임상보고 가능범위의 실증적 연구

장상우 ( Sang Wu Chang ),이상곤 ( Sang Gon Lee ),최호성 ( Ho Seong Choi ),송은영 ( Eun Young Song ),박용원 ( Yong Won Park ),이인애 ( In Ae Lee ) 대한임상검사과학회 2007 대한임상검사과학회지(KJCLS) Vol.39 No.1

The purpose of the clinically reportable range (CRR) in clinical chemistry is to estimate linearity in working range. The reportable range includes all results that may be reliably reported, and embraces two types of ranges: the analytical measurement range (AMR) is the range of analyte values that a method can directly measure on the specimen without any dilution, concentration, or other pretreatment not part of the usual assay process. CAP and JCAHO require linearity on analyzers every six months. The clinically reportable range is the range of analyte values that a method can measure, allowing for specimen dilution, concentration, or other pretreatment used to extend the direct analytical measurement range. The AMR cannot exceed the manufacturer’s limits. Establishing AMR is easily accomplished with Calibration Verification Assessment and experimental Linearity. For example: The manufacturer states that the limits of the AST on their instrument are 0-1100. The lowest level that could be verified is 2. The upper level is 1241. The verified AMR of the instrument is 2-1241. The lower limit of the range is 2, because that is the lowest level that could be verified by the laboratory. The laboratory could not use the manufacturer’s lower limit of 2 because they have not proven that the instrument values below 2 are valid. The upper limit of the range is 1241, because although the lab has shown that the instrument is linear to 1241, the manufacturer does not make that claim. The laboratory needs to demonstrate the accuracy and precision of the analyzer, as well the validation of the patient AMR. Linearity requirements have been eliminated from the CLIA regulations and from the CAP inspection criteria, however, many inspectors continue to feel that linearity studies are a part of good lab practice and should be encouraged. If a lab chooses to continue linearity studies, these studies must fully comply with the calibration/calibration verification requirements of CLIA and/or CAP. The results of lower limit and upper limit of clinically reportable range were total protein (2.1 - 79.9), albumin (1.3 - 39), total bilirubin (0.2 - 106.2), alkaline phosphatase (13 - 6928.2), aspartate aminotransferase (24 - 7446), alanine aminotransferase (13 - 6724.2), gamma glutamyl transpeptidase (16.64 - 9904.2), creatine kinase (15.26 - 4723.8), lactate dehydrogenase (127.66 - 13231.8), creatinine (0.4 - 129.6), blood urea nitrogen (8.67 - 925.8), uric acid (1.6 - 151.2), total cholesterol (48.52 - 3162), triglycerides (36.91 - 3367.8), glucose (31 - 4218), amylase (21 - 6694.2), calcium (3.1 - 118.2), inorganic phosphorus (1.11 - 108), HDL (11.74 - 666), NA (58.3 - 1800), K (1.0 - 69.6), CL (38 - 1230).

1년간의 관리시료를 통한 계통오차에 대한 연구

장상우 ( Sang Wu Chang ),김대식 ( Dae Sik Kim ),서한익 ( Han Ik Sur ),장순모 ( Sun Mo Chang ),여영규 ( Young Gyu Yeo ),김양호 ( Yang Ho Kim ),조영주 ( Young Ju Cho ) 대한임상검사과학회 2000 대한임상검사과학회지(KJCLS) Vol.32 No.3

Bias is an effect tending to produce results that depart systematically from the true value. Bias called systematic error in total quality management field. Systematic Error is an error that always in one direction and is predictable, in contract to random errors that may be either be either positive or negative and whose direction can not be predicted. We studied systematic error in using same quality control material during one year in c1inical chemisσy laboratory in order to evaluate bias from target value with Hitachi 7150 system. Grand means of systematic error were total protein(normal control-0.08, abnormal cα1trol-0.05), a1bm띠n(N-O.06, AB-O.04) , total bi1irubin(N-O.13, AB-O.22), a1ka1ine phosphatase (N-13.6, AB-56.8), glucose(N-2.75, AB-l 1.63), AST(N-1.3, AB-2.8), ALT(N-2.72, AB-7.35), BUN(N-O.27, AB-1.5), uric acid(N-O.2, AB-O.3) , calcium(N-O. 26,AB-O. 29) , inorganic phosphorus (N-O.19, AB-0.47), gama-GTP(N-O.83, AB-2.5), creatinine(N-O.l7, AB-O.07), direct bi1irubin (N-O.Ol, AB-O.07), CK(N-4.l, AB-14.2), LD(N-46.3, AB-73.65), total cholesterol(N-4.6, AB-3.1), πiglyceride(N-4.7, AB-7.5).

검량물질의 목표치 설정에 대한 연구

장상우 ( Sang Wu Chang ),김남용 ( Nam Yong Kim ),홍웅기 ( Woong Ki Hong ),이희경 ( Heui Gyung Lee ),김현정 ( Hyun Jung Kim ),이윤정 ( Yun Jung Lee ) 대한임상검사과학회 2001 대한임상검사과학회지(KJCLS) Vol.33 No.2

Calibration in clinical chemistry laboratory reduce bias that is an error that always in one direction and is predictable, in contract to random errors that may either be positive or negative and whose direction can not be predicted. Target value used in proficiency testing to designate the correct value, usually estimated by the mean of all participant responses, after removal of out1iers, or by the mean established by definitive or reference methods. We studied to prcxluce target value in our own laboratory in using multi-calibrator during 8 months for five times each 10 tests by within-run and between-run. Setting of target value accurately in calibration process contributed to reduce systematic error in order to control total error in clinical chemistry laboratory.

임상화학검사실에서 회수율 실험의 실증적 연구

장상우 ( Sang Wu Chang ),이상곤 ( Sang Gon Lee ),송은영 ( Eun Young Song ),박용원 ( Yong Won Park ),박병옥 ( Byong Ok Park ) 대한임상검사과학회 2006 대한임상검사과학회지(KJCLS) Vol.38 No.3

The purpose of the recovery experiment in clinical chemistry is performed to estimate proportional systematic error. We must know all measurements have some error margin in measuring analytical performance. Proportional systematic error is the type of error whose magnitude increases as the concentration of analyte increases. This error is often caused by a substance in the sample matrix that reacts with the sought for analyte and therefore competes with the analytical reagent. Recovery experiments, therefore, are used rather selectively and do not have a high priority when another analytical method is available for comparison purposes. They may still be useful to help understand the nature of any bias revealed in the comparison of kit experiments. Recovery should be expressed as a percentage because the experimental objective is to estimate proportional systematic error, which is a percentage type of error. Good recovery is 100.0%. The difference between 100 and the observed recovery(in percent) is the proportional systematic error. We calculated the amount of analyte added by multiplying the concentration of the analyte added solution by the dilution factor(mL standard)/(mL standard + mL specimen) and took the difference between the sample with addition and the sample with dilution. When making judgments on method performance, the observed that the errors should be compared to the defined allowable error. The average recovery needs to be converted to proportional error(100%/Recovery) and then compared to an analytical quality requirement expressed in percent. The results of recovery experiments were total protein(101.4%), albumin(97.4%), total bilirubin(104%), alkaline phosphatase(89.1%), aspartate aminotransferase(102.8), alanine aminotransferase(103.2), gamma glutamyl transpeptidase(97.6%), creatine kinase(105.4%), lactate dehydrogenase(95.9%), creatinine(103.1%), blood urea nitrogen(102.9%), uric acid(106.4%), total cholesterol(108.5), triglycerides(89.6%), glucose(93%), amylase(109.8), calcium(102.8), inorganic phosphorus(106.3%). We then compared the observed error to the amount of error allowable for the test. There were no items beyond the CLIA criterion for acceptable performance.

논단(論壇) : 임상병리 기술학의 최근 동향

장상우 ( Sang Wu Chang ) 대한임상검사과학회 1975 대한임상검사과학회지(KJCLS) Vol.7 No.1

임상화학검사항목의 최소검출농도에 대한 연구

장상우 ( Sang Wu Chang ),김남용 ( Nam Yong Kim ),권선득 ( Sun Deuk Kwon ),이희경 ( Hee Kyung Lee ) 대한임상검사과학회 2003 대한임상검사과학회지(KJCLS) Vol.35 No.1

Limit of detection is the single result which, with a stated probability, can be distnguished from a suitable blank. Limit of detection is the lowest amount of analyte in a sample that can be detected, but not be quantified as an exact value. This value is also referred to as the Minimum Detactable Activity(MDA, LLD). Once this value is determined, the linear range of an assay extends from the value for the MDA(LLD) to the value for the highest calibrator concentration. The concentration up to which the method has been shown previously to maintain acceptable linearity. The analytical sensitivity is simply stated as, the positivity of disease; the probability that the test is positive when the disease is present. The analytical sensitivity is determined as the concentration equivalent to the mean counts obtained from the zero sample plus 2 SD for immunometric and chemical assays or the mean minus 2 SD for competitive assays. Analytical sensitivity is also referred to as the Lower Limit of Detection(LLD, MDA). The formal definition of analytical sensitivity is, "the lowest concentration that can be distinguished from background noise." This concentration is properly termed the assay`s detection limit, but it is most commonly referred to as sensitivity. Typically, this value is established by assaying replicates of a sample that is known to have no analyte present. Analytical specificity refers to the freedom of the method from interference from commonly occurring[e.g. lipids(lipemia), hemoglobin(hemolysis), bilirubin(icterus)] and commonly occurring [e.g. lipids (lipemia), hemoglobin (hemolysis), bilirubin (icterus)] and uncommonly occurring substances. The results of MDA that were studied on 18 tests in clinical chemistry are as follows: ALT, Albumin, ALP, IP, Amylase, Glucose, Cholesterol, Uric Acid, UN, Creatinine, and CK. Total Proteins were 0, AST (11.0 U/L), Total Bilirubin (0.7 mg/dL), GGT(2.3 mg/dL), LD(2.3 U/L), Triglyceride(1.0 mg/dL), and Calcium(0.2 mg/dL).

이월오염에 대한 연구

장상우 ( Sang Wu Chang ),김남용 ( Nam Yong Kim ),류재기 ( Jae Gi Lyu ),정동진 ( Dong Jin Jung ),김기유 ( Gi You Kim ),박용원 ( Yong Won Park ),추경복 ( Kyung Bok Chu ) 대한임상검사과학회 2005 대한임상검사과학회지(KJCLS) Vol.37 No.3

Carry over contamination has been reduced in some systems by flushing the internal and external surfaces of the sample probe with copious amount of diluent. It between specimens should be kept as small as possible. A built-in, continuous-flow wash reservoir, which allows the simultaneous washing of the interior and exterior of the syringe needles, addresses this issue. In addition, residual contamination can further be prevented through the use of efficient needle rinsing procedures. In discrete systems with disposable reaction vessels and measuring cuvets, any carry over is entirely caused by the pipetting system. In analyzers with reuseable cuvets or flow cells, carry over may arise at every point through which high samples pass sequentially. Therefore, disposable sample probe tips can eliminate both the contamination of one sample by another inside the probe and the carry over of in specimen into the specimen in the cup. The results of the applicative carry over experiment studied on 21 items for total protein (TP), albumin (ALB), total bilirubin (TB), alkaline phosphatase (ALP), aspratate aminotranferase (AST), alanine aminotranferase (ALT), gamma glutamyl transferase (GGT), creatinine kinase (CK), lactic dehydrogenase (LD), creatnine (CRE), blood urea nitrogen (BUN), uric acid (UA), total cholesterol (TC), triglyceride (TG), glucose (GLU), amylase (AMY), calcium (CA), inorganic phosphorus (IP), sodium (Na), potassium (K), chloride (CL) tests in chematology were as follows. Evaluation of process performance less than 1% in all tests was very good, but a percentage of ALB, TP, TB, ALP, CRE, UA, TC, GLU, AMY, IP, K, Na, and CL was 0%, implying no carry over. Other tests were ALT(-0.08%), GGT(-0.09%), CK(0.08%), LD(0.06%), BUN(0.12%), TG (-0.06%), and CA(0.89%).

검량보정 검증의 실험적 적합성에 대한 연구 -치료적 약물검사를 중심으로-

장상우 ( Sang Wu Chang ),김남용 ( Nam Yong Kim ),최호성 ( Ho Sung Choi ),박용원 ( Yong Won Park ),추경복 ( Gyung Bok Chu ),윤근영 ( Keun Young Yun ),박병옥 ( Byung Ok Park ) 대한임상검사과학회 2005 대한임상검사과학회지(KJCLS) Vol.37 No.1

The purpose of this study was to verify (i) a consistent calibration verification for the assessment of method linearity and (ii) calibration agreement with calibration settings. We validated calibration verification through method linearity with different lot number of individual calibrators that span the working range for 9 tests except salicylate with control sample in test. We evaluated that it covered broad analyte range to assay from near zero to the top of the measuring range with 5 or 6 points every three times for 10 analytes in TDM test. Target values were plotted on X-axis with assigned or observed values on the Y-axis. Working range were as follows. Calibration verification of the measuring range (maximum to minimum values) has been validated asetaminophen 0.1 to 304.6 μg/mL, salicylate 0 to 1005 μg/mL, valproic acid 3.2 to 154.19 μ g/mL, digoxin 0.17 to 5.65 ng/mL, vancomycine 1.3 to 80.51 μg/mL, carbarmazepine 0.1 to 22.3 μg/mL, phenytonin 0.6 to 40.21 μg/mL, theophyline 0.2 to 40.21 μg/mL, primidone 0 to 24.07 μg/mL, phenobarbital 0.6 to 60.0 μg/mL. Drawing a straight line through five or six points of these data showed good linearity. We are sure that it is important to assess the calibration verification of a test method to ascertain the lowest and highest test results that are reliable.

6 시그마와 총 오차 허용범위의 개발에 대한 연구

장상우 ( Sang Wu Chang ),김남용 ( Nam Yong Kim ),최호성 ( Ho Sung Choi ),김영환 ( Yong Whan Kim ),추경복 ( Kyung Bok Chu ),정혜진 ( Hae Jin Jung ),박병옥 ( Byong Ok Park ) 대한임상검사과학회 2005 대한임상검사과학회지(KJCLS) Vol.37 No.2

Those specifications of the CLIA analytical tolerance limits are consistent with the performance goals in Six Sigma Quality Management. Six sigma analysis determines performance quality from bias and precision statistics. It also shows if the method meets the criteria for the six sigma performance. Performance standards calculates allowable total error from several different criteria. Six sigma means six standard deviations from the target value or mean value and about 3.4 failures per million opportunities for failure. Sigma Quality Level is an indicator of process centering and process variation total error allowable. Tolerance specification is replaced by a Total Error specification, which is a common form of a quality specification for a laboratory test. The CLIA criteria for acceptable performance in proficiency testing events are given in the form of an allowable total error, TEa. Thus there is a published list of TEa specifications for regulated analytes. In terms of TEa, Six Sigma Quality Management sets a precision goal of TEa/6 and an accuracy goal of 1.5 (TEa/6). This concept is based on the proficiency testing specification of target value +/-3s, TEa from reference intervals, biological variation, and peer group median mean surveys. We have found rules to calculate as a fraction of a reference interval and peer group median mean surveys. We studied to develop total error allowable from peer group survey results and CLIA 88 rules in US on 19 items TP, ALB, T.B, ALP, AST, ALT, CL, LD, K, Na, CRE, BUN, T.C, GLU, GGT, CA, phosphorus, UA, TG tests in chematology were follows. Sigma level versus TEa from peer group median mean CV of each item by group mean were assessed by process performance, fitting within six sigma tolerance limits were TP (6.1δ/9.3%), ALB (6.9δ /11.3%), T.B (3.4δ/25.6%), ALP (6.8δ/31.5%), AST (4.5δ/16.8%), ALT (1.6δ/19.3%), CL (4.6δ/8.4%), LD (11.5δ/20.07%), K (2.5δ/0.39mmol/L), Na (3.6δ/6.87mmol/L), CRE (9.9δ/21.8%), BUN (4.3δ/13.3%), UA (5.9δ/11.5%), T.C (2.2δ/10.7%), GLU (4.8δ/10.2%), GGT (7.5δ/27.3%), CA (5.5δ/0.87mmol/L), IP (8.5δ /13.17%), TG (9.6δ/17.7%). Peer group survey median CV in Korean External Assessment greater than CLIA criteria were CL (8.45%/5%), BUN (13.3%/9%), CRE (21.8%/15%), T.B (25.6%/20%), and Na (6.87mmol/L/4mmol/L). Peer group survey median CV less than it were as TP (9.3%/10%), AST (16.8%/20%), ALT (19.3%/20%), K (0.39mmol/L/0.5mmol/L), UA (11.5%/17%), Ca (0.87mg/dL1mg/L), TG (17.7%/25%). TEa in 17 items were same one in 14 items with 82.35%. We found out the truth on increasing sigma level due to increased total error allowable, and were sure that the goal of setting total error allowable would affect the evaluation of sigma metrics in the process, if sustaining the same process.

약물검사에서 관리시료의 농축을 이용한 보고 가능 범위의 설정에 대한 연구

장상우 ( Sang Wu Chang ),김남용 ( Nam Yong Kim ),최호성 ( Ho Sung Choi ),박용원 ( Yong Won Park ),윤근영 ( Keun Young Yun ) 대한임상검사과학회 2004 대한임상검사과학회지(KJCLS) Vol.36 No.1

This study was designed to establish working range for reoportable range in own laboratory in order to cover the upper and lower limits of the range in test method. We experimented ten times during 10 days for setting of reportable range with between run for method evaluation. It is generally assumed that the analytical method produces a linear response and that the test results between those upper and lower limits are then reportable. CLIA recommends that laboratories verify the reportable range of all moderate and high complexity tests. The Clinical Laboratory Improvement Amendments(CLIA) and Laboratory Accreditation Program of the Korean Society for Laboratory Medicine states reportable range is only required for "modified" moderately complex tests. Linearity requirements have been eliminated from the CLIA regulations and from others accreditation agencies, many inspectors continue to feel that linearity studies are a part of good lab practice and should be encouraged. It is important to assess the useful reportable range of a laboratory method, i.e., the lowest and highest test results that are reliable and can be reported. Manufacturers make claims for the reportable range of their methods by stating the upper and lower limits of the range. Instrument manufacturers state an operating range and a reportable range. The commercial linearity material can be used to verify this range, if it adequately covers the stated linear interval. CLIA requirements for quality control, must demonstrate that, prior to reporting patient test results, it can obtain the performance specifications for accuracy, precision, and reportable range of patient test results, comparable to those established by the manufacturer. If applicable, the laboratory must also verify the reportable range of patient test results. The reportable range of patient test results is the range of test result values over which the laboratory can establish or verify the accuracy of the instrument, kit or test system measurement response.