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Molecules to Medicine

Molecules to Medicine

Demystifying drug development, clinical research, medicine, and the role ethics plays

Drug screens-any more than theater?

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Under the influence?

I’ve been doing a lot of traveling recently, and am increasingly disturbed by the growing surveillance society and the misplaced reassurances that are used to assuage the public, coined “security theater” by Bruce Schneier. Here we’ll look at this drama in the context of screening for drugs of abuse. In a later post we’ll look more closely at the parallels between drug screening and the TSA. Both are problematic and neither produces the desired outcomes. We’ll look at why.

There are three key issues to consider: one is the accuracy of the test; the second are ethical concerns; the third, the societal and political context of drug testing.

In reading about clinical trials, one commonly misunderstood, yet basic concept is that of the accuracy of clinical test results—are you measuring what you think that you are? I’ve spoken about this a bit in posts about Orasure’s HIV test and turned again for a quick review to Marya Zilberberg’s “Between the Lines.”⁠ We’ll look at evidence and accuracy in a different context here, with our focus being on understanding false negative and false positive results. Drug screening is used as an example, as such screening is increasingly being used in work and social services settings, and raises similar concerns about accuracy and ethics as we see in clinical trials.

Background rates of drug use

According to the government’s Substance Abuse and Mental Health Services Administration⁠1 (SAMHSA) the rate of drug use in the US among full-time workers averaged 8.2%, ranging from 6.1% among health care workers (HCW) reporting use within the past month compared to 16.9% among accommodations and food workers and 13.7% for construction workers. Overall, rates were higher in those younger than 35. Among HCW, nurses had much higher rates than physicians, whose rates varied by specialty, being highest among anesthesiologists and emergency room staff.

Drug screening

Screening is performed in different settings and for different purposes. For example, there is routine screening of long distance truck drivers and airplane pilots, as they are considered a potential public safety risk. Screening can be done pre-employment or, more commonly, in response to a workplace accident. Toxicology screens are also commonly performed in Emergency Departments when evaluating a patient with an unexplained change in mental status or behavior.

Among full-time workers in the US, 42.9% reported that tests for illicit drug or alcohol use occurred as part of "pre-hire" testing—so more than 47 million adults were subjected to testing as part of the hiring process. (2004) Further, 29.6%, or 32 million full-time workers reported random drug testing at work.⁠ A 2010 study reported about 130 million drug screens⁠. Is this necessary? Does this make us safer?

Obviously, we want tests such as these to be accurate – to provide a valid measure of the state of the “real world”. There are two ways in which tests such as these can be correct. They can detect true positives and true negatives: That is, they can give a positive reading when the subject of the testing has used one of more of the drugs that are being tested for, and likewise they can give a negative [or “all clear”] reading when the testing subject has not used drugs within the testing window. They can also err in two ways: They can give a false negative, or a negative reading when the subject has actually used drugs, and they can give a false positive, or a positive reading when the subject of the testing has not used any drug. The ability of the test to return true positives and avoid false negatives is called the “sensitivity” of the test. Similarly, the ability of the test to return true negatives and not false positives is called the “specificity” of the test.

Urine testing

Most commonly, urine samples are used. Urine tests are very sensitive, but not very specific—this means that there are likely to be many falsely positive results. So a positive result will generally be followed up with a more expensive and specific urine (and occasionally blood) test being done for confirmation—but even among these tests, none are 100% accurate.

Urine tests have the advantage of showing drug use over a longer period of time; the drugs are also present in higher concentrations in urine than in blood. The advantage of testing blood is that it more often reflects the parent drug, rather than metabolites, and that it reflects more “real-time” use.

The likelihood of these false negative and false positive errors varies, and depends on both the accuracy of the test, and upon the expected [or “real-world”] percentage of true positive results in the group being tested. Due to a quirk of statistics, if the incidence of drug usage in the population under study is low, there will be higher likelihood of false positives. The smaller the number or % of true positives, the higher the rate of false positives.

For screening tests, false positives are estimated to occur in 5 to 10% of tests, and false negatives in 10-15%. For confirmatory tests, data has been more difficult to find. Estimates of accuracy of the drug tests are < 1% for false positive confirmatory tests, and perhaps 5% false negatives, due to where the thresholds are commonly set.* Using this as an example, and an 8% drug usage rate, we would get, in a 1000 tested workers:

Drug presentDrug absenttotal
Test pos76985
Test neg4911915
total809201000

 

About 4 people will be reported “clean,” a false negative, though they use drugs.

Of 920 who did not use drugs, 1%, or ~9 people will show up as pos.

Of 85 people who test positive, 9/85, or 10.6% will erroneously be identified as drug users. So while 1% error rate (false positive) sounds good, 10% of the positives will be false.

What drugs are being tested for?

Testing conducted according to SAMHSA’s guidelines checks for five illicit drugs plus, in some cases, alcohol (ethanol, ethyl alcohol, booze). These five illicit drugs are:⁠

• Amphetamines (meth, speed, crank, “Ecstasy” (MDMA))

• THC (cannabinoids, marijuana, hash)

• Cocaine (coke, crack)

• Opiates (heroin, opium, codeine, morphine)

• Phencyclidine (PCP, angel dust)”

The typical 10-Panel Test also includes:

• Barbiturates (phenobarbital, butalbital, secobarbital, downers)

• Benzodiazepines (tranquilizers like Valium, Librium, Xanax)

• Methaqualone (Quaaludes)

• Methadone (often used to treat heroin addiction)

• Propoxyphene (Darvon compounds)

Testing is not typically done for alcohol, hallucinogens, inhalants, steroids, hydrocodone, suboxone, or “bath salts” (an amphetamine like drug).

Drugs firms 'creating ills for every pill'

Sites also tell you the length of time that drugs can be detected in blood or urine.⁠

• Alcohol – 1 oz. for 1.5 hours

• Amphetamines – 48 hours

• Barbiturates – 2-10 days

• Benzodiazepines – 2-3 weeks

• Cocaine – 2-10 days

• Heroin Metabolite – less than 1 day

• Morphine – 2-3 days

• LSD – 8 hours

• Marijuana – casual use, 3-4 days; chronic use, several weeks

• Methamphetamine – 2-3 days

• Methadone – 2-3 days

• Phencyclidine (PCP) – 1 week

(Hair testing has extended detection time.)

While testing might pick up some drug use, a whole cottage industry has developed to sell products to defeat the testing, including urine substitutes, or giving advice as to how to beat the tests.⁠ Thus, an individual with a small amount of knowledge could circumvent scheduled screening. This is why drug screens are random, not scheduled, except for pre-employment.

Approaches to testing

SAMSHA ⁠has two different approaches to testing. One is a “zero tolerance” test, which reduces false negatives. Any level of drug detected is considered a positive (or failed) test. The other is the “cut-off” type of test—a drug may be detected in small amounts, but the test will be reported as negative (passed) if below a certain threshold.

False positives

A major concern for those who don’t use illicit drugs and for whom the repercussions of a positive test are grave, is the issue of false positives. Unfortunately, many drugs cross-react with the test, giving potentially erroneous results, especially on screening tests. For example, the USC’s Keck Hospital⁠ notes “more than 300 over-the-counter drugs and foods that can affect the test (see modified table).

If you take or eat:You could test positive for:
Ibuprofen (common pain reliever)Marijuana, barbiturates, or benzodiazepines
Cold remediesAmphetamine
Hay fever remediesAmphetamine
Nasal decongestantsAmphetamine
Diet pillsAmphetamine
Sleep aidsBarbiturates
DHEA (dehydroepiandrosterone )Anabolic steroids
Novocaine (used in dentistry)Cocaine
Dietary supplements containing ephedrineAmphetamine
Poppy seeds**Opiates/morphine
Hemp food productsMarijuana
Quinolone antibiotics (Levaquin, etc.)Opiates
Sertraline

benzodiazapines

 

**Large amounts of poppy seeds—for example, a pastry filled with poppy seeds, not a poppy seed bagel—would need to be consumed to cause a positive test. However, sophisticated testing can discern poppy seeds from opiates.”

A suspected false positive on a screening assay—designed to be highly sensitive but not very specific—is then followed up with testing by another technique. Unfortunately, no test is completely accurate, and even the “gold standard” confirmatory test, gas chromatography-mass spectometry, has false positives and is subject to performer error.

False negatives

In the balancing act, trying to avoid the costly additional testing and potential legalities of a false positive, the threshold set by some labs for reporting a test is high enough that even though drug may be present in low levels, it will not be reported. The Feds are pushing for more stringent reporting.

Other testing nightmares

There are other workplace testing procedures that erroneously punish non-users.⁠ For example, those with “shy bladder”, or those who only void small amounts, have been fired. If urine appears too dilute, employees have been subject to repeat testing and surveillance. Forensic toxicologist Dr. Vina Spiehler ⁠has been particularly critical of “arbitrary cutoffs for creatinine, saying they discriminate against women, vegetarians, the elderly, people who drink lots of water, and people of small body size. Spiehler also argued for greater safeguards for validity testing, since ‘for employees subject to urine drug screening sometimes the penalties for abnormal urine characteristics are more severe than those for the presence of drugs in their urine.’”

Conclusion

This example of drug testing is but one example to illustrate the difficulty in interpreting laboratory tests and studies. For each, you have to try and tease out not only the accuracy of the test in measuring the outcome you wish to examine, but also whether you are measuring the right thing or asking the right question.

In an upcoming post, we'll look at pre-employment screening, its value (or lack thereof), and some of the broader ethical and societal implications of the increasing culture of surveillance.

(*Note: est of false +/- for GC-MS is based on information from toxicologists)

Credits:

Special thanks to: Dr. David Parish

Ed Smith, Drug Detection Lab

Steve Codd, Beckman Coulter

and Dr. George Lundberg

for additional background info and for helping me understand the complexities of this topic, and to my family, for their thoughtful comments.

"Molecules to Medicine" banner © Michelle Banks

Tried that - Jovike/Flickr

Urine testing - publik15/Flickr

Pills for every ill - publik15/Flickr

The views expressed are those of the author and are not necessarily those of Scientific American.

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