HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Electronic Letters to:

Review: Thomas B. Ledue and Nader Rifai Preanalytic and Analytic Sources of Variations in C-reactive Protein Measurement: Implications for Cardiovascular Disease Risk Assessment Clin Chem 2003; 49: 1258-1271 [Abstract] [Full text] [PDF]

eLetters: Submit a response to this article

Electronic letters published:

Clarification of the method of verification of functional sensitivity for high-sensitivity CRP

Jeong-Ho Kim   (24 January 2005)

Re: Clarification of the method of verification of functional sensitivity for high-sensitivity CRP

Thomas B Ledue, Nader Rifai   (2 February 2005)

Clarification of the method of verification of functional sensitivity for high-sensitivity CRP 24 January 2005
Jeong-Ho Kim, Professor Department of Laboratory Medicine, Yongdong Severance Hospital, Yonsei Univ, Seoul, 135-720, Korea Send letter to journal: Re: Clarification of the method of verification of functional sensitivity for high-sensitivity CRP jeongho{at}yumc.yonsei.ac.kr Jeong-Ho Kim	Dr. Ledue and Dr. Rifai's article (1) is an excellent and extensive review article for the high-sensitivity C-reactive protein (hsCRP) assay and seemed to be a very practical guide for the selection and understanding of hsCRP assay. In Fig. 5. on page 1264, I think the Y-axis should be "total imprecision" instead of "within-assay imprecision, % CV" described in the Fig. Roberts et al. (2,3) described the functional sensitivity or limits of quantification of hsCRP was as total imprecision of 10-days (2) or 5-days (3) period. I have also described the imprecision of functional sensitivity of hsCRP either 5-days or 10-days total imprecision(4). References (1) Ledue TB, Rifai N. Preanalytic and analytic sources of variations in C -reactive protein measurement: implications for cardiovascular disease risk assessment. Clin Chem 2003;49:1258-71. (2) Roberts WL, Sedrick R, Moulton L, Spencer A, Rifai N. Evaluation of four automated high- sensitivity C-reactive protein methods: implications for clinical and epidemiological applications. Clin Chem 2000;46:461-8. 3) Roberts WL, Moulton L, Law TC, Farrow G, Cooper-Anderson M, Savory J, et al. Evaluation of nine automated high- sensitivity C-reactive protein methods: implications for clinical and epidemiological applications. Part 2. Clin Chem 2001;47:418-25. (4) Sung HJ, Kim JH, Park R, Lee KR, Kwon OH. Evaluation of Denka-Seiken turbidimetric high-sensitivity C-reactive protein assay. Clin Chem Lab Med 2002;40:840-5.
Re: Clarification of the method of verification of functional sensitivity for high-sensitivity CRP 2 February 2005
Thomas B Ledue, Technical Supervisor Foundation for Blood Research, Nader Rifai Send letter to journal: Re: Re: Clarification of the method of verification of functional sensitivity for high-sensitivity CRP tledue{at}fbr.org Thomas B Ledue, et al.	We thank Dr. Kim for his kind comments and for the opportunity to clarify our work (1). The issues of precision and detection limit ("sensitivity") and limit of quantification (such as the "functional sensitivity") are important variables in the clinical utility of hs-CRP assays. Currently, the only requirement of CLIA ’88 that relates to the latter two issues for automated immunoassay systems is for laboratories to verify the lower limit of the reportable range. Some laboratories accomplish this by determining a detection limit ("analytic sensitivity") defined as the mean + 2 SDs for 20 replicates of a sample in an appropriate matrix with zero concentration. Although this approach is usually adequate for verifying claims in package inserts, it is not the same as determining the more useful limit of quantification (such as a functional sensitivity). In the hypothetical example of an hs-CRP imprecision profile used in our paper, we listed the “within-assay imprecision, % CV” for the y-axis consistent with the cited reference (2). However, as Dr. Kim suggests, the more robust analysis uses “within-laboratory total imprecision,% CV.” Ideally, the protocol should allow the laboratory to determine the lowest concentration associated with the specified goal for interassay imprecision that represents the clinical usefulness for the assay. Selecting samples with appropriate concentrations that span the target range is critical as is randomizing their placement in the run to reflect routine operation and possible carryover problems. Samples should be repeatedly analyzed over a period of days to weeks to ascertain the interassay imprecision. Once the CVs for each sample are calculated the functional sensitivity can be determined. Laboratorians should also be mindful of the impact of an assay’s recovery at this concentration since dose-dependent recovery can result in an inaccurate estimate of an assay’s functional sensitivity (3). 1. Ledue TB, Rifai N. Pre-analytic and Analytic Sources of Variations in C-reactive Protein Measurement: Implications for Cardiovascular Disease Risk Assessment. Clin Chem 2003; 49:1258-1271. 2. Davies C. Assay Concepts. In: Wild D, ed. The Immunoassay Handbook. 2nd ed. New York: Nature Publishing Group, 2001. 3. Price A, Burgin C, Catch I, Cruise M. Functional sensitivity and recovery of thyroid-stimulating hormone. Clin Chem 2001; 47:2067.