원저 Lab Med Online Vol. 4, No. 1: -21, January 214 http://dx.doi.org/1.3343/lmo.214.4.1. 임상화학 Wisecheck 혈당측정기평가 Evaluation of the Wisecheck Glucose Monitoring System 권선희 김하늬 고선영 조치현 김장수 임채승 Seonhee Kwon, M.D., Ha Nui Kim, M.D., Sun-Young Ko, M.D., Chi Hyun Cho, M.D., Jang Su Kim, M.D., Chae Seung Lim, M.D. 고려대학교의과대학진단검사의학교실 Department of Laboratory Medicine, Brain Korea 21 Graduate School of Medicine, College of Medicine, Korea University, Seoul, Korea Background: Glucometers are widely used for self-monitoring and point-of-care testing in diabetes management. We evaluated the performance of the recently developed Wisecheck Glucose Monitoring System (Wisemeditech, Korea) compared to that of 2 other well-known glucometer systems. Methods: The Wisecheck glucometer was evaluated for precision, linearity, and carryover rate. One-hundred fifty samples samples were tested, and the results obtained from the Wisecheck glucometer, ACCU-CHEK Performa (Roche Diagnostics, Germany) and SD GlucoLink (SD Diagnostics, Korea) were compared to those obtained using the laboratory reference method from the Toshiba 2FR (Toshiba, Japan), according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: The coefficient of variation (CV) values for within-run imprecision at low, middle, and high levels were 2.6%, 1.2%, and 2.2%, respectively, and the CV values for total-run imprecision at low, middle, and high levels were 2.98%, 2.41%, and 1.88%, respectively. In the linearity test, the coefficient of determination (R 2 ) was.998 in glucose concentration ranging from 48.6 mg/dl to 428 mg/dl (P <.1). The results obtained using the Wisecheck glucometer were well correlated with those obtained using the Toshiba 2FR (R 2 =.98, P <.1). The carryover rate was.12%. Conclusions: The Wisecheck glucometer showed good precision, linearity, and correlation with the reference method. It provided rapid and reliable measurements of blood glucose levels and seemed appropriate for use in diabetes management. Key Words: Glucometer, Blood glucose, Diabetes mellitus 서론 국내에서당뇨병의유병률은공복혈당수치 126 mg/dl 을기준 으로할때 7.79% ( 남자 8.6%, 여자 7.1%) 로보고되고있으며 [1], 노 인인구의증가에따라당뇨병유병률은더욱높아지고합병증관 Corresponding author: Chae-Seung Lim Department of Laboratory Medicine, Korea University Guro Hospital, 97 Gurodong-gil, Guro-gu, Seoul 2-73, Korea Tel: +82-2-2626-324, Fax: +82-2-2626-146, E-mail: malarim@korea.ac.kr Received: October, 212 Revision received: June 11, 213 Accepted: June 11, 213 This article is available from http://www.labmedonline.org 214, Laboratory Medicine Online This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3./) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 리에대한필요성이증가되고있다. 당뇨병은지속적인혈당감시를통해치료의적절성을평가하고, 치료과정에이를반영하는것이환자의치료와예후에중요하다. 따라서당뇨환자의관리에는지속적인혈당의관리가요구되는데수시로혈당을측정함으로써치료에대한목표혈당수치의도달여부를알수있으며저혈당의예방과약물용량, 임상영양치료, 신체활동의정도조절에유용하게이용될수있다 [2]. 자가혈당측정기는현장검사장비로외래, 병실등에서폭넓게사용되고있으나측정된결과를수작업으로입력하는과정에서발생하는사무적오류로인해체계적인데이터관리가이루어지지못하는단점이있다. 이에비해병원용혈당측정기시스템은바코드스캐너를내장하여현장에서환자의혈당을측정한후혈당측정기를크래들 (cradle) 에꽂으면저장된결과가자동으로중앙검사실에있는서버 (server) 로전송되어빠르고신속하게결과값을처리할수있으며검사수행시환자정보나검사자정보를검사결과와함께저장할수있어자가혈당측정기의단점을보완하였다. 또한기기내부에정도관리및주기설정이가 eissn 293-6338 www.labmedonline.org
능하여내부정도관리데이터가자동으로중앙전산실에연결되어정도관리결과를체계적으로관리하며측정한스트립을손으로직접제거하지않고스트립이젝터를이용하여제거함으로써스트립에묻은환자혈액으로인한검사자의감염을방지할수있다. 국외의경우병원용혈당측정기의연구개발이 Roche ACCU- CHEK Inform Ⅱ System (Roche Diagnostics, Mannheim, Germany), SureStepFlexx (Johnson and Johnson, NJ, USA), Precision PCx (Abbott, Illinois, USA), StatStrip Glucose (Nova Biomedical, Massachusetts, USA) 등에서활발히이루어지고있으며국내에서도병원용혈당측정기에대한개발및연구가지속되어최근병원용혈당측정기 Wisecheck (Wisemeditech, Anyang, Korea) 이개발되었다. Wisecheck의혈당측정원리는최근개발되는대부분의혈당측정기에적용되는전기화학적바이오센서방식을취하고있는데 [3], 전기화학적방식은혈액중의포도당과효소의반응으로발생하는전자의흐름을전극을통하여측정하고이를혈당수치로변환해주는방법으로 [4], 기존의광도측정법보다요구되는혈액량이적고측정시간이빠르고오차가적은것이장점이다. 혈당측정기는측정에사용되는효소에따라크게 hexokinase법, glucose oxidase (GOD) 법, glucose dehydrogenase법으로나뉘며, glucose dehydrogenase 법은다시 glucose dehydrogenase-nicotinamide adenine dinucleotide (GDH-NAD), glucose dehydrogenase-flavin adenine dinucleotide (GDH-FAD), glucose dehydrogenase-pyrroloquinolinequinone (GDH-PQQ) 으로나뉜다 []. 말토오즈, 갈락토오스, 자일로오스등은측정방법에따라화학적간섭효과를일으킬수있는데, GOD법혹은 GDH-NAD법과같이당과교차반응을하지않는혈당측정기를사용하면간섭효과를극복할수있다 [6]. Wisecheck의스트립은당산화효소인 GOD를사용하여간섭물질에의한오차를최소화하였다. 또한, 이전의혈당측정기평가보고에따르면검사소요시간이사용자만족도결정에주요요인인데 [7], Wisecheck의분석속도는 초로기존의보고된혈당측정기의분석속도 1-26초 [3] 에비해사용자가혈당수치를빠르게얻을수있어사용자의만족도를향상시켰다. 그리고 Wisecheck의최소혈액요구량은. μl로다른혈당측정기의최소혈액요구량 1.-1 μl에비해적어서검체채취시깊게찌르지않아도되므로통증에민감한환자들이선호할것으로생각되며검체채취요령이미숙한사용자가충분한양의모세혈관전혈검체를얻지못한경우검사가진행되지않아스트립을낭비하는일을줄일수있을것으로예상된다. 이에본연구자들은국내에서개발된병원용혈당측정기 Wisecheck의수행능과기존에사용중인자가혈당측정기 2종및생화학장비와의상관성을분석하여유용성을평가하고자하였다. 대상및방법 1. 대상 212년 2월 1일부터 213년 2월 22일까지약 12개월동안고려대학교구로병원진단검사의학과에혈당검사가의뢰된환자 명을대상으로하였다. 약 3 ml의정맥혈을 Becton Dickinson사의 Vacutainer EDTA (BD, Fanklin Lakes, NJ, USA) 을이용하여채혈하였고, 동시에손가락끝에서약 1 μl의모세혈관전혈을란셋으로채취하였다. 대상자는모두 18세이상의성인들로, 모든시행과정은임상시험심사위원회 (Institutional Review Board, IRB) 의승인에의해진행되었고모든피시험대상자에게연구에대한서면동의를받았다. 2. 방법 1) 대상기기및원리최근국내에서개발된병원용혈당측정기 Wisecheck를대상으로평가를수행하였다. 이미시판사용중인혈당측정기 2종, SD GlucoLink (SD diagnostics, Yongin, Korea) 와 ACCU-CHEK Performa (Roche Diagnostics, Mannheim, Germany) 를비교기기로선택하였고 hexokinase법으로혈당을측정하는 Toshiba 2FR (Toshiba, Tokyo, Japan) 를참고법으로이용하였다. 2) 정밀도 (Precision) Clinical Laboratory and Standards Institute (CLSI) EP-A2 [8] 에따라 Bio-Rad사의전혈성분의정도관리물질인 Meter Trax TM Control (Bio-Rad Laboratories, Hercules, CA, USA) 을이용하였으며 일간하루 4회씩반복측정하여평균 (mean), 시험내표준편차 (within-run standard deviation), 시험내변이계수 (within-run CV), 총표준편차 (total standard deviation), 총변이계수 (total CV) 를계산하였다. 검사의수행은병리사 1인이모든측정을담당하여시험자에따른차이가발생하지않도록하였다. 3) 직선성 (Linearity) 직선성은 CLSI EP6-A2에따라평가하였다 [9]. 직선성평가에는환자검체를이용하였는데 48.6 mg/dl 의낮은혈당치를갖는검체와 428. mg/dl의높은혈당치를갖는검체를 4: ( 계산치 : 48.6 mg/ dl), 3:1 (118. mg/dl), 2:2 (213. mg/dl), 1:3 (318. mg/dl), :4 (428. mg/dl) 의비율로혼합하였다. 가지단계의농도를제조한후각각 4회반복측정한뒤계산치와측정치간의회귀방정식과결정계수 (R 2 ) 를구하였다. 16 www.labmedonline.org http://dx.doi.org/1.3343/lmo.214.4.1.
4) 상관성 (Comparison) 상관성은 CLSI EP9-A2 에따라 개의임상검체에서 Toshiba 2FR 측정치와비교하였다 [1]. 고려대학교구로병원진단검사의 학과에혈당검사가의뢰된검체중 Toshiba 2FR 로측정된값을 기준으로혈당치가 -4 mg/dl 에걸쳐고르게분포하도록동일 시점에채취한혈장과모세혈을이용하였다. Toshiba 2FR 에서 는정맥혈의혈장으로, Wisecheck, ACCU-CHEK Performa, 그리 고 SD GlucoLink 에서는모세혈관전혈로측정하여단순선형회귀 분석으로상관성을평가하였다. 또한각측정치는 Bland-Altman analysis [11] 를이용한분포점으로표시하였는데이방법은표준 측정값과측정차의분포 ( 측정차의평균 ± 표준편차 2 배수 [2SD]) 를나타낸다. 본연구는국제표준화기구 (International Organization for Standardization, ISO) 와 CLSI 의지침에서요구하는오차 허용범위를적용하였으며혈당치 1 mg/dl 이하인경우참고법 과의차이를 ±12 mg/dl 로, 1 mg/dl 이상인경우 9% 의측정 결과를 ±12.% 로정하고있다 [12, 13]. ) 검체간상호오염 (Carry-over) 평가 검체간상호오염여부를평가하기위해 48.6 mg/dl 의저농도와 428. mg/dl 의고농도의검체를각각 1 개씩선별하여 4 개의시험 관에분주하였다. 고농도검체부터 4 개를먼저차례로측정 (H1, H2, H3, H4) 하고이어서저농도검체를 4 회 (L1, L2, L3, L4) 측정하 였다. CLSI H7-A [14] 따라총 1 회반복측정한후아래의식에의 해검체간상호오염에대한비율 (%) 을구하였다. 평가의허용범위 는검체간상호오염도 1% 이하로하였다. L1-(L3+L4)/2 Carryover rate (%) = (H2+H3)/2-(L3+L4)/2 6) 통계분석 통계분석은 Microsoft Excel 27 (Microsoft Corporation, New York, NY, USA) 과 MedCalC (MedCalc Software, Mariakerke, Belgium) 프로그램을사용하여 Pearson s correlation test 와 Bland Altman test 로상관성을비교분석하였다. 1. 정밀도 (Precision) 결과 저농도, 중간농도, 고농도의전혈성분의정도관리물질에대하 여각혈당측정기로측정한후검사내정밀도변이계수 (within-run CV) 및총변이계수 (total CV) 를구하였다 (Table 1). Wisecheck, ACCU-CHEK Performa, 그리고 SD GlucoLink 모두검사내정밀 도변이계수와총정밀도변이계수는 % 이내로우수하였다. 2. 직선성 (Linearity) Wisecheck 을이용해낮은농도와높은농도의환자검체로조제 한 가지농도의검체를 4 회반복측정한결과 48.6-428 mg/dl 의 농도범위에서 R 2 =.998 (P<.1) 의직선성을보였다 (Fig. 1). 3. 상관성 (Comparison) Toshiba 2FR 과각혈당측정기에의한혈당측정법의방법간 Measured value (mg/dl) 4 4 3 3 2 2 1 Expected value (mg/dl) y=1.12x-34.248 R 2 =.998 (P<.1) Fig. 1. Linearity of the glucose concentrations measured using Wisecheck. Table 1. Precision of the 3 glucometers used for the measurement of 3 different glucose levels Glucometer Level Number of counts (mg/dl) Within-run SD (mg/dl) Within-run CV (%) Total SD (mg/dl) Total CV (%) Wisecheck* Low 2. 1.4 2.6 1. 2.98 Mid 2 117. 1.42 1.2 2.83 2.41 High 2 268.2 3.8 1.64.6 1.88 ACCU-CHEK Performa Low 2 64.1 1.11 1.74 1.48 2.31 Mid 2 3.3 2.44 1.8 2.8 1.86 High 2 382.7 6.23 1.62 8.93 2.34 SD GlucoLink Low 2 8.7 1.82 3.1 2.34 3.98 Mid 2 132. 3.19 2.38.69 4.31 High 2 313.1.71 1.83 1.4 3.32 *Wisecheck (Wisemeditech, Korea); ACCU-CHEK Performa (Roche Diagnostics, Germany); SD GlucoLink (SD Diagnostics, Korea). http://dx.doi.org/1.3343/lmo.214.4.1. www.labmedonline.org 17
Glucose (mg/dl) by Wisecheck Glucose (mg/dl) by ACCU-CHEK Performa Glucose (mg/dl) by SD GlucoLink 4 4 3 3 2 2 1 4 4 3 3 2 2 1 4 4 3 3 2 2 1 Wisecheck y=.938x+6.124 R 2 =.98 (P<.1) Glucose (mg/dl) by Toshiba 2FR ACCU-CHEK Performa y=.94x+.14 R 2 =.987 (P<.1) Glucose (mg/dl) by Toshiba 2FR SD GlucoLink y=.871x+.96 R 2 =.978 (P<.1) Glucose (mg/dl) by Toshiba 2FR Fig. 2. Correlation of glucose concentrations measured using 3 glucometers (Wisecheck, ACCU-CHEK Performa, and SD GlucoLink) with those measured using Toshiba 2FR. 비교에서단순선형회귀분석으로분석한결과 Wisecheck 은기울 기.938, 절편 6.124 그리고상관계수 R 2 =.98, ACCU-CHEK Performa 는기울기.94, 절편.14 그리고상관계수 R 2 =.987, 그 리고 SD GlucoLink는기울기.871, 절편.96, 상관계수 R 2 =.978 로전체농도범위에서우수한상관관계를나타내었으며세장비모두 P값은.1 미만으로통계적으로유의하였다 (Fig. 2). Wisecheck과 ACCU-CHEK Performa, SD GlucoLink의 Bland-Altman plot은 Fig. 3과같다. Wisecheck을포함한각혈당측정기마다다양한양또는음의오차를보였으며참고법과의혈당치차이는 Wisecheck의경우평균 1.3±16. mg/dl, 백분율로는.1±12.4%, ACCU-CHEK Performa 의경우평균.3±12.9 mg/dl, 백분율로는 -.4±1.7%, 그리고 SD GlucoLink는평균 1.1±19.8 mg/dl, 백분율 7.9 ±13.7% 를보였다. 4. 검체간상호오염 (Carry-over) Wisecheck에서측정한혈당의고농도와저농도간상호오염도는.12% 로평가의허용범위 1% 이하를만족하여검체간상호오염은일어나지않음을확인하였다. 고찰 당뇨병은치료가평생꾸준히지속되어야하는만성질환이며, 혈당이높은상태로치료하지않거나관리하지않을때신체에다양한합병증을유발할수있다. 따라서혈당을수시로측정하고이에근거한적절한식이요법및운동, 약물치료등을통하여지속적이고엄격한혈당조절을시행함으로서당뇨병합병증발생을줄이고예후를향상시킬수있다 [, 16]. 당뇨병환자에서혈당측정은혈당조절향상및당뇨병합병증발생감소에상당한기여를하는것으로알려져있다 [17]. 최근혈당측정기의연구개발은결과값관리와병원전산시스템의연동과같은검사정보시스템, 그리고환자의혈당관리와관련하여이루어지며주로결과값을개인컴퓨터, 게임콘솔 (game console), 스마트폰과같은정보기기와연동하여특수한소프트웨어를사용하여당뇨병을관리하는시스템으로고안되고있다. 정보기기와연동하는혈당측정기의경우국외에서는게임콘솔인 Nintendo DS에연동하는 Contour Didget (Bayer Diabetes, Toronto, Canada) 이개발되어사용되고있다 [18]. 대형병원검사실의경우혈당측정기로혈당을정확하게측정하더라도결과치를수기로전산시스템에입력하는과정에서결과값오차가발생하여이에대한적절한개선방안이요구되었다. 본연구에서평가한 Wisecheck 병원용혈당측정시스템은혈당측정을가정이나병원등에서개인이나혹은의료진이현장진단 (point-ofcare testing, POCT) 을할수있으며검사결과를곧바로병원의전산시스템에연결할수있어신속한의료활동에도움을줄수있다. 본연구의결과에따르면 Wisecheck의총변이계수및시험내변이계수가모두 % 이내로미국당뇨병협회와미국임상생화학협회 18 www.labmedonline.org http://dx.doi.org/1.3343/lmo.214.4.1.
Difference (mg/dl) 3 2 2 1 - -1 - -2 Wisecheck 1.3±16. mg/dl glucose (mg/dl) of Toshiba 2FR and Wisecheck 17.3 1.3-14.6 Difference (%) Wisecheck.1±12.4% glucose (mg/dl) of Toshiba 2FR and Wisecheck 12..1-12.2 2 1 - -1 - -2 Difference (mg/dl) 2 2 1 - -1 - ACCU-CHEK Performa.1±12.9 mg/dl 13.2.3-12. Difference (%) 2 1 - -1 - -2 ACCU-CHEK Performa -.4±1.7% 1.3 -.4-11.2 glucose (mg/dl) of Toshiba 2FR and ACCU-CHEK Performa glucose (mg/dl) of Toshiba 2FR and ACCU-CHEK Performa Difference (mg/dl) 7 6 4 3 2 1-1 -2-3 SD GlucoLink SD GlucoLink 3 7.9±13.7% 1.1±19.8 mg/dl 2 2 21.6 1 29.9 glucose (mg/dl) of Toshiba 2FR and SD GlucoLink 1.1-9.7 Difference (%) - -1 - -2 glucose (mg/dl) of Toshiba 2FR and SD GlucoLink 7.9 -.8 Fig. 3. Bland-Altman difference plots and Bland-Altman % difference plots of the mean values obtained using the glucometers, Wisecheck, ACCU- CHEK Performa, and SD GlucoLink versus those obtained using Toshiba2FR. The mean difference (solid line) and limits of agreement (mean±2sd, dotted line) are shown. 에서자가혈당측정기에의한혈당검사시요구하는정밀도수준 % 이내를만족하였다 [19]. 직선성은 48.6-428 mg/dl 의농도범위 에서적절하였으며 (R 2 =.998, P<.1) 검체간상호오염도는.12% 로평가의허용범위 1% 이하를만족하여검체간상호오염은 일어나지않음을확인하였다. 중앙검사장비와의상관성비교를시 행한결과 Wisecheck, ACCU-CHEK Performa, SD GlucoLink 의각 http://dx.doi.org/1.3343/lmo.214.4.1. www.labmedonline.org 19
각의상관계수값은 R 2 =.98 (P<.1), R 2 =.987 (P<.1), R 2 =.978 (P<.1) 로비교적높은상관성을보여주었다. Wisecheck을포함한 3가지혈당측정기로측정된혈당수치는최저 1 mg/dl, 최고 412 mg/dl이며 Wisecheck과참고법과의혈당수치의차이는평균 1.3±16. mg/dl, 백분율로는.1±12.4% 였다. 1 mg/dl 미만인혈당수치범위에서는참고법의 ±12 mg/dl, 1 mg/dl 이상인범위에서는 9% 가참고법의 ±12.% 범위에포함되어국제표준화기구와 CLSI의지침을만족시키고있다. 이상의결과를종합하면, 혈당측정기 Wisecheck은정밀도, 직선성및상관성의분석능평가에서기존의자가혈당측정기와비교하였을때성능의차이를보이지않았다. 또한검사시필요한혈액량이. μl 로다른혈당기의최소혈액요구량에비해적으며분석속도가빠른편이었다. 그러므로, 병원의전산시스템에연동되는병원용혈당측정시스템으로 Wisecheck은즉각적인검사결과가요구되는응급실이나중환자실에서현장검사장비로사용하기에적합할것으로판단된다. 요약 배경 : 혈당측정기는가장보편적인현장검사장비로, 당뇨병환자의엄격한혈당관리와신속한검사를위해병원과가정에서널리사용되고있다. 저자들은최근국내에서개발된병원용혈당측정기 Wisecheck (Wisemeditech, Korea) 의분석성능을기존에사용중인자가혈당측정기 2종과비교하여평가하고자하였다. 방법 : Wisecheck에대해정밀도, 직선성, 검체간상호오염을평가하였다. 총 검체를사용하여 Wisecheck과 SD GlucoLink (SD diagnostics, Korea), ACCU-CHEK Performa (Roche Diagnostics, Germany) 를비교기기로선택해 CLSI 지침에따라중앙검사장비측정치와상관성을평가하였다. 이때혈당측정참고법으로 Toshiba 2FR (Toshiba, Japan) 을사용하였다. 결과 : Wisecheck의검사내정밀도의변이계수는저농도, 중간농도와고농도에서 2.6%, 1.2% 그리고 2.2% 였고, 총정밀도의변이계수는저농도, 중간농도와고농도에서 2.98%, 2.41% 그리고 1.88% 였다. 직선성은 48.6-428 mg/dl의농도범위에서 R 2 =.998 (P <.1) 로나타났다. Wisecheck에서얻은결과는 Toshiba 2FR에서얻은결과와우수한상관관계를보였다 (R 2 =.98, P <.1). 검체간상호오염도는.12% 로나타났다. 결론 : Wisecheck은정밀도, 직선성및방법간비교검사에서우수한결과를보였고, 빠르고신뢰성있는혈당측정결과를제공하여당뇨환자의치료에유용하게사용될수있을것으로판단된다. REFERENCES 1. Cho NH. Diabetes epidemiology in Korean. J Korean Diabet Assoc 21;2:1-1. 2. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care 23;26(S1):S33-. 3. Yoo EH, Cho HJ, Ki CS, Lee SY. Evaluation of COSMOsensor Glucose Monitoring System. Korean J Lab Med 26;26:1-8. 4. Park CY, Ryu MS, Woo JT, Kim SW, Kim JW, Kim YS, et al. Evaluation of GlucoDrTM blood glucose testing system. Clinical Diabetes 22;3: 2-63.. Frias JP, Lim CG, Ellison JM, Montandon CM. Review of adverse events associated with false glucose readings measured by GDH-PQQ-based glucose test strips in the presence of interfering sugars. Diabetes care 21;33:728-9. 6. Bode Bruce W. The accuracy and interferences in self-monitoring of blood glucose. US Endocr Dis Touch Brief 27:46-8. 7. Lee SY, Lee NY, Kim JW. Evaluation of 6 glucose testing system. Korean J Lab Med 23;23:17-9. 8. Clinical and Laboratory Standards Institute. User verification of performance for precision and trueness; approved guideline. 2nd ed. EP- A2. Wayne, PA: Clinical and Laboratory Standards Institute, 26. 9. Clinical and Laboratory Standards Institute. Evaluation of the linearity of quantitative measurement procedures; a statistical approach.; approved guideline. EP6-A. Wayne, PA: Clinical and Laboratory Standards Institute, 23. 1. Clinical and Laboratory Standards Institute. Method comparison and bias estimation using patient samples; approved guideline. 2nd ed. EP9-A2. Wayne, PA: Clinical and Laboratory Standards Institute, 22. 11. Bland JM and Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:37-1. 12. Clinical and Laboratory Standard Institute. Point-of-care blood glucose testing in acute and chronic care facilities; approved guideline. 3rd ed. POCT12-A3. Wayne, PA: Clinical and Laboratory Standard Institute, 213. 13. The International Organization for Standardization. In vitro diagnostic test systems-requirements for blood glucose monitoring systems for self-testing in managing diabetes mellitus. ISO/TC 212/SC. International Standard ISO 197. Geneva, Switzerland: ISO, 23. 14. Clinical and Laboratory Standards Institute. Method comparison and bias estimation using patient samples; approved guideline. 2nd ed. EP9-A2. Wayne, PA: Clinical and Laboratory Standards Institute, 22. 2 www.labmedonline.org http://dx.doi.org/1.3343/lmo.214.4.1.
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