Welcome to the American Osteopathic Academy of Addiction Medicine's web-based program, General Principles of Drug Testing. During this particular presentation, we'll be looking at two broad types of testing. One, that is more informal, office-based drug testing, and the second, which is much more regulatory-bound, and that involves workplace testing of employees. My name is Dr. Gregory Landy, and I will be your narrator throughout this presentation. Let me point out at this time that I have no financial or ethical conflicts involved in the presentation. Office-based drug testing is clinical in nature. It's an important component of facilitating office-based opioid treatment. It can assist you in following the treatment recommendations for your patient and helping you plan your medication-assisted treatment. It's important to keep in mind that office-based drug testing is not meant to catch a patient. A positive result should be an opportunity to explore with the patient the reasons for the positive test and, as necessary, make adjustments in the therapeutic plan. Office-based drug testing is less rigid than that required for workplace drug testing. Even so, there should be clinic protocols that guide your office-based drug testing program. But there can be more variability, certainly in terms of how this program is administered. Laboratory testing for evidence of substance use has several different roles. It can be involved in the initial assessment of your patient. It can definitely be involved in treatment planning. It can be an important component in screening for non-prescribed substances or medications. And as the medication-assisted treatment plan unfolds over time, drug testing can be an important component of monitoring adherence to your treatment plan. And of course, it can be used to monitor the efficacy of your treatment and assist in any mid-course corrections that may be necessary. Now, as I mentioned at the outset, office-based drug testing needs to be monitored and implemented with a clinic protocol. Ideally, laboratory testing should be random. Urine specimens should be observed. But at the same time, it needs to be convenient for the patient. You need to be confident that the methods you're employing are high quality and timely. Urine drug testing is the most common clinical practice. But as this slide indicates, there are different methodologies that can be employed. Each has their advantages and disadvantages, but it's probably prudent to check with your administering lab to find out which is best. In the broadest sense, screening tests are considered qualitative, and confirmatory tests report quantitative results. Screening tests are rapid. They tend to be inexpensive. And they're usually immunoassay-based screenings. They can be performed in a lab or in an office using point-of-care testing. Screening tests are considered presumptive, meaning they tend to be confirmed by a more definitive test. Confirmatory tests are more expensive and time-consuming. And the methodology employed is usually chromatography and or spectrometry. Confirmatory tests are usually performed in a certified lab. So it may take longer to get the results, and it also accounts for being more expensive. But as I mentioned, confirmatory tests produce quantitative results. As a consequence, they're more precise and more specific than screening tests. And their results are usually considered definitive. A typical office-based drug testing program would test for a panel of commonly used substances employing point-of-contact screening tests. Confirmatory tests, which are more expensive, should be reserved for cases where there are disconcordant results or more specificity, particularly if quantitative results are needed. A confirmatory test would probably not be necessary when an expected substance is tested for in the screening test and tests positive, or if the individual discloses the use of a substance and that substance also tests positive. Commonly used screening tests include those designed to detect opiates, which includes morphine, codeine, and their associated metabolites. Buprenorphine, fentanyl, oxycodone, methadone, benzodiazepines require specific testing for those particular compounds. Common screening tests also include those looking for cannabinoids, amphetamines, the cocaine metabolite, and alcohols metabolites, particularly ethylglucuronide and or ethylsulfate. Although there is a popular trend towards synthetic cannabinoids and the cathinones, these are designer drugs. Testing is available, but you need to coordinate this with your servicing lab to find out what sort of panels are available. Another point to keep in mind is that in terms of benzodiazepine screening, clonazepam, parazepam, and alprazolam are sometimes not routinely or reliably detected with common benzodiazepine screening immunoassay tests. Testing for buprenorphine during medication-assisted treatment can be useful to monitor your patient's adherence and to detect possibility of diversion. It's important to keep in mind that buprenorphine is not detected by screening tests for opiates, but it requires its own specific screening and confirmatory tests. Confirmatory testing will help you distinguish between buprenorphine and its metabolite, norebuprenorphine, which is usually present in greater concentrations. Samples vary in the ratio of buprenorphine to norebuprenorphine due to individual metabolism and whether or not they are taking other drugs or medications that can act as inducers or inhibitors of the CYP3A4 system, but buprenorphine with little or no metabolite suggests that a sample is tampered by adding buprenorphine directly to the urine. Keep in mind when doing office-based drug testing that urine samples can be altered in a number of ways. Examples include adding a substance so that it appears to have been ingested, diluting the urine specimen with water to decrease chances of detecting that substances are present through acts of dilution, or providing a sample that was produced by another person or a urine sample that the same individual provided earlier. Some of these can be detected by examining the physical characteristics of the urine, such as its temperature or specific gravity. As I mentioned earlier, office-based drug testing requires you have a clinic policy. The policy should be developed ahead of time and it should deal with how you will respond to positive tests. Incorporate into your policy a signed treatment agreement that covers those particular policies that are important for your patient to understand and comply with. Additional steps you may want to consider include reviewing the medication dose, the intensity of treatment, more frequent visits, observed dosing, additional evidence-based counseling, and addressing co-occurring disorders that may all be a consequence of a drug-positive test result. And, of course, the frequency of testing can also be increased. And it's also important to keep in mind the multidisciplinary treatment team and involve them to enhance care coordination. Inconsistent test results will occur with your drug testing program. It's important to keep in mind why you're doing office-based drug testing, which is to help the patient recover and to lead a drug-free life. That is primarily the discussion you want to have with your patient who does test positive, keeping in mind that you're promoting recovery and not punishment. In discussing the disconcordant test results with your patient, you want to discuss the data that you have available, obviously the test results. And if you have the urine concentration and the pH, that can also be added to the discussion. Prior to meeting with the patient, it's probably an important thing to consider the possibility of false positives. This may require a discussion with an expert, maybe your servicing laboratory or a pharmacist. At some point during this discussion, the need for confirmatory testing should be broached. Again, this will be specific, done through chromatography, spectrometry, and will provide you with quantitative results. At the end of the discussion with your patient, you want to review the goals of care. Discuss any changes in the treatment plan, such as an increased frequency of appointments or urine drug testing or any alterations in take-home drug doses. And review the consequences of continued use of illicit non-prescribed substances. Now you may be wondering at this point in time, how frequently should office-based drug testing be conducted? There are no strict established guidelines or specific evidence to guide the frequency of urine drug testing. Ultimately, it's a clinical decision. You probably want to keep in mind the stages of treatment. Monthly testing has been suggested as a minimum during ongoing addictions treatment. More frequent testing, such as weekly, may be appropriate in the early phases of treatment or if you have concerns about diversion or if the individual continues to use the substance. Other factors that you may weigh in determining the frequency of urine drug testing would be the stability of the patient. Are they adherent to treatment or did they have a recent relapse, for example? You want to consider the half-life of the drugs being tested and the treatment setting. Office-based opioid treatment, opioid treatment programs, federal law mandates a minimum of eight drug tests per year in the latter category. And random testing rather than appointments or pre-scheduled times is recommended in order to obtain a more representative sample and a better idea of drug testing results. As you develop your clinical protocol for implementing office-based drug testing, you want to have some basic familiarity with the servicing laboratory. It's helpful to know the general methodologies they are using, the report forms, and what they mean. What are the drugs screened in a routine panel? What other drug tests can your laboratory perform? How sensitive and specific are the tests? What are the cutoff levels for reporting positive or negative test results? And it's good always, of course, to have a point of contact that you can quickly access to answer those questions that may come up through your clinical practice. And of course, it's always helpful to understand the cost of the screening and the procedures to obtain confirmatory testing when needed. The remainder of this presentation will discuss the role of a medical review officer, an integral component in the workplace drug testing program. This presentation is by no means exhaustive. And as you will discover, to become a medical review officer and conduct workplace drug testing, you will need to undergo training and also become certified through completion and passing of a test. The rules for the conduct of a medical review officer are specified in great detail in the Department of Transportation's Rule 49, Code of Federal Regulations, Part 40. That describes the procedures for conducting workplace drug and alcohol testing. There are a number of sub-parts in this particular Department of Transportation Rule, which includes such areas as collection sites, the forms and equipment and supplies used, urine specimen collections, and particularly Subpart G, the medical review officer's role and the verification process. Again, this particular portion of this presentation is an overview. The Department of Transportation Rule provides specific guidance to answer the question, who is qualified to act as a medical review officer? To be qualified to act as an MRO in the DOT program, you must meet a number of qualifications and requirements. First, credentials. You must be a licensed physician. You must have basic knowledge. That basic knowledge must be in the following areas. You must be knowledgeable about and have clinical experience in controlled substances, abuse disorders, including detailed knowledge of alternative medical explanations for laboratory confirmed drug test results. You must be knowledgeable about the DOT MRO guidelines and the Department of Transportation agency regulations applicable to the employees for whom you evaluate drug test results. And you must keep current on any changes to these materials. You must receive qualification training meeting the requirements of the DOT rule. That qualification training must provide instruction on the following subjects. The collection procedures for urine specimens, the chain of custody, reporting, and record keeping, the interpretation of drug and validity test results, the role and responsibilities of the medical review officer in the Department of Transportation drug testing program, and the interaction with other participants in the program. Following your completion of qualification training, you must satisfactorily complete an examination administered by a nationally recognized medical review officer certification board or subspecialty board for medical practitioners in the field. You must meet the requirements of this section before you begin to perform MRO functions. There's also a section addressing requalification training. During each five-year period from the date on which you satisfactorily completed the examination, you must complete requalification training. And of course, you must maintain documentation and show that you currently meet all requirements of the DOT rule. As a medical review officer, you have certain specific basic responsibilities. As an MRO, you will act as an independent and impartial gatekeeper and advocate for the accuracy and integrity of the drug testing process. The MRO acts as a quality assurance review of the drug testing process for the specimens that you will be looking at. And that includes, but is not limited to, ensuring the review of the forms of the specimen collections for the purposes of determining whether there is a problem that may cause a test to be canceled. As an MRO, you are not required to review laboratory internal chain of custody documentation. No one is permitted to cancel a test because you have not reviewed this documentation. Providing feedback to employers, collection sites, and laboratories regarding performance issues where necessary. And you must determine whether there is a legitimate medical explanation for confirmed positive, adulterated, substituted, and invalid drug test results from the laboratory. While you provide medical review of employees' test results, this part does not deem that you have established a doctor-patient relationship with the employees whose tests you review. You must act to investigate and correct problems where possible and notify the appropriate parties. And of course, you must protect the confidentiality of the drug testing information. The following five drugs or classes of drugs are used in the Department of Transportation drug test. Marijuana metabolites, cocaine metabolites, amphetamines, opioids, and fincyclidine. Workplace drug testing begins with initial screening. And as you can see, there are different test cutoffs for the different substances. The initial test analyte for marijuana metabolites, for example, is 50 nanograms per milliliter. Cocaine is looking at its metabolite, and then the initial test cutoff is 150 nanograms per milliliter. Codeine morphine, 2,000 nanograms per milliliter. 6-acetylmorphine, which is the specific metabolite associated with heroin, is 10 nanograms per milliliter. The confirmatory test has different cutoffs. And remember that a confirmatory test provides a quantitative result. For marijuana, it's THCA. The confirmatory test cutoff is 15 nanograms per milliliter. For cocaine, it's the metabolite at 100 nanograms per milliliter. Codeine and morphine, 2,000 nanograms per milliliter. And for amphetamines, it's 50 nanograms per milliliter. Codeine morphine, 2,000 nanograms per milliliter. And for 6-acetylmorphine, which again is the heroin metabolite, is 10 nanograms per milliliter. Specimen validity testing is an important component of workplace drug testing programs. Specimen validity testing is the evaluation of the specimen to determine if it is consistent with normal human urine. The purpose of validity testing is to determine whether certain adulterants or foreign substances were added to the urine, if the urine was diluted, or if the specimen was substituted. The Department of Transportation rule discusses dilution and substitution. A primary specimen is considered dilute when the creatinine concentration is greater than or equal to 2 milligrams per deciliter, but less than 20 milligrams per deciliter, and the specific gravity is greater than 1.0010, but less than 1.0030 on a single aliquot. A specimen is considered substituted when the creatinine concentration is less than 2 milligrams per deciliter, and the specific gravity is less than or equal to 1.0010, or greater than or equal to 1.0200 on both the initial and confirmatory creatinine tests, and on both the initial and confirmatory specific gravity tests on two separate aliquots. As I mentioned previously, this discussion of the medical review officer's role is an overview, and to become an EMRO requires that you take specific training as we outlined, and also pass a test. The rules also change, and one of the important functions of the EMRO is to remain up to date. With that in mind, let's take a look at the question, on what basis does the EMRO verify test results involving marijuana, cocaine, amphetamines, semi-synthetic opioids, or pencyclidine? Now, as the EMRO, you must verify a confirmed positive test result for these substances, unless the employee presents a legitimate medical explanation for the presence of the drugs or metabolites in their system. In determining whether an employee's legally valid prescription is consistent with the Controlled Substances Act for a substance in these categories constitutes a legitimate medical explanation, you must not question whether the prescribing physician should have prescribed that substance. You must offer the employee an opportunity to present a legitimate medical explanation in all cases. Keep in mind that the employee has the burden of proof that a legitimate medical explanation exists. The employee must present information meeting the burden at the time of the verification interview. As the EMRO, you have the discretion to extend the time available to the employee for this purpose for up to five days before verifying the test result if you determine that there is a reasonable basis to believe that the employee will be able to produce relevant evidence concerning a legitimate medical explanation within that time. If you determine that there is a legitimate medical explanation, you must verify the test result as negative. Otherwise, you must verify the test result as positive. In determining whether a legitimate medical explanation exists, you may consider the employee's use of a medication from a foreign country. You must always exercise your professional judgment consistent with the following principles. There can be a legitimate medical explanation only with respect to a substance that is obtained legally in a foreign country. There can be a legitimate medical explanation only with respect to a substance that has a legitimate medical use. Use of a drug of abuse such as heroin or any other substance that cannot be viewed as having a legitimate medical use can never be the basis for a legitimate medical explanation even if the substance is obtained legally in a foreign country. So now let's take a few moments to look at some specific issues involving these specific drugs. Cocaine, amphetamines, marijuana, the opiates, and the opioids. Keep in mind that cocaine is rapidly and extensively metabolized by the liver and plasma enzymes. Cocaine's major metabolite, benzoyl lecognine, is more persistent, and it's usually detected for approximately two days after a single dose. Cocaine and this major metabolite are not significantly stored in the body. Therefore, even after heavy, chronic use, urine specimens will be negative when collected a few days after the last use of cocaine. Schedule II substances have legitimate medical uses, but of course they also have a high potential for abuse. Both amphetamines and methamphetamine have been used for treating attention deficit disorder in children, obesity, and narcolepsy. Amphetamine is excreted both as unchanged amphetamine and as hydroxylated metabolites. Typically about one quarter of an administered dose is excreted as unchanged amphetamine. Nearly half of a methamphetamine dose is recovered from urine unchanged. Methamphetamine and amphetamine exist in two isomeric structural forms known as enantiomers. Enantiomers are non-superimposable mirror images. The two isomers of each substance are designated as D for dextro and L for levo, indicating the direction in which they rotate in a beam of polarized light. As do many pharmacological enantiomers, the D and L isomers have distinct pharmacological properties. In this case, the D isomer of each substance has a strong central nervous system stimulant effect, while the L isomer of each substance has primarily a peripheral action. Generally, the methamphetamine result reported by the laboratory does not indicate which enantiomer is present because the laboratory procedure is set up to only identify and quantify the methamphetamine and amphetamine that is present. In order to determine which enantiomer is present, an additional analysis must be performed. Workplace drug testing commonly does this. This slide can be a useful reference in terms of understanding how different amphetamines and methamphetamine are metabolized. As you can see, there are equal amounts of D and L amphetamine in such common products as Adderall and Benzedrine and Dexedrine. There are other compounds that metabolize to methamphetamine, such as dimethylamphetamine, and then there are other substances still that metabolize to amphetamine, such as mesocarb. The immunoassay procedures detect multiple metabolites of marijuana, while the gas chromatography mass spectrometry procedure specifically identifies and quantitates the delta-9 tetrahydrocannabinol metabolite. To be reported positive, a specimen must screen positive at or above 15 nanograms per milliliter cutoff, and have a concentration of the delta-9 THCA that is equivalent or greater than 15 nanograms per milliliter, which is the confirmatory cutoff level. Considering these cutoffs, a person with no marijuana experience who smokes a single marijuana cigarette may be positive for one to three days. But with repeated smoking, THC accumulates in fatty tissue, so frequent chronic smokers slowly release THC over a longer time and may continue to produce detectable levels below the cutoff values for protracted periods of time. Heroin, otherwise known as diacetylmorphine, is rapidly deacetylated to 6-acetylmorphine, also referred to as 6-AM, and therefore heroin itself is rarely ever detected in the urine. Heroin's principal and characteristic metabolite, 6-AM, is rapidly deacetylated to morphine and will likely not be detected in most urine specimens of heroin users. Since codeine is a naturally occurring alkaloid in the same opium poppy juice that is the source of morphine used as a starting material for heroin synthesis, codeine may be found in the urine of heroin users. Morphine is rapidly absorbed and excreted as unchanged morphine and as conjugated glucuronides. The primary metabolite is morphine 3-glucuronide. Morphine and its metabolites can be detected in urine up to 4 days after its use. Ingestion of morphine in any form will never account for the presence of codeine in urine. As you know, there are a large number of synthetic or semi-synthetic analgesics available, including but not limited to medications such as hydromorphone, hydrocodone, oxycodone, methadone, liperidine, pentazocine, fentanyl, and even buprenorphine. It's important to keep in mind these drugs do not metabolize to either codeine, morphine, or 6-acetylmorphine. During this presentation, we learned that drug testing is an important component facilitating office-based opioid treatment. It can assist the patient in following treatment recommendations. It can assist you in treatment planning regarding the choice of medication-assisted treatment, its dosing, and ultimately the best level of care. This presentation also briefly looked at workplace drug testing, which requires specialized training and certification. And finally, we spent some time looking at some specific drug class issues. Again, my name is Dr. Gregory Landy. I was your narrator for this presentation, and I would like to thank you for participating in the American Osteopathic Academy of Addiction Medicine's web-based learning system.

drug testing

office-based drug testing

workplace drug testing

urine drug testing

confirmatory tests

medical review officer

confidentiality