Clin Chem Lab Med 2008;46(10):1438–1442  2008 by Walter de Gruyter • Berlin • New York. DOI 10.1515/CCLM.2008.275 2007/166 Article in press - uncorrected proof Analytical quality goals for parathyroid hormone based on biological variation Adie Viljoen 1, *, Dhruv K. Singh 2 , Patrick J. Twomey 3 and Ken Farrington 2 1 Department of Clinical Biochemistry, Lister Hospital, Stevenage, UK 2 Department of Nephrology, Lister Hospital, Stevenage, UK 3 Department of Chemical Pathology, The Ipswich Hospital, Ipswich, UK Abstract Background: Measurement of parathyroid hormone (PTH) is central in the investigation of pathologies of bone and mineral ion metabolism. Knowledge of the biological variation of an analyte forms an essential part of evaluating a new analyte, enabling the objec- tive assessment of changes in serial results and the utility of reference intervals, as well as establishing laboratory quality specifications. Methods: This study determined the biological varia- tion of PTH in 20 healthy individuals, which was cal- culated according to the familiar methods outlined by Fraser and Harris. Results: The within-subject variation was 25.3% and the between-subject variation was 43.4%. The critical difference for sequential values significant at p-0.05 was calculated as 72%. The within-subject variation forms a relatively small part of the reference interval, shown by the low index of individuality of 0.58. Objec- tive analytical quality goals have also been estab- lished, revealing achievable optimum performance for imprecision of ;6%. The desirable analytical bias goal was ;12%. Conclusions: This study has objectively shown that the analytical precision of current instruments is being achieved contrary to the known problems sur- rounding the analytical bias for PTH assays. The lim- itations of using reference intervals for PTH, both in diagnoses and monitoring, are shown. Clin Chem Lab Med 2008;46:1438–42. Keywords: biological variation; laboratory quality specifications; parathyroid hormone; reference change value. Introduction Parathyroid hormone (PTH) is a linear polypeptide of 84 amino acids that is encoded by a gene located on the short arm of chromosome 11 (1). Its major biolog- *Corresponding author: Adie Viljoen, Department of Clinical Biochemistry, Lister Hospital, Stevenage, UK Phone: q44-1438-314333 ext. 5972, Fax: q44-1438-781147, E-mail: adie.viljoen@nhs.net Received April 3, 2008; accepted June 10, 2008 ical effects are through a G protein-coupled receptor, expressed on target cells in the renal tubules and the osteoblastic lineage of bone (2). It plays an integral role in calcium and inorganic phosphate homeostasis and its measurement is central in the investigation of related disorders (3). It is now more than 40 years since the details of the first radioimmunoassay for PTH were published (4). Data on biological variation forms part of the com- prehensive evaluation required for analytes that are measured in the clinical laboratory and is an essential prerequisite to the introduction of new analytes (5). Biological variation data have several important clin- ical and laboratory applications that include: setting analytical quality specifications, evaluating the signif- icance of changes in serial results (the reference change value or ‘‘critical difference’’), assessing the utility of population-based reference intervals, and calculating the number of specimens required to esti- mate the homeostatic set point (6, 7). A comprehen- sive biological variation database of all known analytes that is frequently updated contains more than 300 analytes and references more than 200 publications and serves as a useful reference for many clinical laboratories (8). Interestingly, no data are available for the biological variation of PTH as opposed to many other more esoteric tests. An aspect related to this, namely diurnal variation, has long been known for PTH (9, 10). Without information on biological variation, it remains difficult to objectively assess patient results and data on internal control and quality assessment. We thus set out to generate these data. Materials and methods Subjects A total of 20 apparently healthy individuals w 10 men and 10 women; median age 37 years (range 19–60 years)x partici- pated in the study. All subjects provided consent prior to the study, which had been approved by the local Research and Ethics Committee. Table 1 shows the characteristics and rou- tine biochemistry investigations for this group. None of the subjects were taking any prescription medication, had any illnesses in the recent past (previous 3 months) or during the study that required at least general practitioner consultation, and none had a history of current or previous renal impair- ment or pathology-related bone and/or mineral ion metab- olism. No abnormalities in the relevant routine biochemistry investigations were detected for any of the subjects. Venous blood was collected into 5-mL tripotassium EDTA tubes (Vacuette  , Greiner Bio-One, Frickenhausen, Germany), tak- ing care to ensure that the sample collection vessel was completely filled (11). Samples were collected between 08:45 and 09:30 h on the same day of the week, weekly for 5 weeks as described by Fraser and Harris (7). All the samples were collected by one person. Samples were separated by cen- Brought to you by | Brigham Young University Authenticated Download Date | 5/19/15 12:17 AM