Summary
Previously published work relating to quality control of drug assays has dealt mainly with interlaboratory comparisons. It is suggested that participants in external quality assessment schemes will derive the maximum benefit from their participation if a suitable intralaboratory quality control scheme is established. Such a scheme should be capable of providing estimates of within- and between-batch imprecision over the concentration range for which the assay is used and give an indication of the development of systematic error (relative to previous performance). A scheme using serum pools at 3 concentrations, each to be analysed at least in duplicate, is recommended. Adaptations of this scheme, to be used when the number of patient samples per batch does not justify this number of control samples, are discussed in relation to various analytical situations. A ratio of 1 control sample to 10 patient samples is considered reasonable.
The interpretation of results from external quality assessment schemes using performance indices, graphical assessment of ‘bias’ and standard deviation interval (SDI = bias divided by standard deviation) and the statistical evaluation of proportional and additive error by linear regression (least squares) analysis is discussed. In some cases it has been possible, from the results of interlaboratory studies, to show that a particular method will not generally give satisfactory results when compared either with other currently available methods, e.g. UV-spectrophotometric methods for phenobarbitone, Phenytoin, carbamazepine and theophylline, or on the grounds of clinical requirements, e.g. doubling dilution broth techniques for gentamicin.
Improvement in intralaboratory reproducibility would facilitate the identification of technical factors contributing to interlaboratory variation.
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References
Ayers, G.J.; Goudie, J.H.; Reed, K. and Burnett, D.: Quality control in the simultaneous assay of anticonvulsants using an automated gas-chromatographic system with a nitrogen detector. Clinica Chimica Acta 76: 113–124 (1977).
Boobis, S.; Persaud, N. and Richens, A.: Results of a quality control scheme for the assay of theophylline in serum. Therapeutic Drug Monitoring 1: 257–263 (1979).
Davis, R.B.; Thompson, J.E. and Pardue, H.L.: Characteristics of statistical parameters used to interpret least squares results. Clinical Chemistry 24: 611–620 (1978).
Dijkhuis, I.C.: Quality control of drug assays in therapy and toxicology using calf serum as matrix. (PhD Thesis, University of Leiden, 1979).
Griffiths, A.; Hebdige, S. et al.: Quality control in drug measurement. Ther. Drug Monit. 2: 51–59 (1980).
Healy, M.J.R.: Outliers in clinical chemistry quality control schemes. Clinical Chemistry 25: 675–677 (1979).
Pippenger, C.E.; Penry, J.K.; White, B.G.; Daly, D.D. and Buddington, R.: Interlaboratory variability in determination of plasma antiepileptic drug concentrations. Archives of Neurology 33: 351–355 (1976).
Pippenger, C.E.; Paris-Kuth, H.; Penry, J.K. and Daly, D.D.: Antiepileptic drug levels quality control program: Interlaboratory Variability; in Pippenger et al. (Eds) Antiepileptic Drugs: Quantitative Analysis and Interpretation, pp. 187–197 (Raven Press, New York 1978).
Reeves, D.S. and Bywater, H.J.: Quality control of serum gentamicin assays — experience of national surveys. Journal of Antimicrobial Chemotherapy 1: 103–116 (1975).
Richens, A.: Results of a Phenytoin control scheme; in Schneider et al. (Eds) Clinical Pharmacology of Antiepileptic Drugs, pp.293–303 (Springer-Verlag, Berlin 1975).
Turner, W.S.; Turano, P. and Badzinski, S.: An attempt to establish quality control in the determination of plasma chlorpromazine by a multi-laboratory comparison; in Gottschalk and Merlis (Eds) Pharmacokinetics of Psychoactive Drugs: Blood Levels and Clinical Response, pp. 33–44 (Spectrum, New York 1976).
Wakkers, P.J.M.; Hellendoorn, H.B.A.; Op de Weegh, G.S. and Heerspink, W.: Applications of statistics in clinical chemistry. A critical evaluation of regression lines. Clinica Chimica Acta 64: 173–184 (1975).
Westgard, J.O.; de Vos, D.J.; Hunt, M.R.; Quam, E.F.; Garber, C.C. and Carey, R.N.; Concepts and practices in the evaluation of clinical chemistry methods. III: Statistics. American Journal of Medical Technology 44: 552–571 (1978).
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Ayers, G., Burnett, D., Griffiths, A. et al. Quality Control of Drug Assays. Clin Pharmacokinet 6, 106–117 (1981). https://doi.org/10.2165/00003088-198106020-00002
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DOI: https://doi.org/10.2165/00003088-198106020-00002