Painstaking process of drug monitoring

Karen Titus

August 2016—As optimists like to point out (in their annoying way), showing up is half the battle. But it’s still only half, as other, equally clear-eyed folks might point out.

That leaves plenty to do. And in drug testing for chronic pain management, the work facing laboratories may seem like even more than 50 percent.

While a test can indicate the presence of a drug, “trying to figure out why it’s there, or not there, is the complexity we wrestle with,” says Tai C. Kwong, PhD, a professor of pathology and laboratory medicine and director of the hematology/chemistry laboratory, University of Rochester (NY) School of Medicine and Dentistry. He’s also director of chemistry, UR Medicine. “The fact of the drug being there is not enough.”

For laboratories, it’s becoming crucial to understand this and other issues related to pain management testing.

Barbarajean Magnani, PhD, MD, professor, chair, and pathologist-in-chief, Tufts Medical Center, Tufts University School of Medicine, Boston, sees a crisis today in managing patients who are taking opioids for chronic, noncancer pain—and the laboratory, she says, has a major role in supporting clinical services.

“Prescriptions of opioids have exploded, leading to misuse, abuse, and adverse health outcomes, including an epidemic of unintentional opioid deaths,” says Dr. Magnani, who co-chaired a recent American Association for Clinical Chemistry virtual conference on drug monitoring for pain management. She and others addressed the issues facing laboratories in light of this problem, both at the conference and in speaking with CAP TODAY.

While presenting a typical case and noting the postmortem toxicology report showed, among other substances, the presence of alprazolam (Xanax), diazepam (Valium), oxycodone (OxyContin), and hydrocodone (Vicodin with acetaminophen), Dr. Magnani notes it’s not unusual to see a mixture of medications such as opioids and benzodiazepines in the urine of a deceased patient. “Sedative-hypnotic drugs and opioids together, even at lower concentrations, can provide a lethal cocktail for the unknowing.”

“We hear of the increasing numbers of deaths from opioids,” she says. “But remember: Every number was a life.” The example she gave was from the late actor Heath Ledger.

“If we look at the rate of deaths from drug overdoses between the years 2000 and 2014, it has increased 137 percent,” she says (Rudd RA, et al. MMWR. 2016;64:1378–1382). The rate of overdose deaths involving opioids has increased 200 percent in that same period, a figure Dr. Magnani calls staggering. “And remember that the data always drags a little bit behind where we are currently, in 2016,” she says.

Natural and semisynthetic opioids lead other opioid deaths. In the last few years, however, “We are seeing an unprecedented increase in heroin deaths”—including, she says, in the state where she practices, Massachusetts.

The rate of unintentional drug overdose deaths from 1970 to 2007 has also soared, she says, despite the popular notion that the early 1970s belonged to a so-called drug-culture era. The rate of death at that time was about one in 100,000; by 2007, the rate neared 10 per 100,000. “Prescription drug abuse is the fastest growing drug problem in the United States,” she says, and is accompanied by unintentional drug overdose death rates largely driven by an increase in opioid analgesics.

How did we get here? Dr. Magnani notes that pain is considered the fifth vital sign, and patients have the right to appropriate assessment and management of their pain—it’s a Joint Commission standard.

Most prescription painkillers are prescribed by primary care and internal medicine doctors and dentists, she says. “I see this in my own practice, where it’s mostly the primary care physicians who have difficulty managing patients on chronic opioid therapy and are coming to the laboratory for help in managing those patients.”

What do clinicians need from the laboratory? Dr. Magnani points to what are known as aberrant drug behaviors: not using prescribed medications, not using prescribed medications as prescribed, using nonprescribed medications, using illicit drugs, and diverting prescribed medications. “These are the questions that our clinical colleagues ask us when we run a urine drug test and want to know if their patient is compliant.

“There’s a good reason to identify these behaviors where possible,” she continues. Several studies have looked at urine drug testing and noncompliance. A retrospective study of 470 pain clinic patients, for example, looked at urine drug testing by gas chromatography-mass spectrometry. All results were reviewed and verified against patient charts to check for appropriateness of test results (Michna E, et al. Clin J Pain. 2007;23[2]:173–179).

Only 55 percent of the patients were using the appropriate opioid, while 10.2 percent of the patients were missing the prescribed opioid. Moreover, 14.5 percent had an additional nonprescribed opioid, and 20.2 percent were using illicit substances.

Clinical guidelines for opioid therapy call for, among other things, prescription monitoring program reports, which includes urine drug testing. The written contracts/agreements between physicians and patients who are prescribed long-term controlled substances for chronic pain will include notice that patients can be subjected to random drug testing, says Dr. Magnani. “That’s important, because the presence of unauthorized substances may prompt referral for assessment for either an addictive disorder or may, in fact, even break the contract.”

Another element of clinical guidelines covers monitoring therapy. Physicians need to assess the patient periodically, or with any changing circumstance, she says. Are patients improving? Are they adhering to therapy? Are there adverse events, such as psychological issues or substance abuse? Again, urine drug tests can help with such monitoring. It supplements other tools, such as pill counts, self-reporting, and behavioral monitoring, and can identify problems that might otherwise go undetected. “It really is an objective means to document aberrant drug behavior” as well as a way to check for compliance.

Every guideline recommends urine drug testing, Dr. Magnani says, but the details can be fuzzy. The state of Washington’s guideline, for example, says that urine drug testing is used to “objectively assure compliance,” but provides scant concrete information. What, exactly, does compliance imply? Dr. Magnani asks.

For treating physicians, it meant patients are sticking to the terms of their treatment agreement. Urine drug testing can help with this, but isn’t perfect. It can’t determine if a patient is adhering to exact dosing intervals, for example. “This is a problem for us when we do our consultations,” Dr. Magnani says. “All I can really say is if the drug and its metabolites have shown up in the urine, then it’s most likely they’ve taken that drug prior to the urine collection. I don’t know exactly how much and whether they’re taking it every day. I can’t determine whether they’re taking more or less of that prescribed dose.” As to whether they’re taking a nonprescribed medication, it depends on what the assay targets, though most labs can detect use of illicit drugs.

An equally important issue for urine drug testing is clinicians’ interpretive skills. Dr. Magnani cites a seven-question, multiple-choice survey that assessed the skills of 150 physicians at an opioid education meeting. Among this group, 68 percent used drug testing, and 76 percent prescribed opioids; 19 percent were board-certified in pain management and six percent in addiction medicine or psychiatry. Of those who ordered drug tests, says Dr. Magnani, none answered all seven questions correctly, and only 30 percent scored more than half correctly.

The implications are clear to Dr. Magnani: Clinicians can’t manage their patients’ pain without help from the laboratory.