Medical Device Daily Washington Editor

WASHINGTON — Stories about professional and Olympic athletes trying to beat tests for banned anabolics represent only the tip of the iceberg where drug test cheating is concerned, as any law enforcement officer will tell you, but doctors who prescribe pain relievers based more or less loosely on opium, known as opioid analgesics, face a similar dilemma.

Because the analytical equipment found in a doctor's office is often not up to the task of accurately pegging whether patients in a pain management program are taking what they should be taking — and not taking what they should not be taking — operators of diagnostic labs can reasonably expect an expanding market for their services in this area. However, one of the sessions held yesterday at the annual meeting of the American Association for Clinical Chemistry (AACC; Washington) suggested that even lab operators have to stay abreast of developments in this field if they want to correctly interpret the results of such tests.

Paul Jannetto, PhD, assistant professor of pathology at the Medical College of Wisconsin (Milwaukee), discussed therapeutic drug monitoring (TDM) for these patients, making a clear case for "the vital and key role laboratory tests play in pain management."

Pain is perhaps more commonplace than is commonly appreciated, he said, citing numbers provided by the Centers for Disease Control and Prevention (Atlanta) indicating that in 2006, "25% of all Americans suffered a day-long bout of pain in the previous month," and for one in 10, it lasted longer than a year.

Between 1998 and 2002, prescriptions for opioid analgesics rose from 3.2% to 4.2% of all adults, Jannetto said, but medical examiners say there are also more fatalities in connection with these analogues of opium. He noted that the Joint Commission for Accreditation of Healthcare Organizations (JCAHO; Oakbrook Terrace, Illinois) sees "pain as the fifth vital sign," remarking that "when pain is treated and controlled, patients leave the hospital sooner."

However, he said there is a caveat. "The goal in pain management is to return the patient to a level to allow them to function," but "not necessarily to eliminate pain" altogether. "The No. 1 way is to use drugs," despite the availability of biofeedback and massage.

The most effective pain relievers for those in severe pain are still the opioids, such as oxycodone and hydrocodone, but "because of the risk of diversion and misuse, all pain management programs require patients to sign contracts" that include testing for use of illicit drugs. Hence, therapeutic drug management (TDM) assays are "not something that's routine" now, but labs are almost certain see more such activity in times to come.

Jannetto cited "a number of key issues ... when you talk about opioid testing," including whether the test was done at the point of care or in a lab. Physician interpretation is also an issue because assays vary in their specificities and sensitivities.

However, the doctor is not the only party who has to be up to date on how to interpret analytic data, he said. "Both the lab and the physician have to understand the metabolism of opioids because" a metabolite of one opioid can look like the original drug substance for another.

"Urine is the most common sample our lab sees, which has a two or three day window" for most of this class of analgesic, Jannetto observed, but other media include blood and hair. Urine is commonly used because it is easy to obtain the sample. "A lot of pain management patients do not want to be poked with a needle to get their blood," but urine is "easy to adulterate," he said.

Another confounder is the fact that "the concentration in urine does not necessarily correlate to the dose," Jannetto said, and while screening assays, often done in doctors' offices, are "very fast, quality assays," they are geared toward drug classes "and not a specific drug."

Confirmatory tests are more accurate and "have more optimal sensitivity and specificity" while screening assays can generate "false positives and false negatives," he said, and doctors "should not be making decisions based solely on screening assays." For example, some screens for urine "don't pick up methadone at all."

As an example, Jannetto described the enzyme multiplied immunoassay technique (EMIT), which uses antibodies geared to pick up specific drug substances. EMIT allows for detection but not quantification, and when used for a urine sample, the cut-off for detection is 300 nanograms per milliliter (n/ml) for some opiates. However, some of these opiates are byproducts of the metabolism of other opiates, thus potentially confusing an attempt to check a patient's adherence to the treatment regime. For instance, "morphine is a metabolite of heroin and codeine" so it's important to clarify exactly what is in the sample and what else the patient might be taking.

He said "about 5% of all the samples coming in from pain management clinics are adulterated," with a lot of products "with cute names such as 'Urine Luck' and 'the Whizzinator.'" So-called "clean urine" is also sold on the Internet.

To beat the urine sample scams, labs can test for temperature and acidity/alkalinity, Jannetto recommended, adding that a test for creatinine that returns levels less than 5 milligrams per deciliter "is not human urine." A measurement of creatinine that comes back at more than 5 but less than 20 hints at adulterated urine.

Jannetto said that in the case of a 35-year-old woman who was on oxycodone for fibromyalgia took a follow-up test that checked for a variety of things, including cocaine and cannabinoids. The test came back negative for all illicit drugs, but it also saw no oxycodone, either.

"In this case, the physician is using the urine opiate assay ... which is not specific for oxycodone," e said. Then the prescribing physician asked for a more exhaustive lab test, which picked up the oxycodone.

Jannetto cited a similar example of a 45-year-old truck driver who was on morphine for back pain. His initial test came up positive for cannabinoids, but not for the hydromorphone he was prescribed. Further tests proved the driver was taking only what he was supposed to take but "the concentration was the issue," Jannetto said.

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