Drug Testing, The Technology of Recovery for Professional Health Monitoring Programs

Originally published in Substance, Summer 2016.
Historical perspective and knowledge of the science and ethics of the drug testing industry can bring success where other programs fail, not only to professional health programs, but to all recovery programs.

by David M. Martin, Ph.D.

Drug testing is the technology of drug abuse recovery, much the same way glucose testing is the technology of diabetic recovery. Both are chronic, deadly diseases but can be controlled with appropriate testing and lifestyle changes. Unlike glucose tests, not all drug tests are the same, nor do they use the same technology. Drug testing is one of the most important technologies in the new science of evidence-based medical diagnostics and monitoring of addictive disorders. If done wrong, it may lead to misdiagnosis, compromised treatment and can have tragic consequences.

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The Challenges of Professional Health Monitoring (PHM) Programs

The first documented group of professionals to abuse drugs were gladiators in ancient Rome and athletes in the original Olympic games in Greece. Gladiators and Olympic athletes would use combinations of alcohol, herbs and plant materials to enhance performance and mask pain allowing them to compete. The use of drugs to improve sports performance continues today in amateur, professional and Olympic sports. The sporting world long suspected there was drug abuse in professional athletes such as Lance Armstrong, Barry Bonds, Alex Rodriguez, and scores of other amateur and Olympic athletes, yet they never failed a drug test. This was possible because drug experts at a team, federation and national level provided not only performance enhancing drugs, but also sophisticated guidance in the use of those drugs and how to avoid detection.1

Avoiding detection while using drugs is a growing multimillion dollar industry. As such, it was not surprising when the problem of drug abuse by health professionals first emerged, many of the initial drug tests were negative. To this day, many drug tests performed on active drug abusers still are reported as negative if the wrong technology or wrong type of specimen is used. Health professionals, such as doctors, nurses, pharmacists and therapists hold advanced degrees, have studied pharmacology and are knowledgeable about drug testing. In order to have a successful PHM drug testing program, the program must: test for the right drugs, with the correct technologies, on the best specimen types.

It was first believed that the access to prescription drugs by health professionals was the fundamental reason why so many health professionals were diagnosed with addictive disorder. In 2010, at the John P. Mc-Govern Award Lecture and Symposium on “The Future of International Drug Policy” in Washington, D.C., Dr. Robert DuPont, opened the conference with a frightening statement. He pointed out that the world today is threatened by an epidemic of drug abuse that has never been seen before in the history of medicine. This is because it is only within the past few decades that mankind has been exposed to such a broad spectrum of very powerful, addictive prescription drugs that are cheap, easily available by phone or internet, and can be confidentially delivered to your home by overnight express. The added peril, he predicted, is that the 21st century drug problem will not be simply defined by prescription drug abuse alone. Medical marijuana, legalization of drugs, and new synthetics will create a new spectrum of drug abuse we have never seen before.

Dr. DuPont was prescient and right. Today we have unethical pain clinics, medical and legal marijuana, internet pharmacies, synthetic THC, and new designer drugs that hit the streets every day. Medical professionals do not have to steal drugs from work. They only need a cell phone and a credit card. All this makes a challenging environment for an effective PHM drug testing program.

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A Short History of Modern Drug Testing

May 27, 1981 was a clear, calm night off the east coast of Florida. At 11:51pm, after a training mission, a Northrop Grumman EA-6B Prowler military jet approached the flight deck of the U.S.S. Nimitz aircraft carrier to land. The pilot missed the arresting cable with his tail hook and collided with two Grumman F-14 Tomcat fighter jets, setting off a chain reaction of collisions with more than a dozen other jets and helicopters on the flight deck. Several of the war planes exploded, killing 14 crew men, injuring dozens more, and sending a fireball rolling across the flight deck. Post mortem drug tests found that some members of the flight deck and pilots were positive for drug use.

As a result, a zero tolerance program was put into place in the military and the first drug testing program in the armed forces began. It revealed that as high as 40% of service members were positive for drugs. This resulted in a call for not only a drug free military, but a drug free federal workplace in sensitive areas that affect public safety, such as truck drivers, commercial pilots, and train engineers. In 1986, President Ronald Regan signed Executive Order 12564 establishing a Drug Free Federal Workplace that required drug testing to begin for over 20 million Federal Employees and covered industries beginning in 1988.2

This occurred at a time when there was great concern about the state of drug testing in the United States. Patients undergoing methadone maintenance therapy, whose drug test results were negative for drugs of abuse during weeks of monitoring, were dying from overdoses. Clinicians could not explain the mounting death toll. The CDC ran an extensive nationwide blind testing program on the hundreds of methadone clinic laboratories serving an expanding heroin-addicted population recently returned from Vietnam. The report was titled, Crisis in Drug Testing: Results of CDC Blind Study. At that time, laboratories did not have standardization of technologies, consistent cutoffs, confirmation of positives, or licensure standards to perform drug testing. Error rates as high as 100% in some laboratories made drug testing unreliable and dangerous for patient health and safety.3

After two years of planning, public hearings, closed door meetings and technology evaluations, the National Institute on Drug Abuse (NIDA) came up with the first standardization of drug testing to be used for Federal Employee testing.4 For the first time, NIDA initiated the concept of nationwide standardized cutoffs, the levels of drugs in a specimen above which a test is considered positive. NIDA also required positive confirmation testing by an alternate method to insure initial screening results were accurate. NIDA also instituted standards for record keeping, personnel, methodology, and quality control policies, which, if met, would indicate a laboratory was “NIDA Certified” (now Health and Human Services Certified) and allowed to test federal employee samples. This meant that specimens tested for the ‘NIDA 5’ drugs: amphetamines, cocaine, marijuana, PCP, and opiates, in any NIDA Certified lab, anywhere in the country, would produce standard and equivalent results. It was a historic event in the science of drug testing which set the stage for modern drug testing programs.

The typical PHM urine testing panel used today commonly includes many drug classes beyond those in the initial NIDA 5 test panel. It can test for over 30 drugs including an expanded class of opiates, benzodiazepines, barbiturates, alcohol, and the direct alcohol metabolite ethyl glucuronide (EtG). But there is no national standard for cutoffs or confirmation levels for the drugs tested in the expanded PHM testing panels. As a result, a PHM specimen that is positive in one lab for any of these expanded panel drugs could be negative in another lab, also known as a false negative.

This is a serious problem, because a false negative drug test can compromise treatment, encourage non-compliance, and in some cases be deadly. The causes of false negatives can be biological or a result of the technology and cutoff levels the PHM laboratory is using. Biologically, detection of substance use is highly dependent on choosing the correct specimen type to test (e.g. hair, urine, breath, oral fluid or blood). Alcohol use detection using direct alcohol biomarkers offers an excellent example of the benefits of different specimen testing options.

Ethyl glucuronide (EtG) is a direct biomarker of alcohol use. EtG detection in oral fluid parallels blood alcohol testing and breathalyzer analysis, and is very useful for detecting very recent alcohol use, up to approximately three hours post-consumption. EtG in urine is sensitive enough to detect low levels of alcohol ingestion for up to 2-3 days following consumption. Urine is considered, by some, to be the gold standard of drug testing as it will concentrate drugs, but it is highly susceptible to adulteration and difficult to collect under direct observation. Hair testing is now common in PHM programs and hair ETG offers a window of detection for alcohol use up to three months. Phosphatidylethanol (PEth) is the newest direct alcohol biomarker, which is measured in dried blood spots and has the ability to look back at heavy alcohol use for up to three weeks. Fingernail testing is emerging as the preferred sample for some tests and difficult cases. Like hair, fingernail is a keratin fiber and has a window of detection for EtG up to three months. Unlike hair, fingernail has a much longer window of detection for drugs of abuse, up to six months in many cases. The windows of detection for testing alcohol in the various specimens are easy to remember by using a rule-of-threes: oral fluid/breath can look back approximately three hours, urine for three days, PEth in blood for three weeks, and hair and fingernails for up to three months.

But all this is dependent on what cutoff levels are used in the laboratory to indicate a positive test result.

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Ask Your Drug Testing Lab: “What Are Your Cutoff Levels?”

The entry of liquid chromatography tandem mass spectrometry instruments (LC-MS/MS) into the PHM and pain management laboratories has only occurred in the last ten years. Improved sensitivity of new specimen types, such as hair and nail, which have given us the ability to look back three months or more, have only occurred in the last five years. Confirmation testing with this instrumentation is done at the femtogram level, that is, a quadrillionth of a gram. This level of sensitivity was unheard of only a few years ago. LC-MS/MS instruments cost a quarter million dollars and require very specific expertise to run. It’s like buying a fighter jet, you need an experienced pilot and highly trained ground crew to make it work properly.

Unfortunately, these instruments are now being bought and placed in startup pain laboratories or physician offices as drug testing has now become a profit center. Often, these new entities do not have the proper expertise and staff to operate these highly sophisticated drug testing instruments. Therefore, they cannot produce consistent cutoff standardization and at times are reporting questionable results, an eerie repeat of the CDC report, Crisis in Drug Testing. This is part and parcel to a new expansion of laboratories seen in the last few years, and comes with significant problems.

Drug testing cutoffs determine if a test is positive or negative. If drugs or alcohol are detected at or above the cutoff level calibrated on the instrumentation, the test will report out positive. If the levels of drug or alcohol are below the cutoff level calibrated on the instrumentation, the test will report out negative, not detected. How screening and confirmation cutoffs are established will make all the difference in the success of detection.

Let’s compare two different hypothetical laboratories with two different cutoffs for the opioid analgesic Fentanyl, a frequently abused drug with health professionals that is very difficult to detect. Let’s say, Lab A has a confirmation cutoff level of 100 ng/ml for Fentanyl and Lab B has a confirmation cutoff level of 500 ng/ml. If the concentration of Fentanyl in a collected specimen is below 100 ng/ml, both labs will report the specimen as negative. If concentration level of Fentanyl in a collected specimen is above 500 ng/ml, both labs will report the specimen as positive. However, if the concentration levels of Fentanyl in a collected specimen is between 100 ng/ml and 499 ng/ml, Lab A will report the specimen as positive, while Lab B will report the specimen as negative, because the concentration level did not reach their cutoff level of detection. This is what the industry calls a false negative. Herein lies the problem, although the same instrumentation is being used to test the specimens at both laboratories, different cutoff levels means different results. This compromises treatment by missing non-compliance and may actually encourage continued drug and alcohol use as the participants realize the limitations of the testing. False negatives are dangerous to patient outcomes and can have tragic results.

Why would Lab B have higher cutoffs? Chances are, Lab B uses a less expensive, less sensitive, high throughput method and as such will have fewer specimens that test positive. Lab B can then sell at a lower price, including confirmation, as it will have less expensive presumptive positive confirmations. Does Lab B test for drugs with the right technology? Yes. Will they detect the drugs at levels needed for recovery? Sadly, no.

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Then Ask Your Drug Testing Lab:  “When Was Your Lab Licensed and who are Your PHM Clients?”

In the last 5 years there has been an explosion of laboratories entering the drug testing industry, changing it dramatically. In 1990, there were only 8 NIDA certified laboratories (now HHS). Over the next decade, one lab was certified every month until a high was reached in the year 2000, when approximately 138 certified labs existed. After that, a decline occurred, and today there are only 30 HHS certified labs in the U.S.5 These are important workplace specific certifications, but alone do not qualify a laboratory to perform PHM testing, as this is a specific expertise developed over time by experienced professionals.

In 1990, the concept of PHM or pain management lab testing was unknown, it was a new science. In 2000, a best industry guess is that there were only six major laboratories conducting testing for expanded opiates and other extended PHM drug panels. Around 2010, two events occurred in the drug testing industry that made a huge impact; the monetization of drug testing in pain management and addiction treatment programs; and ownership schemes by drug testing laboratories for prescribing physicians and facilities. This caused an explosion in labs offering PHM and pain management drug tests, some ethically, albeit with high cutoffs, and others unethically, with ownership and billing schemes that continue today.

 Today there are literally over a thousand laboratories offering drug tests of one form or another. New labs pop up every week, some with experienced staff and technologies, others without. Industry associations and government agencies, including the HHS, FDA and Justice Department, are monitoring this situation closely. Recently, Millennium Health settled a False Claims Act case with the federal government for $256 million dollars,6 Cigna Insurance sued Sky Toxicology and its affiliate laboratories for $20 million dollars, resulting in its closure and United Healthcare filed a federal fraud case.7,8,9 A public PHM program was concerned about the low rate of positives, reported by its laboratory. A confidential research program was setup to compare the existing laboratory with another reference laboratory by splitting samples. The exiting laboratory reported approximately 4% positive rate while the reference laboratory reported more than double the rate of positives. When EtG was added to this comparison, the positivity rate was close to 20% higher than the exiting laboratory.

Clearly, there is a new “crisis in drug testing” in the PHM and pain management drug testing laboratories, and as reported over 30 years ago by the CDC, it is all driven by money. To determine the experience and ethics of the laboratory it is imperative to ask how long they have been licensed and to contact their PHM client list for references. 

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Not All Instant Testing Technologies Are Created Equal

The ability to instantly drug test in a PHM treatment program, systematically during admission or randomly throughout treatment and recovery, is a powerful deterrent and essential part of any PHM program. It is important to remember that the professional health population is comprised of sophisticated consumers of drugs and drug testing products. As such, they know how to invalidate instant test cups and laboratory based testing, so direct observation might be required in some cases.

In the last 20 years there has been a blizzard of instant drug testing products that have come and gone from the market. There are over 100 kits of various descriptions on the market, and they do not all perform the same. Like laboratory based testing, they vary in the drugs tested, cutoff levels, and cost, all affecting their performance. Urine instant tests are the best sample and provide the ability to instantly test the largest number of drugs versus newly launched oral fluid instant tests which have a limited menus of drugs. The instant results are clinically helpful, but only if accurate and confirmed, when necessary.

An instant drug test kit for urine should have the most commonly abused drugs at clinically significant cutoff levels with validity tests. Most importantly, the kit should be designed for transport for confirmatory analysis under chain of custody to an experienced PHM laboratory for confirmation of positive findings. It is important to keep in mind that if the instant drug testing kits are to be used clinically they must be CLIA waived, the facility must have a CLIA waived certificate and, in some states, a laboratory license. Currently, there are no CLIA waived oral fluid instant drug tests.

Instant testing is an invaluable tool to PHM recovery programs; however, like laboratory based testing, if done wrong, it may lead to misdiagnosis, compromised treatment and can have tragic consequences.

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Hair, Fingernail and Toenail Testing Strategy

Hair testing has become an important tool in modern PHM programs, but its value has been recognized in other medical disciplines for quite some time. Hair testing was evaluated in the American Journal of Transplantation for substance abusers seeking organ transplants.10 As expected, hair testing generated more drug-positive results than urine testing for all substances. For cocaine and opioids, 50% of positive hair samples were not corroborated by either self-report or urinalysis. Even larger discrepancies were observed for alcohol, with 64% of positive hair tests for EtG not confirmed with self-reports, and 88% not confirmed with breath testing. This is all due to the longer three month window of detection for hair testing vs. the shorter days or weeks window for urine testing. Hair testing is good for long-term monitoring retrospectively, but not for short-term or random testing to insure compliance. Additionally, hair may not be available universally with all patients, which makes the next set of unique specimens so important.

The most intriguing new specimens in modern PHM testing are clippings of fingernails and toenails. The human nails are comprised of keratin and are very similar to hair. The principle structures of the human nail is the matrix (where the nail originates), the nail plate, and the nail bed. The nail that extends beyond the finger or toe tip is called the free edge or free margin. The nail plate lengthens at a rate of approximately 3mm per month. Capillary blood flow in the nail bed gives the nail plate its pinkish color and deposits drugs into the nail plate which traps the drug as the nail plate lengthens and thickens.

ails are approximated four (4) times thicker than hair, so more drug is captured in this specimen. A recent study done at the University of Wisconsin at Milwaukee compared 60 matched pairs of hair and fingernails for marijuana use. Carboxy-tetrahydrocannabinol (THCA), a biomarker of marijuana, was tested and found to be five (5) times more concentrated in fingernails than hair due to the thickness of nails.11 Toenails, as they are thicker, may provide even more of a concentration of drugs and can be tested for drugs and EtG if no fingernails are available.

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Alcohol Testing Strategy: Rule of Three

Alcohol is still the major substance of abuse worldwide and often used with other drugs. The social and economic consequences of drug abuse is a fraction of that of alcohol. For those in treatments for addictive disorders an effective and modern approach of alcohol testing is required.

Testing for alcohol in breath, blood, saliva or urine samples can be limited to a detection window of just a few short hours following consumption. Urine alcohol testing is also problematic due to bacterial growth compromising the test. Collecting a blood sample requires a medical professional to draw the blood and has risk of infection. The “Rule of Three” for direct alcohol biomarker testing is emerging as an effective alcohol testing strategy: breath, blood, saliva or urine alcohol has a window of detection of three hours or more, urine EtG has a window of detection up to three days, phosphatidyethanol (PEth) up to three weeks, and EtG in fingernails or hair for up to three months. These tools provide an effective ensemble of testing strategies and a solid evidence-based combination to monitor abstinence from alcohol.

EtG in urine has been in PHM testing since 2005, but only recently has EtG in hair been available. The Society of Hair Testing suggests a 20 pg/mg cutoff as a marker for binge drinking. A 2013 publication in the journal Addiction, by Dr. Lisa Berger and her group at the University of Wisconsin at Milwaukee, analyzed 606 matched fingernail and hair samples tested for EtG.12 The results demonstrated that fingernails and hair are comparable alcohol testing specimens. Fingernails displayed an advantage in the study, eliminating a bias seen in the hair data that was likely due to naturally thin, colored or cosmetically treated hair.

PEth is a unique direct alcohol biomarker for binge drinking. PEth is produced in, and incorporated into, the red blood cell membrane when an individual consumes alcohol. It is a unique blood test that does not require a blood draw, but can be simply accomplished using dried blood spots.

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Case Studies

Drug testing in PHM programs is invaluable, not only to identify drug abuse, but also to vindicate those accused of drug abuse or non-compliance. A few case studies are presented to illustrating the point.

Case Study #1

A combative and disruptive 48-year-old male surgeon was reported for suspected drug use and asked to provide a urine drug screen. The test came back negative, and a subsequent hair test was ordered. The gentlemen defiantly showed up to work with head and body hair shaven. His finger nails where clipped short. He was given a choice: agree to be tested or be dismissed. He agreed to be tested, and his toenails were clipped for the testing specimen. The result was positive for cocaine at an astonishing 102,000 pg/mg.

Case Study #2

A 38 year old female alcoholic internist presented with a history of relapse and heavy drinking. She began a trial of naltrexone to aid her sobriety. Yet, her work attendance and behavior began to deteriorate, and her sobriety compliance was questioned. A urine sample for naltrexone was ordered, and it was negative. A hair test for naltrexone was ordered, and it too was negative. This was a single mother with two children who was going to lose her job on the basis of these lab tests. She reported weekly visits to the beauty parlor, a potentially confounding factor for the hair test, and agreed to a fingernail test. The fingernail test was positive for naltrexone, and her job was saved.

Case Study #3

A semi-retired pharmacist working in a large manufacturing facility had been in Alcoholics Anonymous for more than ten years. The State licensing agency randomly selected him for hair testing. The hair sample was positive for oxycodone. He denied using. A series of tests were done. His fingernails were also positive, but his urine and oral fluid were negative. He, like the female surgeon earlier, was going to lose his livelihood on the basis of this test. He agreed to a toenail test, which came back with a negative result. As it turned out, he had been assigned to repackage thousands of oxycodone pills manually and had his finger nails and hair environmentally contaminated. His toenails were free of drug as his lawyer pointed out, because he did not count pills with his feet.

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Conclusion

This is only a brief view of just a few of the new drug testing technologies that are available. There are several lessons to learn here. The most important is to always ask the important, three-part question: “What are your cutoffs, when was your lab licensed and who are your clients?” For better testing data, vary your testing panels among different specimen types – urine, saliva, hair, blood, and nails. Nails are especially important, since they not only identify drug use, but abstinence and compliance as well, potentially saving careers and lives. Custom design testing programs to individual patients’ addiction profiles whenever possible, for example, testing more frequently for a drug of choice using different samples. Treat the patient not the drug test. Sometimes drug tests are wrong and need investigation. Your patients and their families will thank you.

References

1. Baron, D.A., Martin, D. M. & Magd, S.A. (2007). Doping in Sports and its Spread to At-Risk Populations: an International Review. World Psychiatry, 6(2): 118-123. Retrieved from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219897/
2. Exec. Order No. 12564, 3 C.F.R. 224 (1986). Retrieved from: http://www.archives.gov/federal-register/codification/executive-order/12564.html
3. Hansen HJ, Caudill SP, & Boone DJ. (1985). Crisis in Drug Testing. Results of CDC blind study. JAMA, 253(16): 2382-7. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/2984441
4. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration. (2008). Mandatory Guidelines for Federal Workplace Drug Testing Programs. Retrieved from: http://www.gpo.gov/fdsys/pkg/FR-2008-11-25/pdf/E8-26726.pdf
5. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration. (2016). Current List of HHS-Certified Laboratories and Instrumental Initial Testing Facilities Which Meet Minimum Standards To Engage in Urine Drug Testing for Federal Agencies. Retrieved from: http://www.samhsa.gov/sites/default/files/workplace/certified-labs-list-march-2016.pdf
6. Department of Justice, Office of Public Affairs. (2015). Millennium Health Agrees to Pay $256 Million to Resolve Allegations of Unnecessary Drug and Genetic Testing and Illegal Remuneration to Physicians [Press Release]. Retrieved from: https://www.justice.gov/opa/pr/millennium-health-agrees-pay-256-million-resolve-allegations-unnecessary-drug-and-genetic
7. Alltucker, K. (2015). Labs, doctors scrutinized over lucrative drug tests for pain-pill abuse. Arizona Republic. Retrieved from: http://www.azcentral.com/story/news/arizona/investigations/2015/12/26/labs-doctors-scrutinized-over-lucrative-drug-tests-pain-pill-abuse/77181470/
8. Connecticut General Life Insurance Company and Cigna Health and Life Insurance Company vs. Sky Toxicology, LTD., Sky Toxicology Lab Management, LLC, Frontier Toxicology, LTD., and Hill Country Toxicology LTD. United States District Court, Southern District of Florida, West Palm Beach Division. Case 9:15-cv-80994-WJZ. Retrieved from: https://www.documentcloud.org/documents/2189942-cigna-v-sky.html
9. Miller, J. (2016, May 2). UnitedHealth names labs, treatment center in federal fraud case. Behavioral Healthcare. Retrieved from http://www.behavioral.net/article/unitedhealth-names-labs-treatment-centers-federal-fraud-case
10. Haller, D. L., Acosta, M. C., Lewis, D., Miles, D. R., Schiano, T., Shapiro, P. A., Gomez, J., Sabag-Cohen, S. and Newville, H. (2010). Hair Analysis Versus Conventional Methods of Drug Testing in Substance Abusers Seeking Organ Transplantation. American Journal of Transplantation, 10: 1305–1311. doi: 10.1111/j.1600-6143.2010.03090.x
11. Jones, J., Jones, M., Plate, C., & Lewis, D. (2013). The Detection of THCA Using 2-Dimensional Gas Chromatography-Tandem Mass Spectrometry in Human Fingernail Clippings: Method Validation and Comparison with Head Hair. American Journal of Analytical Chemistry, 4(10): 1-8. doi: 10.4236/ajac.2013.410A2001
12. Berger, L., Fendrich, M., Jones, J., Fuhrman, D., Plate, C., & Lewis, D. (2013). Ethyl Glucuronide in Hair and Fingernails as a Long-Term Alcohol Biomarker. Addiction, 109(3), 425-431. doi: 10.1111/add.12402

Dr. Martin has authored over 100 publications in drug abuse treatment and testing. He established one of the first professional health drug testing programs in the nation and has been the founder of several drug testing laboratories including Psychiatric Diagnostic Laboratories of America, FirstLab and JMJ Technologies. He is currently the Science Team Director for the Drug Enforcement Administration (DEA) Educational Foundation Global Toxic Adulterant Research Program studying new cutting agents added to street drugs and instant technologies to test for them.