Access to the PPM Journal and newsletters is FREE for clinicians.
13 Articles in Volume 10, Issue #5
An Osteopathic Approach to Fibromyalgia
Co-Morbid Psychological Disorders in Interventional Pain Management
Compliance Monitoring and Effective Risk Mitigation Strategy
Cultural Differences and Pain Management
Electronic Prescription of Controlled Substances
Kinetic Chain from the Toes Influences the Craniofacial Region
Non-responsive Pain Patients with CYP-2D6 Defect
Platelet Rich Plasma for Hamstring Tears
The Iontophore
The Treatment of Achilles Tendonitis Using Therapeutic Laser
Thoracic Facet Injections
Urine Drug Testing as an Evaluation of Risk
Vitamin D Levels In Pain and Headache Patients

Compliance Monitoring and Effective Risk Mitigation Strategy

Compliance monitoring using laboratory screening and confirmation, together with physician education, can support an effective risk mitigation strategy.

Editor’s note: In this article, Dr. Michael Evans et al present a very compelling case for the employment of a reputable testing lab as part of a standardized REMS program.

Robert Foery, PhD, DABCC/TC

For those in the health care profession, all eyes are on the U.S. Food and Drug Administration (FDA) as the agency moves forward with plans to develop a standardized Risk Evaluation and Mitigation Strategy (REMS) for long-acting and extended-release opioid analgesics. Once the formal components are revealed, physicians, drug manufacturers, pharmacists, and other vested stakeholders will be held more accountable in promoting the safe use of opioid drugs as part of a chronic pain treatment plan.

However, while the FDA is expected to present several REMS elements for possible adaptation—ranging from patient package inserts to prescriber/patient agreements—physicians will still face the issue of gauging therapy compliance among their patients, namely, a measurable way to evaluate safe use. Compliance monitoring using laboratory screening and confirmation—coupled with the appropriate education—provides tangible value to practitioners aiming to comply with a risk mitigation plan. It can also reduce drug diversion in a practice over time.

Brief History of REMS

Since the medical community’s acceptance of chronic pain as a valid diagnosis in the twentieth century, there have been concerns surrounding its treatment. Chronic pain is often extremely difficult for a physician to verify, yet its effect on a patient’s quality of life can be so debilitating that the prescription of opioid analgesics is often the most efficient way to provide adequate relief. However, as the use of opioids continues to rise, so do occurrences of abuse, serious injury, and even death. In 2008, nonmedical use of pain relievers was listed as one of the drug categories with the largest number of recent initiates among persons aged 12 or older (2.2 million).1 Prescription pain relievers rank second in categories of the most popular drugs of abuse according to the White House Office of National Drug Control Policy2 and opioid analgesics were involved in almost 40% of all poisoning deaths in 2006, up from about 20% in 1999.3

In response to these and similar data, the FDA Amendments Act of 2007, which significantly amended the Federal Food, Drug and Cosmetic Act to increase the FDA’s authority, was signed into law. Under Title IX, Subtitle A, section 901, the agency may now require drug manufacturers to include a REMS as part of a drug application or to comply with one if it decides that a REMS is necessary as new safety information becomes available. For those drugs that do require a REMS, the FDA will determine which components must be included in its safety strategy.4

“Falling under the “Elements to Assure Safe Use” component of REMS, laboratory-based compliance monitoring supports safe-use conditions by upholding the integrity of the testing process.”

To be considered for approval, a REMS submission to the FDA must include two parts: a brief outline of the strategy and supporting documentation containing more detailed information.5 These pieces work together to provide clear reasoning behind the goals of the REMS, selection of REMS elements to achieve those goals, and a concrete timetable for monitoring its success. A REMS may include one or all of the following: medication guide or patient package insert, a communication plan to healthcare providers, and tangible elements to assure safe use on the part of the appropriate stakeholders. The latter can include requirements for those who prescribe, dispense, or use the drug.

Significance of REMS to the Pain Management Community

In a country where the number of deaths involving prescription opioid analgesics increased 160% from 1999 to 20046—a mere five years—and more than half of all drug misuse/abuse emergency department visits in 2006 involved illicit drugs,7 stakeholders are more aware than ever of their responsibility to curb abuse and reduce harm to those who rely on opioids for pain management. However, despite increased exposure from legislation and the media, awareness of the science behind compliance monitoring is sorely lacking among practitioners. Not all opioids work in the same way and patient tolerance can vary widely between drugs—even those within the same class. This means that physicians, pharmacists, and other stakeholders involved in pain management who are not appropriately educated run the risk of making ill-informed decisions that could result in fatality for their patients. At the 2010 American Academy of Pain Medicine annual meeting, a literature review of poisoning deaths involving opioids from 1999 to 2009 revealed that the number of deaths involving meth-adone were disproportionately high, representing less than 5% of all opioid prescriptions but responsible for a third of the deaths. Fundamental misunderstandings about the properties of methadone on the part of physicians when converting patients from other opioids may be to blame.8

The combination of mass prescribing and incomplete education can lead to tragic outcomes but they are preventable. Stringent REMS initiatives, like the FDA’s, and concerted efforts from physicians to maintain a base knowledge of drug profiles can work in tandem to drastically improve patient safety and reduce a physician’s legal liability. Compliance monitoring using laboratory screening and confirmation addresses each of these needs by offering a measurable way to evaluate safe use and providing educational opportunities for physicians and other vested stakeholders.

Compliance Monitoring and Its Impact on REMS

Compliance monitoring is recognized within the pain management profession as an effective means for identifying illicit and non-prescribed drug use, avoiding toxic drug interactions in patients, and evaluating adherence to a prescribed treatment plan. Immunoassay-based techniques—available through point-of-care (POC) devices and routine hospital testing—attempt to achieve these goals by maintaining traditional cut-off levels originally developed for workplace urine drug testing—levels that are typically as high as 300 or 2,000ng/mL for opiates. In stark contrast, compliance monitoring performed by a reference laboratory follows a more rigorous process that relies on state-of-the-art instrumentation usually found only in a laboratory setting. Cut-off levels are significantly reduced to accurately assess patient compliance and can be as low as 50ng/mL for opiates at a few specialty laboratories. Samples that screen positive are confirmed and quantified using mass spectrometry to generate what is essentially a unique “chemical fingerprint” pattern for each drug.

Falling under the “Elements to Assure Safe Use” component of REMS, laboratory-based compliance monitoring supports safe-use conditions by upholding the integrity of the testing process. Unambiguous identification of drugs eliminates the possibility of confusing substances that share similar chemical properties. In addition, the screening of drugs at extremely low concentrations minimizes the possibility of false-negative results (when drugs and/or metabolites fall within a range below a test’s designated cut-off). This is a critical difference between laboratory testing and POC testing, where the potential for false-negative results is reasonably high.9 These safety measures also prove critical in situations where only a slight dosage difference can influence a patient’s tolerance or toxicity to a prescribed drug.

However, the benefits of laboratory testing are not confined to the testing process. Some laboratories that perform compliance monitoring also include expert consultation as part of their services to assist physicians and other providers with results interpretation. Depending on their level of education and expertise, these experts can educate a physician on a variety of topics including drug physiology and pharmacology and absorption and excretion profiles. Such laboratories may also provide education on the science and practical applications of compliance monitoring, covering the importance and relevance of urine and blood drug screens, trends and myths associated with patient compliance testing, explanations of common metabolic pathways, and interpretation of compliant and non-compliant test results.

As the number of chronic pain sufferers continues to rise, it becomes more important for all physicians, regardless of their specialty, to become more educated in the science and practical applications of laboratory-based compliance monitoring. Those who possess an innate understanding of how testing works, its differences from workplace urine drug testing, and the potential for complex interpretations can implement processes within their practice to identify potential misuse as early as a patient’s first visit. As a result, a physician can improve the standard of care by reducing the number of overdoses and fatalities resulting from improper drug dosages and opioid conversions and increase the amount of time spent with patients facing legitimate chronic pain issues—both of which reduce legal liability.

Compliance Monitoring and Its Role in Reducing Drug Abuse

Compliance monitoring, when performed in a laboratory setting and utilized by a physician who is knowledgeable on cur-rent trends and applications, offers a strategic road map for mitigating risk and reducing non-prescribed and illicit drug abuse within a practice over time. This point is illustrated by the following two case studies where physicians serving two different specialties reach the same goal: reduced diversion and improved patient care.

Applications of Compliance Monitoring: Pain Management

For Dr. Thomas Miller and the rest of the staff at Specialists in Pain Management, an interventional pain management clinic operating in the Chattanooga, Tennessee area, the key to running a practice with a low diversion rate involves managing a strict screening and evaluation process beginning with the generation of new business—referrals only, no walk-ins. Once a potential patient has been referred to the practice, personnel collect and verify as much information as possible to construct a comprehensive medical profile. Concerted efforts are made to gather objective information on the individual, such as pathology reports, vital signs, physician and surgical histories, previous and current diagnoses, and verification of prescription history through Tennessee’s controlled substances data bank. The potential patient is also interviewed to assess pain history, perceived pain intensity, and experience with illicit substances. He/she is also asked to complete a questionnaire that identifies potential addictive behaviors and take a baseline urine drug test.

As soon as the profile is complete, the decision is made whether or not to admit the patient into the practice. If the patient is accepted, the physician determines an appropriate course of treatment (usually involving at least one medication to alleviate symptoms) and outlines expectations for admittance into the practice. This includes random drug testing at least twice per calendar year, a signed opioid agreement that charges the patient to fill prescriptions at a single pharmacy and an informed consent document where he/she acknowledges awareness of the potential risks of any prescribed therapies. Routine office visits for patients include the potential for being tested at any time and surrendering medications for pill counts by a member of the office staff.

In addition to stringent office procedures, the staff at Specialists in Pain Management also value continuing education to stay current on industry trends and developments. Dr. Miller in particular belongs to the American Society of Interventional Pain Physicians (ASIPP) and American Academy of Pain Management (AAPM).

According to data accumulated over eight consecutive quarters ending in 2009, the practice’s combination of zero-tolerance compliance monitoring within a laboratory setting and aggressive therapy awareness significantly reduced instances of diversion during that time period. Abuse of non-prescribed drugs declined from 57.1% in the first quarter to 32.6% in the eighth quarter, while illicit drug use fell from 11.7% in the first quarter to just 3.7% in the eighth quarter (see Figure 1).

Figure 1. Percentage of non-prescribed and illicit drug use for specialists in pain management.

Applications of Compliance Monitoring: Primary Care

Because of her rural location, Dr. Anita Cornett of the Kate Ireland Healthcare Center in Manchester, Kentucky, treats numerous residents for chronic pain conditions despite being a primary care practice. Approximately 35% of Dr. Cornett’s patients from that practice come to her seeking pain relief. Admittance of these patients into the practice involves many of the same tactics used by Specialists in Pain Management, including collecting medical histories, performing a diagnosis analysis, and utilizing the KASPER database (Kentucky All Schedule Prescription Electronic Reporting) to confirm prescription information. Once accepted, patients sign a controlled sub-stances agreement acknowledging the practice’s compliance policies (random testing, pill counts, etc.).

Outside of the office, Dr. Cornett’s continuing education in pain management is achieved through reading industry literature, attending classes, and maintaining membership with professional organizations such as the American College of Physicians and the American Society of Addiction Medicine. She has also sought information from her laboratory’s toxicology staff regarding opioid metabolism and passive inhalation of marijuana.

When it comes to measuring Dr. Cornett’s success, the Kate Ireland Healthcare Center achieved similar results to those produced by Specialists in Pain Management. During an eleven-quarter timeframe also ending in 2009, abuse of non-prescribed drugs declined from 57.8% in quarter one to 25.9% in quarter eleven; illicit drug abuse also decreased from 13.3% in quarter one to 2.5% in quarter eleven (see Figure 2).

Figure 2. Percentage of non-prescribed and illicit drug use for Kate Ireland Healthcare Center.

Compliance Monitoring and Physician Education Should Be Part of Every REMS

Through the development of a formal risk evaluation and mitigation strategy, the FDA is challenging physicians, pharmacy groups, and other vested stakeholders to spend more time managing the risks associated with opioid analgesics in order to increase safe-use conditions for patients while also decreasing harm. The combined benefits of compliance monitoring by means of laboratory screen and confirmation, along with proactive education, offer a powerful strategy for effectively accomplishing the goals of any REMS, namely is to assure that the benefits of prescribing an opioid drug outweigh the risks. Laboratory-based compliance monitoring produces unequivocal precision of results and compelling data that can be used to track adherence to medications and gauge safe use, while education for vested stakeholders, particularly physicians, reduces the number of medication overdoses or fatalities resulting from toxic or even fatal drug interactions.


Dr. Thomas Miller is the owner of Specialists in Pain Management in the Chatta-nooga, Tennessee area. He is currently paid to speak for Forrest Laboratories and King Pharmaceuticals.

Dr. Anita Cornett is the owner of the Appalachian Institute of Addiction Recovery in Manchester, Kentucky, and serves as the medical director for Frontier Nursing Healthcare Rural Health Clinics in southeastern Kentucky, which includes the Kate Ireland Healthcare Center. She is currently paid to speak for Abbott Laboratories, AIT Laboratories, Astra Zeneca International, King Pharmaceuticals, Novartis, and Pfizer.

Last updated on: January 28, 2012
close X