Editors: Olga Pozdnyakova, MD, PhD, Geoffrey Wool, MD, PhD, David Bernard, MD, PhD & Raul S. Gonzalez, MD
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Q. What is the best way to check machine precision? Is it acceptable to run precision replicates in quality control mode?
A. July 2025—It is a little difficult to answer the question because the answer may depend on the type of machine as well as the type of testing. I will limit my answer to chemistry tests.
For your typical chemistry analyte, something like “glucose” that would be performed as a Food and Drug Administration-cleared test on an in vitro diagnostics-approved medical device, my laboratory would do the following:
1. Check the manufacturer’s package insert and review the precision claims when setting the limits of acceptability. For example, the manufacturer might say that total precision for analyte “X” at a concentration of 50 mg/dL is a coefficient of variation of 10 percent.
2. Decide the total allowable error (TAE) that would be considered acceptable (test dependent) and then determine how much imprecision could be tolerated. For example, for analyte “X,” here are three scenarios that could be used:
- The acceptable TAE is 20 percent. For random error, 25 percent would be budgeted; therefore, the allowable imprecision for this test is five percent.
- The acceptable TAE is 10 mg/dL. An acceptable amount of random error is 25 percent; then the random error budget would allow for 2.5 mg/dL of imprecision.
- The acceptable coefficient of variation is less than five percent, less than 10 percent, or less than 20 percent, for example.
3. Precision studies
- Low level of quality control: within day, at least 20 replicates.
- Low level of QC: between day, at least 20 replicates (once a day for 20 days, or something similar).
- High level of QC: within day, at least 20 replicates.
- High level of QC: between day, at least 20 replicates.
- If the test has three levels of QC, then this would similarly be tested, i.e. at least 20 replicates, for within day and between day precision.
4. Evaluate with the mean, standard deviation, and coefficient of variation to determine if the results are within the acceptability limits.
In the question, “QC mode” is used, which suggests the question might be referring to a point-of-care device. Something similar could be done with high and low QC material in QC mode. In the setting where analytic processes differ from how patient samples will be handled, the medical director should determine if precision studies are adequate. If QC mode is used for an overall precision study, performing an additional smaller precision study using real-life materials (that can be run in standard operating mode) could be considered best practice. If you have further questions about using QC mode, you may want to contact your instrument manufacturer.
Michelle K. Zimmerman, MD, MBA
Associate Professor of Clinical Pathology and Laboratory Medicine
Division of Clinical Pathology
Department of Pathology and Laboratory Medicine
Indiana University Health
Pathology Laboratory
Indianapolis, Ind.
Chair, CAP Instrumentation Committee
Q. Several molecular diagnostic vendors circulate across U.S. hospitals and clinics to provide collection kits to physicians and request that those physicians refer tests outside the institution for what is sometimes described as clinical trials or research. The vendors operate using a pharmaceutical company model of selling proprietary testing directly to physicians and patients and bypassing the laboratory. It is a problem because laboratories are often expected to collect and submit samples and then enter complex reports into the electronic health record.
These companies are farming health systems for business and bypassing the accreditation process. When the testing is used not for research but instead for “the purpose of providing information for the diagnosis, prevention, or treatment of any disease or impairment of, or the assessment of the health of, human beings,” under U.S. law it is defined as laboratory testing (section 353 of the Public Health Service Act, 42 USC §263a), which is overseen by pathology laboratories and under pathology’s accreditation. Under this legal definition of laboratory testing, those outsourced tests are not research.
Can you comment on this practice from an accreditation perspective?
A. Under the Clinical Laboratory Improvement Amendments of 1988, a test result that has with it a patient name or even a code name or other personal identifier is considered a laboratory test because it can be used to assess health or treat disease.
The only way the vendors’ practice is appropriate is when all results are anonymized. For example, if the subject’s email address is used as the anonymized identifier, under CLIA ’88 it is still patient testing. In a state that allows direct-to-consumer testing, the diagnostic vendors can sell directly to the patient and bypass the laboratory, but the testing location would still require a CLIA certificate.
As always, we recommend seeking advice and comment through your laboratory- and institution-approved channels.
Denise Driscoll, MS, MLS(ASCP)SBB
Vice President
Laboratory Accreditation Programs
College of American Pathologists
Northfield, Ill.