Proficiency testing of serum enzymes based on medical-needs criteria.

Proficiency testing goals for serum enzymes have been set by statistical methods, by the ex cathedra statements of experts, based on the intraindividual variation of healthy people, and based on responses from the users of enzyme data, ie, clinicians in practice. Clinicians consider small changes in serum enzyme values to be medically unimportant. Medical-needs criteria are probably the most relevant in setting proficiency testing goals for enzymes. The enzyme values that most modern clinical analyzers are capable of producing are more precise than appears to be medically necessary. We surveyed clinicians for their perceived needs; based on their responses, we conclude that tight proficiency testing limits for enzyme tests are inappropriate.

Proficiency testing of enzymes. Charting the way toward standardization.

Laboratories participating in the College of American Pathologists Enzyme Survey (ES) and Comprehensive Chemistry Survey used diverse methods for the same analyte, resulting in a considerable range of values for the commonly performed enzyme measurements. Nevertheless, with the techniques developed for the ES, both the short-term (within-mailing) and long-term (between-mailings) coefficients of variation (CVs) can be determined. The ten-year experience of the ES has shown improvement in the short-term CV; however, long-term stability of enzyme testing requires more effort on the part of the instrument and reagent suppliers and participating laboratories. A reference material with an International Federation of Clinical Chemistry-established aspartate aminotransferase value, National Bureau of Standards RM 8430, is now available and was sent to three large peer groups as part of a special study. Correction of the results to the RM 8430 aspartate aminotransferase value resulted in reducing the range of data from peers using the duPont aca but not from those using the American Monitor KDA or Technicon SMAC. Based on our experience with the ES, goals of 5% for the short-term CV and 10% for the long-term CV are proposed; they are achievable by most laboratories and meet medical needs for biochemical screening. Fixed criteria for the evaluation of enzyme results appear to be appropriate given the way most enzyme data are used clinically.

Determination of reference ranges for serum enzymes via a large interlaboratory survey.

We obtained enzyme data on normal individuals in conjunction with a large interlaboratory enzyme survey. For the 12 largest peer groups using unique methods, we found a simple relationship between the upper reference limits and the laboratories' results obtained from human-enzyme-supplemented survey serum. A conversion to a common base made possible the merging of data on the normal individuals and interconversion of results by diverse methods. We determined the upper reference limits for serum lactate dehydrogenase, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and creatine kinase for approximately 8000 adult men and women believed to be in good health. Using a technique described here, we believe that the results can be transformed to user-specific units, and that the large data base can be applied to the many diverse enzyme methods in current use. With these data, enzyme survey participants will be able to estimate appropriate reference intervals for their particular method.

Survey of serum enzyme analyses. Human tissues as a source of enzymes.

The College of American Pathologists' enzyme survey permits the evaluation of the quality of enzyme analyses in clinical laboratories. Animal source enzymes for lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and creatine kinase are satisfactory as supplements for enzyme survey serum, since they give results equivalent to human source enzymes. This finding makes the interconversion of results by different methods possible, and the estimation of the upper limit of normal based on the results obtained for the enzyme survey serum.

Interlaboratory survey of enzyme analyses: V. A simplified method of reporting participants' data.

The College of American Pathologists' Enzyme Survey continues to provide a valuable measure of the analytic quality of clinical enzymology for its participants and for the laboratory community. An updated reporting format for the participants simplifies the interpretation of Enzyme Survey data and should make it more valuable for detecting short- and long-term changes in accuracy and precision. A short-term CV of 3% and a long-term CV of 6% are recommended as analytic goals for the five enzymes described here. The upper limit of normal used by many laboratories is appropriate for a given enzyme yet remains as an area requiring urgent further study.

Interlaboratory survey of enzyme analyses IV. Human versus porcine tissue as source of creatine kinase for survey serum.

A special enzyme survey was carried out in 185 laboratories on specimens fortified with either porcine heart or human skeletal muscle creatine kinase (CK). All analytical systems were examined to see if they gave different results for porcine and human CK as compared with analysis of the same specimens on the duPont ACA. Analytical differences were found. However, these differences were small, and, with some exceptions, do not prevent interconversion of units based solely on specimens fortified with porcine CK. Both types of specimens serve equally well in estimating bias and variability of CK analyses. Based on the results for the human material, many laboratories appear to use inappropriate reference ranges for CK.

The 1978 College of American Pathologists survey of analyses of five serum enzymes by 450 laboratories.

Sets of survey specimens having known linear interralationships were analyzed on four occasions by approximately 450 laboratories for the five enzymes lactate dehydrogenase, aspartate aminotransferase, creatine kinase, alanine aminotransferase, and alkaline phosphatase. The results are summarized in terms of the apparent precision and relative accuracy of various analytical systems, and some apparent problems in enzyme assays are identified. The results show that interlaboratory differences in enzyme analyses are not due primarily to differences in the way laboratorians utilize their analytical systems but rather are due to fundamental differences in the instruments and reagents supplied to the laboratorians. The attainment of interlaboratory comparability of enzyme analyses is a problem that can best be addressed by the manufacturers of instruments and reagents, rather than by individual laboratorians.

The 1977 College of American Pathologists Enzymology Survey. Principal findings.

A set of linearly related serum survey specimens was analyzed by more than 200 laboratories on four occasions in 1977 for the five enzymes lactate dehydrogenase, aspartate and alanine aminotransferases, creatine phosphokinase, and alkaline phosphatase. The survey technic, which employs specimens that are designed to have multiple informational redundancies for detecting discrepancies in the survey data, was found to be a feasible approach, as a variety of methodologic biases and analytic problems were readily detected. The specimens were shown to be stable,and the mean results obtained by a reference group of laboratories were quite reproducible. Consequently, changes observed in individual laboratories in successive surveys were attributable to intra-laboratory changes. The survey provides each participant with an objective evaluation of the linearity, precision, and calibration of his methods, in comparison with peer and reference laboratories, as well as information concerning the popularities of various methods, and the performances of various analytic systems. For each enzyme there are a few large peer groups and a large number of small peer groups. Differences among the laboratories within each peer group were due primarily to proportional biases that in some cases were clearly due to instrumental or reagent differences, rather than to methodologic differences.