Robert L. DuPont, MD, FASAM, Bruce A. Goldberger, PhD, DABFT, and Mark S. Gold, MD, FASAM
CHAPTER OUTLINE
■ EVOLUTION OF DRUG TESTING
■ THE SCIENCE OF DRUG TESTING
■ ON-SITE VERSUS LABORATORY ANALYSIS
■ CHOICE OF MATRIX
■ INTERPRETATION OF TEST RESULTS
■ LIMITATIONS OF DRUG TESTING
■ ETHICAL ISSUES IN CLINICAL SETTINGS
■ CONCLUSIONS
Drug testing—that is, use of an objective laboratory test for recent use of specific drugs—is useful in deterring and detecting drug use in many settings, including physicians’ offices, the workplace, schools, athletic programs, and the criminal justice system. Testing is needed and expected in sports (1).
Drug testing identifies recent use of specific drugs, including alcohol and nicotine. It does not identify addiction or dependence. Through blood and breath—but not urine— alcohol concentrations roughly correlate with the degree of impairment, while tests for drugs and drug metabolites in urine generally do not. Results of drug tests thus are interpreted as evidence of recent use of specific drugs, rather than as evidence of drug dependence or impairment. The identification of recent drug use has great value because patients’ denial of alcohol and drug use is a cardinal feature of substance use disorders.
Drug testing has many uses in clinical and forensic medicine even though testing has not been included in the curriculum and practical experience of most physicians. As with other recently introduced tests in medicine (e.g., functional magnetic resonance imaging or HIV testing), physician education and expert guidelines are needed to make use of new technologies that have the potential to greatly enhance medical care. Whereas the technology of testing is evolving rapidly, physicians’ use of testing remains in an early stage of development. In fact, some professional organizations have called on experts, to produce guidelines for the use of testing (2). In 2013, the American Society of Addiction Medicine (ASAM) released a White Paper promoting the use of drug testing “as a primary prevention, diagnostic and monitoring tool” (3, p. 1).
Physicians working within larger medical care settings, including drug treatment and hospital and outpatient clinics, often have clinical drug testing available to them. Physicians in office-based practices can collect samples of urine, hair, or oral fluids as they, or their staff, collect other samples for submission to their routine clinical laboratory, virtually all of whom do drug tests. Physicians can also purchase on-site drug testing kits from their usual providers of medical supplies.
This chapter is a practical overview of the use of drug testing in clinical practice, with a focus on improving the application of this technology to improve substance use prevention efforts, as well as the identification, treatment, and long-term management of individuals with substance use disorders.
EVOLUTION OF DRUG TESTING
Fifty years ago, drug testing was an uncommon, expensive, and laborious component of death investigations, but even then, drug testing was commonly employed in emergency departments when a drug overdose was suspected. During the 1970s, the use of drug testing spread rapidly into substance abuse treatment programs and the criminal justice system. In the 1980s, successful use of drug testing in the military led to dramatic reductions in drug use (4) and inspired subsequent use of drug testing in the workplace. Over the past decade, drug testing has been used in drug prevention programs, including within school systems, in highway law enforcement, and in athletic competition.
Over the past five decades, the technology utilized for drug testing has progressed rapidly, permitting the identification of drugs and their metabolites at far lower concentrations, far more economically. These analytical enhancements are related to the development of benchtop mass spectrometry. At the same time, drug testing expanded to include testing of oral fluid (saliva), hair, and sweat. Because drugs also are present in breath, the future holds the promise of breath testing for drugs of abuse (5). The leading issue many years ago—the problem of false positives—has been virtually eliminated (6).
Drug tests now are available over the counter for home use. When drug testing is conducted by families, it is useful for them to be educated about what testing does and does not do and how to handle positive tests most effectively and wisely (7). When drug testing migrated from clinical settings to prevention in the workplace, controversy ensued over the application of modern drug testing technology and the use of forensic standards became commonplace for the first time in toxicology. Drug testing also is used in research and evaluation studies to validate self-reports in surveys of drug use and to evaluate the effectiveness of treatment programs in reducing patients’ drug use (8,9).
Drug testing has expanded in recent years to include pain management clinics and other settings where potent opioids and other medications are prescribed on a regularly basis. Drug test profiles are extensive and include many opioids and benzodiazepines, as well as illicit drugs (including amphetamines, cannabinoids—metabolites of cannabis— and cocaine). These analyses are used to monitor patient adherence to prescribed medications and to identify the potential use and abuse of other, nonprescribed substances.
THE SCIENCE OF DRUG TESTING
Although drugs of abuse, including alcohol, are used primarily for their effects on the brain reward centers and are ingested through many routes of administration (e.g., oral, intranasal, smoking, and intravenous), they are distributed by the blood to all areas of the body. For this reason, drugs and their metabolites can be detected in nearly all body fluids and tissues.
In general, drugs and drug metabolites are detectible in urine for 1 to 3 days after acute administration, although after heavy chronic use, some drugs—especially cannabis— may be detected for longer periods of time. After a single episode of cannabis use, many users have negative urine tests at usual cannabinoid cutoffs within 24 hours, and almost all will be negative within 3 to 5 days of last use. However, with chronic use of cannabis, positive urine tests can be obtained for a month or longer.
The immunoassay screening test makes use of the remarkable specificity and sensitivity of the antigen–antibody reaction. Manufacturers of early drug tests used bacteria to produce patented antibodies that were highly specific for the tested drugs and drug metabolites. In the early years of drug testing, there was some unwanted cross-reactivity to a few of the antibodies being used. Today, with improved antibody specificity, this virtually never occurs. The on-site tests described later in this chapter rely on antibodies to detect low concentrations of drugs and their metabolites in urine and oral fluid.
In standard drug testing, an initial immunoassay screening test is followed by a more sensitive and specific confirmation test that is based on mass spectrometry. The confirmation of drugs and drug metabolites by gas chromatography–mass spectrometry (GC-MS) is now compulsory in many settings, especially when there are serious consequences for a positive test. However, in many clinical settings (such as emergency departments, drug treatment programs, and the criminal justice system), only the initial immunoassay test is required, thereby reducing the cost of testing and increasing the speed with which results are available.
The GC-MS identifies drugs and drug metabolites primarily on the basis of the chemical structure of the compound. It is an accurate method of detecting drugs and drug metabolites; the false-positive rate of GC-MS is nil. The current highest standard is liquid chromatography–mass spectrometry–mass spectrometry (LC-MS), which is a sophisticated technology that is increasingly being used, particularly in the field of pain management.
When there are controversies surrounding or severe consequences attached to a single drug test result, not only is the two-step analytical testing process desirable but the ultimate fail-safe is to retain the positive sample in the original collection container in a frozen state for potential retesting. Such repeat testing is easily done with urine testing. It is the ultimate rebuttal to those who say no drug testing process is completely foolproof.
A frequently asked question is, “How accurate is the drug test?” When the two-step process (including the immunoassay screen and the mass spectrometry confirmation) is employed, the drug identification process is highly accurate. If a specific drug is identified on a drug test of a specimen from a donor, then that drug (or a drug metabolite) was present in the donor’s body. An evaluation by a medical review officer (MRO) usually can determine whether the drug was in the donor’s body as a result of a drug prescribed by a physician. While the highest level of science, including the two-step process, the MRO validation, and the retained positive specimen are desirable in certain cases, such as when there are potential legal challenges, even an immunoassay screen alone is highly reliable for many medical purposes, such as the identification of specific drugs, even though it does not rise to the highest (or forensic) degree of certainty.
ON-SITE VERSUS LABORATORY ANALYSIS
Most drug tests are conducted at clinical laboratories following the collection of a sample at some other site (e.g., at a drug treatment center or a physician’s office). The laboratory-testing process usually requires a day or two from the time of collection until the result is available to the clinician. In recent years, more drug testing is done on-site when the initial immunoassay test is done at the point of collection rather than at a laboratory. In forensic settings, the sample that tests positive on-site is sent to a laboratory for a confirming test before being reported as positive. In many clinical settings, such confirmation may be unnecessary, especially if the donor admits to recent drug use.
The ability to obtain results at the time of collection is enormously useful. However, on-site tests, especially oral fluid tests, may be less sensitive than laboratory-based analyses. In addition, a confirmation test is not available on-site. On-site tests seldom produce false-positive results, although that does happen. False-negative results are more common when using on-site test kits, and this problem mitigates some of the benefits of immediate results. It is possible to define the extent of the problem of false-negative test results with any on-site device by splitting some samples and sending one sample for laboratory-based testing or, in the case of oral fluid testing, by comparing the oral fluid on-site test results with the results of urine samples taken from the same donor at the same time and then analyzed at a laboratory.
CHOICE OF MATRIX
The choice of a testing matrix relates to the period of time after drug use that the drugs and their metabolites are detectable, the distribution of the drugs and drug metabolites, the ease of specimen collection, and the level of vulnerability to cheating.
Urine is a particularly attractive matrix for drug testing because it is easy to collect (compared to blood), most drugs and drug metabolites can be readily detected in urine without complex extraction processes, and drugs and their metabolites often can be detected for longer periods of time in urine than in blood and oral fluid. Nevertheless, testing for drugs of abuse in oral fluid, hair, and sweat is valuable. For that reason, it is important that physicians who use drug tests understand the potential benefits of testing samples other than urine.
Urine
Drug testing outside of the medical examiner’s office and the emergency department began with urine. There are many reasons to recommend urine as a matrix for drug testing, including the fact that virtually all clinical laboratories perform drug tests on urine samples, creating a highly competitive marketplace whose effect is to lower costs and enhance the choice of drug test suppliers.
When urine drug testing first became widespread in drug abuse treatment and the criminal justice system in the 1970s, the standard was to directly observe the collection— that is, to directly observe the urine leaving the donor and entering the collection cup. However, when drug testing came to the workplace in the 1980s, direct observation was considered objectionably intrusive. To accommodate this objection, unobserved urine collection became common practice. That change opened the door for cheating. Donors developed a remarkable range of strategies to cheat on drug tests, which led to one of the more active areas on the Internet and to the publication in 1987 by Abbie Hoffman of a book entitled Steal This Urine Test(10). Thus, began a cat-and-mouse game that continues to the present day, when the Internet provides ready access to information on the latest cheating strategies (11,12). Cheating thus is the Achilles heel of urine as an attractive testing matrix. When cheating is suspected, it is useful to use another matrix and/or to engage in direct observation of the specimen collection.
The determinants of the concentration of drug and drug metabolites found in urine after a single use of a drug are complex. They include the dose of the drug taken and the duration of time between the last drug use and collection of the urine sample. Also important is how the drug was ingested and how much of it was ingested over what period of time in the days prior to collection of the sample. A further variable in urine drug concentrations is the amount of fluid recently ingested because whatever the kidneys excrete of the drug and/or its metabolites is diluted by the fluid excreted between the time of the most recent voiding and the time of collection. By special order, creatinine determinations can be used to normalize drug concentrations, thus removing the dilution problem (13).
Because urine testing is dominant in the drug testing marketplace, it is relatively easy and inexpensive to add drugs to the federal government’s basic five-drug panel, which consists of cannabis, cocaine, phencyclidine (PCP), amphetamines, and opiates. This is a major advantage of urine testing, as a large proportion of drug use involves drugs other than those in the basic panel (14). Widely referred to as the “DHHS-5” because the Department of Health and Human Services (DHHS) manages the federal standards for regulated drug testing, in 2010 confirmatory testing of the panel was expanded by DHHS to include the following amphetamines:methylenedioxymethamphetamine, methylenedioxyamphetamine, and methylenedioxyethylamphetamine. Urine drug test suppliers offer more extensive panels of commonly used drugs and can add additional drugs when needed, usually at substantially higher prices.
Depending on whether confirming tests and MRO validation are required, as well as the volume of tests and the number of drugs in the panel, urine drug tests typically cost $15 to $40. Both on-site and laboratory-based urine tests are widely available.
Hair
Drugs and drug metabolites are incorporated in the hair while it is formed in the hair follicle. Head hair grows approximately 1/2 inch a month. The typical hair specimen is 1.5 inch long, thus producing a record of drug use over the preceding 90 days. However, it takes about 1 week for hair to grow from the base of the follicle to a point at which it can be snipped at the level of the scalp; there is no record in hair of drug use during the week prior to sample collection. Alcohol is not incorporated in hair, although alcohol’s major metabolites, including ethyl glucuronide (EtG), are detectable in hair samples (15).
Over the course of the 90 days covered by a typical 1.5-inch hair sample, even a few uses of most drugs of abuse are detectable. Cannabis is an exception because concentrations of tetrahydrocannabinol (THC) and cannabinoids in the body—including the hair—are significantly lower than the concentrations of most other drugs of abuse. For this reason, cannabis must be used about twice a week for the entire 90 days to produce a positive result at the standard cutoff concentrations. Hair tests are very resistant to cheating because hair collection is always under direct observation.
A problem with urine testing is that recent consumption of poppy seeds can produce a test result that is falsely positive for morphine or a codeine positive test result that is difficult to distinguish from heroin use. This makes the urine test virtually useless in identifying heroin use in contested nonclinical settings. Hair samples are not positive for morphine and/or codeine even after repeated consumption of poppy seeds, which makes hair testing an attractive option when urine tests produce positive morphine and/ or codeine results. Hair testing also is an attractive option when cheating on a urine drug test is suspected.
Because hair testing gives results that cover the period from seven to 90 days prior to collection, while urine tests provide results that cover 1 to 3 days prior to collection, these two matrices do not cover the same time periods. When the issue is drug use in the preceding 7 days, hair testing has no value. However, when the question relates to use of specific drugs of abuse, the question of when the drug use occurred is not particularly relevant.
Hair testing has two additional features of clinical importance. The first is that the concentration in the hair is a rough measure of the intensity of use over the 90 days covered by the typical sample. Thus, at intake into treatment, if it is useful to objectively assess the intensity of use of specific drugs during the preceding 3 months, a hair sample allows a distinction between heavy, moderate, and light use of specific drugs over that time period. Second, a 1.5-inch hair sample can be tested separately for each half inch, thus permitting a separate assessment of drug use in each of the past 3 months. This test, called segmental analysis, is sometimes useful in forensic settings.
Although the same drugs that are identified in urine tests can be identified in hair tests, because hair testing is used less commonly, the laboratories that conduct hair tests are likely to offer only a fairly narrow panel of drugs, often the DHHS-5.
Hair testing has been criticized as racially biased because of an early study finding that when a mouse was given an antipsychotic drug, higher concentrations of the drug were found in the black hair on that mouse than in the white hair. However, it is important to recognize that the claim that hair testing is color biased does not relate to an assertion that black hair or one ethnic or racial group is can be found positive on hair testing without using the drug identified. Rather, the claim is that after drug use, the hair test is more likely to be positive with one hair color than another. The appropriate response to these claims is that, in drug testing, there usually is no attempt to normalize the test results for various biologic factors. Instead, the tests are read to a particular concentration in the tested sample. For example, alcohol tests on the highway use the blood alcohol concentration (BAC) of 0.08 as the cutoff for violations for both men and women, even though a woman typically can reach that concentration at a lower level of alcohol consumption than would a man.
Further, several studies using large samples of tested subjects unanimously found that the proportion of subjects who tested positive are the same for African Americans and whites, based on urine testing, hair testing, and self-report (16–18).
There are no on-site hair tests at this time, although they may become available in the future. Thus, only laboratory-based hair tests are available, from a small number of commercial laboratories. Hair tests typically cost about $40 to $80 per test.
Oral Fluid
The liquid content of the oral cavity (e.g., saliva or oral fluid) can be analyzed for drugs of abuse with both on-site and laboratory-based techniques. Oral fluid testing is highly resistant to cheating, as the oral fluid sample is collected under direct observation. The most significant problem with oral fluid testing is that, like hair testing, the tests are relatively insensitive to cannabis use. While the detection of other drugs of abuse is roughly similar for oral fluid testing and urine testing, significantly fewer recent users of cannabis are detected using oral fluid.
The on-site kits for oral fluid testing are particularly prone to miss cannabis use because they are generally less sensitive than laboratory-based analyses. With both hair testing and oral fluid testing, this sensitivity problem is the result of the lower level of THC and metabolites present compared to the level of other drugs of abuse. As the tests are refined to have greater sensitivity, this limitation of both hair and oral fluid testing can be expected to vanish.
In general, oral fluids are most closely correlated with blood testing, with which saliva is in equilibrium. This means that oral fluid testing generally identifies drug use within the 12 to 24 hours prior to sample collection.
Because oral fluid testing is much less common than urine testing, the panel of drugs identified is usually limited to the DHHS-5 in on-site kits. Even though other drugs and their metabolites are present in oral fluids, as a practical matter, it is not yet possible to identify other drugs with oral fluid using on-site test kits. However, laboratory-based testing of oral fluids can detect other drugs of abuse.
For many applications, oral fluid testing is widely expected to be the test of the future because it does not pose the problems with direct observation of sample collection that occurs with urine and because it is resistant to cheating. On the other hand, the current sensitivity limits of oral fluid testing leave much to be desired. The expectation is that in the future, as the technology improves, oral fluid will deliver on its great promise. An oral fluid test typically costs about $20 to $60.
Sweat
Because drugs of abuse are contained not only in saliva but in sweat, sweat is an attractive matrix for drug testing. A patch that is similar to a nicotine patch worn in smoking cessation is applied to the tested person. The patch is removed after a week or two for analysis at a laboratory. The sweat is collected in an absorbent pad that is protected by a permeable cover. The water in sweat evaporates through the covering membrane, leaving the drug and drug metabolites concentrated in the gauze.
Sweat allows prospective testing from the time the patch is applied, whereas all other drug tests are retrospective from the time of collection. There is no on-site option for the analysis of drugs and drug metabolites in sweat. Sweat testing is resistant to cheating because the patch puckers when removed and reapplied. A sweat patch test typically costs about $35.
Breath
Alcohol is commonly quantified in breath, with the results widely used in clinical and medicolegal settings. In addition, recent studies have demonstrated the presence of amphetamines, THC, and methadone in breath (19–21). Breath testing has become an important tool to detect impaired driving (22). As the test technology improves, including the development of a better collection device, it is likely that drugs of abuse will be detected in breath as they now are for alcohol.
Breath testing for drugs of abuse is likely to become practical well after oral fluid testing is practical, as both depend on improving technology. Moreover, the level of drugs present in oral fluids, while lower than in urine, is far higher than in breath. Nevertheless, the ultimate in drug testing is likely to be achieved with breath testing because it is resistant to cheating and far easier to collect than urine, oral fluids, or hair.
Testing for Alcohol
Since the dose of alcohol needed to produce brain reward is a thousand or more times higher than the dose of the commonly used drugs of abuse, testing for drugs has been more challenging and more reliant on the evolution of technology than it has been for alcohol.
Alcohol is rapidly metabolized, primarily by the liver, so alcohol levels in the blood decrease rapidly—typically to zero within a few hours after the last drink. The acute impairing effects of alcohol are related to the blood alcohol levels as modified by the moderating effects of tolerance and the subject’s familiarity with the task being measured. The alcohol concentration is in equilibrium with the blood at the time the urine leaves the kidneys. The urine in the bladder is a reflection of the blood alcohol levels over the period of time that the urine in the bladder was being produced by the kidneys. For this reason, the urine alcohol level lags the blood level at the time of urination, meaning that the urine alcohol level is lower than the blood alcohol level at the time of urine collection during the ascending slope of the blood level and higher during the descending slope of blood level after drinking stops. The detection window for urine alcohol tests generally is 12 hours or less after drinking has stopped, in contrast to 1 to 3 days for detection of most drugs of abuse.
The concentration of alcohol in the urine is of limited value in settings such as highway safety when the BAC standard is typically 0.08. However, in settings in which there is a zero tolerance policy for alcohol use—such as for underage youth, persons in drug and alcohol treatment, and those facing legal sanctions for any drinking (as may occur in probation or child custody settings)—urine testing for alcohol can be helpful. Urine testing for alcohol is especially practical when drug tests are being conducted on a urine sample, at which time it is easy to add an alcohol test.
An important new testing option is the test for EtG or ethyl sulfate (EtS), both of which are metabolites of alcohol that are found in urine for 5 to 7 days following the consumption of alcohol. These tests are especially useful in settings where alcohol use is completely prohibited (e.g., in persons undergoing drug or alcohol treatment and others under supervision that includes a requirement not to use alcohol). A negative EtG test is especially valuable in establishing that the donor of the urine sample has not used alcohol in the preceding 5 to 7 days. As most EtG tests are negative, this is valuable information in many settings in which abstinence from drinking is required.
Because the EtG tests may be positive when the donor has used an alcohol hand sanitizer or an alcohol-containing mouthwash, interpreting a positive EtG test result requires clinical judgment, especially if the consequences for a single positive test are severe. Individuals who are subject to EtG testing for alcohol should be warned specifically and in detail to avoid alcohol-containing products—which are ubiquitous—or risk a positive test result (13).
Comparing Matrices
Refer to Table 112-1 for a comparison of the clinically available test matrices. There are clinical settings in which each of the four matrices discussed in this chapter is particularly useful. Urine is the default matrix for most drug tests because it is the most familiar and because most clinical laboratories conduct these tests. Urine also is the most practical matrix when special-order tests are required, including tests for drugs that are less commonly used. On the other hand, urine has a much shorter detection window than does hair. In addition, urine is the matrix most vulnerable to cheating. Oral fluids are the most easily obtained matrix but can be less sensitive to drug use and have a shorter detection window than urine. Sweat patch testing is prospective—meaning it identifies drug use after the patch is in place. Like oral fluids and hair testing, sweat patch testing is highly resistant to cheating. Hair testing is particularly helpful in scheduled testing, including pre-employment tests where cheating is common. On the other hand, hair is the most expensive drug test matrix.
Table 112-1 Comparison of Blood, Urine, Hair, Saliva, and Sweat Patch Testing for Drugs of Abuse
(Note that costs vary dramatically based on prices negotiated with laboratories and fees related to collection, administration, and reporting.)
aBlood testing for alcohol is routine, costing about $25/sample, but blood testing for drugs is done by only a few laboratories in the United States. Blood testing for drugs is relatively expensive, costing about $60 for each drug tested for.
bUrine tests for nonroutine drugs are available from most reference laboratories, and costs for broad screens are generally <$200.
cHair testing is commonly performed for the NIDA 5 (cocaine, opiates, marijuana, amphetamines, and phencyclidine). However, a large number of drugs and metabolites can be detected, and routine broad testing is performed in several toxicology reference laboratories. The cost of nonroutine testing of hair is <$500 in most cases.
dCommonly limited to the NIDA 5. Tests can also be performed for alcohol.
DOT, U.S. Department of Transportation; GC-MS, gas chromatography–mass spectrometry; NIDA, National Institute on Drug Abuse.
Victim and Other Drug Testing
Drug use is found in college students who present with accidents, violent arguments, fights, and date rape. Therefore, student health and emergency department personnel routinely perform urine tests on suspected rape and date rape victims (23–26). This is an example of a wide variety of nontraditional settings in which drug testing is increasingly used to identify recent drug use. Another example is the proposal that drug test results be added as a criterion for making the diagnosis of substance use disorders (27).
Smarter Drug Testing
Clinicians who use drug tests should be familiar with both laboratory-based and on-site testing techniques and with all four of the commonly used matrices. In many clinical settings, it is desirable to have access to all of these testing options to discourage cheating and to track the relative effectiveness of each type of testing. It is also desirable to test for a wide variety of drugs, at least from time to time, to identify new or unusual drugs that may appear in the tested population. Strategies for wiser use of the various matrices and testing for a wide variety of drugs have been described as “smarter drug testing” (28).
INTERPRETATION OF TEST RESULTS
When interpreting a drug test result, especially when the donor denies recent use of an identified drug, it is desirable to cast a wide net, seeking the best information available before rendering an opinion. Although difficult situations do arise, the majority of drug test results are easily interpreted and not disputed by the donors.
When interpreting a disputed or ambiguous test result, the physician is wise to consult the laboratory reporting the result because laboratories and drug assay manufacturers have highly qualified forensic toxicologists on staff.
In difficult cases, physicians can consult certified MROs, who are physicians certified in the interpretation of drug test results (Table 112-2). See the accompanying sidebar for a fuller discussion of the role of MROs.
TABLE 112-2 SOURCES OF USEFUL INFORMATION
Sources of Confusion
In interpreting drug test results, confusion frequently arises from an assumption that, because most drug users use infrequently and because almost all drug users minimize (or flatly deny) their drug use, most positive drug test results are related to occasional drug use. Nothing could be further from the truth. Most positive test results are the result of very frequent drug use, as evidenced by the fact that most tests are conducted using urine, which has a window of detection of only a few days. Thus, unless a drug was used during the days immediately prior to collection of the urine sample, the test result will be negative.
A study of the probability of a positive test found that, in random testing, 55% of positive test results reflected daily or near-daily use, while only 7% involved individuals who used drugs only a few times a year (29).
LIMITATIONS OF DRUG TESTING
Tests that use urine and oral fluids can only detect the specific drugs on the test panel and only during the few days immediately prior to collection of the test sample. For hair testing, the window of detection typically is 90 days, while for sweat patches, the window of detection is the period of time the patch is worn—usually a week or two.
Drug tests do not identify recent drug use in general; rather, they identify only the recent use of the drugs specified on a particular test. This means, for example, that if a test does not specifically include ecstasy (methylenedioxymethamphetamine), it will not identify that specific drug even if it is present in the sample.
In fact, a negative drug test does not even prove that the tested individual had not recently used a drug included in the test panel. A negative drug test result indicates that none of the specific drugs in the test panel was identified at or above the cutoff concentration for that test panel. If a drug or drug metabolite is identified, then the donor used that drug within the detection window of the test and at a level of consumption that caused the test results to exceed the cutoff. But if a drug is not detected, it does not establish that the donor did not use the drug within that detection window, only that the drug or drug metabolite was not in the sample at a concentration above the cutoff for that particular test.
Drug testing is valuable in identifying recent use of specific drugs but not in determining impairment, dependence, dose, or recency of drug use. Thus, drug testing is valuable in validating self-reports of drug use in surveys and in detecting use in settings where any use of the identified drug violates the standard for that setting. For example, any use of cocaine or cannabis is strictly prohibited among commercial airline pilots or patients in most substance abuse treatment programs. Similarly, while the use of alcohol is legal for adults and generally permitted, there are exceptions (e.g., any identifiable concentration of alcohol is prohibited for a surgeon in an operating room or a physician enrolled in a physician health program (30). For adults in most other settings, the standard relates to the alcohol concentration, so in most states today, a BAC of 0.08 or higher is considered evidence of violation of the law.
Drug testing does not permit an estimation of the dose or recency of drug use. Drug tests are commonly reported as “positive” or “none detected” at specified cutoff concentrations rather than at specific concentrations, unlike blood and breath alcohol tests. For example, a typical urine test that is positive for cannabis would be reported as positive at or above a cutoff concentration of 50 ng/mL. In contrast, a typical alcohol test might be reported as 0.05 g/100 mL.
In testing for drugs that are illegal for anyone to use at any age, there is a more complex decision to be made about the use of drug tests to identify such use. Parents may be concerned about tobacco or cannabis use and collect a hair or urine sample from their children. Drug testing is viewed positively as a prevention strategy by such parents (31). Although such testing remains controversial, it is clear that parents have access to drug testing technology in pharmacies and on the Internet and can choose to pay for testing (32). This new development, without an MRO or plan for how to follow-up test results, requires education of the users of such tests.
At this writing, 18 states have per se drug laws for driving a motor vehicle, making it a violation of the law to have any identifiable concentration of an illegal drug in the driver’s body (33). This standard, already applied to commercial drivers, is being more widely adopted throughout the United States and in other countries around the world. Similarly, in student drug testing, any drug or metabolite identified in a student is considered a violation of school policy, leading not to arrest or reporting to the police or even suspension from school but to involvement of the student’s family in efforts to help the student become drug-free (34,35). Here, the issue often becomes a question of privacy, which is a matter subject to litigation, especially in public schools, where the constitutional protections of the Fourth Amendment apply. However, in two Supreme Court rulings, the constitutionality of student drug testing has been upheld (36,37).
While much of the initial controversy over drug testing, especially in the workplace and in schools, focused on the problem of false-positives, the more common problem today relates to potentially misleading negative test results. As noted earlier, a negative result does not necessarily mean that no drug was used. Instead, the donor may have used a drug that was not included in the testing panel; the donor may have “cheated” on the test; the drug may have been used outside of the detection window of the test; for example, the amount used was less than required to trigger a positive test result, or that the donor may have consumed a sufficiently large amount of water to dilute the sample so that the drug or drug metabolite concentration falls below the cutoff concentration required to report it as positive.
Thus, as a practical matter, the most common problem with drug testing is that there may have been recent drug use that was not detected by the drug test. For this reason, a negative result on a drug test should not be overinterpreted. A negative test result means that none of the specific drugs or drug metabolites on the panel were identified at or above the specified cutoff level.
Even with the foregoing limitations, drug tests identify far more drug use than do self-reports. The simple bottom line is that modern laboratory-based testing for drugs of abuse uses the highest standards of modern analytical technology to produce reliably accurate results. Further, the technology of drug testing is continuing to improve rapidly (38,39).
ETHICAL ISSUES IN CLINICAL SETTINGS
Some pediatricians consider drug testing a breach of the patient–physician relationship, if not a violation of privacy protections unless the adolescent patient specifically consents to drug testing (40). In this view, involuntary testing is not appropriate in adolescents with decisional capacity—even with parental consent—and should be performed only if “there are strong medical or legal reasons to do so” (41). Such thinking has limited the use of drug tests in a population for whom testing is critical (42). This view ignores the compelling need, incessant minimizing, and denial of use by drug users and does not reflect the legal findings that support drug testing. Still, in some situations—accidents, depression, learning problems, and suicidal ideation, for example—there appears to be a consensus that adolescents ought to be tested for drugs of abuse, with or without their consent. Even in these settings, however, there is merit to securing the young person’s consent for testing. This is especially true when testing is done over time, since one of the primary goals of testing is prevention. One study showed that 40% of adolescents who had an accident tested positive for drugs of abuse in the emergency room (43).
As noted earlier, use of drug testing in the criminal justice system and as part of routine clinical care has not been held to forensic standards, making these types of testing more flexible and less costly. Nevertheless, the primary obstacle to drug testing in these settings is not legal but financial. The major question is whether drug testing is cost-effective. In answering this question, issues to be considered include whether there are consequences to positive and negative drug test results and whether the standard of the program is that the patients be drug free.
CONCLUSIONS
There are few areas of addiction medicine where drug testing is not central, precisely because drug users are likely to lie about their drug use and because drug users commonly use substances without knowing exactly what they contain. A positive drug test confirms recent use of specific drugs, whereas a negative drug test helps to establish that abstinence exists as the necessary condition of the patient’s recovery program (44,45).
It is important for addiction medicine specialists to know how to use drug tests and to know what information drug tests do and do not provide. Physicians are encouraged to discuss questions about the interpretation of drug test results, as well as questions about regulations and legal problems related to drug tests, with the laboratories that conduct the tests, with the manufacturers of test kits, and with certified MROs.
Workplace Drug Testing and the Role of the Medical Review Officer
Robert L. DuPont, MD, FASAM and James L. Ferguson, DO, FASAM
An MRO is a physician whose duty is to act as an impartial gatekeeper and advocate for the accuracy and integrity of a workplace drug testing program. MROs do this by verifying chain-of-custody documentation and interpreting and verifying laboratory-confirmed drug test results.
The MRO receives positive, adulterated, substituted, invalid, and (in federally regulated workplace testing) all negative drug test results before the results go to the individual or the organization that requested the drug test. The MRO’s task is to verify that the proper procedures were maintained in conducting the test, including forensically rigorous chain-of-custody procedures.
In addition, the MRO establishes whether or not there is an acceptable, legitimate medical explanation for laboratory nonnegative results. An example of this process is the verification by the MRO of an Adderall® prescription in the name of a donor who had a confirmed laboratory positive result for amphetamine. In this case, after speaking with the donor and verifying that the prescription for the amphetamine was valid for that individual, the MRO reported the drug test result as negative. In such a case, the employer is not informed by the laboratory of the positive test, the fact that the employee had been diagnosed with attention deficit hyperactivity disorder, or that the employee had been prescribed Adderall for that condition.
On the other hand, the MRO would be responsible for reporting a safety concern to the employer if, in the reasonable medical judgment of the MRO, the prescription for Adderall® is likely to pose a risk to safety or to be a violation of an applicable regulation.
REGULATORY FRAMEWORK FOR MRO PRACTICE
MROs are knowledgeable about the often complex and frequently changing regulations that govern workplace drug testing.
A 1986 Presidential Executive Order directed the U.S. DHHS to develop and publish scientific and technical guidelines for workplace drug testing of federal employees. Those guidelines (1), overseen by the Substance Abuse and Mental Health Services Administration (SAMHSA) within the federal (DHHS), significantly increased public acceptance of drug testing by establishing certification procedures for laboratories and placing final responsibility for the review of drug tests with a physician—designated, for the first time, as an MRO.
The medical review field grew dramatically when the U.S. Department of Transportation (DOT) mandated testing of transportation workers in safety-sensitive positions as part of the Drug-Free Workplace Act of 1988 (2). It also included a requirement for medical review. Further growth in the role of the MRO occurred as the courts and other government agencies and private employers acknowledged the protection offered by the expertise of a physician and as more employers added MROs to their testing programs, even when not required to do so.
The DOT regulations have been updated several times based on the research data and almost three decades’ experience with workplace alcohol and drug testing. Changes have varied in their focus including on the issues of specimen validity to reduce the risk of cheating as well as identifying new drugs to be added to the federal drug testing panel. The May 2012 update reflects the latest testing technology as it focused on the detection of 6-acetylmorphine (6-AM), a unique metabolite of heroin (3,4). Effective July 3, 2012, laboratories and MROs “will no longer be required to consult with one another regarding the testing for the presence of morphine when the laboratory confirms the presence of 6-AM. This rule is intended to streamline the laboratory process for analyzing and reporting 6-AM positive results and will facilitate MRO verification of 6-AM positive results.”
The SAMHSA guidelines and the DOT drug testing regulations together are considered the “gold standard” of workplace drug testing. Many non-DOT testing programs are modeled after the DOT program because they are the most widely used standards and because they have successfully withstood legal challenges. In addition to the DOT regulations—which cover testing of commercial drivers, pilots, mariners, railroad, and other transit workers, among others—separate regulations govern testing of federal employees and employees regulated by the Nuclear Regulatory Commission. When testing is done under any of these regulations, it is essential that the MRO understand the applicable regulations.
This chapter focuses on the DOT regulations because they cover the largest number of workers and because they are considered the gold standard. Although most workplace testing is not regulated by DOT, the DOT regulations provide useful guidance for all workplace settings.
The guidelines initially promulgated by DHHS merely specified that an MRO was a “licensed physician with a knowledge of substance abuse disorders.” Later, it became apparent that additional, more specific qualifications were needed. The 2001 regulations required (under Subpart G—Medical Review Officers and Verification Process) that MROs not only be licensed but have “clinical experience in controlled substance abuse disorders” (5). The updated regulations require certification by a nationally recognized certifying board (the Medical Review Officer Certification Council or the American Association of Medical Review Officers) and recertification every 5 years. Initial and refresher training is required by each of these certifying agencies.
As the laws and regulations governing workplace drug testing change and as drug-using individuals devise ever more challenging ways to evade detection by workplace testing systems, MROs must keep their knowledge up to date. A list of recommended textbooks, resources, and other references, as well as suggestions for finding an MRO, is presented at the end of this article (Table 112-3).
TABLE 112-3 USEFUL WEB SITES
Contractual Issues
Before beginning the process of medical review, the MRO should have a written contract with the employer, spelling out in detail the services to be provided. Medical review is only one of many components of a drug-free workplace program. The successful MRO will either provide the other components or be able to direct the employer to them.
Organizations called “consortia” or “third-party administrators” (C/TPAs) provide overall program management, policy review, educational materials, training programs, and random sampling of employees and contract out for laboratory, MRO, and collection services. MROs may function as C/TPAs, but they must be careful to follow the regulations that prohibit them from having a financial relationship with laboratories whose tests they review.
INITIATING THE MEDICAL REVIEW PROCESS
The medical review process begins when an MRO receives a drug test result from a laboratory and ends when he or she reports those results. When dealing with urine testing for the DHHS-5 drugs (i.e., drugs specified by the DHHS for federally mandated workplace testing programs), it is desirable for the MRO to work with a laboratory that has been certified under the DHHS rules regarding academic credentials, regular inspections, and satisfactory performance in testing regularly submitted blind proficiency specimens (6,7). When testing materials other than urine are used, laboratory selection involves careful review of laboratory credentials and quality control procedures. Consultation with a forensic toxicologist may be desirable in evaluating the competence of a particular laboratory.
Collection of Specimens
Although federal guidelines minimize the MRO’s responsibility for collection of laboratory specimens, the MRO is required to check each chain-of-custody form for signatures and collector remarks. In addition to this administrative function, the MRO should confirm that, in cases involving nonnegative test results, the chain of custody was not broken. The MRO also should be prepared to evaluate problems of “shy bladder” and issues of dilution, substitution, adulteration, and other issues involving interference with laboratory-testing techniques.
Choice of Specimen
The choice of specimen (e.g., urine, hair, oral fluid) affects both the detectability of drug use and interpretation of test results. See Chapter 112 for a discussion of the considerations accompanying the various choices.
Negative Results
When a test result is negative, the MRO’s role is twofold. First, the MRO or an MRO team member who is under the direct personal supervision of the MRO reviews the custody and control form (CCF) and the laboratory result to determine whether the specimen was diluted, whether it was within the acceptable temperature range, or whether there were any other issues that may have had an adverse effect on the testing process.
If identified, these conditions would be reported to the employer, possibly with a recommendation for appropriate action to be taken in response. As the gatekeepers of the drug testing process, MROs are responsible for verifying that correctable errors are, in fact, corrected if it is possible to do so.
Nonnegative Results (Including Positive, Adulterated, Substituted, and Invalid Test Results)
Before reporting a nonnegative result, the MRO should be satisfied that (a) the correct specimen was tested (and not inadvertently confused with someone else’s sample for example), (b) the laboratory accurately performed the necessary analyses, and (c) there was no acceptable, legitimate medical explanation for the nonnegative test result.
To resolve these questions, an MRO must understand forensic collection and chain-of-custody procedures, know what the toxicology laboratory does, and be familiar with the relevant laws and regulations.
Before a test can be called positive, its designated analyte must test positive by an approved immunoassay and by a confirmatory test, typically performed with gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS). The confirmatory test is so specific that it often is referred to as a “chemical fingerprint.” Screening tests are less specific than LC-MS or GC-MS and, in some unusual cases, may be positive on the basis of compounds that are in some way chemically similar to the sought-after analytes. To discount the possibility of drug tests being read as positive in individuals who may have passively inhaled marijuana or cocaine, DHHS has established testing cutoff levels below which an analyte may be present but is not reportable. The DHHS certification program primarily addresses the DHHS-5 drugs (cocaine, marijuana, PCP, amphetamines [methamphetamine, amphetamine, methylenedioxymethamphetamine (MDA), methylenedioxyethylamphetamine (MDEA), methylenedioxyamphetamine (MDA)], and opiates [morphine, codeine, 6-acetylmorphine]). It includes only certification for the testing of controlled substances that are listed in Schedule I or II of the Controlled Substance Act and does not include benzodiazepines or barbiturates, which often are included in nonfederally mandated testing panels. Although opioid analgesics such as oxycodone, oxymorphone, hydrocodone, and hydromorphone are not currently included in the DHHS testing panel, SAMHSA is giving serious consideration to including them in the future.
Each employee who has a laboratory-confirmed non-negative test must be offered an opportunity to be interviewed and the relevant paperwork from the laboratory and collection sites reviewed by the MRO. During this review, the MRO may find it necessary to speak with the designated employer representative (DER), with the individual who collected the urine, with laboratory personnel, and/or with the employee’s physician or pharmacy. On occasion, the MRO may wish to have the worker examined by an independent physician. Additional laboratory testing may be required, possibly including reanalysis of the specimen.
Invalid Tests
Some specimens cannot be tested because of an interfering substance, because they are too diluted or too concentrated, or because their pH is out of range. Some medications interfere with the screening process, and, occasionally, adulterating substances may be added to the specimen. If the laboratory cannot completely identify an adulterant or other interfering substance, the results are reported to the MRO as “invalid.”
The MRO must review such results, interview the donor, and report the results to the employer as “test cancelled.” In many cases, an immediate observed recollection of the urine is ordered; however, if it appears that there may have been a legitimate explanation for the problem (rather than an adulterant), a repeat of the test may not be necessary unless a negative result is required.
Adulterated/Substituted Tests
If the laboratory identifies an adulterant, the result is reported to the MRO as “adulterated.” In cases of extreme dilution that is not consistent with human urine, the results are reported to the MRO as “substituted.” Adulterated and substituted test results also must be reviewed by the MRO. Unless the donor offers a valid medical basis for the result, it is reported to the employer as “refusal to test,” along with the reason (e.g., “refusal to test because of adulteration with glutaraldehyde”).
Recordkeeping
When a test result is reported as nonnegative, a file should be created for all the relevant paperwork, included notes of the MRO’s interactions with the test donor and others. Because the information in such a file may be subpoenaed, the MRO should treat it with at least as much care as is used in a clinical chart. Under federal testing programs, the MRO is required to keep records of all nonnegative tests for 5 years. In practice, this is a good rule for unregulated programs as well. Many MROs retain such records even longer.
THE MRO INTERVIEW
When an interview is required, the MRO should make at least three attempts to contact the donor at the telephone number provided by the CCF during the 24 hours after the information is received. If the MRO is unable to contact the donor during that time, he or she should ask the DER to contact the donor and direct him or her to call the MRO within 72 hours. The DER also should warn the donor that if he or she does not contact the MRO, the MRO will report the results to the employer after 72 hours.
If contact is made, the MRO should identify the donor by asking him or her to provide the identification number used during the drug test collection. This number is often but not always the donor’s Social Security number. Then the MRO should explain the review process and the MRO’s role in that process. Most importantly, the MRO must warn the donor that the MRO is required to provide to the employer and/or appropriate government agencies any information disclosed to the MRO during the review process if it might affect the performance of safety- sensitive duties. Some have called this a drug testing “Miranda warning.”
The MRO should inform the donor of the drug detected and ask him or her about any medication use that might explain the result. (It is not appropriate for the MRO to ask about other medications being taken or about medical treatments other than those that could explain the drug test result.)
Reporting Test Results
At the conclusion of the review process, the MRO notifies the donor and employer of the findings, which may be
• Negative (including reversals on the basis of legitimate medical explanations) and negative, dilute
• Positive (including positives confirmed on reanalysis) and positive, dilute. Positive reports must include the name of the verified positive drug.
• Cancelled because of
° Fatal flaws or uncorrected correctable flaws
° Failure to reconfirm on reanalysis
° Invalid specimens, with or without medical justification
° Shy bladder in a current employee who has an acceptable medical explanation
• Refusal to test because of
° Specimen adulteration/substitution
° Insufficient amount of urine provided, without a legitimate explanation
° Worker late for test or left the collection site before the test could be completed
° Worker refused to permit direct observation of the test, as required
° Worker refused to cooperate with the testing process or refused to take a second test when asked to do so
THE FUTURE OF MRO PRACTICE
The contemporary perspective on alcohol and drug abuse in the workplace is rooted in the current understanding of addiction as a biopsychosocial disorder, with a renewed emphasis on brain biology (8,9). As a consequence, MRO practice is challenging and constantly changing, providing physicians who specialize in addiction medicine with an additional arena in which to exercise their expertise and professional interest. In addition to the rapidly evolving science of addiction, the regulations governing drug testing also continue to evolve.
The MRO provides useful oversight of the drug testing process and sophisticated interpretations of drug test results to help ensure their fairness, accuracy, and the highest level of modern science. Many drug test results are relatively simple to interpret, while others benefit from the sophistication of the MRO.
In a free and open society, the hurdles faced by workplace alcohol and drug programs are complex and will not be dealt with easily. Workplace drug testing programs are important both in substance abuse prevention and in providing a useful path into recovery for many employees who have substance use disorders. In addition, workplace testing programs promote safety and productivity.
The major challenge for the future of workplace programs is to develop and maintain comprehensive programs that are fair and reasonable as well as strong. Such programs must operate in the public interest in ways that respect not only the interests of all parties involved but also the dignity of workers and their families, including the dignity of persons who have addictive disorders.
REFERENCES
1.U.S. Department of Health and Human Services (DHHS). Mandatory guidelines for federal workplace drug testing programs. Federal Register 1988:53:11970.
2.U.S. Department of Labor. Drug-Free Workplace Advisor: Drug-Free Workplace Act of 1988 Requirements. Accessed at http://www.dol.gov/elaws/asp/drugfree/screenr.htm.
3.U.S. Department of Transportation (DOT). Procedures for transportation workplace drug and alcohol testing programs. Overview of 49 CFR Part 40, 2013. Accessed at http://www.dot.gov/odapc/part40.html.
4.U.S. Department Transportation (DOT). Procedures for transportation workplace drug and alcohol testing programs: 6-acetylmorphine (6-AM) testing. Federal Register2012;77(87):26471–26473. Accessed at http://www.gpo.gov/fdsys/pkg/FR-2012-05-04/pdf/2012-10665.pdf
5.U.S. Department Transportation (DOT). Procedures for transportation workplace drug and alcohol testing programs. Federal Register 2001;66:41951. Accessed at http://www.gpo.gov/fdsys/pkg/FR-2000-12-19/pdf/00-31251.pdf
6.DuPont RL. Drugs in the American workplace: conflict and opportunity, part II: controversies in workplace drug use prevention. Soc Pharmacol 1989;3:147–164.
7.DuPont RL. Medicines and drug testing in the workplace. J Psychoactive Drugs 1990;22:451–459.
8.Nahas GG, Burks TF. Drug abuse in the decade of the brain. Amsterdam, The Netherlands: IOS Press, 1997.
9.DuPont RL. The selfish brain: learning from addiction. Center City, MN: Hazelden, 2000.
REFERENCES
1.Martin DM, Baron D, Gold MS. The spread of performance-enhancing drugs from professional sports to adolescents, weekend athletes, and non-athletes. J Addict Dis 2007;25:5–15.
2.Levy S, Harris SK, Sherritt L, et al. Drug testing of adolescents in general medical clinics, in school and at home: physician attitudes and practices. J Adolesc Health 2006;38:336–342.
3.American Society of Addiction Medicine. Drug Testing: A White Paper of the American Society of Addiction Medicine. Chevy Chase, MD: ASAM, 2013.
4.Bray RM, Sanchez RP, Ornstein ML, et al. 1998 Department of Defense Survey of health related behaviors among military personnel. Research Triangle Park, NC: Research Triangle Institute [Report No. RTI/7034/006-FR], 1999.
5.Merlo LJ, Goldberger BA, Kolodner D, et al. Fentanyl and propofol exposure in the operating room: sensitization hypotheses and further data. J Addict Dis 2008;27:67–76.
6.Miller NS, Giannini AJ, Gold MS, et al. Drug testing: medical, legal, and ethical issues. J Subst Abuse Treat 1990;7:239–244.
7.DuPont RL, Bucher RH. Guide to responsible family drug and alcohol testing. Rockville, MD: Institute for Behavior and Health, Inc., 2012.
8.DuPont RL, Newel R, Brethen P. Drug testing in drug abuse treatment. Center City, MN: Hazelden, 2005.
9.DuPont RL, Mieczkowski T, Newel R. Drug testing in the criminal justice system. Center City, MN: Hazelden, 2005.
10.Hoffman A, Silvers J. Steal this urine test: fighting drug hysteria in America. New York: Penguin, 1987.
11.Karch SB, ed. Drug abuse handbook, 2nd ed. Boca Raton, FL: CRC Press, 2006.
12.Ropero-Miller JD, Goldberger BA, eds. Handbook of workplace drug testing, 2nd ed. Washington, DC: AACC Press, 2009.
13.DuPont RL, Skipper GE, White WL. Testing for recent alcohol use. Employee Assistance Digest 2007;28:15–21.
14.Federal Register Notices, Vol. 69, No. 71, Tuesday, April 13, 2004.
15.DuPont RL, Baumgartner WA. Drug testing by urine and hair analysis: complementary features and scientific issues. Forensic Sci Int 1995;70:63–76.
16.Mieczkowski T, Newel R. An evaluation of patterns of racial bias in hair assays for cocaine: black and white arrestees compared. Forensic Sci Int 1993;63:85–98.
17.Mieczkowski T, Newel R. An analysis of the racial bias controversy in the use of hair assays. In: T Mieczkowski, ed. Drug testing technology: assessment of field applications. Boca Raton, FL: CRC Press, 1999.
18.Mieczkowski T, Lerch KM, Kruger M. Police drug testing, hair analysis and the issue of race bias. Crim Just Rev 2002;27:124–140.
19.Beck O, Leine K, Palmskog G, et al. Amphetamines detected in exhaled breath from drug addicts: a new possible method for drugs-of-abuse testing. J Anal Toxicol 2010;34:233–237.
20.Beck O, Sandqvist S, Eriksen P, et al. Determination of methadone in exhaled breath condensate by liquid chromatography-tandem mass spectrometry. J Anal Toxicol 2011;35:129–133.
21.Beck O, Sandqvist S, Dubbelboer I, et al. Detection of Δ9-tetrahydrocannabinol in exhaled breath collected from cannabis users. J Anal Toxicol 2011;35:541–544.
22.Johnson MB, Kelley-Baker T, Voss RB, et al. The prevalence of cannabis-involved driving in California. Drug Alcohol Depend 2012;123: 105–109.
23.Smith K. Drugs used in acquaintance rape. J Am Pharm Assoc 1999;39:519–525.
24.Ledray LE. The clinical care and documentation from victims in alleged cases of date sexual assault. J Emerg Nurs 2001;27:301–305.
25.Mullins ME. Laboratory confirmation of flunitrazepam in alleged cases of date rape. Acad Emerg Med 1999;6:966–968.
26.El Sohly MA, Salamone SJ. Prevalence of drugs used in cases of alleged sexual assault. J Anal Toxicol 1999;23:141–146.
27.DuPont RL, Gold MS. Comorbidity and “self-medication.” J Addict Dis 2007;26:13–23.
28.DuPont RL, Graves H. Smarter student drug testing. Rockville, MD: Institute for Behavior and Health, Inc, 2005.
29.DuPont RL, Griffin DW, Siskin BR, et al. Random drug tests at work: the probability of identifying frequent and infrequent users of illicit drugs. J Addict Dis 1995;14:1–17.
30.Gold MS, Frost-Pineda K. Random mandatory drug testing: a potential system level solution? Rapid response Ann Intern Med 2006. http://www.annals.org/content/144/2/107/reply#annintmed_ el_2657, Accessed June 1, 2012.
31.Schwartz R, Silber T, Heyman R, et al. Urine testing for drugs of abuse: a survey of suburban parent-adolescent dyads. Arch Pediatr Adolesc Med 2003;157:158–161.
32.Levy S, van Hook S, Knight J. A review of Internet-based home drug testing products for parents. Pediatrics 2004;A113:720–726.
33.DuPont RL, Voas RB, Walsh JM, et al. The need for drugged driving per se laws: a commentary. Traffic Inj Prev 2012;13:31–42.
34.DuPont RL, Merlo L, Arria A, et al. Random student drug testing as a school-based drug prevention strategy [for debate]. Addiction 2013;108(5):839–845.
35.DuPont RL, Brady LA. Drug testing in schools: guidelines for effective use. Center City, MN: Hazelden, 2005.
36.Vernonia School District 47J v. Acton, 1995.
37.Board of Education of Independent School District No. 92 of Pottawatomie County, et al, Petitioners v. Lindsay Earls et al, 2002.
38.DuPont RL, Selavka CM. Laboratory and psychological diagnostic testing. In: Galanter M, Kleber HD, eds. American Psychiatric Press textbook of substance abuse treatment, 3rd ed. Washington, DC: American Psychiatric Press, 2003:587–595.
39.DuPont RL, Selavka CS. Testing to identify recent drug use. In: Galanter M, Kleber HD, eds. American Psychiatric Press textbook of substance abuse, 1st ed. Washington, DC: American Psychiatric Press, 2011:53–79.
40.Irwin CE Jr. To test or not to test: screening for substance use in adolescents [editorial]. J Adolesc Health 2006;38:329–331.
41.American Academy of Pediatrics (AAP), Committee on Substance Use. Testing for drugs of abuse in children and adolescents. Pediatrics 1996;98:305–307.
42.Casav M, for the Committee on Substance Abuse and Council on School Health. Schools and at home testing for drugs of abuse in children and adolescents: addendum—testing in schools and at home. Urine drug screening in adolescents. Pediatr Clin North Am 2002;49:317–327.
43.Ehrlich PF, Brown JK, Drongowski R. Characterization of the drug-positive adolescent trauma population: Should we, do we, and does it make a difference if we test? J Pediatr Surg2006;41:927–930.
44.The Betty Ford Institute Consensus Panel. What is recovery? A working definition from the Betty Ford Institute. J Subst Abuse Treat 2007;33:221–228.
45.Jacobs W, DuPont RL, Gold MS. Drug testing and the DSM-IV. Psychiatr Ann 1999;30:583–588.