Getting to the Answer: Screening vs. Confirmation Testing

Clinical toxicology testing helps clinicians and case workers help patients by providing critical information about substances in a patient’s system. There are two main testing platforms: qualitative (meaning the test is either positive or negative) and quantitative (meaning the test measures drug concentration). Screening (also called “presumptive testing”) is a qualitative technique to identify certain targeted drugs. Screening tests yield rapid results, are inexpensive, and are available for a wide variety of drugs, but they are not very precise. A screening result commonly indicates that a class of drugs is positive, not necessarily which specific drug triggered the positive.

Another disadvantage with screening tests is that they are more likely to give false test results due to lack of sensitivity and specificity. A false positive occurs when the screen is positive but the drug is not actually present, and a false negative occurs when the drug is actually present but the screen is negative.

False positives often occur when drugs present in the sample are chemically related to the target drug. For example, the anti-depressant/anti-anxiety drug sertraline (aka Zoloft) can produce a false positive result if the sample is screened for its more dangerous cousin drug class, benzodiazepines. False negatives often occur because screening cutoff levels are unable to detect positive samples at low concentration levels.

The other category of testing is quantitative testing, or confirmation (also known as “definitive testing”). Definitive testing is commonly performed to “confirm” positive screening results, negative screening results for expected drugs or to test for drugs that do not offer screening options.

Confirmation testing uses highly specific and sensitive analytical methodology such as LC-MS (for “liquid chromatography–mass spectrometry”) or GC-MS (for “gas chromatography-mass spectrometry”). These instruments provide a molecular fingerprint of the drugs that are present in the sample and provide corresponding measured drug concentrations with detection limits much lower than screening assays. Compared to screening, confirmation testing has many advantages.

LC-MS/GC-MS testing is far more sensitive and specific than qualitative screening, so confirmation results are much less likely to produce false negative or false positive results. Confirmation results not only determine what drugs are positive and negative but also at what concentrations the positive drugs are present in the patient’s sample. Another advantage of confirmation testing is its unlimited testing options, because LC-MS/GC-MS methods are able to distinguish the specific chemical signature of a drug/metabolite.

This is a huge advantage because it allows us to tell, for example, if a patient took Benadryl rather than PCP, and it also allows us to identify parent drugs and their resulting metabolites, which can be controlled substances on their own. Confirmation testing is not as quick or inexpensive as the simpler preliminary screen tests, but LC-MS/GC-MS results provide greater confidence in what drugs are truly present in a patient sample.

Which type of testing method is best? It depends on what you’re testing for and why. If a doctor only needs a quick yes or no about a low-risk patient, a screen test might be considered sufficient. A chronic pain patient who continues to complain about pain levels despite her current prescriptions probably needs more definitive testing to try to determine what’s really going on. Screening and confirmation testing in combination is required for cases in the criminal justice system, because a positive preliminary result must be confirmed using a different method than the initial test.