Welcome - Paul Schwab 2

Federal Workplace Drug Testing - Dr. Joseph Autry 6

Overview of Alternative Specimens/Technologies 41

- Dr. Yale Caplan

Confirmatory Test Procedures Panel 216

- Moderator: Dr. Richard Hilderbrand

DRUG TESTING ADVISORY BOARD

JOSEPH AUTRY, MD (Chair), CSAP, Rockville, MD

DONNA BUSH, PhD, (Exec. Secretary), CSAP, Rockville, MD

ROSEMARY BAKES-MARTIN, CDC, Chamblee, Georgia

YALE CAPLAN, PhD, CORNING National Center for Forensic Science, Baltimore, Maryland

CHRISTOPHER HOLLAND, MD, HRSA, Bethesda, MD

AARON JACOBS, PhD, USAMC, Fort Sam Houston, Texas

ALAN JONES, PhD, University of Mississippi, University, MS

TAI KWONG, PhD, University of Rochester, Rochester, NY

MELANIE MALLORY, Consultant, Scottsdale, Arizona

RICK ANDERSON, PhD, Biosite Diagnostics, San Diego, CA

DAVID ARMBRUSTER, PhD, PharmChem Labs, Fort Worth, TX

WERNER BAUMGARTNER, PhD, Psychemedics Corp, Culver City, CA

MICHAEL BAYLOR, PhD, Research Triangle Institute, Research Triangle Park, NC

THOMAS CAIRNS, PhD, DSc, Psychemedics Corp, Culver City, CA

ANTHONY COSTANTINO, PhD, DABFT, American Medical Lab, Inc, Chantilly, Virginia

JOHN MITCHEL, PhD, Research Triangle Institute, Research Triangle Park,

NC

SAM NIEDBALA, PhD, STC Technologies, Inc, Bethlehem, PA

MIKE PEAT, PhD, LabOne, Inc, Overland Park, Kansas

TIMOTHY ROHRIG, PhD, DABFT, Osborn Labs, Shawnee Mission, KS

SAL SALAMONE, PhD, Roche Diagnostic Systems, Somerville, NJ

CARL SELAVKA, PhD, D-ABC, NYSDCJS, Albany, New York

MICHAEL SMITH, PhD, DABFT, Armed Forces Medical Examiner Office, Washington, DC

ROBERT WILLETTE, PhD, President, DuoResearch, Denver, CO

DR. BUSH: Good morning. My name is Donna Bush. I am with the Drug Testing Section, Division of Workplace Programs, Substance Abuse Mental Health Services Administration.

It is my pleasure to welcome you to the Washington, D.C. area, and to this meeting of the Drug Testing Advisory Board.

I would like to introduce Mr. Paul Schwab. Mr. Schwab is presently the deputy administrator of the Substance Abuse and Mental Health Services Administration of the Department of Health and Human Services.

In 1996 Dr. Schwab served as the acting director of the

Health Resources and Services Administration, HRSA, the Bureau of Health Professions, having served as the bureau's deputy director since 1988.

In earlier years he was HRSA's associate administrator for

policy coordination and was the executive secretary of several national public advisory committees, including the Council on Graduate Medical Education, the Graduate Medical Education National Advisory Committee, and the National Council on Health Planning.

He has authored a number of publications and is frequently

consulted on the areas of health, work force analysis, and the application of continuing quality improvement principles in public administration.

A Phi Beta Kappa graduate of George Washington University,

Mr. Schwab has also earned graduate degrees in economics and public administration from Indiana University and the Kennedy School at Harvard respectively.

He has received numerous honors and awards, including the

Presidential, Distinguished and Meritorious executive rank awards, the HHS Secretary's award for exceptional achievement, and the Public Health Service Superior Service Award. Mr. Schwab.

Agenda Item: Welcome.

MR. SCHWAB: Thank you, Dr. Bush, for that introduction. I promise you I will try to keep my remarks briefer than the introduction this morning, but I appreciate it. I do want to welcome you all, and good morning, here.

The Administrator of the Substance Abuse and Mental Health Services Administration, Dr. Nelba Chavez, was not able to join with us this morning, but I do send her greetings.

SAMHSA, which is the agency in which our program here is housed, is not always a household word, to say the least, in terms of government agencies.

It is very unique as far as government health agencies are

concerned in being really the only part of the federal government where substance abuse and mental health come together. Our agenda, working with the public, is quite broad.

In Dr. Chavez' absence, it is indeed my pleasure to welcome

you today to this meeting of the Drug Testing Advisory Board, the scientific meeting on drug testing of alternative specimens and technologies.

We have invited you here today because of our commitment to making our work places safe from drugs.

The statistics clearly tell the story. Seven out of ten

drug users hold down jobs. Economists say now that work place drug abuse costs us somewhere between $60 and $100 billion a year in lost productivity.

Whether it is hospital workers or truck drivers, mail

carriers or mechanics, the results are always the same. They are always tragic.

That is why our federal work place drug testing programs are critical and why this meeting is so important.

Just a brief word on the board itself. The board was first chartered in 1990. It advises the Administrator of SAMHSA and recommends new areas for emphasis or de-emphasis, new or changed directions, and mechanisms or approaches for implementing recommendations.

As part of this function, the board periodically reviews scientific areas on new areas of abuse and the methods necessary to detect their presence.

We consider this meeting, and you, all helping us to

maintain high standards for our federal work place drug testing programs.

That means we must enlist you as a resource as we develop

our knowledge of the scientific advances. We regard this meeting as an open and objective forum for the presentation of new technologies, and focus on the science, and be as fair as possible in reviewing that science.

In that regard, we are indeed pleased that so many

distinguished scientists have joined us today. There is a great deal of interest on our part in evolving drug testing technologies and alternative specimens, so that the determination of substance abuse can remain state of the science, and so that less invasive techniques or specimens can be used fairly, accurately, and reliably.

in closing, it is going to take all of us working together

to get drugs out of the work place, and to send a clear message to American workers that if they use drugs, we will not hire them.

Now I would like to present Dr. Joe Autry, the director of

the Division of Work Place programs, who will tell you more about this meeting. Thank you.

DR. BUSH: Thank you, Mr. Schwab. Now I would like to

introduce Dr. Joseph Autry. For those of you who don't know, he is my boss.

Dr. Autry received his bachelor's degree from Rhodes University with majors in chemistry and psychology. He received his doctorate of medicine from the University of Tennessee.

He completed an internship in internal medicine at Baptist

National Institute of Mental Health, St. Elizabeth's Hospital, model residency training program.

He was board certified by the American Board of Psychiatry

and Neurology in 1976.

Dr. Autry had an active career as a practicing psychiatrist prior to coming to the Washington area, joining the National Institute of Mental Health and becoming the director of extramural research, taking on responsibility for basic research, clinical research, treatment research and applied research.

He took on the challenges of directing the Office of Policy Analysis and Coordination for the National Institute of Mental Health, and then for the Alcohol, Drug Abuse and Mental Health Administration, NIMH's parent organization, for NIMH.

In 1990, Dr. Autry decided to move back into research, and

became the director of the Division of Applied Research at the National Institute on Drug Abuse, with responsibility for work on drug-free work place programs, work place policies related to substance abuse and AIDS in the work place, health services research, research on HIV infection and AIDS in the community.

He had oversight for the national laboratory certification

program, which certifies laboratories to conduct drug testing for federal drug free work place programs and the federally regulated industries.

Following the reorganization of ADAMHA in 1992, Dr. Autry became director of the Division of Work Place Programs for SAMHSA, the Center of Substance Abuse Prevention, with oversight responsibility for all the federal drug free work place programs and the national lab

practice of psychiatry, which he frequently describes as his link to the non-bureaucratic world, and an opportunity to constantly infuse his federal research and services responsibility with a continuing need for new knowledge to deal with the problems of mental illness and substance abuse in clinical practice. Dr. Autry.

Agenda Item: Federal Workplace Drug Testing.

DR. AUTRY: Actually, what I have said is that private

practice is frequently my link to sanity.

Let me just start by saying that it is real pleasure to see

so many friends and colleagues and other interested parties at this Drug Testing Advisory Board.

As Paul told you, the board periodically reviews emerging

drug testing technologies, alternative specimens and inclusion of additional drugs and drug classes, and has provided ongoing advice to the National Laboratory Certification Program and the federal drug free work program since 1990.

It is a key component in formulating or recommending any

those of you who know Mike, that has been a while -- that the board has formally reviewed the principles and criteria necessary for any workplace drug testing program to be forensically defensible.

Then, it is to evaluate all the emerging and current

technologies and alternative specimens, to see how they meet these principles and criteria.

If there are areas in which they are deficient, they are to

make recommendations on how they can meet these criteria.

I want to emphasize for all of you that the focus of this

meeting is on the science of testing technologies and alternative specimens.

It is not a meeting to advocate for any testing technology

or alternative specimen.

Let me tell you what the meeting will not do. The meeting

will not result in the recommendation of any emerging technology or alternative specimen for inclusion in the federal drug free workplace program, or the mandatory guidelines.

What it will do is to formalize the principles and criteria necessary for a forensically defensible work place program, and it will gather all the extant scientific data that is available for the current or emerging technologies and alternative specimens for future evaluation and recommendation.

What we will do today is we will start with an overview of

the forensic and scientific requirements for a workplace drug testing program, followed by an overview of the alternative technologies and specimens that are currently available.

We have asked Dr. Ed Cone, who most of you know, from the

National Institute on Drug Abuse, Addiction Research Center, and Dr. Yale Caplan of Quest Diagnostics, to present these two overviews.

As you can see from the program, each one of the essential areas for a successful workplace program will then begin with a brief overview of the principles and criteria necessary for that area, followed by a response from representatives of current or emerging technologies or alternative specimens.

These include urine specimen, hair testing, saliva testing, sweat testing and on-site testing.

The moderator of each session will give a brief overview.

The respondents were chosen by a scientist or other representative who works in the field of the testing technology or alternative specimen.

conflict of interest or bias in selecting the respondents.

The coordinators who chose these respondents are as follows:

for urine testing, Walt Vogel who works with the National Laboratory

Certification Program; for hair testing Don Kippenberger from Psychemedics; for saliva testing Sam Niedbala from STC Technologies; for

sweat testing Neil Fortner from PharmChem; and for on-site testing Dave Evans who works with the National On-Site Testing Association.

We are going to limit the overview remarks in each session

to five minutes and each respondent will be limited to 15 minutes.

Each presenter has been asked to finish his or her sentence upon hearing the signal indicating that time is up, and not to go on beyond that sentence.

Hopefully we will allow additional time for discussion and

comments at the end of each session.

Questions and answers are going to be limited to board

members and presenters. If members of the audience have questions that they wish to address to presenters, please write them on the four-by-six cards which you will be provided and pass them up front. We will make sure that the board members get them for consideration.

We have set aside Wednesday morning, April 30, for

presentations and comments from the public. You must sign up in advance, and I underscore that. You must sign up in advance to present or comment on Wednesday morning.

The order of presentation or comment will be determined by

the order in which you sign up. The time that each presenter has will be determined by taking the total amount of time we have available and dividing by the number of people we have signed up. That will be announced to you either late Tuesday or first thing Wednesday morning.

by the board, the meeting will adjourn, and there will be a press conference at the end of the meeting for any interested members of the press.

The board will reconvene sometime in mid-summer to consider

all the scientific information and deliberations, and to at that time make recommendations about the status of the existing or emerging technologies or alternative specimens.

Of course, we will make sure that all of you know well in

advance when that meeting will be scheduled and where it will be scheduled.

If this approach is as successful as I hope it will be, we

will schedule periodic updates and public meetings of the board to do this same thing again, so that we can constantly look at emerging technologies and alternative specimens and their applicability in the work force for the federal drug free workplace program.

With that, I am going to be quiet and let us turn to the

focus of this meeting, and that is the science. Thank you.

DR. BUSH: Thank you, Dr. Autry. We now have two major presentations. They are going to be full of great science and great overviews for us.

I have a biosketch for each of these scientists, Dr. Ed.

Cone and Dr. Yale Caplan.

We try to make these bios brief. But you know, when people have a long and illustrious career in science, they are not brief, they have done so much.

I want to read Ed's bio to you. It is a bit lengthy, but

bear with me, and consider all the information that you hear. I think that will better seat his presentation in his mind, the depth of experience that comes from it.

Edward J. Cone received his BS in chemistry from Mobile

College and earned his PhD in organic chemistry from the University of Alabama.

From 1971 to 1972, he held a post-doc appointment in the department of chemistry, University of Kentucky, under the direction of Professor Ellis Brown.

His work at the University of Kentucky was in the area of

tobacco chemistry.

In the summer of 1972, he joined the staff of the Addiction Research Center, National Institute on Drug Abuse, where he currently serves as chief of the chemistry and drug metabolism section.

Dr. Cone is a commissioned officer in the United States

Public Health Service and has the rank of permanent director grade, CO-

06.

He was appointed as a member of the Research Officers Group of the United States Public Health Service in 1989.

From 1977 to 1985, he served as a member of the adjunct faculty in the Division of Pharmaceutics and Pharmaceutical Analysis, School of Pharmacy, University of Kentucky.

Presently he is adjunct professor in the toxicology program, University of Maryland at Baltimore.

Dr. Cone has maintained his academic association, by

training four candidates for their PhD degree in forensic toxicology, by presenting lectures to medical, pharmacy, pharmacology and toxicology students on the chemistry and toxicology of drugs of abuse, and by hosting graduate students -- post-doctoral fellows and visiting foreign fellows -- in his laboratory.

In addition, Dr. Cone's laboratory has served as a training station for three World Health Organization fellows from Thailand and Malaysia.

He was a member of the editorial boards of the Journal of

Drug Metabolism and Kinetics, and Employment Testing, and is presently serving on the editorial board of the Journal of Analytical Toxicology.

Institutional Review Board for the intramural research program, NIDA, in Baltimore.

His major research interests are in the disposition and

metabolisms of drugs of abuse, and drug-induced behavioral effects.

Dr. Cone's early research led to the elucidation of two new metabolic pathways for the environmental exposure to drugs of abuse, and on saliva and hair testing as means of identifying drugs exposure has been recognized internationally.

Dr. Cone has presented his findings at numerous

international meetings, conferences and workshops.

Currently he is conducting clinical research on the

relationship of behavior and performance to specific levels of drugs in blood, saliva, sweat, urine, hair and skin.

Dr. Cone's research has resulted in the publication of

numerous book chapters, and over 200 scientific articles on the analysis of drugs in biological media.

Dr. Cone was cited by Science Watch, a journal which tracks trends and performance in basic research, as being the most highly cited author in forensic science over the period 1981 to 1993.

Dr. Cone was awarded the Irving Sunshine Award in clinical toxicology, in recognition of pioneering work in clinical toxicology in 1995, at the International Association of Therapeutic Drug Monitoring.

Officers Association as the CIPAC Career Scientist of the Year Award in 1996.

This award was to acknowledge an exemplary career of

pioneering research on the detection of psychoactive drugs in humans, and for the broad implication of discoveries to improve drug abuse, prevention and treatment. Dr. Cone.

(Applause.)

Agenda Item: Forensic and Scientific Requirements for a

workplace Drug Testing Program.

DR. CONE: It is truly a real honor to be here. As Donna overstated many of the things that I have done, I have been involved in drug analysis for many years and have met many puzzled expressions on the clinical ward when I have walked down. They have looked at me and said, you want to test what?

Thank you, anyway, for being here, and welcome to this conference. It is an honor to be invited to present this opening talk.

impose upon our society, by the epidemic of drug abuse that currently engulfs our nation.

The scourge of drug abuse robs us of many valuable lives, intellect and property that we can sorely afford to lose.

Among the many approaches that we can take to eliminate the

problem, the application of our unique scientific talents is the one that we in this room can most contribute.

It is really my belief that solutions must first begin with acknowledgement of the problem and good tools. I think that drug testing technology offers the clinician the tools to work on the problem, recognition of whether a person is using drugs, is under the influence or has been exposed to drugs. I think that is what we are here to talk about.

It is my charge to review briefly the forensic and

scientific requirements for a workplace drug testing program. That is a pretty big charge.

What I am going to try to do very quickly is go through and

talk briefly about the alternate matrices and, as well, many of my comments will be applicable to on-site drug testing.

I am going to spend most of the time talking about, first,

how forensic standards have been established through promulgation of the guidelines.

I will go through many of the specific requirements, now,

that I think we have evolved for forensic requirements in drug testing in the work place.

We are going to talk about how you go about validating a

specimen, an assay, and the need for quality assurance methods and quality control materials.

Finally, I am just going to spend a very brief amount of

time talking about the maturation and how technology evolves, and how this technology affects public health.

I want to start with this quote from Walter Haines in 1904 who said that there is scarcely a part of the body that may not be examined with profit.

Clearly, what he means is that you can find out a lot of

information from drug testing.

This is a slide that I have used many times now in talks

where I have illustrated the luxury and richness of the availability of different biological fluids in tissues for drug testing.

Many of them we are going to be focusing on today are

specific ones of sweat, hair, saliva, as compared to urine and on-site testing.

There are other possible tissues that you will be hearing about in the future we are hearing about. Commercial methods are already available for marconium.

We are still working on how to drug test for sneezes, but there are a number of things that we can get from alternate matrices.

is unique information, surely, in different biological matrices that you can't get from urine or blood.

There are other advantages that one could possibly get.

specific specimen within a few days that represents almost the identical specimen, something you can't do, of course, with liquid samples.

Some of the other advantages, quite often now in urine we test for inactive metabolites. In different alternate matrices you often find the parent drug.

It is much more satisfying when you are trying to interpret what is happening to a subject to know that you are testing actual active drug rather than an inactive metabolite.

Some of the matrices also may exhibit greater stability than urine, lower disease risk, easy collection, shipment and storage.

through these days in terms of what the advantages are there.

There may be disadvantages as well. You have to consider

the difference in matrix as you collect and begin to develop tests for different biological specimens.

You have to consider, of course, the stability of the

analyte, what the analyte is, the stability, how you go about getting the analyte out in a pure form, what form of assay is going to be

developed.

A very important function is how are you going to develop QC materials that go hand in hand with the development of the assay that are appropriate for that specific assay.

There are major differences. Urine, of course, is mainly an aqueous matrix. Saliva offers some advantage, in that it is somewhat easier to collect and a little bit less embarrassing to collect.

It is also an aqueous base, but it has other things like mucous, that also affects things like how easy it is to pipette a specimen. So, it is a little bit more difficult to measure saliva.

means of adsorption onto some sort of collection device.

You have to worry about how do you get the drug off the collection device. You have to worry about absorption.

You also have to worry, if you are using a collection device

that applies to the skin, about environmental contamination, both before you put the specimen on, the patch on, and during the process of taking the collection device off the skin. Environmental contamination is certainly a possible risk.

Specific advantages, we have mentioned already a little bit about hair. It is a very different matrix. It is a dry, protein complex.

So, it presents its own problems in terms of how do you get

the drug out of the complex as well. Of course, there are risks from environmental contamination.

There is the issue of what effect does melanin have, or what

is the effect of melanin on the type of drug and the amount of drug that is present.

So, there are major differences in the matrices that we will

be talking about throughout the conference. We want to look at them objectively, fairly, and consider what they offer in terms of new information, and advantages over existing technology.

Now, in terms of what are standards, we have seen over the

last decade an incredible evolution toward where we are today in terms of forensic drug testing standards.

President Reagan issued his Executive Order in 1986, 12564, where he stated essentially that he wanted to achieve a drug free federal workplace.

That really set the standard of where he wanted us to be. Over the years we have certainly established some specific standards.

technical guidelines for drug testing programs, and those standards have been published and updated.

They have been put into effect and really become the

expected standard for forensic drug testing over the years.

Not only have federal agencies adopted these guidelines, but

so have DOD, DOT, states, as well as private industry have come to expect the quality of drug testing that was established through this program.

This is a quote about where we have come to in terms of

society's acceptance of drug testing. It simply says:

"Over the past decade, incumbent presidents and Congress

have not only authorized drug testing by public and private employees, but have required or encouraged it in some work places...

"...the policies of previous administrations, the

legislature and judicial systems have all contributed to establishing drug testing as a major component of the nation's `war on drugs'."

what context we are trying to apply them, in this specific instance the workplace setting.

It is a very unique setting. It is a setting where a single test result is generally the only piece of evidence involved in hiring, forced treatment, or firing of employees.

So, it is very important that we place the highest degree of expectation of accuracy on our drug testing processes.

The quality of the tests, we know, is only as good as the

sum total of the entire process of collection, the testing process, reporting and review by medical review officers.

Now to those standards. There are a host of very specific

standards laid out in the guidelines. I would like to start out by saying these are the guidelines for urine drug testing.

I fully understand that the matrix that we are talking about

is different and the guidelines may not apply to the matrix that we are talking about in this conference as well as on-site testing, but they certainly provide a place to start.

They are the expected standards for forensic testing as it

exists today.

We are going to go through very quickly and just talk about some of these different sections of forensic workplace drug testing and how they should apply.

When we are talking about drug testing, we first have to identify specifically, exactly what happens to the specimen during the entire course of collection, handling and storage of specimens.

That has to be clearly stated in a standard operating

procedure document. This document is the legal description of what actually happens to the specimen. It has to be an accurate updated version which includes all processes in the receipt, collection, handling, testing and storage of the specimen.

It should describe in detail how a chain of custody is

applied to these processes. It should describe how quality control and quality assurance practices are implemented at each step along the way.

personnel. It should have considerations of what is needed in the facilities and how it is organized, and an entire detailed description of the other related issues like instrumentation and processes for reporting. This has to be a complete document.

There are considerations for how the test facility should be organized. In urine drug testing, there is the requirement that screening and confirmation be performed at the same site, that security be given the highest order of magnitude for consideration, that forensic work be generally separated from non-forensic work, and there be limited access to the drug testing areas, to specimens and to records, and there be a general infrastructure of support.

Chain of custody I couldn't say much about the importance of

an adequate chain of custody. This is just a definition, one definition, which says:

Procedures to account for the integrity, identification and security of specimens by tracking their handling, storage from of collection, to the final disposition of the specimen.

This is the legal document that tracks and identifies how it

was collected, when it was collected, how it was shipped to the laboratory, what the laboratory did to it and the final disposition.

It is an essential document that has to exist in the context of workplace drug testing.

The requirement, of course, for workplace drug testing is

that each and every test can potentially result in litigation, and every step along the way has to be defensible.

The chain of custody covers collection, as I said, transport

to the laboratory, what is happening in terms of accessioning and processing and testing throughout the laboratory, all the way through to the final reporting of the result.

Security at the collection site is also an important consideration, how do you collect the specimen, how do you identify the specimen, how do you get it into some form of container that can then be either tested or shipped to the laboratory.

These are all considerations that we are very familiar with,

but they have to be adapted to the new types of specimens.

In some cases they may be a challenge, but it requires that

we have specific methodologies for assuring that the specimen belongs to the subject or the employee, that it not be tampered with, that it not be adulterated, that there be no switching.

So, these are important procedures that we have to think

about when we are designing collection processes.

The security at the test facility, as I said, is absolutely

of the highest regard. Access must be restricted to authorized personnel.

Security procedures must be in place, both during and after working hours. There is the highest level of security accorded to both specimens and, frequently forgotten, those important records.

Security has to be considered when you are designing your

computer systems, the laboratory information system, as well as documentation of the processes that are used in security.

Many laboratories are designing their facilities so that

frequent tours -- there is always somebody wanting to take a tour of a laboratory -- so that those tours are performed so that they can be performed without having the people on the tour go into the test facility.

They are actually designing laboratories -- this has been

done for a number of years now -- so that you can take the tour and walk around the outside of the test facility and look in through usually protected areas.

The test methods themselves are usually composed of a

screening test, which has traditionally been immunoassay as a requirement for urine drug testing.

The screening test is followed by a confirmation test.

There is a requirement, of course, that the confirmation test be based on a different chemical principle or a different chromatographic principle than the initial screening test.

This has also been traditional GC/MS. There is no reason

why it can't be LC/MS or some other acceptable substitute.

A few words about the screening test. You have to, when

designing your initial testing procedure, take into consideration, of course, the differences in the matrix, how you are going to handle that matrix, how you are going to extract, if necessary, and how you are going to apply your assay to this rather unique, different biological specimen.

There is a need for at least some form of semi-quantitative response, and of course you have to define the operational parameters that are needed to assess the performance of the assay, sensitivity, specificity, accuracy, precision and so on.

You certainly have to identify the other materials that may cross react, potential interferences.

You have to make sure that there are available reference materials. The QC issue is a real problem sometimes with new matrices, and we will talk a little bit more about that.

A real trouble spot is establishing a new cut off for a biological matrix. This is probably one of the most challenging things, once you have developed an assay for a specimen, is to come up with the appropriate cut off concentration.

There are very good, solid methods, scientifically based

methods, for determining what optimal cut offs are with the use of receiver operating curves, and the like.

Other considerations in the screening assay, you must think about what is going to happen after the screening is done, and consider the confirmation assay.

You need to approximate, to some degree, the analytical sensitivity of the confirmation method. You don't want an assay that is far more sensitive than your confirmation assay. You certainly don't want one that is less sensitive.

So, you must think about the development of the screening in

the context of what the confirmation method is going to be.

There is certainly a need for sensitivity. Then

specificity, we said this already but I mean this in a clinical sense, the clinical definition now of sensitivity, which means the ratio of true positives plus false negatives.

So, you want to maximize the identification of true

achieve this goal, where you maximize true negatives and minimize false positives.

There is some need for linearity around the cut offs so you

can have good precision. Finally, of course -- we have said this already -- the consideration of what the cut off is going to be is going to be one of the major decisions that you are going to be facing.

The confirmation assay is also an issue where you have to consider -- again, even more important, you have to identify now a way to get the drug or the analyte out of the specimen, generally, if you are going to use the combined methodologies.

You have got to get it somehow into usually a liquid matrix.

So, you have got to consider, how do you get the analyte out of your

unique matrix and into a form that can be analyzed by one of the combined technologies.

Now we insist upon quantitation and accurate quantitation,

and of course the other performance parameters, including specificity, accuracy and precision.

You need to evaluate and make sure that there are no

interferences, and define the LOD LOQ linearity and so forth.

Again, we get back to this issue of pharmacologically

relevant cut off. How do we do that? That is usually somewhat problematic.

This is a slide where I have sort of tried to illustrate the overlap between the two major considerations in establishing a cut off concentration, the pharmacological issues versus the analytical issues.

you are trying to establish a cut off concentration.

You have to select a cut off or a concentration that can be detected by your assay. So, of course you certainly have to have the sensitivity from your requisite analytical assay. You also have to know what is there and how to detect it, and in what concentration in that particular biofluid are you going to find drug.

You also have to worry about setting the cut off

concentration such that you can distinguish, we would hope, active use from potential environmental contamination.

You have to take into consideration other issues like, are there going to be major influences from route of administration or passive exposure and so forth.

So, what I have tried to do is illustrate this by throwing

in an extra slide here. This is sort of like selecting a cut off where you have to have really sound scientific reasons for selection, when you grab the tiger by its tail. Otherwise, he might turn around and bite you.

What I tried to do here is illustrate that I think this

company has done a pretty nice job of selecting a cut off that is well removed from the possibility of environmental contamination.

The noise from their assay system, passive exposure, contamination carry over and so forth, this looks like they have done a pretty nice job of establishing that cut off.

Another company didn't quite get the message. You can see

we have a problem here. I would characterize this situation as the company being somewhat alligator challenged.

We have a lot of ground to cover and I am going to go

through these quickly. Quality control we will spend an entire session on.

It is absolutely essential that the appropriate reference materials be available, and that you somehow devise a method whereby you can supply and utilize quality control materials that simulate or are very close to real clinical specimens.

That has been a real problem with many of our alternate

matrices, is coming up with appropriate QC materials.

There is an entire science behind developing these

materials. But it is a very important consideration if you are developing an assay for a new matrix or even an on-site test.

I would make a quick comment about on-site testing. There is quite often a QC check on the on-site test device.

It is my contention that most of these devices are not actual QC controls in the traditional sense of being a positive or a negative.

They are very good QC checks for the operation of the assay

and the reagents. But they do not fit the traditional definition of a control.

So, in addition to those very nice checks that are built

into on-site devices, you still need appropriate control materials to be run, both in an open and a blind manner.

You need to assess the performance of the assay and of

course the accompanying quality assurance issues.

Reporting, the guidelines require that reporting results

only go out to medical review officers. There are good reasons for that. We will talk a little bit about that in a minute, that prohibit telephonic reporting.

Again, security. The form of reporting must be secure. Certified copies are sent to the employers -- I should say MROs. The standard forms really simplify things as well.

Storage, you have to consider the requirement for not only protecting the specimens and the records with secured storage, but then they have to be retained in forensic testing.

The standard is for positive specimens for a year, and

records for at least two years.

Personnel. Personnel are probably your most important

aspect in laboratory operations. They have to be trained in forensic drug testing methods.

You have to have training documented for all your personnel.

As you go up the chain, the documentation needs increase for your

supervisors and your certifying scientists, as well.

There must be very good personnel records throughout that document the training of your people in the laboratory.

The facility or the lab director is the ultimate person in charge, must be involved in day-to-day operations, and must have adequate training in forensic toxicology to serve in this role.

want to protect individual rights at the same time.

There are a number of ways to do this; by employee ideas instead of names, strict reporting rules, reporting security, and the use of MROs.

I want to say a word about MROs. They have really served an extremely important component of the urine drug testing program that is outlined by the HHS.

Their job is to review routine custody and control forms and determine whether the test result looks like a valid test result of not.

positive, and who may have a valid reason for testing positive.

They can intercede for those positives who are legitimate

and make sure that they are not accused of being a drug user because of a legitimate excuse.

They have access to medical records. They can order

retests, and they can protect the confidentiality of the medical records.

So, this is an extremely important function that the MRO serves. I can tell you that they have prevented several mistakes from happening over the years in the drug testing program. They have served a very important function in this role.

Finally, in the accreditation area, there is a need for consideration of accreditation, whereby an independent body reviews the drug testing.

They can utilize performance testing, inspections and remediation. Hopefully there are enough teeth in the program to allow for those labs that are not meeting standards to have their certification suspended or even revoked.

I am going to move and change my focus and go through

quickly now the issue of how do you validate an assay.

I am going to turn from forensic requirements and talk

quickly about what validity means.

I think one of the simplest and most elegant definitions of validity of testing has been defined by Chuck Oredetsky as the ability of an assay to detect a drug or its metabolites in biological fluids following human drug administration.

This is a very simple and elegant explanation, but it encompasses a variety of issues that one must consider, including the things that we said already -- sensitivity, specificity of the assays, the metabolic and pharmacologic variables such as dose, route of administration, concentration of the drug in the biological fluid, the pH and intersubject variability and absorption, metabolism and excretion.

Not only do you have to validate your analytical assay -- we spent enough time on that -- but you need to perform pharmacological assessments.

These are best done with clinical dosing studies. .You have

to ultimately apply the assay in a real setting to determine how it works.

You need to define what detection times are and ultimately

build a scientific base of what the testing positive means in terms of results.

We need that scientific base to be able to provide interpretation of positive and negative specimen results.

The validity has to go through a variety of components, of

understanding what the pharmacology of the drug is, how it is distributed, and what is distributed into the different biological matrices, and most important, for interpretation, we need to understand time course and the relationship between concentration of drug in the matrix and relationship to dose.

We have to worry, of course, about the issue of multiple

dosing and accumulation in tissues.

This is a slide that I put together that I think reflects my view now about how technology can evolve over time.

The development and improvement of a new technology does not stop when the test becomes available for use in the work place.

At this early stage, the scientific and legal challenges

have just begun. There will be continual scrutiny by the forensic community of an assay's strengths and weaknesses over the entire lifetime of a product.

Legal challenges are likely to be made based on its use in

the work place.

New applications are often discovered in products that were

not imagined by the original designers. Important weaknesses may also be identified that require adjustments in product design or process design.

Ultimately, inferior products fall by the wayside, while

good products get better.

The development of a new test, its commercial introduction, application and use by the public, and general acceptance by the forensic and legal communities can take a variety of courses.

Many new methods may never make it to the status of general

use and acceptance. How a technology evolves is dependent on many factors.

Frequently, the philosophy of a company that seeks to market

a technology is an important factor in its evolutionary path.

Scientific acceptance general begins with publication of studies in peer reviewed journals. These studies general establish the assay's performance and describe possible new applications.

As the number of supporting applications build, a product

may attain a comfort level of acceptance within the scientific community.

In a few cases, FDA review and approval provides additional assurances of adequacy or comparability to existing products.

By their very nature, new products will face a tougher

challenge in facing broad acceptance and use.

This is the final slide. It really reflects how I feel

from design to marketing, developers should evaluate how their products are viewed and used.

Ethical companies strive to produce companies that employers and employees trust and rely upon to be fair and accurate.

At the same time, employees have the right to expect that

their test results will be kept confidential, and that the intrusion into their privacy will be as minimal as possible.

Fairness and due process must be incorporated into the

program, and there should be opportunities in which the accused can be evaluated to determine if they have legitimate explanations of test results.

Overall, the important goal of keeping the work place environment drug free and safe should be balanced against protecting basic individual rights.

The creation of accurate test methods can be an important contribution in advancing the public good and health of our people and our nation. Thank you for your attention.

(Applause.)

DR. BUSH: Thank you very, very much, Dr. Cone. It is now

my pleasure to introduce Dr. Yale Caplan.

He received his bachelors degree in pharmacy and a PhD in

medicinal chemistry from the University of Maryland at Baltimore.

After a year as a research associate and supervisor in experimental toxicology at Sinai Hospital in Baltimore, Dr. Caplan came to the Office of the Chief Medical Examiner as an assistant toxicologist, and served as the chief toxicologist and scientific director of the State of Maryland's alcohol testing program.

Dr. Caplan is now director of the National Center for

Forensic Sciences and director of forensic toxicology for Quest Diagnostics, Incorporated.

Dr. Caplan has been very active in his profession. He is president of the American Board of Forensic Toxicology, of which he is a diplomate, director, and was secretary/treasurer.

He was the president of the American Academy of Forensic Sciences from 1987 to 1988, previously holding other offices, including chairman of the toxicology section.

He was the recipient of the Academy's 1989 Rolla N. Harger

award for outstanding contributions to forensic toxicology, and the 1996 distinguished fellow award for a lifetime of service to the forensic sciences profession.

He was the president of Society of Forensic Toxicologists in 1981, and is a member, and was chairman, of the National Safety Council's Committee on Alcohol and Other Drugs.

He was chairman of the Maryland section of the American

Chemical Society, and recipient of the 1994 Maryland Chemist Award.

Dr. Caplan is adjunct professor in the department of

pharmaceutical sciences at the University of Maryland School of Pharmacy.

He has served as clinical professor in the university's school of medicine, director of forensic toxicology in the universitywide program in toxicology.

Dr. Caplan has contributed over 200 chapters, papers and

abstracts to the scientific literature. He serves on the editorial boards of the Journal of Forensic Sciences, the Journal of Analytical Toxicology, and Forensic Science Review.

Dr. Caplan was a recipient of the 1986 distinguished service award of the Maryland State Alcohol Control Administration, and was a member of the Governor's Commission to study deaths resulting from building fires.

He is the director of national scientific services and

serves as an advisor of attorneys regarding alcohol and drug testing issues, and has regularly testified as an expert witness in court.

He is a member of the Substance Abuse and Mental Health

Services Administration Drug Testing Advisory Board, and an inspector

and an instructor for the national lab certification program.

He has also served as a consultant for the Department of Transportation Office of Drug and Alcohol Policy and Compliance, and the National Transportation Safety Board. Without further ado, Dr. Caplan.

Specimens/Technologies.

DR. CAPLAN: Thank you, Donna. She left out the one thing,

that she was one of my students. I think she was afraid to admit that here.

It is a pleasure also to be here this morning. I understand

why Dr. Cone wanted five more minutes. It is just so Donna can get through these introductions.

Here we are after a number of years with work place drug testing, asking many questions. I have been asked to sort of give an overview this morning about some of the various technologies and things you are going to hear in greater detail.

I am going to talk a bit about what the core subject for the several days will be, alternative technologies and some of the factors that are supporting just general information about what they are and some notations about them.

First, there are a few things to focus in on this

conference. Dr. Cone asked you some of them.

We are going to be looking at, I think, research. Good

researchers must doubt even the most widely accepted premises.

If we take this as a guiding light for the rest of the week, although I am going to show you some general information that might show some preconceived ideas, I think the idea here is to go through the next few days with an open mind.

Second, we have to transfer scientific information in a

credible manner. The fact that there are various points of view, communication and the ability to both transmit and understand these scientific principles is somewhat paramount.

If we think these things -- and if you remember nothing

else, there are these two cartoons and I have three at the end -- you can figure out what is in between.

In general, though, we need to look at a variety of things and Ed has already talked about a few of them.

Also, let me point out that all the slides I have are in the handout. Some of them I may not use in the interest of time, or go through them fairly quickly.

These are the specimens that we are here to talk about. I

have blood on this slide. It is not one that we are going to be talking about, but it is sort of a point of comparison. So, there is some information on the handout, looking at some of the same characteristics for blood.

The characteristics that were looked at, or need to be

looked at when you consider these things, include physiology, pharmacology, which drugs can be detected in the medium, the various collection methodologies, testing methodologies.

I am going to talk about what the current uses are, and how

that may change, the accuracy of testing, scientific acceptability, litigation, risk, cost, advantages and disadvantages.

So, within the handout, there is a characteristics slide on

each one of these elements for each of the types of technologies, and I am going to be talking a little bit more about each of those.

There are some caveats. You have to have a disclaimer

before you do any of this before such a wide group.

I am going to try to give you a very rapid overview of the

state of testing. What you are going to hear and what is in the handout are some contemporary notations that are the result of a report that I, with Dr. Cone, prepared for HHS at the end of last year.

It has the same ideas coming along as to where these things might be going, what do we know today, what are the various thoughts.

So, the idea is that this is to serve as the basis for the meeting going forward. I am going to make the disclaimer that there are some statements in there that a lot of people may disagree or not agree

upon, and others may agree very favorably with.

The idea is that they are presented as one liners, as

thought processes, as thoughts that are held by some or many people in the relevant community. So, there are some caveats in what we do.

have some different characteristics.

We are well aware of urine, production by the kidneys, the

volume and the fact that there is a stabilization of that and a validation following creatinine and the ability to eliminate creatinine.

fixed growth rate. It is going to be around for a much longer period of time. It has a crystalline structure. It can deteriorate, also, with age.

Blood, by way of comparison, is really the most dynamic of

all the specimens. It is not used, or has not been used for a number of reasons.

If one wants to make assessments about intoxication,

impairment, cause of death, blood is the fundamental specimen.

It is stable in the body. Its volume changes very slowly. Therefore, it gives us dynamic representation of what is going on, has a fairly fixed volume in the body.

Sweat is produced by eccrine glands. Its production,

though, is highly dependent upon environmental conditions.

While it may follow or parallel a variety of drugs that are excreted, the ability to collect sweat has been a problem until recently.

It is mostly water. As you can see, the blood has got a lot

of protein substances, and the urine has a lot of other substances, and is also mostly water, but sweat is almost 100 percent water.

The last of the ones that we are going to talk about --

saliva -- is secreted by various glands in the body.

Its flow is dependent upon neurotransmitter stimulation, and

the flow does vary widely.

Saliva composition is dependent upon flow. If you want to

come and pair off these specimens, saliva is one that might parallel blood in some regards and is the closest one that might be utilized for determination of impairment purposes, whereas each of the specimens -- I think that is what the purpose of the rest of the meeting will be -- may allow us to do something different, to ask and answer a different question.

In science, as you all know, it is not the information that

you get, it is the question that you ask. If you ask the right question, then the information that the test can produce can be used validly.

If you ask the wrong question, it can be misinterpreted.

So, in the end, asking the right question and getting an answer that is useful is the goal of what we are all going to try to do in the next few days.

I am going to now kind of quickly go through the various

specimens or technologies with a bent on comparing them to each other along the lines that I mentioned earlier.

The drugs that can be tested in urine, we have extensive knowledge, as you all know, regulated tests. There are the five major analytes with the a couple of other drugs like 6-acetyl morphine.

Other drugs, the NRC and the military have included

barbiturates, benzos, LSD from time to time. In the non-regulated arena, barbiturates, benzos, propoxyphene, methadone, methaqualone and LSD have also been included.

So, the drugs which are detectable have been clearly

identified, and you will find that there are many similarities throughout the various matrices.

With laboratory based collection for urine, we rarely see observed collections. We are generally dealing with non-observed collections. It is the common practice.

There is a concern about limiting adulteration or substitution. We do collect about 60 milliliters of a specimen into a particular container.

We are using, as Ed described, custody control form

documented processes, and we are commonly now today using split specimens.

I want to point out also, before I go further with this,

that this might be a little more difficult to visualize here.

The best way to look at this might be as a matrix when you compare them. But it doesn't really fit too well on slides, to put

based urine, again, as you know, regulatory testing, screening by enzyme immunoassay followed by GC/MS confirmation is mandated.

Non-regulated laboratory testing, they follow the same methodology, or it may be different. A confirmation may or may not be included out of the regulated arena, and adulteration testing is possible.

There is much to be heard of concern with adulteration of

specimens as we go forward with new technologies.

The current uses for laboratory based urine testing is

widespread in the implementation and function of the current drug testing programs.

It is also used extensively, and has bene used for many

years prior in treatment in correction programs.

The accuracy of this testing can be described as

essentially, with the controls and situations with MROs and all that have been put in place, regulated testing is essentially 100 percent accurate.

We have extensive, in regulated tests, we have extensive PT programs available, multiple types, that have maintained a degree of credibility in maintaining the accuracy.

Non-regulated testing may be equally accurate. However, there is a choice as to whether to include various mandatory requirements or not.

Procedures utilized, screening without confirmation does occur. When in that arena, they are subject to some false positives.

based urine which can be highly accurate if properly practiced.

It is practiced very widely inside and outside this arena, where you might have some diversion from that kind of activity.

we have a vast body of scientific literature addressing all aspects of urine testing.

I guess 10 years ago when a lot of these things started one would have said, urine is just not that important and we don't need to know that much about it.

Most of the previous forensic work was based on blood and

tissues and other specimens.

I have to say, in the last 10 years we have done an awful

lot of research. Every day, it seems like every couple of months a new technical scientific issue arises with regard to a specimen that maybe 10 or 15 years ago we would have almost discarded, as being relevant and having a lot of science surrounding it.

Properly conducted and evaluated urine tests are accepted

and effectively utilized. That is the key underlying statement for what is going on this week.

Then an ultimate question is, are there other technologies

or situations that can be equally accepted and equally effectively utilized.

This surrounds also the fact that we have passed the legal scrutiny with regard to urine testing, that has been generally upheld in various court cases, and urine testing has been documented.

In the many years that we have been doing it now, it has not been adversely affected.

In a summary of the urine specimen, here are some of the

advantages to using laboratory based urine. Drugs and metabolites are highly concentrated. That is why we use the specimen in the first place.

There is a high propensity to find and detect these

substances with conventional techniques. The drugs, particularly through their metabolites, are there.

The specimen can be obtained without physical risk to the

donor. The main reason that blood is not widely utilized is the concerns for obtaining the blood specimen.

There is an extensive scientific basis now for the testing

methodology. It has been utilized in many labs and documented extensively.

PT testing is liberally practiced. Results are frequently

and regularly accepted in court.

As Ed had pointed out -- this is one of the over-riding

things in looking at the other technologies -- we do have uniform testing criteria and well established cut offs.

We may want to change them for different reasons, but they

have been well established and are documented.

We have methods which are of a commercial nature which are easily available so we can utilize these. We do have tests that are FDA approved as part of this process. There are many advantages to dealing with urine.

Some of the disadvantages, though, and things that might be

of concern, is that the detection period is very short, two or three days.

Recent research shows that for some of the drugs that may be even less than we had originally anticipated, depending upon dose.

There are no dose concentration relationships. We can't say

a great deal about exactly when the drug was used or what level of impairment there may be, if that is desirable.

Drug concentrations are greatly influenced by water intake.

The amount of water that an individual ingests, particularly for certain drug classes, will significantly affect the deductibility of those drugs.

In your laboratory based urine, we do have a relatively time consuming process, a laboratory based process with extensive laboratory costs.

You have to build a laboratory, you have to have a lot of

personnel, and there is a fairly large cost involved with doing it.

Those are some of the advantages and disadvantages of doing

the urine laboratory based.

As the first other modality we could look at is on site

testing. We have a number of drugs which are fairly similar.

Most of the common analytes are also available and we are

reasonably certain that, if there is a need, other ones could become available.

This methodology is now single drug kits for single drugs

one at a time, multiple kits and various combinations thereof.

Some of the kits, because of the clinical application, do

include one drug class anyway, tricyclates, which are not generally included in abused drugs.

This technology includes all the drugs and can probably be

easily modified, because you are going to end up using the same antibodies and things that you use for other laboratory based urine testing, and just put them in kit form. So, the drugs would be similar.

difference here is that we would need to consider the acceptability of having results readily available to the collector.

In fact, if that is deemed acceptable, then there is

probably going to be no difference. That will happen. We know that if we do an on-site test, that result is going to be immediately available.

devices simultaneously. So, there are a lot of novel items in the technology which could be very useful with on-site technology.

Right now split specimens are not common. Again, that could

be altered very readily if necessary.

So, we have a collection methodology which is similar to the laboratory based, with the exception of the identification of the various subjects to the collector.

The methodologies are, again, basically immunoassays. Some have -- and I think Ed mentioned this -- built in controls.

We do have to consider, as we go forward, how you would really quality control such a program. There is some controversy, I think, about the built-in controls, actually only monitoring the reagents as opposed to monitoring the process.

There is minimum space required, though, compared to a

laboratory.

Some of these processes are temperature dependent. While

you use these kits, the temperature in which they are used could affect the timing and the outcome.

At least right now adulteration testing, which would still

be difficult, in the laboratory based there can be other things done, other tests with the specimen when it gets to the laboratory.

The kits themselves, at least the way they are currently configured, do not lend themselves toward any adulteration testing and we will have the same types of specimens, whether it is laboratory based or on site, and the same propensity for alteration or adulteration of the specimen. So, that would be an issue.

Current use, fairly limited for work place purposes,

although there are some mostly used in treatment and correction programs, and certainly used extensively in hospital emergency rooms and other arenas outside the work place arena.

Accuracy, some comments on accuracy. HHS regulated and

common non-regulated analytes are all available.

Adequate procedures are not developed to ensure reliability.

So, right now we do have kits out there. While most of them are FDA

approved, although some in the forensic arena might not require FDA approval, there is some lack of uniformity amongst the products.

There is a concern, I think, about the end point

determination being subjective in nature. When you read these things, I think all the kits except one read a positive by the absence of color. Color goes away.

When using kits, one has to be concerned about visual

acuity, color blindness. The kits that are out there today have a lot of variability in their end points.

It is not that this isn't correctable. I think this is due,

at least at this time principally, to the fact that we have a situation in which there are not rules.

there is a lot of variation in cut off concentrations and how those concentrations actually operate.

So, we have a group of devices out there which we will hear

a lot more about, which require principally more individual concern as to the assessment of the end result, and some variability as to the concentrations that are detected.

With on-site testing and scientific acceptability, they have not generally been used for forensic purposes. They are not supported at this time by any real court experience, and there is a relatively limited body of scientific literature.

That is not to say that there is not a large body of

scientific literature about urine in general, but about the actual application or applicability of the various test kits to these processes, there is limited publication.

There is obviously some publication on the initial

evaluation of the kits in comparison to their deductibility in a patient population, but that is not too extensive at this time.

The summary there, the advantages of on-site urine are

fairly similar in many respects to urine in general.

Laboratory based, drugs and metabolites are highly

concentrated, specimens can be obtained without physical risk.

The testing can be performed with non-scientific personnel.

That would be an additional advantage to this technology.

Minimal space and resources are required. That would be

another pretty distinct advantage and we don't have to build a laboratory to do these things.

The other major advantage are the rapid turn around time of

in a certain forensic arena, are approved by the FDA.

So, we do have a number of modalities which would make this very attractive.

Some of the disadvantages of on-site urine, again, are

similar to urine in general -- the detection period, the dose concentration relationship, the water relationship.

The other major ones on the bottom, the presumptive results

may be acted upon inappropriately. So if one is to use this in a regulated structured arena, there have to be means to ensure that presumptive results are dealt with appropriately.

There is a possibility to compromise objectivity, from the collection process, since the individual doing the test may have access to the result.

The scientific basis, it is not as definitively established; that is to say, the actual use of these kits around cut offs, et cetera.

purposes. Uniform testing criteria cut offs have not been established, although there are a lot of claims that there are various cut offs, that they meet certain criteria. Again, these have not been uniformly decided upon and tested.

There is, essentially, no performance testing program

available, except that which a particular manufacturer might offer. There is no centralized performance testing program in on-site testing.

and the possibility of testing for drugs is hair.

Again, a wide variety of drugs have been detected in hair.

All the common drugs of abuse, including heroin, 6-acetyl morphine, actually a preponderance of the ability to find the parent drug in hair has been demonstrated.

Other drugs, metals, over the time period have also been

detected.

So, the methodology and the various drugs have been

established and shown to be present in hair. So, we can find the same drugs we are interested in, in different varying amounts.

Collection methodology as compared to urine would be substantially different. We are cutting hair usually at the scalp surface, at the vertex at the back of the head, and you can measure and document the length from the root to the tip out.

The hair can be stored in protective containers. It can readily be shipped to laboratories. Hair from other parts of the body can also be utilized.

We have a large source in the human body of hair. We have

the ability to detect the drugs. We have some ease in getting the specimens from the collection sites to various laboratories for testing.

often present, which is pretty different from urine situations.

Few laboratories are currently available that routinely test hair. Again, if there is an acceptance of this technology this could rapidly change.

Specially adapted amino acids are currently used for

screening, GC/MS for confirmation.

One of the major points, I think, for hair testing is that

it is laboratory based and we may need more sophisticated equipment to

really go to appropriate sensitivity levels, as has been demonstrated by the need for tandem mass spec in order to really be able to appropriately detect cannabinoids.

So, the conventional laboratory that is doing urine testing would have to, to be doing hair testing, would have to be a little bit

more sophisticated and some more costly equipment involved.

The methodology is essentially there and I think it has been extensively looked at and adapted in the arenas that are practicing it.

employment testing. There has been limited use in the work place, although some.

There has been some utilization in other investigations,

particularly death investigations where other specimens are not available and prior drug exposure is an issue. It has been used in other forensic investigations. There are possibilities for use in various arenas with hair.

Accuracy, with regard to hair, there are currently no proficiency testing programs that exist. There have been some attempts at round robin testing with the limited laboratories. I think there are some external services that provide a type of specimens to laboratories performing this.

So, there is an attempt at that process, but there are no

structured proficiency programs at this time.

There are some variations in analytical results. The matrix itself is not uniform. One could argue there is a benefit in an attempt to measure time with long enough hair.

On the other hand, if you take a random sample or a sample

from a fixed portion of the hair or fixed length, as compared to other places, the matrix is somewhat different, the deposition may be different. There is a lack of clear uniformity there.

There have been some NIST surveys -- this round robin --

where some false negatives and false positives have been reported.

While this technology is clearly -- while it clearly has possibilities, there is clearly some concern from this point of view.

ethnic bias has been of concern. The feasibility of marijuana testing is somewhat uncertain depending upon laboratory capability.

The advantages of hair, longer estimate of time of drug use.

That is a distinct advantage. Ease of obtaining, storing and shipping

of specimen, low risk of disease transmission in the handling of samples. In the second specimen, one can go back to the hair and get another specimen and test it.

Disadvantages of hair, inability to detect recent drug use.

It takes a while for the drugs to go into the hair. So, if it is very

recent use, that is an issue.

The bias of color, ethnic origin and sex needs to be

resolved or dealt with. The limited number of laboratories able to do this service is a disadvantage at this time.

Also, there is the possibility of an environmental

contamination for some drug biases, lack of PT, and these procedures are not FDA approved.

I have in the handout -- I am going to skip through this.

This is just for comparison, some points about blood.

Blood is not really one of the things we are going to be

looking at. So, I am going to skip through these. I put them in there mostly because they were in the report and they would allow you to compare some of the specimens to a dynamic specimen which has been widely utilized in the scientific community for therapeutic drug monitoring and for post mortem assessments.

In quick summary, some of the advantages are that you can

interpret these behavioral relationships that many of the other specimens don't allow. There is a large data base of information.

The major disadvantage is that there aren't set cut off

concentrations, and the concentrations of the analyte are generally much lower and the time of detection is also much lower.

Let's look at the last two, sweat and saliva. There is a

little bit less to say about them from the data base.

Again, we can identify, in sweat, many of the same drugs.

In addition, alcohol is going to be excreted in the sweat. If you

collect it for drug testing purposes, it is obviously going to evaporate.

The collection methodology, we have the sweat patch which is now available. So, there is now a technology to actually collect this in a documented fashion. Before it was much more difficult.

This can be worn for days to weeks, and it can be readily

sent to laboratories.

The testing has been limited but essentially follows the

same conventional immunoassay and GC/MS methods, and we do have the capacity to find the parent drug here.

The current use is mostly in the criminal justice system. There is interest in the use of this in the general treatment community.

the FDA and there has been a limited scientific evaluation and some publications on that.

The advantages are that there seems to be high subject acceptability to wearing this patch and a low incidence of allergic reactions.

So, there is the ability to monitor drug intake for a period of weeks. It is a relatively tamper proof and FDA approved product.

advantages to possibly using it.

Disadvantages, variation in sweat production. There are a limited number of collection methods available. There is still high

inter-subject variability. Risk of removal, risk of contamination are issues that have to be dealt with if we are going to use this for other purposes.

Saliva, which is the final specimen, has again -- we can

detect all the drugs. You can also detect alcohol.

There are some commercial devices available for collecting saliva. The parent drug is frequently present. The immunoassay methods generally need to be targeted to parent drug.

This is another issue following one of the things Ed said,

how the assays are set up. If we are looking more at parent drug or the metabolite, that may affect the nature and structure of some of the assays.

Their reactivity, conventional confirmatory procedures can

be utilized, and we are looking at generally lower cut off concentrations.

Saliva is not widely used. It is limited to the private

sector for insurance purposes. There is a device for alcohol. No PT programs.

There have been a fair amount of things written about the scientific acceptability of saliva, but mostly limited to purposes other than the work place.

The advantages, readily accessible for collection, may be

related to behavioral performance. This is probably the only other specimen that really has this possibility.

So, if we are really looking for recent drug use, it has

some major advantages there.

Disadvantages, possibility of contamination by oral smoke, internasal routes. The same disease collection concerns we have for other specimens, not FDA approved.

In the way of a summary here, urine laboratory based, we

detect metabolites. We are looking at a two to three day detection window. We have laboratory turn around times to deal with. We are concerned about adulteration.

On-site testing, also detects metabolites, same detection window. The major difference there is we have a rapid turn around time.

For those industries for which that is useful, that might be valid. Also, adulteration concerns.

Hair, detects parent drug, long detection window, generally months. We do still have a laboratory turn around time and we still do have some concerns about environmental contamination.

Saliva detects the parent drug. There is a short detection window, less than a day. But it has a rapid turn around time, on site.

Contamination is possible. You can coincidentally do alcohol on the

saliva sample, if that is otherwise warranted.

Sweat looks at both parent drug and metabolites. There is a long detection window in the way of weeks. It is a lab turn around time and there are concerns about variation in sweat production.

These are the other three slides. This is where we are

probably today, at the beginning of this conference. We are down in the pits and we are going to look at everything that is going to happen.

significant resolutions.

This is a slide I have never had a chance to use before, but this did seem appropriate. It says up here, this raging war with spears over there on the left. I don't have time to talk to some salesman. He has got a battle to fight.

Of course, I guess this guy has got the first model of the

old gatling gun here. That would be very significant, if we had time to stop and think about using it appropriately, and I think that suggests this.

Then finally, we have to make decisions. In reviewing the

data, I think we need to look at it objectively, and then ultimately decide which way we want to go, for those of us who are able to do those things.

Finally, the common parameters that we will be needing to develop as we go through the rest of the week is to look at scientific acceptability, court legal acceptability, community acceptability, whether these are FDA approved or that is necessary, establishing cut offs, quality assurance and PT and the cost/benefit to the various technologies.

Hopefully, in an abbreviated amount of time, I gave you a

rough overview or at least my view of where some of the technologies are today and where we may be going with them.

With that, I will conclude and Donna won't have to put her

second note up.

(Applause.)

DR. BUSH: Thank you very much. What a great kick off to

this meeting. I am very, very, very pleased with your attention on a Monday morning and the number of you who showed up to join us for such a great kick off.

Now, let me do some housekeeping things. There are a lot of people here, in case you didn't notice. Everyone is going to want to get up and rush for the coffee.

If you want to reclaim your seat, you may choose to leave

will be out the back door of this conference room. (Further housekeeping matters discussed.)

On that note, it is about five after 10. We will take a 15minute break. We will convene at 10:20. We are going to start on time because we have so much to cover. Please join us back. Thank you.

DR. BUSH: It is time to get started. That is the Monday morning crowd. They got up, got a cup of coffee and walked around, and now they are very active.

In order to kill a little bit of time while everybody is

taking their seat again and quieting down, I would like to take the opportunity to introduce myself to those of you who don't know me.

I know there are many friendly faces out there, Dr. Rohrig.

Anyway, I would just like to let you know how I fit into things, where

I am and what I do for a living.

Since December of 1989, I have been the chief of the drug testing section in the Division of Workplace Programs at the Center of Substance Abuse Prevention at SAMHSA.

I am responsible for planning and directing the National Lab Certification Program administered by the U.S. Department of Health and Human Services.

This certification program was established to ensure

forensically and technically sound drug testing of federal employees and employees of federally regulated industries, such as the Department of Transportation and the Nuclear Regulatory Commission.

This effort directly supports the achievement of a drug free federal workplace as ordered by the President, and covers more than 10 million employees.

I am executive secretary of the Drug Testing Advisory Board, chartered to provide guidance to the Secretary of the Department concerning drug testing technology and policy implications.

In my other life, I also serve as faculty for the American

Society of Addiction Medicine and the American Association of Medical Review Officers, to train medical review officers in the review and interpretation of urine drug test results.

Additionally, I serve as faculty for the Florida School of Addiction Studies and the Southeast School of Alcohol and other Drug Studies.

Prior to this job, I served with the Department of Defense

as Deputy Chief and Technical Director of the U.S. Army Forensic Toxicology Drug Testing Laboratory at Fort Meade, Maryland.

I provided expert witness testimony and advice on drug

testing issues for all military agencies.

I received a bachelors of science in chemistry from Loyola

College in Baltimore, a masters of science and medicinal chemistry from the University of Maryland at Baltimore, a master of science in toxicology from the Johns Hopkins University School of Hygiene and Public Health, and a doctorate of philosophy degree in forensic toxicology from the University of Maryland at Baltimore School of Medicine, where Dr. Caplan had a very easy time with me as his graduate student.

I am an active member of the Society of Forensic

Toxicologists, I am a diplomate of the American Board of Forensic Toxicologists, a fellow of the American Academy of Forensic Sciences, and I have been nominated for inclusion in Who's Who in Science and Technology.

(Applause.)

Now it is my pleasure to introduce Dr. Robert Willette. Dr. Willette has formed DuoResearch in 1981 for the primary purpose of providing consulting services to employers in the public and private sectors, on the design and implementation of work place alcohol and drug programs.

Dr. Willette has helped to establish policies, procedures,

laboratory inspections and blind quality control programs for the U.S. Navy, Administrative Office of the U.S. Courts, the Federal Bureau of Prisons, the Drug Enforcement Administration, the Federal Bureau of Investigation and numerous private companies.

As chief of the Research Technology Branch of NIDA, Dr.

Willette was responsible for overseeing the federal proficiency testing programs for drug testing laboratories conducted by the Centers for Disease Control from 1973 to 1981.

At NIDA, Dr. Willette was also responsible for multiple

studies on the disposition of drugs in the body and their detection in biological specimens.

In addition to these specific efforts directed toward

quality control programs, Dr. Willette is serving, or has served as a consultant on drug testing programs to the White House Office of Drug Abuse Policy, the U.S. Navy, the U.S. Army, NIDA, Federal Aviation Administration, Federal Railroad Administration, National Highway Traffic Safety Administration, the Postal Service, the DEA, FBI, Customs Service; in other words, pretty much most of the federal agencies.

This included the development and administration of the National Lab Certification Program for HHS, for which he currently serves as a certified inspector.

Dr. Willette received a bachelor of science in pharmacy from Ferris Institute, now Ferris State University, and a doctor of philosophy degree in medicinal chemistry from the University of Minnesota.

He has held research appointments at Upjohn, University of Michigan, Australian National University, and the Commonwealth and Scientific Research Organization of Australia.

He has served on faculties in schools of pharmacy at Ferris State and the University of Connecticut.

Dr. Willette, I will turn this panel over to you and adjourn to the back, and good luck to you, sir.

Agenda Item: Specimen Collection/Chain of Custody Panel.

DR. WILLETTE: Thank you very much, Donna.

It is appropriate that the first panel address the first

step and subsequent steps in handling the specimens that are going to be tested.

Prior to 1981, most drug testing was done in the context of

drug treatment programs, whether it was in the work place, the private sector, criminal justice or the military.

The process that was used to collect specimens and to handle specimens and throughout the entire process and the data followed fairly traditional clinical chemistry practices.

Because there was not strict control over the identification

of who provided the specimen or the handling of the specimen in the laboratory with literally hundreds of people that had access to them, many errors occurred. Many people received false laboratory results.

The consequences of that were minimized by the fact that

generally for the purposes that the testing was being conducted, that severe consequences didn't occur.

Usually people were either extended in the treatment and so forth.

That all changed in 1981 when two events happened in sort of conflicting motion. The Department of Health and Human Services got out of the laboratory proficiency and laboratory inspection and monitoring business, but the military got into it.

The military embarked upon a massive random testing program

of military personnel. This prompted the necessity to develop a totally new system for conducting drug tests.

This was to merge together the high volume clinical

practices with forensic principles. That emerged slowly during the early 1980s, spreading into other federal agencies, into the private sector, and then culminating in the development and implementation of the federal mandatory guidelines for federal work place programs in 1988.

Those looked at all of these critical steps which Dr. Cone has outlined.

It seems only appropriate to then bring together the people that have played critical roles in this. Some of you may notice uniforms in the audience.

There are at least eight people who are presenters over

these days from that military background. They played a critical role in the evolution of this whole system.

The panelists that we have to start off with on collection

and chain of custody represent views from each of the major subject areas that are the focus of this three-day hearing.

I have been told by the organizers that the order in which

these areas are covered have been randomly selected throughout each of the different panels.

Just to prove that the lottery works, it seems most

appropriate that the system selected our first speaker.

Dr. Michael Walsh was, in one of his many roles in the government, the person at the point at the lead and responsible for the development of, and the implementation of the mandatory guidelines and the national certification program.

Dr. Walsh is currently the president of the Walsh group,

which is a research and consulting firm located in Bethesda, with the focus on providing consulting services and substance abuse policy research in this field, and certainly the technology.

From 1989 to 1993, Dr. Walsh served as the executive

director of the President's Drug Advisory Council in the Executive

Office of the President.

He also acted as the associate director of the Office of the National Drug Policy Control.

Prior to those appointments, Mike was the director of the Division of Applied Research at the National Institute on Drug Abuse, and served in many capacities, overseeing the development of drug policy, drug effects on performance and driving, drug testing programs, employee assistance programs and in AIDS treatment research.

Prior to joining NIDA, Dr. Walsh was a scientist, a civilian scientist with the Naval Medical Research Institute in Bethesda, where he conducted and oversaw research in various aspects of the effects of drugs on human performance, the areas of psychopharmacology, behavioral toxicology and hyperbaric medicine.

When Mike came to NIDA, he went from studying the effects of drugs on diving to studying the effects of drugs on driving. So, all we had to do is stick an R in that title.

Dr. Walsh received his doctoral degree in psychology here in town, the American University, in 1973. He is licensed to practice in the state of Maryland.

He has published more than 60 articles, books and chapters

in various research publications, and has been in demand as an invited speaker at many, many conferences and meetings.

With no further ado, I am going to turn this over to Michael

and start his timer.

DR. WALSH: Thanks very much, Bob. Bob and I worked

together on the drugs and driving program at NIDA, and co-edited the WHO document.

Although they translated it into Spanish and French and

German and I think Russian, they played it as if it was a new publication every year. So, we had about seven or eight citations from that one publication.

They haven't done anything since, in a long time. It is

about time to do it again.

I would like to congratulate Dr. Autry and the staff of the Division of Workplace Programs and the Drug Testing Advisory Board for their leadership in convening this conference to examine alternative specimens and technology.

I would like to just say a few personal words about Joe

Autry. As Joe's predecessor, I became acutely aware of the fact that no matter how hard you work, how professional you are, you still can't please everybody all the time.

As a result of this, there are times when it gets real

personal in terms of some of the criticisms of the way in which you are running the program.

When I took the bull's eye off my chest and gave it to Joe,

I was delighted to get rid of it, but I think that Joe deserves a lot of credit for wearing that bull's eye with pride and a lot of professionalism.

The mandatory guidelines for the federal workplace program

were originally drafted in 1986. While science was the guiding principle, or the basic philosophy by which we developed the guidelines, much of the details were driven by legislative mandates and legal concerns of that time, of the middle 1980s.

Nearly 10 years have passed now since the final

implementation. I really believe that federal scientists and policy makers now need to be open to new technology and new methods.

I think a desirable goal would be to incorporate the new

advances in technology, to make drug testing programs more efficient and more cost effective without sacrificing any scientific integrity.

With regard to the on site technologies, I believe there is a need in many work place settings to have the capability for rapid screening -- fitness for duty, pre-performance testing, safety sensitive, post-accident, incidence and so on -- where negative specimens could be rapidly separated from those needing further laboratory evaluation.

I believe that on-site technology has reached the point

where it is feasible to produce accurate and reliable results, and that procedures can be established to utilize this technology within a forensic program.

Over the next two days, the speakers representing the on-

site technologies will attest to the fact that on-site urinalysis procedures, the methods, the reagents, internal and external quality control, confirmation procedures, and reporting of test results, really vary little from that which is currently mandated in the federal guidelines.

For example, with regard to specimen collections,

maintaining the integrity of the specimen at the collection site, specimen chain of custody and control, we really believe that standard procedures as described in the HHS guidelines can and should be followed, whether the test is conducted on site or sent on to a lab.

I think, and set up of a collection site is a key to minimizing the problems in specimen collection.

These procedures are really no different whether the

specimen is analyzed on site or sent to a lab. You have got to limit access to water and other potential dilutants.

You have got to put some dye in the toilets to inhibit

adulteration. You need to check photo ID of the donor.

You need to have the individual remove excess clothing. It

is good to provide some kind of security for the contents of pockets or a purse.

The temperature of the specimen has to be assessed, and the collector is going to have to check the color and the order at an absolute minimum of the specimen, to deal with the issues that Dr. Caplan so clearly laid out.

Properly trained collection personnel is also key. Training

for collectors should include education about site preparation, about the responsibilities of a collection site person, ensuring how to ensure specimen security and chain of possession.

Collectors need to be trained about specimen substitution issues, dilution and adulteration, laboratory and medical review officer procedures, and proper completion of the chain of custody and control forms.

In addition, there are additional responsibilities if the

collector is going to be the on-site testing person. They have got to be familiar with the package insert information for any device that is going to be used on site.

They should be required to at least have observed a manufacturers training video. They should be required to perform a number of tests and interpret the test results under supervision.

Some of the clients we have dealt with actually have a

second person interpreting the results and signing off on the chain of custody, so that the one single individual cannot be so easily compromised.

If you are going to be an on-site testing person, you need

to be trained to develop a standard operating procedure and so on.

In terms of the actual collection, it may differ, depending

on the type of device to be used. Some devices allow for testing within the collection cup, while others require an aliquot for on-site testing.

introducing any kind of a foreign body into the urine specimen, there aren't any really special procedures that are required.

A standard chain of custody can be completed while the test

is running. When the test is completed, the cup can be sealed with tamper evidence seals, and the donor dismissed with his or her copy of the form.

The test results can then be read, and with a positive, the sealed specimen should be shipped off to the laboratory. Negatives should be disposed of and results reported out.

For devices which require pipetting of specimen or

introducing something into the specimen, I would recommend that an aliquot be poured off and the remainder of the specimen sealed for shipment, and the chain of custody initiated.

Typically in a lot of cases people use a disposable cup anyway, and then fill two smaller bottles to be shipped to the lab.

specimen being analyzed. If it is a positive on site, the specimen to be sent to the lab are already sealed and ready to go.

In terms of maintaining chain of custody and control, I

believe the chain of custody should be initiated for every specimen, bar coding or some form of coding should be used to label the sealed specimen and any aliquot used for on-site testing.

All specimens testing positive should be sent to a certified

lab for further evaluation.

In terms of copies of control forms, I believe every donor

copies can be returned to the referring agency. If it is a positive onsite test, the standard procedure of sending the original to the lab, copy to the MRO, and so on, would be done.

The specifics of the on-site testing device is going to

depend on the device. I believe that typically the actual on-site test can be done after the chain of custody is complete and the bottles are sealed.

That way, it doesn't have to be done in view of the donor.

If it is a positive, it is going to go on to the lab, all sealed and ready to go.

The Department of Transportation has established regulations

for on-site screening for alcohol. Criteria have been developed to evaluate test devices, and they have established the conforming products list.

I believe that similar standards can and should be

established for on-site drug testing devices, to evaluate sensitivity, specificity, precision around the cut offs, and other variables, to determine suitability for incorporation in federal programs.

Model collection and screening test personnel and procedures

for quality assurance and quality control can also be established for using these devices, as they have for on-site alcohol test devices in the DOT programs.

I am going to give you a little time here, because I am

going to summarize up by saying that I think this meeting really represents a significant opportunity to move the field of drug testing forward, and to broaden the application of testing into these other areas where it is so badly needed, in which the current system is either not feasible or too costly. Thank you all very much for listening.

DR. WILLETTE: Thank you, Michael. We have another Michael

from the draw of the hat that is going to follow.

Dr. Michael Peat joined Lab One in Lenexa, Kansas in June of 1994 as the senior vice president for toxicology, and currently serves in that capacity as the executive vice president.

In this role, he is responsible for the operation of the

toxicology lab, as well as the entire substance abuse sales force and client services of that facility.

Prior to that, Dr. Peat was the vice president for

forensics science lab at the new Scotland Yard in London.

He has had a long, interesting journey from London to

Kansas, and yes, this is Kansas.

He served at the Center for Human Toxicology at the

doctorate in pharmacology, and is certified by the American Board of Forensic Toxicology, to which he presently serves as the director of that board.

He has been a member of this Drug Testing Advisory Board

until 1994, and serves as a consultant to the College of American Pathologists on their toxicology resource committee.

He is the author of many peer reviewed articles and book

chapters, and is also in demand as a speaker.

Dr. Peat is going to talk to us about the chain of custody

and collection procedures surrounding that of saliva.

DR. PEAT: Thank you, Bob. I had to move to Kansas. It was the only time zone I hadn't lived in.

I am going to talk today about saliva, for the next few minutes. Before I get into the collection and chain of custody issues associated with it, I would like to give you a little background as to saliva and what is currently being done with