Study on innovative algorithm and reference database helps clinicians to identify potential opioid misuse, abuse, and diversion among chronic pain patients

September 9, 2011
  • More people die each year in the U.S. from prescription opioid overdose than from cocaine and heroin use combined
  • Traditional urine drug testing, while important, has limitations with respect to distinguishing adherence versus potential opioid abuse or diversion
  • Conducted at Beth Israel Medical Center in New York and presented at PAINWeek annual meeting in Las Vegas, the study showed that a large database of patients who were clinically assessed as adherent can serve as a reference to help evaluate potential opioid use across diverse patient populations – providing clinicians with an important tool to improve patient care through pain medication monitoring

BALTIMORE, MD (September 9, 2011)—AmeritoxSM, the nation’s leader in pain medication monitoring, in conjunction with Beth Israel Medical Center, this week announced the results of a new study showing that the company’s reference database tool, Rx Guardian CDSM, based on urine drug monitoring results from a large database of oxycodone-prescribed patients who were clinically assessed as adherent, generalized well to a geographically and demographically distinct group of patients.  Study findings were presented today at PAINWeek®, the national conference on pain for frontline practitioners, the nation’s largest pain conference.

Results of this study indicate that Rx Guardian CDSM, when combined with other clinical indicators of non-adherence, may enhance clinicians’ ability to help identify potential non-adherent patients using chronic opioid therapy.

Russell Portenoy, MD, Chairman of the Department of Pain Medicine and Palliative Medicine at Beth Israel Medical Center in New York, was principal investigator of this study sponsored by Ameritox. The purpose of the study was to determine whether the proprietary model, based on a database of patients from Wisconsin who were clinically assessed as adherent, would generalize well to a different population of oxycodone-treated patients from New York City who were also clinically assessed as adherent.  Study results confirmed that the reference ranges calculated from a Wisconsin patient sample generalized well to the New York City sample, further demonstrating the applicability of the tool across diverse patient populations.

“Prescription opioid therapy is a critical lifeline for millions of patients suffering with chronic pain, but careful monitoring is important for both individual and public safety – in addition to health concerns, misuse, abuse and diversion of prescription opioid therapy costs payers millions,” said Dr. Harry Leider, a contributing author of the study and Chief Medical Officer of Ameritox.  “By developing tools based on new drug monitoring technologies that can help physicians better detect non-adherence, we are contributing to improved quality of care and potentially reducing costs to the healthcare system.”

In this era of health care reform, reduction of unnecessary medical spending is an important goal. A major 2011 study published in The American Journal of Managed Care demonstrated that patients on chronic opioid therapy who were likely non-adherent, as determined by urine drug monitoring results, spent 35 percent more time in the hospital and had 14 percent higher health care costs than patients who were likely adherent.  A separate study, published this year in The American Journal of Pharmacy Benefits, found that non-adherent patients had average excess medical costs of $20,546 per year, per privately insured patient, when compared to likely adherent patients.

While most patients and physicians use or prescribe chronic opioid therapy with the best of intentions, a recent national study of nearly one million prescription monitoring tests showed that, for a variety of reasons, the majority of pain patients may not be using their medication correctly – indicating potential misuse, abuse, diversion or non-adherence. For example, 11 percent of patients were found to be taking an illicit drug and more than 30 percent had no detectable level of their prescribed medications – despite being prescribed a chronic regimen of opioid therapy.

Study Methodology

The purpose of the study was to determine whether the Rx Guardian CDSM model, based on a database of patients from Wisconsin who were clinically assessed as adherent, would generalize well to a population of oxycodone-treated patients from New York City who were also clinically assessed as adherent.  A cohort of pain patients receiving a stable regimen of oxycodone therapy was identified from a larger study at New York’s Beth Israel Medical Center (BIMC).  Investigators clinically assessed adherence to opioid therapy using multiple criteria including: appropriate self-reported medication use, the Morisky Validity of Medication Adherence survey, and urine drug testing results demonstrating the absence of illicit drugs or non-prescribed controlled medications, and the presence of the prescribed opioid. Quantitative urine oxycodone levels, measured with mass spectrometry, were obtained and adjusted for hydration and lean body weight using the proprietary algorithm. These adjusted urine drug levels were compared to reference ranges derived from a pre-existing database of patients, who were rigorously assessed to be adherent by a pain medicine program in Wisconsin. Study investigators computed the percentage of patients classified as adherent by BIMC that also fell within the reference ranges (with corresponding 95% binomial confidence intervals). Study investigators reported these values separately for patients on variable or fixed dosing regimens.


In total, 108 BIMC patients receiving chronic oxycodone therapy provided 112 urine samples; 60 samples were from patients taking a fixed total daily dose of oxycodone and 52 were obtained from patients on flexible but stable doses.

These urine drug levels were adjusted for hydration and lean body weight using the proprietary algorithm and were then compared to the pre-established reference ranges derived from the Wisconsin cohort of patients clinically assessed as adherent. Of the total 112 BIMC samples from patients clinically assessed as adherent, 99 or 88.4% (95% CI: 81%, 93.7%) were found to be within range. For patients on fixed dose oxycodone, 54 of 60 or 90% (95% CI: 79.5%, 96.2%) were found to be within range; for those on variable dose oxycodone, 45 of 52 or 86.5% (95% CI: 74.2%, 94.4%) were found to be within range.

Study Implications

Chronic pain is the most common cause of long-term disability in the United States, affecting 50 million Americans. Treatment with prescription narcotics (i.e., opioids) is an effective and critical treatment for a significant subset of this population with severe pain that cannot be controlled with other medications and treatments.  However, opioid misuse, abuse, diversion and non-adherence is a major threat to patient safety and impacts negatively total healthcare spending.  Traditional drug testing approaches, such as urine drug testing alone, cannot distinguish between patients taking their opioid regimen correctly from patients taking too little opioid (potential non-adherence or diversion) or taking too much opioid (potential misuse or abuse).  This study demonstrated that the proprietary Rx Guardian CD tool, based on a large database of patients in Wisconsin who were clinically assessed as adherent, can be applied to diverse patient populations across the country to help identify potential misuse, abuse or diversion of opioid therapy – thereby providing clinicians with an important tool to improve patient care and potentially impact medical costs.  Study results are available online at

About Ameritox

Ameritox is the nation’s leader in Pain Medication Monitoring Solutions®, offering specialized laboratory testing and reporting services. Ameritox’s expertise and innovative science provide physicians with insights and support to enhance and optimize the care of chronic pain patients. Ameritox offers the most thorough pain medication monitoring lab process – Rx GuardianSM – with Rx Guardian CDSM, the only pain medication monitoring tool with a proprietary normalization algorithm and a reference database of pain patients who were clinically assessed for medication adherence. Patient results are compared against this database, helping physicians assess whether patients are taking their pain medications correctly. Monitoring through urine drug testing helps physicians make more informed clinical decisions and manage the risks and complexities associated with prescribing pain medications. Ameritox is headquartered in Baltimore, Md. with laboratory facilities in Midland, Texas and Greensboro, N.C. Ameritox can be found online, on Twitter @Ameritox, or on Facebook at