Lab professionals and providers are forging an alliance in the battle against the opioid epidemic

By Scott Howell, MD, MPH and TM, CPE


Chronic pain affects an estimated 100 million adults in the United States, and as populations age its prevalence will grow. Chronic pain can have significant impact on quality of life for patients and their caregivers. In addition, the economic burden to the United States exceeds that of heart disease, diabetes, and addictions combined. In 2011, more than 25% of workers’ compensation prescription drug claim costs were for opioid pain medications, despite evidence indicating that this approach does not result in better treatment outcomes.

Research shows that high doses and prolonged use of opioids for work-related injuries can lead to addiction, increased disability, work loss, and delayed recovery. In fact, it’s become an imperative to understand the implications and impact of this “epidemic” on America’s workforce, gain a more comprehensive understanding of how deeply this issue cuts, and take action (Figure 1).



Consider these eye-opening numbers: 70% of the 14.8 million Americans who abuse drugs are employed. When an employee abuses drugs, employers and payers take on the risk of workplace injuries, compromised productivity due to absenteeism and presenteeism, and liability. Drug abuse may cost US Business owners more than $140 billion every year, including the costs of high turnover among employees who ab use drugs. The drugs at the root of this issue include cocaine, ecstasy, heroin, methamphetamine, and prescription drugs. In 2015, workers’ compensation payors spent $1.54 billion on opioids.

Pharmacogenomics, including tests for the metabolism of drugs and certain genomic markers in a clinical setting, rather than a clinical trial setting, has emerged as an important discipline in the evaluation, safety, and efficacy of pharmaceutical therapies. Taking the most well-known example of drug metabolism in an individual patient, consider clopidogrel, sold under the brand name Plavix. This antiplatelet medication prevents platelets from sticking together. Variants in an individual’s genetic coding have the potential to cause the body to metabolize this medication at an abnormal rate, and affect the medication’s efficacy and risk of side effects.

Physician Best Practices
By improving opioid prescribing practices through clinical practice guidelines, it’s possible to improve patient access to safer, more-effective chronic pain treatment and reduce the number of people who misuse, abuse, or overdose from such drugs.

Improving Prescribing Methods
The Centers for Disease Control and Prevention (CDC) guideline for prescribing opioids for chronic pain provides recommendations for the prescribing of opioid pain medication for patients 18 and older in primary care settings. The guideline addresses patient-centered clinical practices, including conducting thorough assessments, considering all possible treatments, closely monitoring risks, and safely discontinuing opioids.
In any epidemic, the identification of patients with long-term use of opiates is critical. Inappropriate use should be identified as being for either pain or addiction issues. To identify and track patients who may be at risk for abusing opioid medications, physicians should consider the following practices.

• Develop a quality measurement current procedural terminology (CPT) code for creation of pain management contracts.
• Check state programs or claims history for opiates obtained outside of the pain contract.
• Monitor the urine drug-screen frequency of pain contracts by accessing their claims history.
• Look for use of opiates with no pain-related diagnoses and concomitant use with benzodiazepines.
• Watch for visits to multiple pharmacies or multiple providers.
• Monitor patients when prescribed more than 100 mg morphine equivalents (MME) per month.
• Be alert to patients who pay cash for opiates and have previous claims history for substance abuse.

Physicians should prescribe the lowest amount of opiates, use non-opiate drugs when appropriate, and evaluate for major depression with chronic pain. A surveillance system, however, must be in place to identify excessive or aberrant behaviors.

Population-Based Surveillance. Opioid addiction requires early recognition, referral, and timely subsequent treatment. The only way to effectively measure opioid quality outcomes is population-based, through key metrics of opiate surveillance and subsequent treatment outcomes of chronic pain and addiction services.

Dosage. Surveillance of a patient population – whether the patient is part of a managed care program or accesses care via a state Medicaid or Medicare program – should focus on opioid outcomes and should identify people who are taking opioids, whether appropriate or not. The use of any opioid can lead to overdose, but research shows that exposure to a higher dose of all opioids increases the risk of overdose. Opioid doses of more than 100 MME are disproportionately associated with overdose-related hospital admissions and deaths. The use of long-acting opioids, such as methadone and oxycodone has also been associated with an increased risk of overdose. At the same time, higher dosages have not been shown to reduce pain in the long term. A randomized trial determined that there was no difference in pain or function between a more liberal opioid dose escalation strategy (with average final dosage 52 MME) and maintenance of current dosage (average final dosage 40 MME).

Elevated Risk. Several identifiable characteristics among patients have been reliable associated with an elevated risk of opioid overdose. Factors include:
• History of overdose.
• Health problems associated with respiratory depression or concurrent prescription of any medication that has a depressive effect on the respiratory system, such as benzodiazepines and sedative hypnotics.
• History of suicidal thoughts or attempts
• Diagnosis of major depression.
Recommended mitigation strategies include an overdose risk assessment and urine drug screening before prescription or re-prescription of opioids to verify absence of drugs of abuse.

Overprescribing. Overprescribing of opioids is thought to be a major contributor to the opioid epidemic, with two-thirds of opioid misuse being attributed to opioids obtained through a single physician. Overprescribing can lead to opioid diversion and increase the possibility for addiction. Surgical patients are almost four times more likely to receive post-discharge opioids than nonsurgical patients.
In its Star Ratings, the Centers for Medicare and Medicaid Services (CMS) screens for the use of opioids from multiple providers or pharmacies, or at high dosage – in people without cancer and not in hospice care – as part of the agency’s opioid over-utilization measures. A patient being prescribed morphine, for instance, from four different providers and four different pharmacies will be flagged at the claims level, integrating the medical and provider component.

Length of Prescription. The duration of the prescription – and not dosage – is the key to misuse in the early post-surgical period. Ana analysis has quantified the association of prescribing choices on opioid misuse, and identified levers for potential effects. Several organizations have taken reactive steps toward opioid surveillance. Aetna, for example, is working to mitigate the trend with integrated pharmacy, behavioral health, and medical programs. Such programs connect healthcare providers and offer seamless access to the right support for members fighting addiction. This approach can save millions of dollars for the healthcare system.

Lab Testing and PCPs
For physicians struggling with this complex topic, lab professionals are playing an increasingly vital role in helping them to choose and interpret pain management tests, monitor patients on opioid therapy, stay abreast of drug testing needs in local communities, identify flaws in pain panels, and assess individual patient needs and their risk of abuse for drugs – especially with the use of pharmacogenomics as an important diagnostic tool.

Pharmacogenomic testing will be important for primary care physicians (PCPs), because the majority of all drug prescriptions are written by these providers. Many of the drugs commonly prescribed by PCPs, such as fluoxetine, metoprolol, simvastatin, and warfarin are affected by pharmacogenomic variations.

Several factors have contributed to the slow integration of pharmacogenomic testing into the primary care setting. Besides having limited time, physicians may be unfamiliar with basic tenets of pharmacogenomic testing and may require more education on the subject. Physicians would also need to learn how to engage patients in an effective way in order to communicate the purpose and benefits of testing, as well as some of the practical limitations of testing in the primary care setting.¹⁴ All of this is further complicated when it comes to opioid prescribing.

Overview of the Opioid Crisis
Sales of prescription opioids in the United States nearly quadrupled from 1999 to 2014, but there has not been an overall change in the amount of pain Americans report. During this period, prescription opioid overdose deaths increased similarly (Figure 2).



An estimated 1 out of 5 patients with non-cancer pain or pain-related diagnoses are prescribed opioids in a physician’s office. From 2007 through 2012, the rate of opioid prescribing has steadily increased among specialists more likely to manage acute and chronic pain. Prescribing rates are highest among specialists in pain medicine (49%), surgery (37%), and physical medicine/rehabilitation (36%), but primary care providers account for about half of opioid prescriptions for pain relief.

Impact of the Opioid Crisis on Employers. According to the National Safety Council, employees who abuse prescription drugs are two to five times more likely to take unexcused absences, be late for work, be injured or violent at work, file workers’ compensation claims, or quit or be fired within 1 year of employment. The upside of this equation is that employees are more likely to undergo treatment when it is fostered by an employer, and individuals in recovery go on to become better workers – using less healthcare, taking less unscheduled leave, and involving slightly less turnover than their non-abusing colleagues. In fact, each employee who recovers from a substance abuse disorder saves a company more than $3,200 a year.

Employers affected by this crisis don’t know where to turn, especially in the case of workplace injuries that are tied to opioid abuse. Among US employers, 71% say they have been affected in some way by employee misuse of legally prescribed medications, including opioids. Most employers have a drug-free workplace policy directed at illegal drugs, but fail to test for prescription drugs despite growing misuse of opioids.

Employers should work with employee assistance programs to develop policies that include conducting pre- and post-employment drug testing for prescription drugs, teaching managers to spot addiction and developing a strategy to intervene. They should also find insurance plans that cover treatment, a system for supporting employees returning to work after treatment, and an assessment of whether the company culture encourages substance abuse.

Workplace Drug Testing. Up to 20% of work-related fatalities test positive for drugs or alcohol. Substance abuse endangers employers and coworkers, as well as consumers, clients, or partners. Workplace accidents due to drug abuse can have far-reaching implications. In such instances, the abusers may not realize the danger they create by using at work, or while recuperating from substance abuse. Substance abusers are ten times more likely to miss work, negatively affecting themselves and others by jeopardizing their jobs and creating backlogs.

Safety is one of the main reasons that employers opt to perform random drug tests on employees. Such testing is especially important in a company where employees drive, work directly with consumers, operate machinery, or perform manual labor. The construction and manufacturing industries in particular have an especially high rate of on-the-job drug use.

When an employee is caught using drugs, the employer can help by putting them in a recovery program that’s paid for by the business or health plan. After completing the recovery program, the employee can return to work, saving the employer the expense of hiring and training a new employee. With this strategy in mind, it’s important to have the right lab resources available. Lab experts can play a critical role in helping employers and health plans solve these issues.

In the pain management setting, the presence of an illicit or unprescribed drug does not necessarily negate the legitimacy of the patient’s pain complaints, but it may suggest a concurrent disorder such as drug abuse or addiction. The patient must be prepared to accept assessment and treatment of both disorders to achieve outcomes in either. Otherwise, the diagnosis of a concurrent addictive disorder, when present, fails to refute a legitimate pain disorder. In fact, it complicates it.

The Genetics of Opioid Metabolism
Patients can be classified by their genetic disposition to metabolize a medication. A normal metabolizer (NM) responds as expected when given a medication and has two normal or ‘wild-type’ alleles. An intermediate metabolizer (IM) can have partially active alleles or one fully defective allele. A poor metabolizer (PM) has two abnormal alleles with minimal gene activity. A rapid metabolizer (RM) has at least one highly active allele, and an ultra-rapid metabolizer (UM) can have many copies of the normal gene, leading to activity many times the baseline level.

Changes in alleles can have an enormous impact on pain perception and opioid use. For instance, a retrospective chart review analyzed the DNAQ of female p[postoperative patients and found that smokers and individuals possessing the PM genotype were more likely to have severe postoperative pain than other patients (71% versus 26% in all the other groups combined), based on self-reported pain scores and opioid intake.

Clinicians have found a wide range in patient response to opioid pain medications. Historically, this has been attributed to differences in gender, body mass, or cultural factors affecting pain perception.¹⁹ Genetics, however, appears to play a more significant role in the clinical effectiveness of opioid medications than previously believed.

Pharmacogenomics  – Risks, Benefits, Limitations, and Alternatives
It’s important to understand that identification of a genetic change or metabolic activity does not always indicate an absolute diagnosis of nonresponse, or that a side effect will or will not result from use of a given drug. Furthermore, federal law prohibits any use of genetic information by health insurers or employers, although other groups may still use this information.

PEPs also grapple with patient confusion, as a “normal” pharmacogenomic test result doesn’t always mean the patient is not at risk for adverse events or nonresponse. Tests only capture known variants in known genes. Also, other factors, such as test cost, insurance coverage, and risk of delayed treatment while waiting for test results, can sometimes affect the patient’s decision to have a test administered.

When a patient turns down testing, the PCP should explore alternative interventions with the patient to limit the risk of side effects or nonresponse. For instance, first-dose choice can be minimized, dose escalations can be tempered, a review of associated drugs for potential drug-drug interactions can be conducted, and choice of other drugs in the same class with fewer pharmacogenomic interactions can be considered.

The Role of Lab Professionals
Despite the sharp rise in opioid drug overdose deaths in the United States, these drugs remain a mainstay of pain management, upping the stakes for monitoring prescription compliance and detecting abuse. To address these concerns, there is a need for in-depth collaborations between lab professionals and physicians, many of whom don’t have the time or bandwidth to keep pace with the rapidly evolving, highly sophisticated tests available today.

In this increasingly vital role, it’s important for lab professionals not only to guide providers, but also to advise them about tools they can deploy to help them navigate the nuances of drug testing. Options include a comprehensive platform of solutions designed to help clinicians perform risk stratification for each patient on the basis of morphine equivalent dosing ranges, pain, and function scores, opioid misuse risk scores, and automated prescription drug monitoring program (PDMP) checks.

Because PCPs have limited time with patients, their ability to share information with patients about pharmacogenomic testing as a narrow window of opportunity., The talking points in this paper provide guidance on the basic information that should be covered to reach an informed decision about pharmacogenomic testing. As patients learn more about pharmacogenomic testing as a standard of care, they will begin to focus more on the test results and their impact on drug selection and dosing.

For lab professionals, the key issues related to pharmacogenomic testing include:
• The growing value of in-depth collaborations between lab professionals and physicians.
• The rise of clinical lab tests in the fight to curb opioid abuse
• Increased emphasis on educating physicians about pain management.

As for employers, by establishing a drug-free workplace, employers can help employees and their families through referrals to community resources and services. Considering that the United States represents 5% of the world’s population and consumes 60% of the world’s supply of illicit drugs, drug testing can be viewed more as an investment against the cost of low productivity.

Scott Howell, MD, MPH and TM, CPE, is Chief Medical Officer at RDx Bioscience