Effective Monitoring of Opiates in Chronic Pain Patients
Earlier this year, the U.S. Food and Drug Administration (FDA) announced its intent to require manufacturers of two dozen opioid formulations to construct detailed Risk Evaluation and Mitigation Strategies (REMS) for their products in order to verify that their benefits to pain management continue to outweigh the potential risks associated with abuse and misuse. In addition to individualized REMS for certain branded and generic drugs, the FDA also plans to issue a formal REMS for the opioid drug class as a whole, which may take up to a year to develop.1 However, the FDA’s Amendment Act of 2007 paints a reasonable picture of what the pain management industry can expect from this type of REMS, including six general elements that can be used to assure safe use and with two of those elements calling for a more rigorous approach in documenting patient care:2
- Dispensing to patients with evidence or other documentation of safe use conditions such as laboratory test results;
- Each patient receiving the drug is subject to certain monitoring.
Drug developers are not the only constituents that stand to be affected. Physicians prescribing natural, semi-synthetic, and synthetic opioids to relieve chronic pain symptoms will also be held to more stringent guidelines in regards to determining whether or not patients are following treatment regimens as directed.3
Testing patients to prove compliance will play a critical role in satisfying the FDA’s desire for more stringent risk management. And for physicians with patients taking high doses of opiates, compliance monitoring within a laboratory environment is the most appropriate way to do so. Compliance monitoring is recognized as a mechanism to minimize drug diversion, avoid overmedication, and evaluate if a patient is using illicit or non-prescribed drugs that may put the patient’s safety at risk while taking medication prescribed by their physician.
Comparing Methodology of Traditional Urine Drug Testing to Compliance Monitoring
While historically urine drug testing has been used for pre-employment, workplace monitoring, and law enforcement applications, extending its reach to compliance monitoring of patients receiving prescription opiate pain relievers presents new challenges in both procedures and interpretation of test results. For workplace drug testing, administrators are looking for negative test results to verify that individuals are not misusing narcotics or other illicit drugs. In this case, traditional cut-off levels (normally as high as 300 or 2,000ng/mL for opiates) are well suited for detecting drug concentrations typically associated with abuse. However, traditional cut-off levels are not as effective in providing accurate assessments of patient compliance. Modern-day urine drug testing to monitor patient compliance requires lower cut-off levels that typically are only achievable using state-of-the-art instrumentation utilized in a laboratory setting (normally as low as 50ng/mL for opiates). These lower cut-off levels provide healthcare practitioners with an objective method for monitoring patient compliance while also achieving the goal of traditional urine drug testing—identifying patients who may be misusing drugs.
Although procedures may vary between laboratories, compliance monitoring usually consists of an initial screening test followed by a confirmation test. Most laboratories perform initial screening by immunoassay, a relatively quick and cost-effective procedure. If a specimen screens negative by immunoassay, no further testing is performed and the specimen is reported as negative. Specimens that screen positive are confirmed by a second technique involving mass spectrometry, an analytical method considered to be the “gold standard” in identification and measurement of drugs.
Traditional workplace urine drug testing achieved by point-of-care (POC) devices and routine hospital testing techniques are usually based on immunoassay technologies and indicate the presence of a certain drug or drug class through the formation or absence of a color indicator. The cut-off for each drug or drug class represents the minimum amount of drug and/or metabolite that must be present to be considered positive, and standard POC and hospital testing rely on elevated cut-off levels to identify drug abuse when urine concentrations are expected to be high. While these methods are successful in detecting drug abuse, their cut-off levels are not conducive to assessing patient compliance, as their lack of sensitivity allows for the possibility of false-negative results. To achieve a false-negative result, drugs and metabolites must fall within a testing range below the designated cut-off. When this happens, testing will indicate that the specimen tested negative for those substances even if they were present at low levels. The ability to distinguish between drug abuse and therapeutic compliance has become increasingly important in the field of pain management, as patients who diligently abide by their treatment plans may produce urine with drug concentrations too low to register on a traditional urine drug test.
Many medical practices still attempt to evaluate patient compliance using POC devices and hospital testing despite the sensitivity limitations described above. But when it comes to ensuring patient safety and minimizing physician liability, compliance monitoring conducted in a laboratory setting—focused on supporting physicians in pain management—provides the best, and perhaps only, objective measure.
Comparing Test Results of Traditional Urine Drug Testing to Compliance Monitoring
When POC devices and routine hospital testing are used in place of compliance monitoring, the results are vastly different. At AIT Laboratories—a full-service toxicology laboratory performing pain management, forensic, clinical, and pharmaceutical testing—test results from 111,872 urine specimens collected over a one-year time period from pain treatment facilities throughout the U.S. They were evaluated in order to quantify the number of specimens that may have tested negative according to traditional urine drug testing devices but tested positive in the laboratory where lower cut-off levels were utilized. Samples were submitted using standard urine collection devices supplied by AIT Laboratories and arrived at ambient temperature by mail or hand delivery. The specimens were then screened by Cloned Enzyme Donor Immunoassay (CEDIA, Thermo Fisher Scientific, Fremont, Ca.) utilizing cut-off levels conducive to compliance monitoring (50ng/mL). Of the 77,881 specimens that screened positive for opiates at levels of 50ng/mL or higher in the laboratory, an alarming 59.05 percent (n=45,991) fell below typical POC device cut-off levels of 2,000ng/mL. Additionally, 23.34 percent (n=18,175) fell below 300ng/mL, the typical cut-off level used by clinical, hospital, and reference laboratories.4 This suggests that of those patients who were prescribed opiates, a substantial proportion of positive specimens may have gone undetected unless specimens were submitted to a laboratory using a low cut-off level for initial screening.