Pediatrician and patients

Recognizing that interpreting drug test results can be “exquisitely complex even for experienced clinicians,” the American Academy of Pediatrics (AAP) recently issued some much-needed guidance on the difficult topic of testing for drugs of abuse in children and adolescents. Produced by AAP’s committee on substance abuse, the document replaces an earlier clinical report that had expired after 5 years. The new guidance emphasizes the practical aspects of an admittedly complicated subject.

“Drug testing is kind of put out there as a very simple procedure, but once you start doing it, you realize it’s not simple at all. It’s a complicated series of laboratory tests; not even one test,” said the report’s lead author, Sharon Levy, MD, MPH, assistant professor of pediatrics at Harvard Medical School and director of the Adolescent Substance Abuse Program at Boston Children’s Hospital. She added that research shows pediatricians generally lack the skills to order and interpret drug tests efficiently.

While the report is aimed at pediatricians, Levy hopes that knowledge of it will give laboratorians a starting point for advising clinicians about drug testing. “I think having the laboratory medicine people understand what we’re doing in primary care, and what we’re trying to achieve would be enormously helpful,” she said.

Thinking Through the Consequences of Testing
In keeping with the prior document, the authors discuss the ethics of drug testing in youth and called upon pediatricians to consider how a test result will be managed before they send it out for testing (Pediatrics 2014; doi:10.1542/peds.2014-0865). The committee advises against involuntary drug testing but describes several situations in which testing would be appropriate, including in emergent circumstances, such as after a suicide attempt or an accident, and suggests strategies for managing adolescents who refuse indicated tests. Drug testing also would be warranted to assess a youth’s behavioral problems, when parents suspect drug use, or as part of a substance abuse treatment program. The document comes out against both widespread school-based drug testing and home-based testing.

The Limitations of Immunoassays
The authors describe the universe of drug testing specimen types but emphasize that urine testing is by far the most common. A survey found that more than 90% of pediatricians and family practitioners have used urine drug testing with adolescent patients in their offices. How knowledgeable these clinicians might be of the limitations of urine drug tests is another matter. “Clinicians are often not aware of the metabolic patterns of drugs. Also, they don’t necessarily understand the concept of a cutoff and what that means in the laboratory,” explained Kara Lynch, PhD, DABCC, associate division chief of clinical chemistry and toxicology at San Francisco General Hospital. “The thing I worry about is how many times doctors have questions about results and don’t take the time to call the lab to try to figure it out.” Lynch did not contribute to the AAP report.

The authors take pains to describe several instances in which urine immunoassays in particular can lead to false-positive or false-negative results, particularly when young patients might be taking prescription medications. For example, fluoroquinolone antibiotics can cross-react with immunoassay opiate screens, and clonazepam, which adolescents commonly misuse, may not be picked up by benzodiazepine panels.

These finer points elude many pediatricians as well as parents, according to Jennifer A. Lowry, MD, chief of clinical toxicology at Children’s Mercy Hospital in Kansas City, Missouri. “They think that the test result is going to tell them all the information they want,” she observed. “However, the laboratories report what they can report based on the test. Some of these immunoassay results are like flipping a coin in that false-negatives and false-positives are common. So if you have a positive, you need to confirm it because there are so many things that can cause a false-positive and you’re making decisions that can impact the child for quite some time.” Lowry did not serve on the guideline panel.

What’s the Clinical Context?
Chromatography and mass spectrometry-based confirmatory tests may not have cross-reactivity challenges, but by virtue of their higher sensitivity, underscore the need for clinicians to consider results in the context of patients’ clinical circumstances. For instance, an adolescent taking amphetamine and dextroamphetamine for attention deficit hyperactivity disorder will test positive for amphetamines. This positive result, though correctly indicative of drugs in the patient’s system, would be a false-positive for drug abuse.

The authors also point out that negative screening results don’t necessarily provide a definitive answer about the child’s use of illicit drugs. In addition to the possibility of adulterated samples, drug use can be missed if the lab’s cutoff is too high, or if the patient has used a drug that’s not detected in the lab’s standard test panel, a rather frequent occurrence, according to Lynch. “It’s common now, unfortunately, for adolescents to use designer drugs, and most of our urine drug screens in laboratories will not detect those compounds,” she said.

Starting a Conversation
The document provides a table of the window of detection for various drugs and metabolites, ranging from alcohol and amphetamines to semisynthetic opiates like hydrocodone and oxycodone. Lynch called this a “good start,” but emphasized, as does the guideline, that pediatricians can’t be expected to know the ins and outs of interpreting drug tests, all the more reason to reach out to laboratorians.

Although Lynch’s lab primarily tests specimens from adults, one of the most common questions she fields from physicians deals with test results that don’t match patients’ clinical picture. “I’ll get calls about interpretation of confirmatory results. Especially for opiates,” she explained. “They’ll ask, ‘Is my patient taking what I’m prescribing them?’ because they see results that indicate the patient is positive for X, Y, and Z opiate. They want to know whether that result is consistent with what they’ve prescribed the patient.”

In her practice in a substance abuse program Levy is “constantly on the phone with the laboratory,” something she would like to see pediatricians not as well-versed in drug testing do. She gave her own experience as an example of the productive collaboration between clinicians and laboratorians when it comes to drug testing. “We started noticing that some of our patients who had serial testing were having results come back with parameters within two or three percent of each other on multiple occasions. Nearly identical creatinine, pH, specific gravity, and marijuana levels,” Levy recalled. Dialogue with the lab helped her get to the bottom of this run of similar results, ultimately “helping us take better care of these kids,” she added.

Lowry supports this type of collaboration, but stressed that labs may need to do more outreach than just making clear report comments. “Lab reports state that positives need to be confirmed with [gas chromatography-mass spectrometry]. I understand what that means, but the average pediatrician is not going to understand the importance of this,” she said. “So a conversation between the laboratorian and the physician about the limitations of the testing, what information is coming from the test, and how it can be used would be really helpful.” In Lowry’s view, such discussions happen all too rarely.

New Cutoffs, Panels?
In addition to improved dialogue with clinicians, Levy, Lowry, and Lynch all noted the need for better adolescent-specific cutoffs and panels that test for substances kids are more likely to abuse. “The guidelines that are put out there by [the Substance Abuse and Mental Health Services Administration] were made for workplace testing and it’s just not the same thing with kids, so those guidelines are not always appropriate for primary care pediatrics,” Levy explained.

Lynch also encouraged labs to take a look at their testing procedures and panels. “Many laboratories use a model that was developed years ago and haven’t really changed anything over the years. Beyond the cutoffs not being useful, the actual panel itself might not be useful.” She cited the fact that many panels still test for PCP, which was commonly used in the past, but, at least in the case of San Francisco General Hospital, is now “rarely seen.”

Lowry agreed with the need to review testing panels, but cautioned that drug abuse patterns tend to be regional, so labs would need to take into consideration their own populations when doing so. Kansas City, she added, still sees “a bit of PCP” and has high methamphetamine use, which is less popular on the East Coast. In her view, not including barbiturates in testing panels would be a better choice.

With all the nuances of drug testing in children and adolescents, perhaps the guideline’s best advice is summed up thusly: “The practitioner should not hesitate to ask for assistance in ordering the correct test or interpreting results.”