sure we're in a position to take a full answer at that right now, but I'm not sure that the specimen right there would be thrown in the trash. There's going to be a lot of recordkeeping involved with this type of testing.

DR. SAMPLE: We also have the requirement for the quality assurance program as well which is a part of it. But we certainly welcome your comments. None of this is a done deal by any means.

MR. EDGELL: Barry, what was the basis for the test being performed after the donor leaves the test site? Are you concerned about safety of the collector?

DR. BUSH: I don't know that we said they had to have left the test site, but it's just with the donor not present.

MR. EDGELL: They must leave prior to performing the test, so you can't watch.

DR. BUSH: No, you cannot watch and that was the whole thing.

DR. SAMPLE: You can't watch.

DR. BUSH: That was the whole thing.

MR. EDGELL: And the basis for that?

DR. SAMPLE: Is to try and avoid any possible confrontation between the donor and the collector.

VOICE: They watch alcohol tests.

DR. BUSH: That was a concern that we had early on with the alcohol tests. You could have a confrontational setting there. But that's really not been raised.

DR. SAMPLE: I think there are also some industry groups that have recommended segregating the donors from the collectors in performing a point of collection test.

MR. EDGELL: Industry groups?

MR. EVANS: If we are an industry group, our position on this is: "In order to avoid potential conflicts and provide for a smooth work flow, it is not recommended that the test be conducted in front of the donor." I think that the work flow is the primary issue, because the tests sometimes take two or three minutes to bring back the results and if people are standing around it's just difficult to move people through.

DR. CAPLAN: It's also anticipated that places doing this may be doing many more than one device or one thing. They may be collecting all specimens. Some are going to laboratories in other places. Julie, when you're doing one thing it's probably going to be easier the way you said.

MS. MURDOCH: But we have 1200 contract collection sites.

DR. CAPLAN: They're only doing one test, they're only doing one test with one kit.

MS. MURDOCH: No.

DR. CAPLAN: It's very likely that in this scenario there would be collections that are being sent to a laboratory. There could be hair going to a laboratory, there could be urine going to a laboratory, and there could be multiple ones. It just makes it more difficult.

MS. MURDOCH: That's true for many of the contract collection sites, but with almost 400,000 tests we've never had a confrontation or a work flow problem.

DR. CAPLAN: Well, certainly put that in. We're looking to the comments. These are thoughts. We're telling you what the small group thought about it.

MR. EVANS: Our primary concern was not that there were confrontations. Our evidence is that there aren't confrontations, but it's mainly the work flow, preserving confidentiality. We also think that, in case somebody might oversee the result of the test, see the positive result, we feel that it's management's job, not the test collector's job but management's job, the company management, to tell the employee about any positive or negative results.

DR. CAPLAN: The other part of this is that there is going to be a selected quality requirement that a certain number of negatives are going to go in, so a person will have observed a negative test and then his test is still going to get sent in. I think all the things that you've said, the permutations and combinations, it appears that it's better not to have the person watch.

MS. BOONE: Not to belabor the point, but with four years of real world experience, the collectors do feel that there is the opportunity for confrontation. When the employee does view the presumptive positive result then they get that information before the employers, and the employers want to make sure that they are the ones or the MRO's are the ones who get that information first.

DR. SAMPLE: Good point. Thank you, Wanda.

MR. FORTNER (PharmChem): 12.6. It seems that it says "qualifications."

DR. SAMPLE: Yes. It really should say "responsibilities."

MR. FORTNER: These are really responsibilities. Is there a separate section for qualifications?

DR. SAMPLE: There will be, or at least separate guidance for qualifications. As I mentioned earlier, we're looking at a CLIA general supervisor type level of model, to be consistent.
I think the rest of this section, or at least the next couple pages of this section, are very analogous to a laboratory-based test where it talks about what are the inspection requirements and who may do the inspection, what happens if they don't satisfy those requirements, and where is the list published. As much as possible we're cutting and pasting and using a model that already exists.
In section 12.22, summary reports, again summary reports are required. These would be a summary report for that point of collection testing where it talks about the number of specimens tested, the number that were negative, and the number that were non-negative on the initial test.
Section 12.23, what type of relationship is prohibited between a point of collection provider and a medical review officer? That refers to the MRO section, subpart N, but it's the same verbiage as what occurs in the laboratory section that prohibits a relationship between the point of collection -- between the testing function, I should say, and the medical review officer.
What type of relationship may exist between a point of collection test provider and an HHS-certified laboratory? The point of collection test provider could freely enter into any relationship with an HHS-certified laboratory, and the view is that often times those point of collection test facilities will simply be an extension of the laboratory.

MR. LIPOV (HHS): On 12.13, what are the specifications for PT specimens rather than the formal test requirements? Isn't there another section in the guidelines for performance test requirements, what you grade, how you grade it, and perform the test? It says the specifications for the PT specimens.

DR. SAMPLE: It may be. We'll have to look and see whether the question is worded properly and compare that as well to the laboratory-based one. It appears that it talks a lot about the composition, you're right, at least in the first part of it.

DR. VOGL: It should be just what are the performance test requirements. That's the question.

MR. EVANS: Barry, the FDA-cleared onsite immunoassays all have a built-in quality control. In other words, the device tells you whether it's working or not working. What we recommended was that you do quality control on each lot of onsite test devices. You seem to be recommending that you do quality control every day, without differentiating between various lots. What was the rationale for that? I mean, why wouldn't it be sufficient to do a quality control on a lot of tests and then that will be okay for that entire lot and then you could just run that lot? I hope I expressed that properly so that people here will know what's my concern about that.

DR. JACOBS: I think our thought was that certifying a lot is a good idea, but what if you only do one test a day and that lot sits there for two and a half years. All other tests we do, all other matrices we're looking at, have daily qualifications and we wanted to duplicate as nearly as we could the same qualifications, the same standards, and the same controls.

MS. MURDOCH: But the net effect of these requirements will be to eliminate the possibility of onsite testing being done by small clinics and small operators. That's obvious. Was that intentional? We've looked at the requirements, people, daily QC's.

DR. JACOBS: If you want to throw all the controls and all the standards and everything out the window, then maybe we should look at all matrices not having any standards.

MS. MURDOCH: That doesn't answer the question.

DR. JACOBS: No, that was not our goal.
DR. SAMPLE: That was not our goal.

MR. LODICO: The goal was to maintain quality control and quality assurance, across all matrices.

DR. SAMPLE: All testing locations and all specimen types have similar types of requirements for the performance of those tests.

DR. JACOBS: There are urine drug laboratories that only do one or two samples in this program a week
and they still have to do all of these things.

MR. FORTNER: In previous DTAB meetings we had all these discussions, if you're going to go on alternative matrices you're going to model it after the urine-based testing program. Was not the concept of the urine-based testing to say if I went to certified laboratory one, laboratory two, laboratory three, I'd always get the same results -- consistency within the program, and it has quality control and quality assurance within that program, even though with one of the alternative matrices I don't think we would want to be running a lesser quality control program than a urine-based program.

VOICE: If the POCT device has a built-in "test valid", what's the difference between that and the currently used urine device where you also have your "test valid" to protect the validity of the procedure you're running?

DR. SAMPLE: The question is, it relates to "test valid," the control line that appears on many of these testing collection devices. That is a different type of control. That is really verifying that you're getting migration of fluid from one end of the test device to the other end of the test device. It really is not validating that that device is performing from a sensitivity at the cutoff or specificity standpoint.

VOICE: But it is reflecting that there is an immunoassay reaction occurring.

DR. SAMPLE: Yes, but not necessarily the appropriate one, and that's why there's still a requirement for fortified controls to be analyzed on a regular basis, just as you do for a traditional laboratory-based test, again trying to have uniformity in process across all testing locations and specimen types.

MR. EVANS: Let me see if I understand it, then. You're basically talking about these are going
to be adjuncts of laboratories, then, that a business would not be able to do this?

DR. SAMPLE: No, that's not necessarily the case. It would not necessarily be an adjunct of a laboratory. There are a number of occupational clinics, third party administrators, even companies with medical departments or smaller companies perhaps, if they so choose, that would be permitted under the regulations to do all of this testing. The only requirement is that they meet the requirement that would be set forth in the guidelines once they're finalized and published.

DR. CAPLAN: They would have to have the QC as dictated and they would have to have an RT supervising it.

MR. EVANS: We could have an occupational clinic that does this for a variety of small, mom and pop companies within a neighborhood?

DR. SAMPLE: Absolutely.

MR. STEPHENSON: My thought is you're probably addressing non-regulated testing that would be done in the private sector, perhaps under the broad umbrella of under the guidelines, but not fall under the regulation or controls. I would suggest to you that those conditions exist right now. In those environments for mom and pops for the local area, you can go out and sell whatever product you choose and you can perform whatever tests you feel that they can afford to buy.
This program is generated on the basis of quality control for protection of all parties: the program, the agencies who have a responsibility to get a proper result, and for the individual who's subject to the testing under our federal guidelines. This does not extend necessarily to all other forms of testing that might be enjoined across this country under whatever conditions someone wants to do it as a business.

DR. SAMPLE: I would add to that, in somewhat response to your question, David, is that mobile onsite or mobile point of collection testing facilities would also be permitted under these regulations so long as they met all the requirements and criteria. You could even go one step further in terms of variety of different customers or types of donors that would be coming into that facility.

MS. MURDOCH: Just out of curiosity, have you done any estimates on how many FTE's are going to be needed to conduct this application process and the inspections, run the PT program, that sort of thing?

DR. BUSH: No, we haven't examined the number of FTE's, the types of inspectors who would need to be trained or evaluated to do this, or the types of proficiency programs to be set up. But again, as with the existing drug-free workplace program system that we have in place now with the laboratory inspections and the PT's and the certification program, it's self-supporting. We would need to do that kind of cost-benefit analysis, the cost analysis, and be able to set up a fee schedule like we do with the laboratories, and we'd have to find out the interest of participants so that we could gauge all of that, and that's the next step down the line, one future step down the line after we review these guidelines.

MR. STEPHENSON: I think the importance here is that this is not only a self-sustaining program, but it is a self-improving program. The industry, working together with those people who've purchased the services in the regulated and the private sector both, and now extending over into treatment, therapeutic communities, and into the criminal justice area, benefit from everything that we have collectively done, every step that's been improved.  Every mechanism that's been created and incrementally improved over time has been paid for by the commercial marketplace, not by government regulation. This whole initiative is based on us working as partners, working together to develop and consistently improve the resources that we are bringing to bear.
I think the whole issue here is that we will not throw away quality assurance, quality control or competency as an expedient to simply provide the opportunity for an open door for anybody to do a test and to make a buck by selling that service. There must be quality in service for service rendered.
If you're not regulated by these programs, then you don't need to comply. The will of Congress has been that we are not universally the control point or the gatekeeper for all quality assurance throughout this country, but only in very specific areas. Others who choose to follow the model do so based on the fact that they perceive some value in doing it.
We're trying to provide honest guidelines and honest attempts to provide quality assurance. I'm not being defensive on this. I'm trying to be supportive of the process that we've gone through in the past that has made such huge gains. There's very little else you can look at across this country where really the people who have funded all of the developments have been those people that have paid for the services out there and the industry has responded by continuing to improve incrementally the quality, sensitivity, and cost effectiveness of the individual tests.

DR. CAPLAN: One quick corollary to that is that, in response to several of the questions like the one about the control and the frequency, there is a requirement or has been a requirement of this program from the beginning to be concerned about false positives, but also ensure a minimum number of false negatives.

MR. STEPHENSON: Absolutely.

DR. CAPLAN: That's why you have to do it. You can't ensure a minimum number of false negatives if you don't have these types of things in place.

DR. SAMPLE: Subpart M. This section deals with the instrumented initial test facility. This facility is a remote site that meets all the laboratory requirements to perform screen-only testing. Essentially it's a screening-only laboratory. Consequently, all of the requirements under the laboratory section having to do with the initial test have been moved into this section. That's essentially how we should view this section, but I'd still like to go through some of the items.
13.3, what is an instrumented initial test? An instrumented initial test is a device that's used to conduct initial tests for drugs or for determining specimen validity. The data generated by the instrument is based on calibrators or controls registered by the instrument's detectors. Again, that's a difference from the point of collection device that only has two controls. In this case, where you have an instrumented initial test facility, there are both calibrators as well as controls that are used to validate that assay before it's used to test donor specimens.
What types of initial tests are there? Again, a repeat of what we talked about before, point of collection test device, which can either be instrumented or non-instrumented, and, B, the instrumented initial test, which really applies in this section.
What are the requirements for an instrumented initial test facility? The instrumented initial test device must be cleared by the FDA, again validation studies, a validation procedure must demonstrate the ability to differentiate positive and negative samples, the performance of the test around cutoff, the concentration, and the performance of the test results at several concentrations between zero and 150 percent of the cutoff.
These are the same requirements that are required for the traditional laboratory-based test.
13.9, what are the qualifications, which really should be what are the requirements or the responsibilities, for a responsible technician? Those are the same as for a point of collection test facility. There's no difference. An RT is an RT. One thing that we failed to mention during the previous discussion about the responsible technician is that a responsible technician may have -- is permitted to have responsibility for multiple sites. It's not a one RT, one facility scenario, like you have one RP and one laboratory. An RT can have responsibility for multiple locations, which is something different than the traditional laboratory-based model.
The QC requirements in 13.12 are analogous to what's required in the laboratory-based test, where you have controls above and below the cutoff, you have negative controls, requirement for one blind control with a minimum of one percent inserted to appear as a donor specimen in the laboratory analysis. 10 percent of the batch must be calibrators and controls. No different than traditional laboratory-based testing, and those really flow throughout with respect to the PT requirements, inspection requirements, specimen validity testing.

MS. MURDOCH: I apologize if I missed this at the beginning of the section, but I know some of the onsite manufacturers are developing optical readers for their devices, but they're single specimen at a time readers. Is that an instrumented testing facility or non-instrumented?

DR. SAMPLE: The question is if you have a device that is instrumented, it's really a point of collection test type device that has an instrumental reader, is that an instrumented initial test or is that a point of collection test device?
In the scenario you're talking about, Julie, that is still a point of collection test device, which may either be instrumented or non-instrumented. If you look at part A of 13.4 on page 34, I believe that answers your question.

DR. ISENSCHMID: Article 12.2 says, if you go back to the point of collection test, "an instrumented initial testing device."

DR. SAMPLE: Yes. 12.2 says the same thing, I believe. You can think conceptually of the instrumented initial test as picking up the screening department in a traditional laboratory and moving it to a remote site. That's the best analogy I could give it.

DR. SAMPLE: Subpart N, the medical review officer, the only clarification or new stuff in here has to do with relationships and what's permitted or prohibited between an MRO, a laboratory, a point of collection test provider, and an instrumented initial test facility. Analogous to the prohibited relationships currently between a medical review officer and a laboratory, those prohibitions would also be extended to a point of collection testing provider or facility, as well as an instrumented initial test facility, because the MRO would then be placed in the position of reviewing their own results if they had that type of relationship.

DR. GUARNIERI (DTAB): Can I offer just a couple of comments on the MRO end of it? I'll be happy to write these in, but at some point in the definition of MRO, beyond the fact that someone is an MD or a DO and has some knowledge of drug abuse disorders, we've got to put in the comment that they know how to interpret drug test results. I mean, you could be a wonderful clinician and understand what someone's cocaine high may be, but you may not have any clue when you get a positive drug test result. Just for your consideration. As the word "verify" is to the Department of Transportation the word "confirm" is for the NRC. Wherever we have in here your "verified result," please add to that "confirm" in the definition, as well as throughout here. So it's "verify" and "confirm." I know Garwin isn't here today, but that is NRC lingo.

DR. SAMPLE: It's a good point.

DR. GUARNIERI: NRC says "confirm."

MR. SCHOENING (DTC): I'd like to know if HHS is going to mimic DOT in the MRO certification requirements that they put in the NPRM?. Is that under consideration? That would address part of the concerns that have just been raised.

DR. BUSH: Yes, we are. I think here Dr. Guarnieri's pointing out that NRC even has a different word; their MRO's "confirm" drug test results as opposed to "verify." This is what we need to know, where are the similarities, where are the differences.

DR. SAMPLE: I think HHS is also going to be looking, along with DOT, at the comments that came back from the NPRM and take that into consideration as we're moving forward with this document.

MR. SCHOENING: The question is will MRO's be required to be certified? It's the only entity that is not.

MR. LODICO: That is a recommendation from the DOT-HHS laboratory directors meeting. The laboratory directors unanimously agreed that they would recommend that the MRO's be registered and certified, so that is something that we will probably incorporate into this document.

DR. CAPLAN: It's certainly under consideration and the outcome will depend upon coordination with some of these final things with DOT to be consistent with what DOT says and does. We'll let them take the heat first.

DR. SAMPLE: I'd like to reiterate that this is just a first pass. You notice it's draft number one. It hasn't been through all the members of the Board. It hasn't been through the interagency work yet. We appreciate everyone's comments today and, please, if we've missed something, if we didn't get it right, please give us your input, questions, answers, if we've left anything out.
MR. STEPHENSON: Our intentions are to put the PT data and the draft of the mandatory guidelines on our web site. We will do the mandatory guidelines and include some of the changes addressed today. We will incorporate those before we put it out on the web site, so you will see a slightly improved and clarified version.
We will not go for a regulatory process review at this time. Again, this is simply what did we miss, what have we got wrong that you needed to bring to our attention dramatically.

MR. EDGELL: Something that I missed -- you have definitions for "adulterated" and "substituted," but the testing is limited to the drugs. What happened with specimen validity testing?

DR. JACOBS: We had actually talked about that a little earlier. We have addressed that. We will incorporate the specimen validity testing under the guidance document area. I think the issue of definition and the area of some specificity must be incorporated in terms of process.
We do want to follow the lead of DOT and the experience that you have through your responses to your NPRM and the review that we do, because I think it will be very instructive for us, helpful from the comments that public has made and those other interested parties during this process. Our intentions are to put it out more than a guidance document.

DR. SAMPLE: There is also discussion about specimen validity testing in each of the various sections. Under the laboratory section, under the point of collection test section, and under the instrumented initial test section, there is discussion about performance, not requirements initially but performance of specimen validity testing.

MR. STEPHENSON: The words "validity testing" are there.

DR. BUSH: We're waiting for you. We didn't want to put out too many conflicting thoughts on how to proceed at this time. DOT has already asked for public comment. We certainly have our policies and procedures disseminated to the laboratories, to the medical review officers, the collection sites as best we can at this time. We're just going to take a step back on that one and wait.

MR. STEPHENSON: Our written guidance goes back to September 1998 and to mid-1999, and the interest and issues that have come from it are basically in the DOT environment and the opportunity for discussion and clarifications will best serve your population first, and we will try to make sure that we are consistent with that.
We've made a comment in our discussions with our federal agencies that it is our intention to review the DOT components and then to come back to the 120 federal agencies that we have oversight responsibility for and discuss the issue of mandatory compliance for validity testing as one of the components. If that's where you come down, that's probably where we're going to come down. Although we can't dictate that to them, we are part of the executive committee with the Executive Office of the President that addresses these issues. I feel we can be helpful in guiding it in that direction if this is where it comes down.

MR. EDGELL: You mention in talking about the laboratory that only does the initial test that the RT's can have the responsibility for multiple locations. Is that the RT with respect to the initial testing site as well as the RT in the point of collection test site?

DR. SAMPLE: That applies to both, yes.

MR. EDGELL: And what's your thinking there as to how many? Do they ever have to visit these sites?

DR. SAMPLE: I think that's to be determined. It's obviously going to be volume dependent. If it's an instrumented initial test facility that has a volume analogous to a large laboratory, that may probably not be able to adequately fulfil their role and oversee multiple sites. But if it's a number of smaller facilities, they most likely could oversee a number of sites.

VOICE: How does CLIA control that?

DR. SAMPLE: I think that's varies somewhat state by state in terms of how many facilities a given director can have responsibility for and oversee.


Public Comments

PAT (Last name withheld): Good afternoon. My name is Pat. I'm a former police officer who lost a position to a positive result of cocaine obtained through a hair analysis test. I am not and was not a user of cocaine.
Throughout the past three and a half years since that test was administered on me, I have made approximately a thousand phone calls, written a hundred letters, and today marks the third time that I have been to the D.C. area in the hope of getting help and making sure that everyone is aware that hair analysis is an erroneous test and should not be used in the workplace.
Obviously, I am not a scientist or an expert in this field. I am just an average middle class working man, the same average middle class working person that the majority of these hair tests affect. Do not take me wrong. I have researched hair testing to the best of my ability and it certainly is not without any merit. But it is definitely not at the stage where it should be used in the workplace, especially without any other corroborating evidence.
I have learned that there has been talk throughout the last year or so that a ratio of BE to cocaine, I believe it is 10 percent, would be considered a marker of use as opposed to exposure. At my own unemployment hearing, which I lost, it was stated by a so-called "expert" from the laboratory that performed my hair analysis that BE could only metabolize through use and not exposure. The latter statement, at least in my opinion, is just pure ignorance.
With regard to the 10 percent ratio, I am here to inform you that this is incorrect. There were three different tests performed on my hair sample. The results for each test were as follows: for cocaine, 23.6 nanograms per 10 milligrams, and BE, 6.4 nanograms per 10 milligrams; for cocaine, 39.2 nanograms per 10 milligrams, and BE, 13.9 nanograms per 10 milligrams; for cocaine, 31.6 nanograms per 10 milligrams, and BE, 11.8 nanograms per 10 milligrams. No coca ethylene was found in any of my tests.
I did not use cocaine. At this time I have no court case pending with regard to ever regaining my position as a proud, dedicated police officer. I have no court case pending with regard to suing for a financial benefit.
It has cost me $7,000, money that I did not have, just to try and be awarded unemployment benefits, benefits that if I were to win would have only given me back that $7,000. I took off work and got on a train at 1:30 a.m. this morning to be here today. I will be back on that train at 7:00 o'clock this evening and arrive home at 2:00 o'clock in the morning in order to be back at work tomorrow. Today cost me $300.
For those of you sitting here for just a few minutes, put aside the scientific facts of hair testing, facts that in my opinion show the unreliability, not the reliability, of the test. I implore you to use your common sense. Why would I spend $7,000 in an unemployment case just to have a chance to win back $7,000? Why, three and a half years later, would I spend $300, travel 600 miles, and stay up for over 40 straight hours to be here today, if I had nothing financially to gain, if I am never going to get my position as a police officer back?
Why would I do all of this if I really used cocaine? I'll tell you why. It's about pride. It's about feeling good inside again. It's about losing that hurt, that wanting to cry every day. It's about hopefully saving one or maybe even a thousand other people from being unjustly accused and going through what I have gone through and am still going through.
It is a shame to say, but I feel that if I were a multimillionaire I would not be here today. Not because I would be financially set, but because I would have been able to have paid for the best lawyers and the best scientists in this field to testify on my behalf. I truly believe that I would have been able to go into a court of law and prove that hair testing is not reliable in all cases. I would be patrolling the community as a police officer instead of standing here before you.
Please, for those of you out there that know in your hearts that what I am saying about hair testing is the truth, get up, speak up. This is not right.
I would like to thank the DTAB for giving me the opportunity to speak. Have a nice day. Thank you.

MR. THISTLE (Psychemedics): I have the unemployment insurance decision that was rendered on Pat. It speaks for itself. I'll give it to anybody here. It starts off: "The credible evidence establishes."
Pat was represented by counsel. Pat had expert witnesses. Pat went before an administrative law judge. He lost. He went before an administrative board. He lost. He had experts. Again, the decision simply speaks for itself: "The claimant has not provided sufficient evidence to substantiate his suggestion that he accidentally ingested cocaine."
Pat is right, this has been going on for three years and it is time to stop it. He has filed an appeal, I believe, in this case, but I can assure him that the results will be the same.

DR. McCOY (MedTox): I would like to congratulate this group. I don't think there are very many of us not on the Board who expected to see a draft document today, so I think most of us were surprised, and in my own case at least I was pleasantly surprised. Thank you very much, and I think it's quite thoughtful.
One question, if you have any ideas to the guidance. As I understand it, for the two different types, new types of laboratories or testing that are described, it talks about sending off 20 percent of the specimens, perhaps on a daily basis, off for referral. You're shaking your head, Barry, that's not correct?

DR. SAMPLE: 5 percent. One out of 20 for the point of collection test.

MR. McCOY: You're right, one out of 20, 5 percent. I'm wondering about what kind of guidance is going to come out on the results that don't correlate or agree between the initial test and the subsequent test. Is there any thought about how those would be handled, not on a program level, but on the individual test level?

MR. STEPHENSON: There are some areas that we have been instructed in by past experience with NRC with proficiency examinations looking at the onsite specimen tests that were provided in the nuclear regulatory environment that's authorized under their regulations and then what happened when those went forward to a laboratory. There was a requirement that there was a six month concordance period where they had to demonstrate at least an 85 percent agreement between the screening results and the confirmation. The watchdog for the false negatives has come out of the NRC and I suggest that we have to learn that lesson again with alternative specimens and with point of collection testing again.

MR. McCOY: Yes, I'm actually in favor of the concept, and I tried to couch my question not as a program question, because I can see how in a programmatic fashion you can review the results and make sure everything's working right and, if not, address those. My question is on an individual basis where perhaps somebody in the field was reported as negative to the employer and referral to the laboratory showed a different result for that individual.

MR. STEPHENSON: I think the guidance for that will come out of regulatory process that would be -- for instance, under DOT it would have to be addressed under their protocols as to how to address this. In other kinds of settings, it will be one of those things we'll have to wrestle with. Any time you have an error that you're able to document and you learn something from it for the program, you've got an advantage. The impact on the individual and the role an employer would have for the public safety aspects that might be involved have to be given appropriate attention and I'm sure they will be. We're not going to solve it today.

DR. McCOY: I thought I understood all the definitions talked about today until some of the very last few comments about instrumented devices and non-instrumented devices. For example, there is a cup being used in the field as a point of care device that you cannot read without an instrument. Is that an instrumented device or a non-instrumented device?

DR. SAMPLE: That is an instrumented point of collection test device. It is not an instrumented initial test facility.

DR. McCOY: It would be performed in a point of care test facility, not an instrumented facility?

DR. SAMPLE: That is correct. I believe that the requirement for the QA mechanism is only for the point of collection test, not for the instrumented initial test facility, because it has the plus and minus controls, it has the blind, it has all the same quality control and quality assurance procedures that would occur in a traditional laboratory based test.

DR. McCOY: I noticed that there were no specifics about adulteration testing. Just a repeated plea I have made before: Please make these guidances general for new compounds, more class specific type of recommendations, but do require laboratories to have a screening method and a separate confirmation method similar to the drugs.

MR. ARAMUNDO (Consultant): In looking at the makeup of the Board, why is there not one representative from the point of collection test industry, a reputable science individual like a Sal Salamoni or somebody like that? Secondly, on the issue of daily quality control using samples at plus or minus 25 percent of the cutoff, we've heard from some of our colleagues here that one of the reasons for this is to ensure consistency in testing from facility to facility. Again, I'd like to ask the Board, we know there are some laboratories, HHS laboratories, that dilute reagents when they test and we know there are some that do not. Is this consistent?

MR. STEPHENSON: I'm going to only take the first one. There is a wisdom here. It may not be apparent, I know, but there is a wisdom here. The first thing is that, in terms of the representative from point of collection testing, we consider for each of the industry working groups that they are, for the purposes of informing this Board, partners in this process. We have convened them. We have wherever possible facilitated travel, helped with documentation, but allowed them to respond to the charge that they generate within their own environments and then come back and report that. We will continue with that partnership. The fact that there is not an individual who has in his repertoire a responsibility for commercial products development that sits on this Board as a member today is not an issue in terms of how well the industries are being represented in the process we're going through. That goes for each one of the areas. If there is anybody in the industry working groups that has participated who disagrees with me, please raise the issue right here, right now.

DR. SAMPLE: With respect to the second question, it's performance based. The purpose of the controls are to validate that the assay, that the procedure is performing properly, and whether a laboratory is extending or diluting reagents, you're still running the same controls to validate the performance of that individual assay, and that's really the purpose of the quality control materials and that's a requirement. Whether it's a traditional laboratory based test, a point of collection test, or an instrumented initial test facility, there's still a requirement for quality control and quality assurance.

DR. CAPLAN: There's also a requirement for method validation. If a laboratory is doing, using something that is different and establishes its own, it must validate that. That data is checked at the semiannual inspections on a regular basis.

MR. ARAMUNDO: My question was is that consistent?
DR. CAPLAN: Yes.

DR. SAMPLE: From a performance standpoint, yes.

MR. EVANS: I know a record is going to be made of this, so I wanted to just have a few comments. As far as participation in the process and the working groups, I am not aware that anybody from NOTA has ever been invited to a working group. At one point we did submit a list of names that we suggested from our organization. I'm not aware that anybody ever officially represented NOTA. We do represent eight point of care test manufacturers, the leaders in the field. We have been in the business of setting standards for some time now. We have come up with our own draft guidelines. We have done this in cooperation with DATIA, the Drug and Alcohol Testing Industry Association. We sent them to HHS at least several weeks ago. I hope that the members of the working group had the benefit of being able to read them. Anybody who reads this transcript, if they'll contact NOTA we'll be happy to send you a copy of the draft guidelines. These were developed with DATIA. DATIA is the organization of specimen collectors, representing several thousand specimen collectors in the United States. We have worked on these guidelines for about a year now, I guess, going back and forth. We've had several drafts. We would make them available and the comments we've received to anybody that's interested in hearing about it.
As far as some of the things that have been suggested here, we have wrestled for some time now in those states that require laboratories for all employment drug tests. Some of those states require CLIA standards and we have suggested to employers some of the same things that you have suggested -- you know, the roving recreational vehicles that you can set up for specimen collection and doing onsite tests. In fact, I represented, and I have a private law practice, a company on Long Island that did that very thing. I think they had five RV's. They went all over Long Island. They could not make a financial go of it for a variety of reasons. Just simply the practicality doesn't work.
We've also suggested to companies, as I did to Wells Fargo, who wanted to use an onsite test, that they comply with CLIA, because some states require CLIA compliance, and that they do what you are suggesting, go out and get this technician and so on and so forth. It proved to be very, very difficult to do.
I suggest that a lot of the companies that are going to be confronted with having to meet all these standards are just going to stick with the old system, and I don't think that's your intent. I think your intent -- I would hope that we share the goal of fighting drug abuse in the workplace and that we would keep an open mind and look at what is cost effective, what is practical, and what preserves the good quality. We have always advocated good quality.
I know sometimes you get us mixed up with some of the irresponsible onsite test manufacturers. We are not that. We recommend that things be done a certain way.
We have incorporated some of the principles that you're advocating here today into state legislation that we have supported. Hawaii, Oklahoma is about to go onsite, and Oregon, and other states. The legislation that we have proposed talks about having some kind of a central certification process, that people be trained and certified who administer the tests, and that they put in quality control. I hope you'll keep an open mind.
Now, as far as the daily quality control, it makes a lot of sense when you're using an instrument to do that, to make sure that that particular instrument is working, because you run the instrument and it's the same instrument that's going to do the tests that then follow. The problem with an onsite test is that each one is individualized and so you can run an onsite test and that test then gets used up, which is not the case with an instrumented test. It gets used up and then you have to use a separate individual test to run it again.
That's why we advocate running tests on the lots, because that's the only thing that really makes sense. There should be monitoring about the lot to make sure that the lot has not expired. You might even periodically check the lot. But doing it every day just logically doesn't make sense because you use up the test and then you get a fresh test.
I'd like you to at least look at that, rethink that a little bit, and look at preserving that the tests are not expired, that they're kept in the proper temperature, which will affect the tests, and all the other things that the manufacturer recommends. That's what you ought to monitor and focus on that.
I really salute what you've done. We think that we've come a long way in this and we believe that you will keep an open mind and will look at what's practical.
We feel that we have not done our job in persuading you on some of these issues. We are going to go back and develop our arguments, get you some information. One of the things we'd like you to look at is that issue of quality control. Do you have any evidence that our quality controls that are built into our tests do not serve the function that they are intended to serve, and that they would then need to run every day? If you do have that evidence, we'd like to see that.
We are going to come back with some additional information and I hope that you'll make our draft guidelines available to every member of DTAB because they reflect what we believe are the best and most practical methods of proceeding.
Thanks.

MR. STEPHENSON: Thank you for supporting the activities for the point of collection testing component of this with your organization and your association. We want this to be an inclusionary process. There's no intent to exclude anyone from this. We will be more than happy to add your name to the group, when and how they meet and the things that they process, the data from this point forward.
Are there any other issues that anyone else would like to raise at this time? I feel this has been a productive meeting. It's been one that we've gotten a lot of new things out. We've probably overwhelmed you a bit with some of the level of technical data and so on.
This is a process that is only going to accelerate. It's not going to get less intense over the next six months. So don't expect this to just be a rare event. From now on, it's full court press, and we'll be asking you for an awful lot of input and we'll be expecting you to provide it.
I want to thank everybody who worked on these various projects.

DR. BUSH: The next DTAB will be September 6 and 7 (Wednesday and Thursday of Labor Day week). We haven't set up the agenda, but likely the open session will be a full or part day on September 6th.

The meeting was adjourned at 3:45 p.m.