I have discussed some shortcomings about how interferences are handled. This reminded me of something that I and my coworker published a number of years ago (1).
The origin of this publication came from Dr. Stan Bauer at Technicon Instruments. He was a pathologist with a passion for statistics. He had hired Cuthbert Daniel, a well-known consulting statistician who developed a protocol for the SMA analyzer. This was a nine sample long run of three concentration levels that provided an estimate of precision, proportional and constant bias, sample carryover, linear drift, and nonlinearity. The reason that the protocol worked was the choice of the sample order provided by Cuthbert Daniel.
In 1985, I chose to make a CLSI standard out of the protocol – EP10. It is now in version A3 AMD. (I have no idea what the AMD means).
The protocol could be extended to provide even more information by adding a candidate interfering substance to up to all three concentration levels. Since each level is repeated three times, the interference is added to only one replicate. Using multiple regression, one can now estimate 8 parameters – whereby in addition to the original parameters, the bias (if any) for each of the three interfering substances.
Now one run is virtually useless, but at Ciba Corning, we ran these protocols repeatedly during the development of an assay, so that with multiple runs, if a substance interfered, it would be detected.
Krouwer JS and Monti KL: A Modification of EP10 to Include Interference Screening,. Clin. Chem., 41, 325-6 (1995).