Can you please explain why confirmation cutoff levels are lower than screening levels?
For drug screening tests, a cut-off is chosen that will optimize drug detection but minimize the number of false positive results. It is important to note that a negative sample doesn’t mean that it is drug free; it might contain a drug at a concentration that is lower than the defined cut-off.
Screening and confirmation testing are performed using different methodologies that necessitate different cutoff levels. The cutoff levels of an immunoassay screen are typically higher than those of a more sensitive GC/MS or LC/MS/MS confirm test, because they screen for a larger group of parent compounds, metabolites and other structurally similar compounds.
If a screening test detects a drug (above the screening cutoff level) the presumptive positive specimen will be sent to GC/MS or LC/MS/MS confirmation testing. Many times, these individual compounds are present in concentrations much lower than the total immunoassay response, thus resulting for the cutoff levels being lower for the GC/MS or LC/MS/MS test.
The screening test is very general and the confirmation test is very specific.
A specific example:
The cut off for marijuana on the screen is 50 ng/ml, which is a composite of all 31 metabolite concentrations. If the sample is below this level the test is over as a passing status. If the sample is over 50 ng/ml the sample is sent on to a GC/MS for confirmation. The cutoff for the confirmation is lower at 15 ng/ml because the machine only identifies one of the 31 metabolites which is the 11-nor-D-9-tetrahyrocanibinolic acid. To pass, the one metabolite must be below the 15-ng/ml cutoff.