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Labs Concerned New Draft CDC Opioid Guidelines Downplay Role of Toxicology Testing


NEW YORK – Some in the clinical lab space are concerned that the US Centers for Disease Control and Prevention's recently updated draft guidelines for prescribing opioids downplays the role of toxicology testing in patient monitoring and management.

Released in February, the new draft guidelines recommend toxicology testing with an evidence level of B, indicating that testing is not necessarily appropriate in all patients, and suggest only that doctors "consider toxicology testing to assess for prescribed medications as well as other prescribed and non-prescribed controlled substances."

This represents a softening of the existing CDC guidelines, which state that "clinicians should use urine drug testing before starting opioid therapy."

The new draft guidelines also highlight the cost of toxicology testing, and the high cost of liquid chromatography- and mass spectrometry-based confirmatory testing, in particular. They recommend that clinicians use confirmatory testing only when it is necessary to detect specific agents that cannot be identified using less expensive immunoassays and when the results can "reasonably be expected to affect patient management."

Additionally, the guidelines call into question whether research supports the use of toxicology testing, noting that clinical evidence reviews "did not find studies evaluating the effectiveness of toxicology screening for risk mitigation during opioid prescribing for pain."

Paul Jannetto, director of the clinical and forensic toxicology laboratory at the Mayo Clinic, said that taken altogether, the draft guidelines, in his opinion, "de-emphasize" the role of toxicology testing in managing patients using opioids for pain.

Jannetto added that while CDC guidelines are not binding, they are something clinicians and healthcare systems follow. He also noted that while the CDC states that the guidelines "should not be applied as inflexible standards of care across patient populations by healthcare professionals, health systems, pharmacies, third-party payers, or state, local, and federal organizations or entities," there is concern they could impact payor coverage decisions.

"Payors start to look and say, wait a second, here is a national body saying maybe [toxicology testing] isn't as necessary as we once thought it was," he said. "Is this something that we should look at? Because it can be a costly endeavor."

Jeff Gudin, an anesthesiologist and pain management specialist at the University of Miami Miller School of Medicine as well as senior medical advisor to Quest Diagnostics' drug monitoring and toxicology franchise, said that toxicology testing is essential to a physician's understanding of what other drugs might be in a patient's system and whether or not they are using their medication as prescribed.

"Drug testing is the only way prescribers have of knowing what is in a patient's system and whether they are behaving or misbehaving with their medicines," he said. "These are critical points for us to understand. You can imagine that clinicians like myself, as well as labs, their feathers got ruffled a bit when they saw the new recommendation for 'consider' drug testing."

Gregory Polston, an anesthesiologist and pain management specialist at UC San Diego Health, suggested, however, that the draft guidelines represented a reasonable correction to what he said was overuse of toxicology testing by some doctors when prescribing opioids.

He said that a number of factors have come together to push doctors to order toxicology testing more than may be necessary. A major driver, he suggested, is doctors looking to protect themselves legally.

"State legislatures have gotten involved and mandated screens but they haven't necessarily said what tests need to be run," Polston said, noting that this has led doctors to overtest "for fear of violating statutes."

He cited as an example Georgia state law that requires regular drug screening of patients prescribed opioids for 90 or more days for chronic pain.

That law "doesn't state that it has to be a liquid chromatography test with a large panel, but some people have interpreted that as what is needed to protect their medical license and comply with statutes even though it is not necessarily in the best interests of the patient," he said.

Polston also highlighted a project California launched in 2015 in which the state medical board reviewed death certificates from patients who died from prescription opioid overdoses and investigated those patients' providers to determine if they had managed patients inappropriately. Several hundred doctors had complaints filed against them through the program with several facing potential disciplinary actions, including revocation of their licenses.

Given this environment, and the desire to prevent overdoses among their patients more generally, some doctors have erred on the side of caution, choosing to over-, rather than undertest. That doesn't make it desirable, though, Polston said.

"The question is always do we need to do the full panel of all the drugs patients are taking with liquid chromatography?" he said. "Do we really need to confirm that they are taking all of their antidepressants, all of their muscle relaxants, all of their anti-seizure medications by doing these large panels? Physicians will do some of these tests repeatedly to protect themselves from not identifying patients who are abusing."

"But I think that, not unlike with other laboratory tests, we need to be more precise," he said.

Furthermore, Polston said, there is not good evidence showing that urine screening actually reduces overdoses in patients being prescribed opioids.

Opioid overdosing "is a significant issue, and if we can find ways to intercede, it would obviously have significant impacts on the health and safety of individuals and our society," he said. "Unfortunately, it has been difficult to show the clear advantages of urine screening."

One challenge, Polston said, is that the entire opioid prescribing landscape has shifted in recent years, which makes it difficult to isolate any specific contributing factors in retrospective reviews.

"There has been a complete change in all of how we treat [opioid prescribing]," he said. "We are prescribing less opioids. More physicians are checking prescription drug monitoring programs. More people are attempting to use screening tools and changing indications for opioids. And none of this has been done in isolation."

Polston's comments echo the CDC's statement in its draft guidelines that evidence of the effectiveness of toxicology testing is lacking. Jannetto said, however, that the American Association for Clinical Chemistry 2018 practice guidelines for the use of lab testing in managing patients using opioids (which he edited) found solid evidence in the clinical literature to support use of regular toxicology testing.

The AACC guidelines also depart from the CDC draft guidelines in that they recommend the use of definitive drug testing via approaches like mass spec as a frontline screen replacing immunoassays, while the CDC guidelines recommend that frontline testing continue to be done mainly via immunoassays with more expensive definitive testing used only when necessary.

Gudin acknowledged that some parties, particularly among payors, remained dissatisfied with the current evidence supporting toxicology testing. He suggested, though, that generating this evidence would be very difficult — in large part due to the importance of such testing.

"When I first came to work for Quest, they gave me one task," he said. "They said, 'When we talk to payors, they all say there is no level one evidence supporting the use of toxicology testing. Help us design that trial.'"

The challenge, though, is that for the sort of randomized controlled study required, a control group is needed, Gudin said. "And that means you would take a group of at-risk patients and not drug test them. It's very difficult to collect level one evidence."

"But we can't use that as a reason not to perform the only objective test that we have to know what a patient is taking," he said. "We don't need a study to tell us drug testing makes a difference. When I pick up benzodiazepines and opioids together, that's an at-risk overdose patient. And the only way I know that is by drug testing them."

Of course, the question isn't about whether to do any toxicology testing at all but when and how to do it.

Polston said he believed the more conservative approach to testing suggested by the draft guideline was appropriate.

"It acknowledges the need to do urine screens, but it also acknowledges that there needs to be further evidence and further research into the best way to use it," he said. "We should use it, but we need to use it wisely."

Gudin and Quest remain concerned, however, that the draft guidelines will cause clinicians to use less than toxicology testing than is needed.

"We just think it is an error for [CDC] to lighten up on drug testing in the midst of our country's greatest opioid epidemic ever," he said.

The period for public comment on the guidelines closed on April 11. The CDC said it expects to release a final version of the new guidelines in late 2022.