To effectively monitor pain management in patients, should labs report results based on an assay’s limits of detection? Or, should they report standard cutoffs from commercial assays? Two experts sound off on this topic in the Journal of Applied Laboratory Medicine’s special January issue on supporting pain management.
William Clarke, PhD, associate professor of pathology at Johns Hopkins School of Medicine in Baltimore, believes that evidence-based standardized cutoffs make the most sense for managing pain, given the variations in limits of detection (LOD) and assay results, which make interpreting results difficult. Labs that decide to move away from standard cutoffs may not have the same technological capacity to detect drugs, Clarke cautions. For example, “a laboratory cannot detect substances all the way down to ‘zero’ concentration,” he writes.
Without standard concentration cutoffs, how can a lab consistently interpret results? asks Clarke. “If 1 laboratory has an LOD cutoff of 2 ng/mL and another uses a concentration cutoff of 2000 ng/mL, do qualitative positive results mean the same from both labs? ”he writes. In his view, it should be plausible to develop cutoffs specific to patients on long-term therapy. Adapting cutoffs set by the Substance Abuse and Mental Health Services Administration (SAMHSA) developed for workplace drug testing is one avenue to explore, he emphasizes.
“Although it is important to note that the SAMHSA cutoffs were not established with pain management and long-term opioid therapy in mind, it is possible that they can be modified to reflect long-term dosing of certain opioids while maintaining existing concentration cutoffs for illicit drug use,” Clarke suggests.
Two groups of analytes should factor into setting these cutoffs for toxicology screening in pain management. “For prescribed medications, one would want the cutoff sufficiently high to account for long-term recurrent dosing while avoiding a positive result for sporadic or nonadherent use. For illicit drugs, lower cutoffs are desirable to maximize the windows of detection to assess exposure at any point,” he recommends.
In her editorial, Gwendolyn A. McMillin, PhD, a professor of pathology at the University of Utah School of Medicine and medical director for toxicology and pharmacogenetics at ARUP Laboratories in Salt Lake City, counters that setting a rigid cutoff concentration may not be the best choice for patients, given the variations that occur among drug and dosing regimens and analytical methods and test results, not to mention each patient’s unique circumstances. In her view, thresholds are determined somewhat arbitrarily and are thus not very meaningful.
“Cutoffs are not typically determined based on clinical relevance, and drugs are frequently detected below SAMHSA cutoffs. Physicians want to know if there is any detectable drug in a sample, which means we need to go as ‘low as we can go’ analytically,” she explained to CLN Stat.
McMillin proposes that labs could rely on assay LOD or limits of quantification in lieu of standardized cutoff concentrations to reliably detect minimum drug and drug metabolites in urine, offering up several arguments against using traditional methods. “Cutoffs may restrict the detection of drugs and metabolites when the efficiency of hydrolysis reactions, extraction recoveries, derivatizations, and other preanalytical reactions that are designed to prepare a sample for analysis vary,” she indicates. “Although standardization among laboratories that offer drug exposure testing in urine for chronic pain and addiction management patients is a noble goal, much remains to be learned before rigid standardized cutoff concentrations can be proposed or applied to the many drugs and drug metabolites relevant to this clinical population.”
Pick up January’s special issue of JALM to get more details on this debate on monitoring pain management. The issue also features AACC Academy’s first laboratory medicine practice guideline on pain management.