Clinical Uses of Drug Testing

1
Clinical Uses of Drug Testing

• Robert L. DuPont, M.D.
• Certified by ASAM and ABPN and certified as an
  MRO
  
• President, Institute for Behavior and Health,
  Inc.
  
• First Director, National Institute on Drug Abuse
  (NIDA) 1973 to 1978
  
• Second White House Drug Czar (Nixon and Ford)
• www.ibhinc.org

2
ASAMs 2008 Review Course in Addiction Medicine

• ACCME required disclosure of
• relevant commercial relationships
• Dr. DuPont discloses that Bensinger DuPont
  Associates has a contractual relationship with
  Ortho-McNeil Janssen Scientific Affairs LLC.

3
History of Drug Testing

• 1960s and earlier
• Medical Examiners and Emergency Rooms
• 1970s
• Drug Abuse Treatment and Criminal Justice System
• 1980s
• Workplace and the Military
• 2000
• Schools and Highways

4
Today Drug Testing is

• Highest level of modern biotechnology
• Workplace drug testing meets the highest standard
  for medical tests the forensic standard

5

• What Drug Tests Detect
• Recent Drug Use, Period.

• What Drug Tests Do Not Detect
• Impairment
• Addiction
• Abuse
• Dependence

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Alcohol Testing is a Misleading Precedent

• Levels of drug detected do not correlate with
• Impairment
• Amount of drug used
• Recency of drug use
• Recent fluid consumption is big factor in urine
  levels!

7
Drug Test Results Cut Offs

• Drug tests are not read quantitatively but as
  yes or no using specific cut-offs
  
• Standard drug test cut-offs are determined by
• The limits of the sensitivity of the testing
  technology as commonly used
  
• To eliminate the risk of passive or inadvertent
  exposure
  
• As a custom order laboratories may use limits of
  detection (LOD) as cut-off

8
Drugs in the Body

• Drug users seek brain reward
• Drugs are carried in the blood to every tissue of
  the body
  
• Drugs and their metabolites are found throughout
  the body after use at concentrations that rapidly
  decline after use stops
  

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Commonly Used Specimens for Drug Tests

• Urine
• Hair
• Oral Fluid
• Sweat
• Breath (for alcohol only now)

10
The Standard 5-Drug Screen

• Drug tests do not test for drugs in general but
  for specific drugs The SAMHSA Five
  
• Marijuana
• Cocaine
• Amphetamine/Methamphetamine
• Morphine/Codeine
• PCP
• More extensive panels are available usually
  costing more
  
• Virtually all drugs can be detected by tests in
  all specimens but few labs offer a full range of
  abused drugs

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The Standard Two-Step Drug Testing Process

• Immunoassay Screen
• Gas or Liquid Chromatography/Mass Spectroscopy
  Confirmation or equivalent

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How Immunoassay Tests Work

• Proprietary monoclonal antibodies are highly
  specific to individual drugs or their
  metabolites
  
• Automated in laboratories or built into on-site
  drug detection devices
  
• High sensitivity (e.g., low levels of drug
  detected) but may not be specific
  
• Relatively inexpensive

13
How LC/MS or GC/MS Confirmation Works

• Uses two separate highly specific processes, GC
  or LC and MS, to precisely identify a single
  substance
  
• No cross reactivity, highly specific and highly
  sensitive
  
• The marijuana example for urine LC or GC/MS
  identifies a single metabolite therefore the LC
  or GC/MS reading is about 40 of the immunoassay
  level because the immunoassay identifies several
  THC metabolites. For this reason the standard
  cut-off is 50 ng/ml on immunoassay screens and 5
  ng/ml on the LC or GC/MS)

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The Medical Review Officers Role

• Validating the testing process and separating
  medical from nonmedical use
  
• Mostly limited to workplace and school testing
• The MRO FUNCTIONS are important in all drug
  testing

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Standards for Drug Testing

• In most treatment and criminal justice settings
  confirmation and MRO are not used to reduce
  cost and speed results
  
• In these settings a single positive test seldom
  leads to severe consequences

16
Confirmatory Tests

• A confirmation test and an MRO are wise
• Whenever a single positive test is disputed by
  the donor and when it produces severe
  consequences such as loss of job or
  incarceration
• Whenever litigation is a threat for example,
  child custody or visitation monitoring

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Drug Testing in the Workplace

• Workplace drug testing mandated by the federal
  government is controlled by Federal Guidelines
  
• Cover only laboratory-based urine testing for the
  standard 5-drug panel
  
• Other drug testing is NOT restricted to these
  Guidelines
  
• However, because workplace drug testing dominates
  the drug testing marketplace, much drug testing
  is within these limited parameters

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Specimen Options

• Different specimens have different strengths and
  weaknesses
  
• All specimens use the same solid science and have
  the same two step options
  
• Only urine and oral fluid now offer on-site
  testing options
  
• No one specimen is better than the others in all
  applications

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Urine

• The Pluses
• By far the most commonly used specimen
• Most potential suppliers of the tests
• Lowest cost
• On-site testing widely available
• Virtually unlimited number of drugs can be
  identified in urine
  
• In disputed results the original sample can be
  retested

• The Minuses
• Cheating is a huge problem especially in
  scheduled drug tests and when collection is not
  observed directly
  
• The bathroom problem
• Samples difficult to handle and transport,
  require gloves in handling
  
• Relatively short drug detection window (DDW)
• Poppy seeds can give morphine/codeine positive

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Hair

• The Pluses
• Cheating virtually impossible
• Longer DDW standard is 90 days for 1 ½ inch
  sample of hair
  
• Discriminates between light, moderate and heavy
  users over 90 day period
  
• Poppy seed consumption does not give a positive
  result for morphine/codeine
  
• No bathroom or hygiene problems
• In case of a disputed sample, a safety net test
  is an option

• The Minuses
• More expensive 40 per test rather than
  10-20
  
• Limited number of drugs identified on most hair
  tests
  
• Fewer providers of hair tests
• No on-site option
• To test positive for marijuana, use must be about
  twice a week for the 90 day period covered by the
  hair sample

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Racial Bias in Hair Testing

• A controversy about hair testing that is refuted
  by abundant and repeated study
  
• The claim is not that one race in this case
  Blacks are inherently positive on hair tests,
  but that if Blacks and Whites use the same amount
  of drug (in this argument the concern is often
  cocaine) the Blacks will have higher levels in
  the tested hair sample given the same amount of
  drug use therefore, Blacks are more likely to
  test positive on hair tests

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Comparisons by Race in Pre-Employment Testing in
Police Applicants
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Comparisons by Race in Pre-Employment Testing in
Police Applicants
The number of positives is too small to create
a reliable odds ratio
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Hair Color as a Biasing Factor in Hair Analysis
Summary

• All the large N studies and most small N studies
  do not demonstrate a statistically significant
  correlation between hair color or curvature and
  drug connection
• Small N studies were often initially reported
  showing differences between mean concentrations,
  however mean value comparisons can be deceptive
  
• Significance cannot be determined by visual
  inspection
  
• Means are sensitive to extreme scores
• Mean differences cannot be evaluated without
  consideration of deviation values
  
• Codeine concentration may be uniquely related to
  melanin but effects are probably small

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The Facts

• In all larger studies, the same relative
  proportions of Blacks and Whites are positive on
  hair test, urine test and self-report
  
• These findings could not occur if hair (or urine)
  tests were biased against Blacks

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Oral Fluid

• The Pluses
• Easy to collect
• No bathroom problem
• Cheating difficult
• More laboratories are now doing oral fluid
  testing
  
• On-site options widely available
• Costs comparable to urine

• The Minuses
• On-site oral fluid testing not sensitive to
  marijuana use
  
• Less experience than with urine or hair
• Very short DDW (12 hours or less)
• Like urine, requires gloves for handling

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Sweat

• Pluses
• Tests prospectively, not retrospectively, for one
  to three weeks
  
• Cheating not a problem
• Costs similar to urine and oral fluid tests

• Minuses
• Only one provider of sweat tests
• Limited experience with these tests
• Limited range only the Standard 5-drug panel
  currently available

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Clinical Examples of Advantages of Various
Specimens

• Advantage Urine
• When drugs other than the standard 5 are being
  used
  
• When cost is a major factor
• When on-site testing is the choice
• Advantage Hair
• When using a scheduled test (e.g., pre-employment
  testing)
  
• In return to work after an extended absence
  (vacation, travel, illness, etc.)
  
• When cheating is suspected
• Address Poppy Seed positive urine tests where
  heroin use is suspected
  
• Advantage Oral Fluid
• As random alternative to urine when cheating is
  suspected
  
• In settings where bathrooms are not available for
  collection roadside drug tests
  
• Advantage Sweat
• Monitoring early in treatment or in other setting
  where continuous monitoring for a couple of weeks
  at a time is desirable

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Coping with Cheating The Achilles Heel of Urine
Testing

• Observe collection
• Test on random basis and, where possible, do not
  give donor the opportunity to consume excessive
  fluids or ingest substances which can foil the
  test
• Test for common adulterants and measure pH,
  specific gravity and temperature
  
• Use alternative samples (hair or oral fluid) when
  cheating is suspected

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Go to the Internet and search How to Beat Drug
Tests to see how robust the market is for
cheating
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Praise from Abbie Hoffman in Steal This Urine
Test Fighting Drug Hysteria in America, 1987

• In the small world of drug testing, these four
  Angarola, Bensinger, DuPont and Willette are
  affectionately referred to as the Gang of Four.
  Dr. John Morgan explains, They are the ones
  responsible for a good deal of drug testings
  success, and some of the fear that goes with it.
  Remember these names. These men are among the
  most competent and knowledgeable about drug
  testing scientifically and politically. They
  are well-informed they have to be. Their
  livelihoods depend on their credibility.
  Unfortunately their expertise represents the
  greatest threat to the civil liberties we seek to
  protect. Know your enemy.

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Bob DuPonts Advice for Drug Test Monitoring Over
Time

• Use more than one matrix so donors do not know
  which sample will be taken when they are tested
  
• Keep track of the rate of positive drug test
  results with the various matrices to get a handle
  on the biggest problem with drug testing
  clinically false negatives
• Rotate drugs tested so donors do not know which
  drugs are being looked for

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Interpretation of Drug Test Results One

• Question
• Can passive exposure cause the positive?
• Answer
• With current cut-off levels this is not possible
  for commonly used drug tests
  
• Passive exposure to crack or marijuana smoke does
  not produce positive results in real-world
  situations

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Interpretation of Drug Test Results Two

• Question
• Did my prescription or OTC medicine cause the
  positive?
  
• Answer
• If the result is LC or GC/MS confirmed, only the
  identified substance can cause the positive
  result
  
• The prescription may have the substance in it,
  e.g., Adderall is D-Amphetamine Desoxyn is
  Methamphetamine
  
• If only an immunoassay screening test is done,
  check with the laboratory or device manufacturer
  for whether some other specific substance is
  known to cross react with their antibody
• This is possible but rare and when it does occur
  it can be identified
  

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Interpretation of Drug Test Results Three

• Question
• Couldnt my positive test come from long-ago
  drug use (e.g., before treatment)?
  
• Answer
• Most urine samples are negative within a few days
  of stopping drug use, even for marijuana except
  for heavy, chronic users and most of these
  samples turn negative within a week or two after
  stopping use
• When repeat testing continues to be positive, the
  most likely explanation is continued drug use
  
• When credible disputes arise, it is possible to
  normalize the tests for creatinine and determine
  whether the THC metabolite or other drug
  concentration is or is not falling over time

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Fail-Safe for Drug Testing

• The Laboratory confirmation and MRO
• The retained positive sample which can be
  retested in case of a dispute
  
• For hair testing, a repeat sample is called a
  safety net test

39
Alcohol Testing

• Alcohol is present in far higher concentrations
  than drugs of abuse making it easier to
  identify
  
• Alcohol is quickly eliminated from the body
  making its detection difficult more than a few
  hours after use

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Principles of Alcohol Testing

• Can be done in any tissue urine, oral fluid and
  blood but breath testing is the most widely
  used form of alcohol testing
  
• Blood testing may be expensive and sample
  collection is difficult
  
• Alcohol levels in oral fluid and breath are in
  equilibrium with blood and therefore correlated
  with impairment
  
• Urine alcohol levels reflect the blood levels
  over the time the urine in the bladder at the
  time of collection was produced by the kidneys
  typically several hours and therefore urine
  alcohol levels are not closely correlated with
  blood levels (or impairment) at the time of
  collection

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Interpreting the Blood Alcohol Concentration (BAC)

• The standard for under the influence of alcohol
  on the highway is 0.08 BAC
  
• In the workplace, the federally mandated standard
  is 0.04 BAC for removal from duty
  
• Impairment can be detected as low as 0.02 BAC

42
Back-fitting the BAC

• When drinking stops, alcohol levels in the blood
  (and therefore in oral fluid and breath) fall at
  about 0.015 BAC per hour and a half
  
• Thus, a BAC of 0.08 when tested at 1 am could be
  used to estimate the BAC at 10 pm of
  approximately 0.11, assuming that drinking had
  stopped about 9 pm

43
EtG and EtS Testing

• Ethylglucuronide (EtG) and ethylsulfate (EtS) are
  metabolites of ethyl alcohol, which may be
  present in the urine for up to 7 days after heavy
  drinking and for up to 1 day after a single
  drink
• EtG is a marker of recent alcohol use
• EtG is not useful in identifying impairment
• EtG can be synthesized by bacteria if alcohol is
  present in urine
  
• EtS is only positive after alcohol consumption
  not after fermentation in urine containing
  glucose or alcohol

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EtG Formation

• Via conjugation of ethanol with activated
  glucuronic acid in the presence of membrane bound
  mitochondrial UDP glucuronyl transferase (UGT)

Seidl S., Wurst F.M., Alt A. Skipper, G.
Addiction Biol 6, 2001
45
EtS Formation

• Via conjugation of ethanol with sulfa catalyzed
  by sulfo transferase in cytoplasm.

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Uses of EtG and EtS

• EtG and EtS are only useful in monitoring
  programs when no alcohol use is the standard
  e.g., after treatment or in the criminal justice
  system
• EtG in urine is new and widely available at a
  cost of about 10-25 and EtS costs an additional
  50 cents per test
  
• Breath testing for alcohol may be ineffective in
  monitoring because the tests are negative a few
  hours after alcohol use has stopped

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The False Positive Problem with EtG and EtS

• EtG and EtS tests are occasionally positive at
  the cut-off of 100 ng/ml for EtG or 25 ng/ml for
  EtS as a result of innocent exposure to low
  levels of alcohol in products such as
  alcohol-containing hand washes, mouth washes, and
  other common products
• In clinical settings the vast majority of
  positives reflect recent alcohol beverage
  consumption
  
• To minimize the problem of false positives, do
  not rely on a single positive EtG test when
  severe consequences are imposed, and educate
  donors about the importance of avoiding products
  that contain alcohol
• Perform EtS test to help clarify when needed

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Summary of Incidental Ethanol Exposure
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The Bottom Line on EtG and EtS Testing

• A negative EtG and/or EtS test establishes that
  no significant alcohol use has occurred by the
  donor in the prior several days
  
• This evidence of no alcohol use is valuable to
  the donor and to the monitor
  
• A positive EtG or EtS test raises a red flag of
  possible recent alcohol use and deserves careful
  follow-up investigation
  
• Many donors admit use when confronted
• Useful in excluding fermentation in ethanol
  positive urines containing glucose

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In a community sample among drug users

• Annual Users 55
• Monthly Users 37
• Daily Users 8

DuPont, R.L. Random Student Drug Tests Are They
Effective for Identifying Occasional Users?
Rockville, MD Institute for Behavior and
Health, Inc., 2003.
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Who Tests Positive?

• At any testing frequency
• About 52 of positive tests are from Daily Users
• About 41 are from Monthly Users
• Only 7 are from Annual Users

DuPont, R.L. Random Student Drug Tests Are They
Effective for Identifying Occasional Users?
Rockville, MD Institute for Behavior and
Health, Inc., 2003.
52
Likelihood of Identifying Drug-Users at Varied
Testing Frequencies
DuPont, R.L. Random Student Drug Tests Are They
Effective for Identifying Occasional Users?
Rockville, MD Institute for Behavior and
Health, Inc., 2003.
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Help with Drug Testing

• You dont need to be a toxicologist to wisely use
  drug and alcohol tests
  
• When in doubt get help
• ASAM Textbook three good articles on drug
  testing (in various settings)
  
• The laboratory or the manufacturer of the device
  you are using get to their toxicologist with
  your question
  
• Call a local MRO
• Call colleagues in ASAM