NACB - Scientific Shorts
NACB - Scientific Shorts (formerly NACB Blog)
By Roger L. Bertholf, PhD

In 1986, President Ronald Reagan issued Executive Order 12564, which mandated a drug-free federal workplace. The concept was not new. The Department of Defense had established a program for detecting and punishing drug use among military personnel nearly 20 years earlier, during the Nixon administration. Reagan’s initiative expanded surveillance to all federal employees, and eventually to anyone working in a job that is regulated by a federal agency. Many state governments and private employers followed suit with their own drug-free workplace programs, and within a few years workplace drug testing grew into the enormous industry it is today. Analytical specifications for urine drug testing (UDT) were codified in federal law, and laboratories meeting those specifications were eligible for certification and regulation by federal agencies. Most state and private drug testing programs adopted the federal standards. In these drug testing programs, use of drugs could constitute a criminal offense, so the specifications for UDT were designed to meet the evidentiary standards of criminal law.

Over the past decade UDT has increasingly been applied under very different scenarios: monitoring compliance with prescribed use of opioids for management of pain, and surveillance of patients enrolled in substance abuse recovery programs. In these settings, the aim of UDT is distinctly different from ensuring a drug free workplace or penalizing illegal drug use, yet the same analytical standards often are applied. For example, a negative result on a urinary opiate screen that meets the standard for workplace drug testing does not necessarily rule out compliant use of an opioid (for which the assay may have limited sensitivity) by a patient under legitimate medical treatment. Likewise, methods designed to detect ethanol intoxication (blood or breath ethanol) are mostly inadequate for determining whether a patient has remained abstinent, and detecting ethanol metabolites in the urine of a patient required to be abstinent may not reflect intentional use, but rather innocent exposure to ethanol-containing products, such as the ubiquitous hand sanitizers health care workers (and just about everyone else) are encouraged to use.

(Reminded of this, I just noticed the dispenser of hand sanitizer on my desk and robotically cleansed my hands for the third of fourth time today.)

Increasingly, UDT is being used for purposes it was not designed to meet, and with analytical specifications that may not be pertinent to the clinical questions being asked. Clinicians want to know whether their patients are responsibly adhering to prescribed opioid therapy or diverting the medication for profit. Clinicians want to know whether their patients are abstinent from drug use, or have violated the terms of their treatment plan. There is currently a demand for UDT in support of pain management and substance abuse recovery programs, and laboratories have responded with services ostensibly tailored to that demand.

That’s a good thing. Clinical laboratories are, after all, in the business of providing economical and worthwhile services that meet the needs of healthcare providers in every clinical setting.

But here’s the point: the use of UDT in pain management, or in substance abuse monitoring programs, has not been validated to the degree we ordinarily require of analytical methods used for clinical decision making. In some respects, these are “off label” applications of UDT. For example, what concentration of urinary opioids or their metabolites is sufficient to verify adherence to prescribed opioid therapy? What concentration of urinary ethanol metabolites confirms the use of alcoholic beverages? Does the presence of multiple metabolites in the urine reflect the use of more than one drug, or minor pathways for metabolism of a single drug? These are important questions, and data on which to base their answers are scarce. Drug testing services for pain management or substance abuse recovery programs are a large and growing industry that offers many incentives for clinical laboratories to enter that arena (not the least of which is virtually guaranteed reimbursement). However, laboratories should exercise caution in how these services are marketed, aware of the fact that UDT was developed for a different purpose, and its application to pain management and substance abuse recovery programs involves limitations that clinicians rarely understand.


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Posted by Naal Painmanagemetnt
On 1/10/2013

Great info!

Posted by AACC\bgarman
On 6/17/2011

Dr.Berthoff is raising issues pointing to some significant aspects of current pain Medication compliance monitoring issues. The current reporting threshold based on NIDA, DOT or Non DOT, UDT may not be ideal for assisting physicians in assessment and adjustment of patient medication. As mentioned in the article, a negative result on an opiate urine screen or a Benzodiazepines screen does not necessarily rule out compliant use of an opioid or a benzodiazepine. To assist the physicians to decide whether their patients are abstaining from drug use, not being compliant with the prescribed dosage and use of the medication, or whether they are selling or giving away the drugs, and above all to establish and maintain a therapeutic dosing regimen, the current UDT Criteria and cut off levels are not sufficient. We noticed that the adulteration issues in a pain management scenario are different from that of a routine urine drug testing. Adulteration of urine specimen was usually intended to mask drug detection, but in pain management monitoring we have seen that the drug as powder/as liquid is added to the urine sample and the lab reports the patient as consistent with medication. In one instance the collector found the donor scraping the nail to drop drugs that had been hidden in the nail into the specimen. So I think the laboratories should alert the physicians if an elevated drug level is detected in urine without a metabolite. Furthermore, the lab should monitor the primary and secondary metabolites with or without the parent drug. The importance of lower cutoffs, the time of urine collection, and MS/MS analysis are only some of but not all of the factors to be considered. Thank you Dr. Berthoff for bringing up this issue and thanks Dr.Winter for the follow up question. Thomas David M.S, FTS-ABFT Castle Medical, Smyrna, Georgia

Posted by AACC\bgarman
On 6/16/2011

Roger - If you view UDT as a measure of compliance, are you saying that a person can be taking their prescribed opiates yet test negative using current cut points? Are work-place drug testing cut points above the "therapeutic" cut points? If somebody is prescribed oxycodone and they test negative for oxycodone during the window of time when you expect that they should be positive (which is a separate immunoassay from the opiate screen on many platforms), does this suggest that the oxycodone is being given/sold to others (or the patient may simply be non-compliant)? What do you recommend be done to improve the measurement of opiates for compliance monitoring? Bill Winter, MD University of Florida

About the Author
Roger L. Bertholf, PhD
Roger L. Bertholf, PhD 

Additional Reading

Couto JE, Webster L, Romney MC, Leider HL, Linden A. Use of an algorithm applied to urine drug screening to assess adherence to an OxyContin regimen. Journal of Opioid Management 2009;5(6):359-64.

Reisfield GM, Goldberger BA, Crews BO, Pesce AJ, Wilson GR, Teitelbaum SA, Bertholf RL. Ethyl glucuronide, ethyl sufate, and ethanol in urine after sustained exposure to an ethanol-based hand sanitizer. Journal of Analytical Toxicology 2011;35(2):85-91.

Reisfield GM, Salazar E, Bertholf RL. Rational use and interpretation of urine drug testing in chronic opioid therapy. Annals of Clinical and Laboratory Science 2007;37(4):301-14.

Reisfield GM, Goldberger BA, Bertholf RL. “False positive” and “false negative” test results in clinical urine drug testing. Bioanalysis 2009;1(5):937-52.