Test validation

Medical Laboratory Observer, June, 2004 by Steven C. Kazmierczak

I have been a tech for 32 years, am of above-average intelligence, and I still do not understand CLIA's latest requirement for test validation. I have read Westgard's book, and have asked the pathologist, but no one seems to explain it adequately. Why do we have to validate test procedures if we are following manufacturer's instructions?

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Prior to obtaining clearance by the Food and Drug Administration for a particular assay method, manufacturers are required to submit detailed documentation concerning the analytical aspects (precision, analytical measurement range, interferences) of the assay. The responsibilities of each laboratory in evaluating the performance characteristics of a new method or instrument are outlined in the Clinical Laboratory Improvement Amendments (CLIA). (1)

Validation of an assay or instrument is not only required under CLIA but is also good laboratory practice. (2) Assay performance may be substantially different from laboratory to laboratory, depending on a variety of factors. These include the type of specimen used (i.e., serum or plasma) for analysis, the type of patient population served, and the age of the specimen being analyzed.

Regarding sample type, there is a substantial body of literature describing differences in measured analyte values between these two sample types. Manufacturers may not specify the type of sample used when reporting the performance characteristics of an assay. Another factor that can adversely affect the performance of an assay is the patient population being served. For example, assay performance described following testing in a healthy adult outpatient population may perform substantially different when applied in a setting such as a children's hospital where the majority of samples are icteric and/or hemolyzed.

Finally, the age of the specimen at the time of analysis may impact assay performance. Assay performance characteristics may be very different when an older specimen is being analyzed, as may occur in a reference laboratory setting vs. analysis of relatively fresh specimens seen in a hospital STAT laboratory setting.

In summary, performance characteristics reported by manufacturers should be viewed as general guidelines showing how the assay should perform, usually under optimum conditions. Each laboratory needs to assess for itself how an assay will perform. Assay validation is not just a CLIA requirement, but is an integral part of good patient care.

References

1. U.S. Department of Health and Human Services; Medicare, Medicaid, and CLIA Programs; Regulations implementing the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Final Rule, Federal Register. 1992, February 28;57:7002-7186.

2. National Committee for Clinical Laboratory Standards. Preliminary Evaluation of Quantitative Clinical Laboratory Methods; Approved Guideline Second Edition Wayne, PA. EP10-A2 NCCLS: 2002.

--Steven C. Kazmierczak, PhD, DABCC

Department of Pathology

Oregon Health and Sciences University

Portland, OR

Edited by Daniel M. Baer, MD

MLO's Tips from the Clinical Experts department provides practical, up-to-date solutions to readers' technical and clinical issues from a panel of experts in various fields, Readers may send questions to Dan Baer by e-mail at tips@mlo-online.com.