By Gary and Marleen Wolfe

A Web search on “OxyContin®,” a widely prescribed, FDA-approved musculo-skeletal pain reliever, generated 36,489 hits. On the first four search pages alone, 40 of 60 Web addresses were directly linked to, or described by, words such as “abuse,” “addiction,” “withdrawal,” “detox,” “diversion,” “rehab,” “overdose,” “painkiller drug bust,” and “hillbilly heroin.”

The unfortunate reality is that OxyContin and numerous other prescription drugs are routinely abused by both genders, in every age group over 12, at every socioeconomic level, and among virtually every racial and ethnic group in America, albeit with some variation among the different groups.

SAMHSA Statistics Reveal Growing Abuse Trend
In 2002, SAMHSA (the Substance Abuse and Mental Health Services Administration) conducted in-home surveys of almost 70,000 people. SAMHSA spokesperson Leah Young says, “The second most popular category of drug abuse after marijuana involves the nonmedical use of prescription medications, the majority of which are narcotics used as painkillers. In the past month, we estimate that 6.2 million people, or 2.6% of the US population, age 12 and over, were current, nonmedical users of prescription drugs. Of those, 4.4 million were using narcotic pain relievers.”

Other statistics from SAMHSA give a strong indication of the growing problem of nonmedical drug usage. “SAMHSA tracks the number of ‘mentions’ of individual drugs, because a majority of drug-related visits to emergency rooms involve individuals taking multiple drugs at the same time. The term ‘mentions’ refers to any substance that was recorded in hospital records for a drug-related incident. For example, a person who came to an ER for a drug-related episode might conceivably have been drinking alcohol, smoking marijuana, and taking a narcotic analgesic and LSD; therefore, four drugs would be mentioned in the record. From 2001 to 2002, ER mentions of narcotic analgesics and their combinations rose approximately 20% from 99,317 to 119,185. From 2000 to 2002, however, the overall increase in mentions was 45%.”

According to Young, various reasons are suspected (though not scientifically validated) to explain the increase. There is a belief that FDA-approved prescription drugs are safer to obtain and to use than street drugs. Prescription drugs are easily found in local pharmacies, hospitals, clinics, and physicians offices, as well as on the Internet. Many prescription painkillers can be taken orally instead of by injection. Sometimes individuals choose to sell some or all of their legitimately prescribed painkillers to make money. And sometimes children simply get the drugs from their parents.”

Laboratories Face Unusual Challenges
Regardless of the circumstances, prescription drug abuse and addiction pose unusual challenges for the medical community. For example, if patient urine testing in the lab or at the point of care detects the metabolites of an illicit drug—such as marijuana or heroin—some level of abuse may be inferred.

On the other hand, if testing detects the metabolites of a legal drug (or drugs) then this information leads to other questions: Are the prescriptions legitimate? Do the drugs really belong in this patient’s system? Is the mix of drugs reasonable in view of this patient’s condition? Are the concentrations consistent with acceptable drug doses or are they excessive? And, are there any aspects of the test results that might either suggest or rule out abuse or addiction?

Keeping Pace Is a Daunting Task
Addressing prescription-drug abuse is a daunting task for the diagnostics industry, according to Paula Stonemetz, director of business development for Microgenics Corp in Fremont, Calif. Stonemetz, who has a background in diagnostics and public health, and participates in a number of roundtable groups that interact with the FDA, the American Association for Clinical Chemistry, and commercial manufacturers, explains, “A major challenge facing the diagnostic industry is the rapidity with which new versions of prescription drugs are entering the marketplace. Some of these have unforeseen abuse potential.

“Pharmaceutical manufacturers don’t want their drugs to be considered unsafe or addictive. However, negative potential uses may not show up during clinical trials. Therefore, drugs—such as OxyContin, which is basically an opiate derivative—become popular prescription pain medications. Pain medications have tremendous abuse potential and many are quite addictive. This has led to an entirely new and growing area of medical treatment and drug testing referred to as pain management.”

Other Experts Interpret Laboratory Findings
Scott Ramey, product director responsible for San Diego–based Biosite Inc’s Triage® Panel for Drugs of Abuse and Triage® TOX Drug ScreenPanel, says, “Point-of-care and laboratory assays can only distinguish the presence or absence of a prescription drug (or a combination of drugs) relative to the qualitative assay’s cutoff based on the concentration of the drug at the time the urine sample was collected.

“The assays alone cannot determine if the patient is abusing or addicted to the drug based on just a positive initial screening result. Negative results can mean two things, either no drug is present, or a drug may be present but at a level below the detection limit of the assay. It remains for other experts, such as psychotherapists and drug treatment specialists, to balance the test data against their professional observations and tests of the patient’s physical and mental state in determining the legitimacy of the drug usage.”

Kelly Ryzewski, director of marketing for North America for all Dade Behring Inc drug-testing products concurs. “No matter how good the testing, there always has to be intervention by a professional who can observe the individual, ask questions, and take a look at all the evidence before determining whether a person is an abuser or just someone taking a prescribed drug to make it through the day,” Ryzewski says.

Civilian and Military Approaches to Drug Testing Differ
Ryzewski has an unusual perspective on drug testing that originated early in her career during an 8-year stint as a trained US Navy medical technologist. “Both the civilian and military sectors take drug testing and drug abuse very seriously, but they deal with these issues in different ways.

“The military’s zero-tolerance policy forces them to run a very tight program and they set their own criteria, which has helped them achieve a lower positive rate than the general populace. By contrast, the civilian sector tends to follow SAMHSA guidelines, and it takes longer for the civilian community to adopt needed changes in policies and regulations,” Ryzewski says.

“For example, the Federal government requires that federally mandated workplace testing within the civilian sector test for the SAMHSA-5, but the military may also test for benzodiazepines, barbiturates, or other drugs, whether prescription or not,” she says. “In fact, the military screens for several drugs for which commercial screening assays are not yet available, such as ketamine. As a consequence, the civilian side always seems to be a step behind the military.”

Drug Testing Objectives Are Still Evolving
Ryzewski says that in the past, the objective was often to look for drug abuse, but not necessarily legal use. “Today, the objective has evolved. Caregivers want to be able to detect these compounds under any circumstance, whether it involves legal use or abuse, since a proper diagnosis and treatment strategy depends on knowing exactly which drugs and how much of them are in the patient.”

Jim Linehan, product manager for drugs of abuse reagents at Roche Diagnostics Corp, agrees. “What we typically observe is that physicians and attending nurses ask patients presenting to the emergency department what, if any, drugs they are taking. If the caregivers believe the patient’s gross pathological signs are indicative of drug abuse, a urine specimen is collected and sent to the central laboratory for testing. Thus, knowledge of the patient’s drug profile through patient feedback, indications, and testing results can help the caregivers assess whether they are dealing with a drug of abuse or a drug being used for therapeutic reasons. However, drug levels themselves do not necessarily indicate abuse, since in some polydrug-abuse cases, the concentrations may be similar to therapeutic levels,” he says.

Representative Drug Screening Product Offerings
Drug-screening products are offered by numerous companies; the following are only a small sampling. Most offer panels that test for the NIDA-5 (National Institute for Drug Abuse), also called the SAMHSA-5: amphetamines/methamphetamines, cocaine, THC (marijuana), opiates, and PCP (angel dust), per Federal government mandate for DOT (Department of Transportation) drug tests. Supplemental panels are also offered to identify additional drugs and their metabolites, and these are typically specified by hospitals according to institutional requirements.

Microgenics Corp
Paula Stonemetz at Microgenics says, “We provide the entire testing market with a comprehensive menu of qualitative and semiquantitative CEDIA® and DRI® immunoassays, calibrators, and controls for drugs of abuse, therapeutic drugs, and immunosuppressive drugs. The drugs-of-abuse products typically screen for illegal substances and their metabolites in urine samples. These products are available in formats for all needs, ranging from microLINE™ dipstick cards and A-sure cassettes for point-of-care use to liquid-form kits for high-volume laboratory analyzers.”

“Some testing facilities, such as forensic laboratories, use these products to evaluate other body fluids, such as blood or serum, as well,” Stonemetz says. “Our drugs-of-abuse products are used in Federal workplace testing, probation, and parole programs; methadone treatment and addiction clinics; hospitals; commercial laboratories; and forensic investigational labs. We also sell a line of point-of-care products that can screen for the commonly abused drugs in a format very similar to that of a pregnancy test.

“We have also developed tests specifically to address the challenges that accompany drug screening and the methods of diversion to which many drug addicts resort in attempts to beat the drug tests. For instance, we manufacture a line of specimen-validity products, which detect adulterants that abusers will add to their samples when trying to mask drug use. We have invested research efforts in new drugs of abuse, such as Ecstasy and other rave drugs, as well as in addiction-treatment drugs, such as methadone, methadone metabolite, and, most recently, buprenorphine.”

Biosite Inc
Scott Ramey at Biosite says his company offers a variety of easy-to-use panels to perform rapid drug screening. The credit card–size Triage® Drugs of Abuse (DOA) Panels for hospital point-of-care and laboratory use are nonwaived, single-use, multi-immunoassay devices that yield visual results on urine samples in less than 15 minutes. They disclose the parent drugs as well as numerous drug metabolites. Although the tests are qualitative, they have quantitative attributes in that obtaining positive readings require that chemical concentrations meet or exceed precisely predefined thresholds. This minimizes false-positive/false-negative problems.

The Triage DOA Panels come in five different formats. Ramey explains, “The basic panel carries analytes for the NIDA-5. The 7-analyte test panel adds barbiturates and benzodiazepines. There are two 8-analyte test panels: both add trycyclic antidepressants to the seven analytes previously noted, but the second substitutes methadone for PCP. Finally, the 9-analyte test panel adds propoxyphene to those found on the first 8-analyte panel.”

Biosite also offers the Triage TOX Drug Screen Panel specifically configured for use with the Triage MeterPlus™, a POC instrument on which hospital laboratories and ERs can also run other panels for diagnosing heart attacks and congestive heart failure. This panel carries the same analytes as the first 8-analyte DOA panel. The Triage MeterPlus provides direct positive and negative readouts in less than 15 minutes and easily interfaces with hospital and laboratory information systems.

Finally, Biosite produces two Express Test™ Panels for occupational health, drug rehabilitation, employee screening, and criminal justice applications. These are comparable to the 5- and 7-analyte Triage DOA Panels except that the cutoff for opiates is 2,000 ng/mL versus 300 ng/mL.

Dade Behring Inc
Dade Behring’s Ryzewski says, “We offer a wide range of high-volume chemistry analyzer products for central laboratory and ER use—notably the Dimension® series of general chemistry analyzers (RxL™ and Xpand™) and the new V-TWIN™, a dedicated drug-testing system. The analyzers can run drugs-of-abuse tests on urine and can also perform serum toxicology assays.” Because of their multifunctionality, Ryzewski describes these systems as workstation consolidation vehicles.

Complementing these systems is Dade Behring’s extensive family of Syva® laboratory and point-of-care reagent products: Emit® II plus (which includes an extensive line of kitted liquid drugs-of-abuse products compatible with most high-volume analyzers); Emit d.a.u.® (which is a line of lyophilized drugs-of-abuse tests), and the RapidTest™ (which is a small card that tests up to 10 different drugs at the same time and is available in more than 20 drug test combinations).

Roche Diagnostics
Jim Linehan of Roche Diagnostics says, “Roche Diagnostics offers the Abuscreen ONLINE® drugs-of-abuse reagents for use in hospital laboratories and reference labs. Roche’s broad menu is critical in helping our customers satisfy the needs of clinicians and other decision-makers as they strive to stay on the cutting edge of a rapidly changing market. To this end, we have recently introduced a second generation of reagents, which offer improved specificity and larger dynamic ranges for more accurate results. Moreover, our laboratory systems streamline drugs of abuse testing with other routine and special chemistries and immunochemistries. That way, the laboratory can use one system to conduct all their needed testing, saving valuable time and resources.”

Roche’s general chemistry analyzers include the COBAS Integra® and the Roche/Hitachi MODULAR systems, which are high-throughput systems capable of performing qualitative or semiquantitative screening for drugs of abuse. Also available from Roche for central-lab or point-of-care use is the TesTcard 9 Panel, a single-use cartridge for the simultaneous detection of nine drugs in 3 to 5 minutes.

For more information, contact:

SAMHSA
(Substance Abuse and Mental Health Services
Administration)
Room 12-105, Parklawn Building
5600 Fishers Ln
Rockville, Md 20857
(301) 594-8040
www.samhsa.gov

Microgenics Corp
46360 Fremont Blvd
Fremont, Calif 94538
(510) 979-5177
www.microgenics.com

Biosite Inc
11030 Roselle St
San Diego, Calif 92121
(858) 455-4808
www.biosite.com

Dade Behring Inc
1717 Deerfield Rd
Deerfield, Ill 60015
(847) 267-5300
www.dadebehring.com

Roche Diagnostics Corp
9115 Hague Rd
Indianapolis, Ind 46250-0457
(800) 428.5074
http://us.labsystems.roche.com