By Marleen and Gary Wolfe
The extent of drug abuse in the United States is astonishing in both its cost and social impact. On April 29, Nora D. Volkow, MD, director of the National Institute of Drug Abuse, put the problem in context when she testified before the House Subcommittee on Labor-HHS-Education appropriations in conjunction with her organizations FY2005 budget request for an allocation of more than $1 billion.
To put it in dollar figures, said Volkow, substance abuse, including smoking, illegal drugs, and alcohol, costs our nation more than $484 billion per year. Illicit drug use alone accounts for about $161 billion according to a report from the Office of National Drug Control Policy. Drug abuse is inextricably linked with the spread of infectious diseases, such as HIV/AIDS, STDs, tuberculosis, and hepatitis C, and is also associated with domestic violence, crime, child abuse, accidents, teenage pregnancies, and other adverse effects. Substance abuse is also a problem that occurs frequently in patients with psychiatric disorders.
One consequence of drug abuse is that it exerts an enormous burden on a health care infrastructure that is already struggling to meet its obligations. To gain a better understanding of the impact on the test industry, we spoke with representatives of several firms at the forefront of drugs-of-abuse testing to capture their opinions on some of the key challenges facing the industry today, and what the future may hold for the clinical lab community.
New Drugs of Abuse Drive Need for New Assays
Possibly the foremost problem facing the test industry and the clinical laboratory community is the rapidity with which new drugs of abuse gain popularity among abusers ranging from the casual to the hard core. Whether these are illicit drugs or prescription drugs being used in an illicit manner, the challenge is always to develop effective assays to detect them within a shrinking window of time.
Designed specifically for the toxicology lab, the Dade Behring V-Twin drug-testing system is a complete on-site system for drugs-of-abuse testing.
Kelly Ryzewski, director of drug testing marketing, North America, for Dade Behring, says, A constant challenge is how to prove abuse of prescription drugs versus illegal drugs. If someone is using an illegal drug, any confirmed presence of the drug in the urine indicates an abuse problem. But how do you prove if someone is using a legal drug beyond the limit of a prescription? Considering that there is variability in the way that individuals may metabolize the same drug, how do you tell at what point they are abusing it? It is very difficult to establish appropriate cutoff levels that can capture misuse or abuse, whether it is for a urine test or an alternative saliva or hair test. The industry is always going to be one step behind in developing assays to keep up with drug-abuse trends. There is no concrete advance warning about a drugs abuse potential, and it is not until after the abuse becomes a huge problem that a need arises to develop an assay for it. Then, depending on the complexity, it can take anywhere from 1 to 2 years to develop an assay. This is a challenge the industry always has to address.
Abbott Laboratories recently expanded its ARCHITECT c8000 and ci8200 menus by adding the following tests: amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, ethanol, methadone, opiates, phencyclidine, and propoxyphene.
Dave Armbruster, scientific affairs manager for Abbott Laboratories Diagnostics Division, says, Drugs-of-abuse testing is intended to detect people who are taking recreational drugs, like heroin, not people who are taking prescription drugs. Opiates used to have a cutoff of 300 nanograms per mil [ng/mL] and people taking prescription drugs would test positive at that level, so SAMHSA [Substance Abuse and Mental Health Services Administration] increased the cutoff to 2,000 ng/mL. At that higher level, you should not detect people who are legally taking prescription drugs containing morphine or codeine, but you will detect heroin users or individuals taking prescription opiate drugs in massive quantities. Still, there are times when the lower cutoff is preferable, such as when working up a patient in the ER to detect the drugs in their system. Depending on whether a test is being performed for forensic (legal) purposes or for clinical (medical) purposes, there may need to be two different sets of cutoffs for the assays. Determining the right cutoffs is a key factor Abbott considers when developing new assays.
Voicing similar sentiments, Raphael Wong, president of Branan Medical Corp, says, From the manufacturers standpoint, our challenge and our responsibility is to produce high-quality tests and test devices that meet all required cutoffs as mandated by the government. It is extremely important that these cutoffs are met to make sure a test does not come out positive when in fact it was really negative.
David Heibel, director of product management marketing for Beckman Coulter Inc says, Almost one in five of the 15 to 30 age group has used or abused drugs. Opiates are changing very quickly; OxyContin is the newest. Accessibility makes it easy for growth. I do not see this shrinking. In the 10 years we have been in this marketplace, we have only seen drug usage grow. Our major challenge is the fad: What is the drug of choice today? It is important for assays to have the required sensitivity and specificity. This requires updating the product line to be specific enough to pick up the variants of the drugs that are being used and sensitive enough to detect the drugs at the right cutoff level. We have a proactive process for adding new drugs to the panel in addition to the ones we already have to make sure we have a full spectrum of products, both for customers who need to be SAMHSA-compliant and for those who dont. Keeping pace is a challenge with anything to do with drugs today.
Many UTAK drugs of abuse in urine (DAU) toxicology controls have been specially designed to follow SAMHSA confirmation guidelines.
From a product development standpoint, the issue of keeping pace is assuredly a multifaceted one. Christina Plutchak, sales and marketing manager for UTAK Laboratories Inc, says, The industry faces four major challenges: 1) developing new or improved quantitative and qualitative assays and reagents with appropriate analyte concentration ranges; 2) developing new quantitative analytical techniques that have the sufficient sensitivity to readily identify any drug that may be abused by the patient; 3) developing controls and standards in a biological matrix that analytical laboratories can easily utilize to confirm not only the validity of the assays but also the day-to-day assay precision; and 4) keeping abreast of cutoff controls set by SAMHSA and the government.
Steve Wasserman, group vice president, Olympus Diagnostic Systems Group, emphasizes the importance of standardization and consistency of results as a major objective for the industry as it moves forward. Instruments must be precise enough to achieve the throughput and reliability levels that will produce a consistent testing process. Standardizing across various platforms so that different instruments have the same operating system, reference ranges, optics, and user interface, is an important way to deal with the fact that follow-up tests often are not done on the same instrument as the original screen, he says.
New Alternatives to Urine Testing
The emergence of new classes of drugs-of-abuse tests that use samples other than urine represents an important potential growth area for the industry. However, some caution that key issues must be resolved before such alternative testing can gain a foothold.
Abbotts Armbruster says, SAMHSA has proposed testing specimens using alternate matrices including sweat, saliva, or hair, although such testing is not widely performed yet. SAMHSA is being very proactive about looking at these alternate matrices, and proposing guidelines for testing. SAMHSA is also proposing using point-of-care (POC) testing on-site as opposed to the traditional central lab testing. There are several on-site tests for drugs of abuse, but correlation with the standard central lab tests can sometimes be problematic. A POC test could be positive, but a central lab test could be negative. Similarly, when testing a hair sample that detects drugs from a couple of months ago, it is not clear if that person used the drug personally or was around people who did. A person could test positive for a hair sample and negative in a urine sample. Which one is true? This opens up a whole new area of interpretation and is a gray area right now until guidelines are established.
The OnTrak TesTcup II incorporates an innovative cup design and offers easy-to-read outcomes, long-lasting results, one-step testing, and data-management integration with Varians TesTrak system.
Randy Cole, manager of business development for Varian Inc, says, If accepted, SAMHSAs new guidelines for alternative testing using an oral fluid sample would require a duplicate urine sample to be collected. This brings up an obvious question: if they are in favor of alternative testing, why still mandate urine testing along with saliva testing? Collecting and performing two tests will add more costs, and the net result will be that nobody will opt to perform drug tests using a saliva sample. It will be a challenge to get people reoriented to the idea of using alternative tests, but there are definite advantages. For example, an oral test is good for determining drug usage within the last 24 hours, a urine test is good for determining usage with the last 3 to 5 days, and a hair sample test is good for determining usage within the last month.
Branans Wong says, The good thing about the saliva test is that it is much easier to watch a person take the test versus having them go to the bathroom with somebody and handle the sample. However, the new types of tests present an education issue. Some of the compounds being analyzed are a little different. Often you are just testing the parent drug. The concentration in saliva is much lower than in a urine sample. Also, the window of detection is different. In urine you can detect drugs 2, 3, even 5 days out. But in saliva, you are looking at detection in one day. Depending on timing, you can have a negative saliva test but a positive urine test. People have to understand the different usages and windows before they can come to accept these types of tests.
Beckman Coulters SYNCHRON LXi 725 clinical system can perform nearly 150 tests, including a wide range of assays for drugs of abuse.
Finally, Heibel at Beckman Coulter Inc offers another valid justification for performing tests on samples other than urine. Patients who come into an ER are often comatose and it is very hard to get urine samples from them. This is one reason we are looking at bringing some drug tests in as part of a serum panel, he says.
Strengthening the Chain of Custody When Handling Samples
Controlling the sample as it moves from patient bedside to laboratory and on to the patient record is a perennially important matter, whether in forensic testing or routine lab work. Fundamentally, the way in which samples are handled is beyond the scope of the companies that produce the assays. It is largely up to the laboratories and forensic collection agencies to control specimen security. Nevertheless, companies that develop test products have adopted strategies that provide tools to help improve specimen security.
The AU series from Olympus is the industrys largest line of random-access chemistry-immuno analyzers with a fully standardized design. They all offer consistent system-to-system results and reference ranges using the same 122-test menu, reagents, calibrators, and controls. Shown here: the AU400e.
Wasserman at Olympus Diagnostic Systems Group says, The JCAHO [Joint Commission on Accreditation of Healthcare Organizations] has recommended bar coding samples as a way to improve patient safety and track samples. As hospitals implement these systems, the need for special handling for potential drug-abuse-related samples may diminish because the new protocols developed to handle all samples will provide a positive tracking mechanism for all patients, samples, and providers.
Combating Sample Adulteration
A matter of growing concern in drugs-of-abuse testing is adulteration of samples and the measures that must be taken to counter this problem. In one respect this problem relates to how laboratories and sample collectors maintain the chain of custody. But in another sense, it also demands some innovative technical solutions from the test industry.
Abbotts Armbruster, says, When a new narcotic, recreational, or designer drug becomes available, it may not be readily detectable with current assays. Moreover, people who abuse drugs will often try to beat the system by using adulterants so that the tests will come up negative. As a result, there is enormous pressure on manufacturers to develop assays specific for the new drugs, and also to make the assays impervious to adulteration.
Branan Medical Corp manufactures urine and oral fluid drug-screening products.
Branans Wong says, A urine test is the most acceptable matrix right now. It is inexpensive and easily defended in the courts. Urine tests will be the choice for the immediate future. However, you always have to worry about adulteration. The biggest challenge to urine tests is that people try to beat them by taking in extra water or a diuretic to dilute the test, or by adding chemicals to the urine to make a positive test become negative. SAMHSA guidelines require an adulteration test before running a urine test. The most advanced class of adulterants will disappear within 5 hours. If you are sending a sample to a central lab, 24 hours may elapse before the test is done, at which time neither the drug nor the adulterant may be detectable, so there is a good reason to do the testing on-site instead.
Drugs-of-abuse testing will undoubtedly remain a major factor in the growth of the clinical diagnostics industry for the foreseeable future as the problem of drug abuse remains widespread and new drugs are constantly becoming available. Alternative testing, using samples other than urine, shows great potential for future development, but questions about the exact role such tests will play, how to interpret the results in a context relevant to other modes of testing, and how they will come into widespread use remain to be answered. Other compelling issues relate to keeping pace in developing assays to meet SAMHSAs new cutoff levels, standardizing tests across multiple platforms, maintaining the chain of custody when handling samples, and devising methods to safeguard against adulteration. The numerous challenges are intimidating, but many in the clinical-test industry believe they are well prepared to confront them successfully.
|Diagnostic Companies That Provide Drugs of Abuse Testing
Abbott Laboratories, Diagnostics Division (www.abbottdiagnostics.com) is a global leader in in vitro diagnostics. It offers a range of innovative instrument systems and tests across key segments in the global diagnostics market, including hospitals, reference labs, blood banks, physician offices, clinics, and consumers.
Beckman Coulter Inc (www.beckmancoulter.com) offers instrument systems and tests that simplify and automate laboratory processes. Offerings range from integrated laboratory automation solutions to centrifuges and blood analyzers to diagnostic rapid-test kits.
Branan Medical Corp (www.brananmedical.com) develops, manufactures, and markets unique products for drugs-of-abuse testing, and offers a complete line of rapid, on-site drug and adulteration tests in urine and oral fluids, as well as quality-control products.
Dade Behring Inc (www.dadebehring.com) manufactures diagnostic products for a range of core areas, including cardiac diagnostics, infectious diseases, chemistry-immunochemistry, microbiology, plasma proteins, drug monitoring, and homeostasis.
Olympus Diagnostic Systems Group (www.olympus.com) provides high productivity, random access, chemistry-immuno systems for hospitals, integrated health care delivery networks, blood banks, reference labs and pharmaceutical labs.
UTAK Laboratories Inc (www.utak.com) manufactures drug and metal controls used in industrial, forensic, and clinical toxicology. Custom controls are available in blood, serum, and urine. Blood, lead, alcohol, and serum trace elements controls are among the leading products.
Varian Inc (www.varian-onsite.com) offers a comprehensive line of on-site, single-use, nonclinical toxicology and drugs-of-abuse test products used in workplace settings for preemployment screening, reasonable cause or incident-driven assessment, routine workplace testing, or court-mandated compliance.
Marleen and Gary Wolfe are contributing writers for Clinical Lab Products.