ANNUAL REPORT Annual Report on the External Quality Assessment Scheme for Immunoassay Tests in Korea (201

ANNUAL REPORT https://doi.org/10.15263/jlmqa.2016.38.4.194 Annual Report on the External Quality Assessment Scheme for Immunoassay Tests in Korea (2015) Hyon-Suk Kim, Young Lan Kim, and Jung Eun Shim, as the Immunoassay Subcommittee, Korean Association of External Quality Assessment Services Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea Corresponding author: Hyon-Suk Kim Department of Laboratory Medicine, Yonsei University College of Medicine, 50-1 Yonseiro, Seodaemun-gu, Seoul 03722, Korea Tel: +82-2-2228-2443 Fax: +82-2-364-1583 E-mail: kimhs54@yuhs.ac pissn: 2384-2458 eissn: 2288-7261 Two trials of external quality assessment were performed in 2015, with 13 test items grouped into four test categories. The first trial materials were sent on May 19, 2015 and the second trial was performed on November 9, 2015 with 13 items including tumor markers, thyroid hormones, cardiac marker troponin (troponin T or troponin I), and procalcitonin (PCT) as biomarkers by immunoassay methods. The bone marker, carboxy-terminal collagen crosslinks (CTX) was replaced by procalcitonin since 2014, because a limited number of institutions performed assays with CTX. External quality surveys of 13 immunoassay test items with 16 control materials were conducted, as scheduled. In total, 13 control materials were used, which consisted of six tumor markers, namely alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carcinoma antigen (CA) 125, carbohydrate antigen (CA) 19-9, human chorionic gonadotrophin (HCG), and prostate specific antigen (PSA). In addition to tumor markers, 5 thyroid markers, namely thyroid hormone (T)3, T4, thyroid stimulating hormone (TSH), free T4, and thyroglobulin (TG) were included. Furthermore, troponin, as a cardiac marker, and procalcitonin, as a new biomarker, have been adopted since 2014. Five home-made pooled sera and 3 commercial control sera were used as survey materials. MAS Tri-point Liquimmune level 3 (Medical Analysis Systems Inc., USA) was used for thyroid hormones. Procalcitonin and troponin control materials were from Elecsys Precis Control Varia and Elecsys Precis Control Troponin (Roche, Germany), respectively. The number of laboratories participating in the external quality assessment for Immunoassay Subcommittee was 719 institutions in the first trial survey (response rate 98.7%) and 730 institutions in the second survey (94.9%). The test items most frequently used in immunoassays were TSH (93.2%, 93.1%), free T4 (90.3%, 90.2%), and AFP (89.4%, 89.0%), whereas recently adopted biomarkers were less frequently used: troponin I (36.6%, 37.1%), procalcitonin (24.1%, 26.7%), and thyroglobulin (10.3%, 10.7%). The quality of the laboratories participating in the survey seems to be continuously improving, according to their peer group results. (J Lab Med Qual Assur 2016;38:194-213) Key Words: Immunoassay, Quality assurance, External quality assessment, Surveys, Tumor marker, Thyroid marker, Cardiac marker, Troponin, Procalcitonin 서론 2015년도에도전년도에이어 2회의외부정도관리신빙도조사사업을실시하였다 [1]. 각회당 8개씩의관리물질들을냉장택배로우송하였고, 검사종목은종양표지자 6종, 갑상선표지자 5종및, 전년도에이어올해도면역단백종목에서새로운표지자로 thyroglobulin과심장표지자 troponin을포함하였고, 작년에골흡수표지자 carboxy-terminal collagen crosslinks (CTX) 대신새로운급성기바이오표지자종목으로도입한 procalcitonin을올해도대상으로하였다 [2-4]. 종목선정은외부기관의자료를통하여현재우리나라임상검사실에서 immunoassay 방법으로가장활발히검사가실시되고있는종목들을선택하였다. 즉종목수로총 13종의면역측정법검사종목을대상으로하였다. 대상기관은지난해까지 Immunoassay 분과사업에참여해온기관들과올해신규가입기관, 그리고새로참여의사를밝혀온우리대한임상검사정 194 Copyright 2016 Korean Association of External Quality Assessment Service

도관리협회회원기관들을대상으로하였다. 2015년도신빙도조사사업에사용한관리물질은각기관당 1년에총 16개였는데, 원칙적으로원가절감을위하여주관기관에서자가제조하였다. 즉주관기관에서각종목별로검사후남은양성및음성혈청을수집하여 pooling해서제조하였다. 각종목별로임상검사실결과치를살펴보고높은결과치를보이는검체와낮은결과치를보이는검체들을각각수집하여레벨별로 pooling하였다 [3-5]. 이렇게자가제조한관리물질을포함하여각회당 8개씩총 16개의관리물질을사용하였는데, 결과치가높은검체를얻기가어려웠던갑상선호르몬종목을포함하는관리물질과새로도입한심장표지자 troponin의고농도관리물질은상품화된제품을구입하여사용하였다. 즉 2015년한해동안 2회의외부정도관리신빙도조사를총 16종의관리물질을가지고 13종목에대해실시하였다. 재료및방법 1. 관리물질외부정도관리신빙도조사를위한관리물질은 2회의검체발송시에각 8종씩, 총 16종을사용하였다. 1회와 2회째모두갑상선호르몬검사용관리물질과새로운바이오마커인 troponin 종목의고농도관리물질은상품화된제품을구입하여사용하였는데, 높은결과치를보이는혈청을구하기어려웠기때문이었고, 그외의관리물질은자가제조하는것을원칙으로하였다. 제조방법은환자검사및건강검진쎈터에서의뢰된혈청들을대상으로각종목마다결과치를검토하여각종목에따라 level별로수집하였다가 pooling하여제조하였다. 자가제조한관리물질과상품화된갑상선호르몬고농도용물질 (MAS Tri-point Liquimmune level 3; Medical Analysis Systems Inc., Camarillo, CA, USA), 그리고 2년전부터새로추가된 troponin은 Elecsys Precis Control Troponin (Roche, Mannheim, Germany) 을구매하여개별포장하여냉장택배로배송하였다. 각검사종목별로해당검체를사용하여검사하도록각검체별로검사종목을지정하였다. 즉총 2회의외부정도관리신빙도조사사업에각 8종씩의관리물질을우송하였고, 종양표지자, 갑상선호르몬과새로운바이오마커인 procalcitonin과심장표지자검사를종목별로각검체를지정하여해당검사를실시하도록하였다. 검체발송은 1 차는 5월 19일에, 2차는 11월 9일에발송하였다. 2. 검사종목종양표지자종목으로 alpha-fetoprotein (AFP), carcinoembryonic antigen, human chorionic gonadotrophin (HCG, β-hcg), prostate specific antigen (PSA) 및 carcinoma antigen 125 (CA 125) 와 carbohydrate antigen 19-9 등 6종목을대상으로하였으며, 갑상선기능검사종목으로 thyroid hormone (T)3, T4, thyroid stimulating hormone 및 free T4 외에 2013년부터새로추가된 thyroglobulin을대상으로하였다. 그리고이때 2013년부터혈청면역단백검사를 immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), complement (C)3 및 C4 등 5종대신새로도입된심장표지자종목 (troponin T/troponin I) 과 CTX를그리고 2014년부터는 CTX 대신 procalcitonin에대하여외부신빙도조사를실시하였다. 3. 결과의분석및보고방법검사결과의분석및보고방법은평균, 표준편차, 변이계수등으로분석하였으며, 참여기관에서사용하고있는방법과장비에따라각기기별로분류하여결과를분석하였다. 협회에서전산화를추진하여완성되었기에우리분과의외부신빙도조사결과입력은물론, 전체방법과기기별통계, 그리고각기관의결과지까지도인터넷을이용하여입력은물론, 결과지출력까지도우리협회홈페이지에서가능하게되었다. AFP의경우검사결과보고단위로농도및국제단위의두가지가있는데, 현재는 ng/ml의단위가더널리사용되고있는추세임을감안하여이미 2010년부터는 ng/ml 의단위로모두환산하여분석하고있다. 각기관에서사용하는 immunoassay 검사방법으로서 reversed passive hemagglutination법같은정성이나반정량검사를사용하는기관들도아주적은수이지만있었는데, 양성과음성으로만결과를보고하였기때문에통계처리대상에서는제외하였다. 그리고갑상선호르몬검사종목들은각기관마다보고하는단위와참고치가달라서복잡하였다. 이들결과치는통일하여입력하도록하였고그결과를통계처리하였다. 그런데각병원마다아직도장비에따라보고단위가다른것을통일하지않거나계산결과가이상한결과치가발견되기도하였다. 그결과를일괄통계처리하기전에이상하다고생각되는경우에는다시각기관에전화를걸어확인하였는데, 일일이해당기관에전화를하여확인하였고그래도확인하기어려운경우도있었다. www.jlmqa.org J Lab Med Qual Assur 2016;38:194-213 195

Table 1. Schema of external quality assessment of immunoassay subcommittee in 2015 No. of laboratories invited Participating laboratories (%) Date for procurement of sera Date of results 1st trial 719 710 (98.7) 2015. 5. 19. 2015. 7. 3. 2nd trial 730 693 (94.9) 2015. 11. 9. 2015. 12. 31. Second trial response rate was decreased due to the laboratory consolidation policy of the centers belong to Korea Association of Health Promotion. Table 2. List of laboratories participating in the assessment of immunoassay tests in 2015 Test marker Participating laboratories 1st trial (%) 2nd trial (%) Tumor markers 635 (89.4) 617 (89.0) Thyroid markers 662 (93.2) 645 (93.1) Cardiac markers Troponin T 78 (10.9) 87 (12.6) Troponin I 260 (36.6) 257 (37.1) New biomarker Procalcitonin 171 (24.1) 185 (26.7) Results received 710 (100.0) 693 (100.0) Total no. of institutions invited 719 730 결과 1. 참여기관 외부정도관리사업을위한검체발송은 2015 년 5 월현재정 도관리협회에등록된기관중지난해까지본분과사업에참여 하였거나또는이번에새로참여의사를밝힌기관과신규가입 한기관을본부홈페이지에서내려받아대상기관을파악하였 으며, 1 차에는 719 기관에, 2 차에는 730 기관에검체를발송하 였다. 2015 년도에외부정도관리사업결과, 회신기관수는 1 차 710 기관, 2 차 693 기관이었다 (Table 1). 전체참여기관수는 2005 년도 2 차 305 기관에비하여현재 2015 년에는 2 배이상으로참 여기관이많이증가하였다. 참여한기관들에서실시하는각각의검사종목별로살펴보 면종양표지자종목에는 1 차와 2 차에각각 635 기관과 617 기 관, 갑상선호르몬종목에는 662 기관과 645 기관, 그리고새로 운종목에는종목에따라서 troponin-t/troponin-i 는 1 차와 2 차각각 78/260 기관, 87/257 기관에서검사결과를회신하였다 (Table 2). 또 procalcitonin 의경우 1 차 171 기관, 2 차 185 기관 에서회신하였다. Table 3. List of currently participating laboratories testing the immunoassay items in 2015 1st trial 2nd trial Tumor markers Alpha-fetoprotein 635 (89.44) 617 (89.03) Carcinoembryonic antigen 554 (78.03) 527 (76.05) Carcinoma antigen 125 441 (62.11) 412 (59.45) Carbohydrate antigen 19-9 482 (67.89) 454 (65.51) Prostate specific antigen 543 (76.48) 513 (74.03) HCG 155 (21.83) 155 (22.37) β-hcg 7 (0.99) 7 (1.01) Thyroid markers T3 571 (80.42) 550 (79.37) T4 133 (18.73) 124 (17.89) Free T4 641 (90.28) 625 (90.19) Thyroid stimulating hormone 662 (93.24) 645 (93.07) Thyroglobulin 73 (10.28) 74 (10.68) Cardiac markers Troponin T 78 (10.99) 87 (12.55) Troponin I 260 (36.62) 257 (37.09) New biomarker Procalcitonin 171 (24.08) 185 (26.70) Results received 710 (100.00) 693 (100.00) Total no. of institutions invited 719 730 Values are presented as number (%). Abbreviations: HCG, human chorionic gonadotrophin; T, thyroid hormone. 2. 검사종목별회신율 Immunoassay 정도관리검사종목별회신기관수는 Table 3 에표시하였다. 전년도에비하여대상기관수와회신기관수 는꾸준히늘어나고있음을알수있다. 특히 10 년간별로실 시하는기관이늘지않은혈청면역단백종목들대신에새로운 표지자를시도하였는데전년도에이어심장표지자검사는참 여기관의 47.6% (1 차 ) 와 49.6% 이상의기관에서실시하고있 었다. 또한동일기종을사용하는기관들간에는편차가크지 않았다. 그러나다른종류의장비간에는다른종목과마찬가 196 J Lab Med Qual Assur 2016;38:194-213 www.jlmqa.org

Table 4. Control materials used for immunoassay external quality assessment in 2015 Test marker Test item 1st trial 2nd trial Tumor markers Alpha-fetoprotein Specimen no. 1, 2 (15-IA-1, 2) Specimen no. 9, 10 (15-IA-9, 10) Carcinoembryonic antigen Carcinoma antigen 125 Carbohydrate antigen 19-9 HCG β-hcg PSA Specimen no. 3*, 4 (15-IA-3*, 4) Specimen no. 11*, 12 (15-IA-11*, 12) Thyroid markers T3 T4 Free T4 Thyroid stimulating hormone Thyroglobulin Cardiac marker Troponin T Specimen no. 7*, 8* (15-IA-7*, 8*) Specimen no. 15, 16 (15-IA-15, 16) Troponin I New biomarker Procalcitonin Specimen no. 5, 6 (15-IA-5, 6) Specimen no. 13, 14 (15-IA-13, 14) Abbreviations: HCG, human chorionic gonadotrophin; T, thyroid hormone. *Commercial sera: others were pooled sera prepared by Immunoassay Subcommittee. 지로면역자동분석기의특성대로결과치에는차이가있음을알수있었다. 2015년도외부정도관리에사용한관리물질을 Table 4에정리하였다. 3. Immunoassay 검사방법및장비의사용현황 2015년도 Immunoassay 정도관리사업에참여한기관들의각검사종목을검사방법및기기별로구분하여 Tables 5-19에정리하였다. Enzyme immunoassay 장비들에서 chemiluminiscence immunoassay 장비들로거의전환되어, 현재참여하고있는임상검사실들에서주로사용되고있는것은 chemiluminiscence immunoassay를이용하는자동면역장비들이었다. 4. 정도관리물질올해정도관리에사용한상품화된정도관리물질 (MAS Tripoint Liquimmune level 3; Medical Analysis Systems Inc.) 은갑상선호르몬검사에사용하도록지정하였고, 나머지다른관리물질은환자와건강인의 pooled sera를 level별로모아냉동보관하였다가자가제조한것이었다. 각검사종목별로환자들의검사결과를확인하고혈청을 pooling하여각 level을제조하였다. 단, 높은농도의검체를대량구하기어려운갑상선호르몬종목과새로운표지자로선정한심장표지자검사용은상품화된물질을구입하여제조하였다. 일부 level 검체들은 정상인의혈청을가지고희석하여제조하였다. 5. 분과워크숍 2015년협회추계학술대회와전체통합워크숍이있었는데우리 Immunoassay 분과에서필요한내용을선택하여 면역측정검사의정도관리 라는제목으로세명의연자가강의로참여하였다. 고찰 최근에 Immunoassay와관련된분야에서는검사방법이민감도와특이도가높은화학발광면역법과이에따른여러가지유사한검사방법들인 electro chemiluminescence immunoassay 등의방법들이도입되었다. 즉 immunoassay 검사중많은종류의검사가기존의 radioimmunoassay 방법에서부터 enzyme immunoassay로, 다시 chemiluminescence immunoassay로빠르게대치되었다 [6-10]. 이는 immunoassay검사에도입되는면역효소법및화학발광법이이제는방사성동위원소검사법보다더높은민감도와특이도를가지게되었으며유효기간이더길다는등장점이많고자동화가가능하여최근임상검사실의요구를충족할수있기때문으로생각된다 [11]. 종양표지자검사종목들은원래스크리닝목적으로사용하는 www.jlmqa.org J Lab Med Qual Assur 2016;38:194-213 197

Table 5. Immunoassays conducted using the alpha-fetoprotein marker (ng/ml) 15-IA-1 15-IA-2 15-IA-9 15-IA-10 Enzyme immunoassay 1 96.6 1 3.61 1 73.31 1 3.25 Fluorescent immunoassay 21 121.54 14.64 12.05 21 1.88 0.5 26.81 22 69.23 6.53 9.44 22 1.97 0.45 22.89 Turbidimetry 5 105.99 7.55 7.12 5 3.8 1.2 31.63 7 61.55 11.04 17.93 7 3.42 1.31 38.24 Chemiluminescence 336 129.7 7.56 5.83 336 3.07 0.36 11.69 331 70.02 4.99 7.13 331 3.06 0.34 11.25 Electrochemiluminescence 267 126.53 6.9 5.45 267 2.73 0.21 7.66 252 68.74 4.3 6.25 252 2.72 0.34 12.39 Other 4 110.05 9.74 8.85 2 3.5 1.77 50.51 4 82.29 38.7 47.03 3 3.58 3.1 86.64 Total 634 632 617 616 Architect series 158 127.87 4.69 3.67 158 3.07 0.13 4.08 158 68.97 2.18 3.16 158 2.97 0.14 4.56 ADVIA Centaur CP 16 134.14 9.66 7.2 16 3.22 1 30.93 16 73.15 4.26 5.82 16 3.14 0.51 16.25 ADVIA Centaur XP/classic 85 134.67 6.11 4.54 85 3.06 0.51 16.76 82 74.55 3.26 4.37 82 3.34 0.48 14.27 Access, Access II 14 126.99 6.25 4.92 14 3.21 0.2 6.28 13 68.39 6.16 9.01 13 3.11 0.31 10.11 Beckman DXi 30 122.05 5.96 4.88 30 3.03 0.2 6.5 32 64.44 3.39 5.26 32 2.99 0.18 6.15 VIDAS 18 119.25 17.54 14.71 18 1.74 0.28 16.39 19 70.07 7.91 11.28 19 1.86 0.22 11.71 Immulite, Immulite 200 10 120.54 13.96 11.58 10 1.67 0.42 25.13 8 64.92 9.69 14.93 8 1.54 0.21 13.73 BRIO, ARIO 1 96.6 1 3.61 1 73.31 1 3.25 Liason 2 132.9 1.41 1.06 2 3.45 0.33 9.65 2 65.99 8.33 12.62 2 2.72 0.23 8.32 Hitachi Chemstry 4 109.24 2.37 2.17 4 4.25 0.76 17.87 3 56.2 6.61 11.77 3 4.43 1.5 33.93 Vitros ECi/Vitros3600 10 116.52 9.88 8.48 10 2.73 0.25 9.26 10 60.72 5.87 9.67 10 2.65 0.3 11.36 Modular DP 1 68.28 1 2.96 E170/e601/e602 139 125.26 5.34 4.26 139 2.71 0.15 5.72 127 68.04 2.92 4.29 127 2.71 0.18 6.75 Elecsys 1010 2 122.95 1.48 1.21 2 2.61 0.1 3.79 Elecsys 2010/e411 127 128.78 8.49 6.59 127 2.73 0.26 9.59 125 69.24 5.57 8.04 125 2.73 0.43 15.86 COBAS c111 2 73.47 4.04 5.51 2 2.36 0.16 6.91 Toshiba Chemstry 1 93 1 2 1 47 1 3 Tosoh 3 123.2 5.62 4.56 3 3.53 0.21 5.89 3 69.83 3.21 4.6 3 3.4 0.72 21.21 LUMIPULSE G1200 10 145.07 6.37 4.39 10 3.82 0.25 6.51 10 76.68 3.46 4.51 10 3.67 0.07 1.93 Other 4 110.05 9.74 8.85 2 3.5 1.77 50.51 4 82.29 38.7 47.03 3 3.58 3.1 86.64 ADVIA Centaur Ultra 1 123 1 2.6 Total 635 633 617 616 Mean, SD, and %CV are of peer group (no.). 15-IA-1 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 1 specimen. 198 J Lab Med Qual Assur 2016;38:194-213 www.jlmqa.org

Table 6. Immunoassays conducted using the carcinoembryonic antigen marker (ng/ml) 15-IA-1 15-IA-2 15-IA-9 15-IA-10 Enzyme immunoassay 1 91.2 1 4.22 1 107.29 1 2.8 Fluorescent immunoassay 10 47.76 2.75 5.76 11 1.6 0.48 29.87 11 71.68 5.77 8.05 11 1.55 0.33 20.98 Turbidimetry 1 61.06 1 1.88 Chemiluminescence 301 53.87 7.16 13.29 301 2.27 0.71 31.4 293 68.34 9.67 14.15 293 1.97 0.46 23.63 Electrochemiluminescence 239 46.1 2.38 5.16 239 1.86 0.14 7.79 219 59.36 2.98 5.01 219 1.84 0.21 11.62 Other 1 47.66 1 1.87 2 40.64 23.15 56.97 2 1.39 0.78 56.67 Total 552 553 527 527 Architect series 144 58.89 3.17 5.38 144 2.94 0.28 9.68 141 73.92 4.09 5.53 141 2.33 0.24 10.5 ADVIA Centaur CP 10 44.33 4.31 9.72 10 1.61 0.39 24.05 11 55.33 2.82 5.09 11 1.33 0.35 26.06 ADVIA Centaur XP/classic 80 44.87 2.22 4.96 80 1.49 0.25 16.46 77 55.72 2.05 3.67 77 1.49 0.16 10.76 Access, Access II 11 54.89 4.96 9.04 11 1.96 0.29 14.75 10 78.21 8.64 11.04 10 1.99 0.23 11.48 Beckman DXi 27 51.34 1.91 3.72 27 1.81 0.1 5.69 29 71.8 5.56 7.74 29 1.76 0.12 6.93 VIDAS 9 46.98 1.54 3.27 9 1.41 0.08 5.95 9 71.39 5.19 7.27 9 1.46 0.14 9.64 Immulite, Immulite 200 13 63.44 2.25 3.55 13 2.12 0.18 8.25 9 86.9 5.32 6.12 9 2.17 0.17 7.84 BRIO, ARIO 1 91.2 1 4.22 1 107.29 1 2.8 Liason 1 53.3 1 2.23 1 65.2 1 1.89 Vitros ECi/Vitros3600 8 55.66 1.24 2.23 8 1.54 0.1 6.57 8 78.33 3.17 4.05 8 1.6 0.18 11.36 Modular DP 1 61.06 1 1.88 E170/e601/e602 139 45.28 1.51 3.33 139 1.81 0.1 5.25 123 58.38 2.02 3.46 123 1.79 0.08 4.52 Elecsys 1010 2 46.12 0.73 1.58 2 1.85 0.07 3.82 Elecsys 2010/e411 98 47.84 3.02 6.31 98 1.96 0.18 9.43 96 60.88 3.88 6.37 96 1.89 0.3 15.85 Tosoh 1 67.6 2 4.5 2.26 50.28 2 72.85 10.39 14.27 2 2.75 0.49 18 LUMIPULSE G1200 7 61.41 3.47 5.65 7 2.26 0.11 5.02 7 73.28 2.83 3.86 7 2.17 0.12 5.59 Other 1 47.66 1 1.87 2 40.64 23.15 56.97 2 1.39 0.78 56.67 ADVIA Centaur Ultra 1 44.7 1 1.14 Total 553 554 527 527 Mean, SD, and %CV are of peer group (no.). 15-IA-1 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 1 specimen. www.jlmqa.org J Lab Med Qual Assur 2016;38:194-213 199

Table 7. Immunoassays conducted using the carcinoma antigen 125 marker (U/mL) 15-IA-1 15-IA-2 15-IA-9 15-IA-10 Enzyme immunoassay 1 62.4 1 4.73 1 75.95 1 14.76 Fluorescent immunoassay 8 59.79 1.03 1.73 8 8.38 0.33 3.99 7 60.96 4.87 7.98 7 15.25 0.79 5.17 Chemiluminescence 228 75.2 9.8 13.04 228 11.75 1.53 13 220 71.79 7.23 10.08 220 20.77 2.83 13.61 Electrochemiluminescence 201 66.07 2.67 4.04 201 12.22 0.67 5.45 182 65.36 2.63 4.02 182 20.36 0.88 4.3 Other 2 52.25 3.01 5.77 2 8.09 2.08 25.7 2 45.7 7.5 16.4 2 12.24 3.04 24.84 Total 440 440 412 412 Architect series 116 82.23 6.63 8.06 116 12.74 1.12 8.81 113 76.3 6.39 8.38 113 22.76 2.14 9.39 ADVIA Centaur CP 4 66.08 2.09 3.17 4 11.63 1.15 9.92 5 78.28 19.74 25.22 5 22.1 6.44 29.16 ADVIA Centaur XP/classic 53 65.2 3.34 5.13 53 10.52 1.04 9.86 53 68.88 3.73 5.42 53 19.2 1 5.19 Access, Access II 5 80.72 5.95 7.38 5 11.68 0.99 8.44 3 70.1 3.69 5.26 3 21.47 1.99 9.25 Beckman DXi 26 76.11 2.9 3.81 26 11.11 0.66 5.94 27 64.5 3.82 5.92 27 17.95 1.22 6.77 VIDAS 7 59.79 1.03 1.73 7 8.38 0.33 3.99 6 59.84 4.22 7.06 6 15.25 0.79 5.17 Immulite, Immulite 200 11 65.6 4.79 7.31 11 8.97 0.41 4.59 8 65.54 6.29 9.59 8 16.33 1.69 10.36 BRIO, ARIO 1 62.4 1 4.73 1 75.95 1 14.76 Liason 1 93.31 1 12.44 1 67.17 1 18.05 Vitros ECi/Vitros3600 5 60.3 3.67 6.09 5 7.94 0.81 10.18 5 61.76 2.22 3.6 5 15.92 0.7 4.41 E170/e601/e602 134 66.14 2.13 3.22 134 12.15 0.46 3.81 118 65.81 1.74 2.64 118 20.42 0.59 2.88 Elecsys 2010/e411 68 65.5 3.94 6.01 68 12.38 1.07 8.66 64 64.66 3.96 6.12 64 20.09 1.47 7.31 Tosoh 1 102.3 1 17.5 1 67.7 1 20.2 LUMIPULSE G1200 6 70.68 4.13 5.84 6 12.82 0.44 3.47 5 67.3 3.05 4.53 5 20.9 1.52 7.26 Other 2 52.25 3.01 5.77 2 8.09 2.08 25.7 2 45.7 7.5 16.4 2 12.24 3.04 24.84 ADVIA Centaur Ultra 1 68.3 1 10.8 Total 441 441 412 412 Mean, SD, and %CV are of peer group (no.). 15-IA-1 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 1 specimen. 200 J Lab Med Qual Assur 2016;38:194-213 www.jlmqa.org

Table 8. Immunoassays conducted using the carbohydrate antigen 19-9 marker (U/mL) 15-IA-1 15-IA-2 15-IA-9 15-IA-10 Enzyme immunoassay 1 135.5 1 13.4 1 240 1 15.89 Fluorescent immunoassay 11 132.28 14.73 11.14 11 8.67 2.29 26.41 11 472.25 87.75 18.58 11 12.96 2.67 20.63 Chemiluminescence 241 320.57 134.68 42.01 241 11.35 2.63 23.17 230 888.1 310.59 34.97 231 20.09 3.5 17.41 Electrochemiluminescence 226 103.13 5.29 5.13 226 9.27 0.89 9.59 209 281.8 15.69 5.57 209 11.9 0.98 8.24 Other 2 56.58 20.56 36.33 2 7.13 2.4 33.64 2 242 113.99 47.1 2 12.03 0.37 3.12 Total 481 481 453 454 Architect series 113 458.83 38.56 8.4 113 10.42 1.61 15.43 109 1,200.00 110 21.91 2.02 9.24 ADVIA Centaur CP 5 233.98 9.07 3.88 5 16.67 2.04 12.24 6 673.07 44.79 6.65 6 23.73 3.42 14.39 ADVIA Centaur XP/classic 62 231.19 13.14 5.68 62 14.64 1.69 11.55 59 691.49 16.75 2.42 59 19.87 1.32 6.62 Access, Access II 7 162.93 18.03 11.06 7 8.4 0.69 8.21 5 548.96 66.15 12.05 5 12.98 2.19 16.9 Beckman DXi 25 148.63 6.59 4.43 25 8.29 0.46 5.5 28 445.23 29.45 6.61 28 12.57 1.14 9.1 VIDAS 9 136.77 4.2 3.07 9 7.81 0.34 4.4 9 500 9 11.83 1.07 9.05 Immulite, Immulite 200 12 160.94 23.49 14.6 12 10.62 2.71 25.53 9 465.63 43.05 9.25 9 19.11 2.9 15.16 BRIO, ARIO 1 135.5 1 13.4 1 240 1 15.89 Liason 1 156.7 1 8.1 Vitros ECi/Vitros3600 7 192.14 6.23 3.24 7 11.24 0.53 4.7 7 732 31.86 4.35 7 17.15 1.95 11.38 E170/e601/e602 144 103.4 4.17 4.04 144 9.51 0.48 5.08 129 284.17 10.27 3.61 129 12.12 0.52 4.29 Elecsys 1010 1 100.1 1 9.38 Elecsys 2010/e411 82 101.76 6.98 6.86 82 8.84 1.13 12.73 80 278.29 23.42 8.41 80 11.45 1.47 12.87 Tosoh 2 88.9 4.24 4.77 2 15.6 0.85 5.44 2 211.2 15.98 7.57 2 18 0.28 1.57 LUMIPULSE G1200 8 220.67 14.47 6.56 8 14.43 0.8 5.57 7 488.21 175.49 35.95 7 20.2 1.02 5.06 Other 2 56.58 20.56 36.33 2 7.13 2.4 33.64 2 242 113.99 47.1 2 12.03 0.37 3.12 ADVIA Centaur Ultra 1 217.3 1 10.93 Total 482 482 453 454 Mean, SD, and %CV are of peer group (no.). 15-IA-1 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 1 specimen. www.jlmqa.org J Lab Med Qual Assur 2016;38:194-213 201

Table 9. Immunoassays conducted using the prostate specific antigen marker (ng/ml) 15-IA-1 15-IA-2 15-IA-9 15-IA-10 Fluorescent immunoassay 4 764.52 88.61 11.59 4 16.43 2.31 14.07 5 272.52 20.58 7.55 5 2 Chemiluminescence 96 739.76 45.89 6.2 96 16.92 1.66 9.81 95 271.1 17.7 6.53 92 1.48 0.55 36.87 Electrochemiluminescence 54 686.11 30.63 4.46 54 15.03 0.74 4.9 54 247.52 8.02 3.24 54 0.69 0.08 11.56 Total 154 154 154 Architect series 47 736.37 36.53 4.96 47 16.33 1.25 7.64 48 273.12 13.9 5.09 45 1.2 0.1 8.41 ADVIA Centaur CP 1 727.1 1 17.8 1 294.9 1 4.1 ADVIA Centaur XP/classic 22 783.91 28.82 3.68 22 19.67 1.26 6.41 20 284.77 8.64 3.04 20 2.67 0.57 21.51 Access, Access II 6 697.17 38.67 5.55 6 16 1.11 6.91 6 269.92 38.2 14.15 6 1.85 0.74 40.04 Beckman DXi 16 706.06 37.67 5.34 16 16.01 1.12 7.02 18 250.34 13.74 5.49 18 1.3 0.18 14.05 VIDAS 4 764.52 88.61 11.59 4 16.43 2.31 14.07 5 272.52 20.58 7.55 5 2 Immulite, Immulite 200 3 704.33 47.96 6.81 3 17.87 1.17 6.56 3 258.67 31.26 12.09 3 1.23 0.31 24.82 E170/e601/e602 45 687.78 28.42 4.13 45 15.1 0.69 4.59 44 249.26 6.46 2.59 44 0.7 0.06 8.64 Elecsys 2010/e411 10 669.82 45.06 6.73 10 14.18 1.13 7.99 10 243.72 8.64 3.55 10 0.57 0.12 21.43 ADVIA Centaur Ultra 1 897.1 1 15.3 Total 155 155 155 152 Mean, SD, and %CV are of peer group (no.). 15-IA-1 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 1 specimen. Table 10. Immunoassays conducted using the human chorionic gonadotrophin marker (IU/L) 15-IA-1 15-IA-2 15-IA-9 15-IA-10 Fluorescent immunoassay 6 857.08 70.72 8.25 6 16.68 1.27 7.63 5 245.09 24.45 9.97 5 1.82 0.4 22.11 Chemiluminescence 1 549.5 1 12.7 2 234.25 60.32 25.75 2 1.55 0.78 50.18 Total 7 7 7 7 ADVIA Centaur XP/classic 1 276.9 1 2.1 VIDAS 5 877.29 56.45 6.43 5 16.69 1.42 8.52 4 253.37 18.45 7.28 4 2 Tosoh 1 756 1 16.6 1 212 1 1.1 VISTA 1 549.5 1 12.7 1 191.6 1 1 Total 7 7 7 7 Mean, SD, and %CV are of peer group (no.). 15-IA-1 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 1 specimen. 202 J Lab Med Qual Assur 2016;38:194-213 www.jlmqa.org

Table 11. Immunoassays conducted using the β-human chorionic gonadotrophin marker (ng/ml) 15-IA-3 15-IA-4 15-IA-11 15-IA-12 Enzyme immunoassay 1 13.1 1 7.47 1 14.57 1 0.33 Fluorescent immunoassay 16 27.52 1.89 6.86 16 10.1 0.88 8.67 15 29.04 1.9 6.54 15 0.53 0.04 6.84 Turbidimetry 2 27.75 1.2 4.33 2 6 0.14 2.36 3 25.66 2.02 7.88 3 0.99 0.96 96.89 Chemiluminescence 278 23.27 2.01 8.63 278 8.9 1.17 13.16 267 23.61 2.43 10.29 267 0.41 0.03 8.25 Electrochemiluminescence 241 23.37 1.47 6.28 241 8.85 0.52 5.9 221 24.16 1.42 5.88 221 0.43 0.03 5.96 Other 3 20.32 5.31 26.14 4 8.53 0.82 9.58 6 24.13 1.55 6.41 6 0.4 0.05 12.62 Total 541 542 513 513 Architect series 140 24.09 1.21 5.04 140 9.6 0.54 5.67 137 23.89 1.38 5.77 137 0.41 0.02 5.86 ADVIA Centaur CP 9 21.62 1.27 5.85 9 7.24 0.45 6.27 9 22.18 2.16 9.72 9 0.41 0.02 5.27 ADVIA Centaur XP/classic 71 21.29 1.01 4.73 71 7.35 0.31 4.26 69 21.81 1.24 5.7 69 0.42 0.02 5.12 Access, Access II 8 28.24 3.4 12.05 8 10.26 0.98 9.52 6 32.05 4.56 14.24 6 0.51 0.05 10.19 Beckman DXi 22 27.75 1.46 5.24 22 9.95 0.41 4.15 23 28.85 1.06 3.68 23 0.48 0.04 7.38 VIDAS 14 27.7 1.97 7.12 14 10.07 0.94 9.34 13 29.34 1.88 6.41 13 0.53 0.04 6.95 Immulite, Immulite 200 12 20.91 1.26 6.04 12 8.7 0.34 3.9 9 19.77 0.73 3.68 9 0.33 0.06 17.08 BRIO, ARIO 1 13.1 1 7.47 1 14.57 1 0.33 Hitachi Chemstry 2 27.75 1.2 4.33 2 6 0.14 2.36 2 25.79 2.84 11.02 2 1.26 1.2 95.22 Vitros ECi/Vitros3600 7 23.76 1.77 7.45 7 9.58 0.89 9.34 7 23.87 1.19 5 7 0.39 0.02 5.2 Modular DP 1 25.4 1 0.46 E170/e601/e602 147 24.12 0.85 3.53 147 9.12 0.32 3.47 133 24.69 0.82 3.3 133 0.44 0.02 3.44 Elecsys 2010/e411 95 21.79 1.54 7.06 95 8.32 0.55 6.63 88 22.88 2.05 8.98 88 0.41 0.03 6.99 Tosoh 2 26.4 0.57 2.14 2 10.25 0.21 2.07 2 27.25 0.78 2.85 2 0.5 LUMIPULSE G1200 8 22.9 0.85 3.69 8 8.51 0.67 7.89 7 24.05 0.57 2.35 7 0.39 0.02 4.62 Other 3 20.32 5.31 26.14 4 8.53 0.82 9.58 6 24.13 1.55 6.41 6 0.4 0.05 12.62 ADVIA Centaur Ultra 1 21.24 1 7.48 Total 542 543 513 513 Mean, SD, and %CV are of peer group (no.). 15-IA-3 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 3 specimen. www.jlmqa.org J Lab Med Qual Assur 2016;38:194-213 203

Table 12. Immunoassays conducted using the thyroid hormone T3 marker (ng/ml) 15-IA-3 15-IA-4 15-IA-11 15-IA-12 Fluorescent immunoassay 16 2.32 0.38 16.53 16 1.15 0.26 22.89 13 2.13 0.17 7.87 13 0.95 0.11 11.79 Nephelometry 1 2.77 1 1.02 Turbidimetry 1 3.04 1 1.2 Chemiluminescence 311 2.13 0.51 24.04 311 1.07 0.08 7.23 308 2.17 0.53 24.14 308 1.03 0.07 6.87 Electrochemiluminescence 244 3.14 0.21 6.68 244 1.29 0.09 7.15 226 3.22 0.2 6.25 226 1.22 0.09 7.18 Other 1 2.03 1 0.71 Total 571 571 550 550 Architect series 149 1.65 0.08 4.64 149 1.05 0.05 4.93 148 1.68 0.07 4.36 148 1 0.04 4.45 ADVIA Centaur CP 12 3 0.34 11.43 12 1.25 0.22 17.44 11 2.9 0.12 4.09 11 1.14 0.08 7.23 ADVIA Centaur XP/classic 80 2.65 0.11 4.06 80 1.07 0.07 6.12 83 2.7 0.12 4.46 83 1.05 0.06 6.04 Access, Access II 13 2.63 0.18 6.86 13 1.14 0.06 5.63 12 2.79 0.29 10.38 12 1.11 0.17 15.18 Beckman DXi 24 2.41 0.12 5 24 1.08 0.08 7.47 23 2.49 0.14 5.58 23 1.02 0.08 8.28 Beckman Immage 1 2.77 1 1.02 VIDAS 13 2.38 0.4 16.73 13 1.23 0.33 27.08 10 2.12 0.19 9.03 10 0.91 0.07 7.41 Immulite, Immulite 200 8 2.81 0.18 6.57 8 1.01 0.1 9.41 8 2.82 0.18 6.25 8 0.99 0.05 5.33 Liason 2 2.47 0.66 26.68 2 1.29 2 2.78 0.18 6.61 2 1.03 0.02 2.07 Vitros ECi/Vitros3600 11 2.5 0.12 4.89 11 1.32 0.06 4.28 11 2.48 0.07 2.83 11 1.16 0.03 2.94 Modular DP 1 3.04 1 1.2 E170/e601/e602 138 3.06 0.14 4.71 138 1.28 0.07 5.29 125 3.17 0.11 3.49 125 1.23 0.06 5 Elecsys 1010 2 3.59 0.66 18.34 2 1.46 0.28 18.95 Elecsys 2010/e411 104 3.25 0.25 7.66 104 1.29 0.12 8.97 101 3.27 0.3 9.04 101 1.2 0.11 9 Tosoh 3 2.07 0.2 9.65 3 1.01 0.08 7.98 3 2.15 0.08 3.69 3 1.08 0.12 11.39 LUMIPULSE G1200 11 1.86 0.13 7.11 11 1.04 0.09 8.27 10 1.92 0.1 5.18 10 0.95 0.06 6.61 ADVIA Centaur Ultra/Other 1 2.73 1 1.18 1 2.03 1 0.71 Total 571 571 550 550 Mean, SD, and %CV are of peer group (no.). 15-IA-3 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 3 specimen. 204 J Lab Med Qual Assur 2016;38:194-213 www.jlmqa.org

Table 13. Immunoassays conducted using the thyroid hormone T4 marker (μg/dl) 15-IA-3 15-IA-4 15-IA-11 15-IA-12 Fluorescent immunoassay 4 10.38 0.39 3.76 4 7.69 0.17 2.16 4 11.05 0.81 7.3 4 6.95 0.37 5.39 Chemiluminescence 66 8.62 1.01 11.72 66 7.82 1.01 12.98 62 8.67 0.78 9.06 62 7.55 0.94 12.47 Electrochemiluminescence 63 10.22 0.52 5.12 63 9.28 0.51 5.47 58 10.15 0.49 4.8 58 8.35 0.29 3.47 Total 133 133 124 124 Architect series 26 8.07 0.66 8.16 26 6.81 0.48 7.09 26 8.23 0.33 3.98 26 6.59 0.3 4.57 ADVIA Centaur CP 1 11.2 1 10.3 1 9.2 1 8.6 ADVIA Centaur XP/classic 22 8.45 0.37 4.38 22 8.18 0.31 3.8 21 8.59 0.42 4.84 21 8.13 0.2 2.45 Access, Access II 1 9.38 1 8.33 Beckman DXi 8 11.13 1.33 11.9 8 9.78 0.9 9.22 7 11.39 2.23 19.56 7 8.99 0.64 7.14 VIDAS 3 10.57 0.09 0.86 3 7.62 0.11 1.4 3 11.43 0.31 2.67 3 6.76 0.07 1.04 Immulite, Immulite 200 4 9.65 0.07 0.73 4 7.91 0.28 3.58 4 9.86 1.46 14.8 4 8.3 0.84 10.1 Vitros ECi/Vitros3600 3 9.62 1.49 15.46 3 9.3 1.91 20.56 3 9.39 0.88 9.38 3 8.63 0.62 7.13 E170/e601/e602 47 10.14 0.44 4.32 47 9.24 0.47 5.08 46 10.1 0.38 3.72 46 8.37 0.25 2.93 Elecsys 2010/e411 16 10.59 0.65 6.1 16 9.32 0.55 5.86 12 10.13 0.87 8.61 12 8.3 0.56 6.73 Tosoh 1 9.8 1 7.9 1 9.9 1 7.5 LUMIPULSE G1200 1 9.7 1 9.3 Total 133 133 124 124 Mean, SD, and %CV are of peer group (no.). 15-IA-3 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 3 specimen. www.jlmqa.org J Lab Med Qual Assur 2016;38:194-213 205

Table 14. Immunoassays conducted using the free thyroid hormone marker (ng/dl) 15-IA-3 15-IA-4 15-IA-11 15-IA-12 Enzyme immunoassay 1 36.3 1 3.07 1 33.2 1 1.69 Fluorescent immunoassay 25 27.79 1.68 6.04 25 2.69 0.18 6.85 25 29.01 2.12 7.32 25 1.89 0.11 5.75 Nephelometry 1 25.66 1 1.86 Turbidimetry 1 29.65 1 1.9 Chemiluminescence 344 26.39 2.21 8.38 344 2.3 0.26 11.08 341 26.3 2.69 10.23 341 1.64 0.21 12.84 Electrochemiluminescence 288 27.32 1.29 4.71 288 2.49 0.13 5.02 273 27.62 1.37 4.97 273 1.85 0.08 4.17 Other 2 26.21 1.71 6.53 2 1.71 0.88 51.84 3 28.84 5.33 18.48 3 1.72 0.03 1.78 Total 660 660 645 645 Architect series 161 25 1.06 4.23 161 2.1 0.15 7.08 159 24.52 1.25 5.08 159 1.46 0.07 5.09 ADVIA Centaur CP 15 28.45 1.32 4.64 15 2.43 0.12 5.11 15 29.07 1.47 5.07 15 1.78 0.11 6.1 ADVIA Centaur XP/classic 82 28.46 1.15 4.05 82 2.44 0.1 4.2 85 28.89 1.12 3.88 85 1.81 0.06 3.51 Access, Access II 17 25.27 1.62 6.39 17 2.61 0.11 4.35 18 25.07 2.2 8.76 18 1.89 0.14 7.49 Beckman DXi 26 25.06 1.42 5.65 26 2.78 0.15 5.53 25 25.08 1.68 6.69 25 1.91 0.15 7.64 Beckman Immage 1 25.66 1 1.86 VIDAS 21 27.65 1.7 6.14 21 2.67 0.18 6.85 21 28.36 1.49 5.25 21 1.88 0.11 5.7 Immulite, Immulite 200 13 30.18 1.35 4.48 13 2.7 0.12 4.32 11 30.96 2 6.45 11 2.01 0.05 2.53 BRIO, ARIO 1 36.3 1 3.07 1 33.2 1 1.69 Liason 2 26.8 3.96 14.76 2 2.63 0.29 11.12 2 27.84 2.07 7.44 2 1.85 0.09 4.77 Vitros ECi/Vitros3600 11 34.65 1.77 5.12 11 2.42 0.19 7.74 11 36.18 2.77 7.65 11 1.87 0.1 5.52 Modular DP 1 29.65 1 1.9 E170/e601/e602 151 27.37 0.86 3.14 151 2.52 0.07 2.77 136 27.83 0.86 3.09 136 1.86 0.06 3.22 Elecsys 1010 2 26.14 0.33 1.27 2 2.47 0.06 2.29 Elecsys 2010/e411 136 27.14 1.72 6.33 136 2.44 0.15 6.24 137 27.37 1.75 6.38 137 1.83 0.1 5.28 Tosoh 4 29.7 2.31 7.77 4 2.79 0.18 6.41 4 33.21 3.53 10.62 4 2.08 0.29 14.14 LUMIPULSE G1200 12 28.29 0.71 2.52 12 2.19 0.07 3.35 11 28.53 2.7 9.45 11 1.55 0.07 4.84 Other 2 26.21 1.71 6.53 2 1.71 0.88 51.84 3 28.84 5.33 18.48 3 1.72 0.03 1.78 ADVIA Centaur Ultra 6 29.2 0.69 2.37 6 2.49 0.07 2.74 4 29.29 1.73 5.92 4 1.84 0.09 4.68 Total 662 662 645 645 Mean, SD, and %CV are of peer group (no.). 15-IA-3 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 3 specimen. 206 J Lab Med Qual Assur 2016;38:194-213 www.jlmqa.org

Table 15. Immunoassays conducted using the thyroid stimulating hormone marker (μiu/ml) 15-IA-3 15-IA-4 15-IA-11 15-IA-12 Enzyme Immunoassay 1 6.93 1 3.32 23 4.47 0.29 6.43 23 1.16 0.08 7.03 Nephelometry 1 1.85 1 1.07 Turbidimetry 1 4.81 1 1.3 Fluorescent immunoassay 22 4.23 0.24 5.6 22 1.11 0.09 8.46 Chemiluminescence 340 2.29 0.83 36.35 340 1.13 0.09 7.66 338 2.41 0.98 40.85 338 1.15 0.1 8.62 Electrochemiluminescence 274 4.98 0.27 5.52 274 1.33 0.06 4.29 259 4.92 0.3 6.08 259 1.38 0.08 5.78 Other 2 4.82 0.16 3.38 2 1.19 0.3 25.66 3 4.29 1.47 34.21 3 1.11 0.33 29.89 Total 639 639 625 625 Architect series 159 1.61 0.07 4.57 159 1.11 0.04 4.02 157 1.6 0.07 4.18 157 1.1 0.04 3.78 ADVIA Centaur CP 18 2.94 0.24 8.21 18 1.29 0.09 6.65 18 3 0.29 9.54 18 1.38 0.08 5.89 ADVIA Centaur XP/classic 88 3.38 0.21 6.16 88 1.17 0.06 5.11 90 3.7 0.18 4.88 90 1.22 0.07 5.73 Access, Access II 15 1.55 0.07 4.82 15 0.99 0.04 3.92 16 1.6 0.21 13.4 16 1.08 0.08 7.79 Beckman DXi 25 1.84 0.09 5.13 25 0.97 0.07 7.29 24 1.88 0.15 7.83 24 1.04 0.09 8.61 Beckman Immage 1 1.85 1 1.07 VIDAS 19 4.24 0.25 5.87 19 1.08 0.06 5.62 19 4.53 0.18 3.96 19 1.13 0.05 4.6 Immulite, Immulite 200 11 3.39 0.13 3.75 11 1.22 0.02 2.01 10 3.61 0.2 5.64 10 1.24 0.08 6.83 BRIO, ARIO 1 6.93 1 3.32 Liason 2 2.61 1.37 52.56 2 1.01 0.21 20.4 2 3.66 0.2 5.41 2 1.11 0.01 1.27 Vitros ECi/Vitros3600 11 6.99 0 0.05 11 1.39 0.15 10.8 10 6.99 0.01 0.08 10 1.55 0.1 6.2 Modular DP 1 4.81 1 1.3 E170/e601/e602 150 4.89 0.2 4.07 150 1.3 0.03 2.62 136 4.9 0.2 4.14 136 1.34 0.03 2.4 Elecsys 1010 2 5.23 0.17 3.24 2 1.38 0.06 4.63 Elecsys 2010/e411 123 5.07 0.33 6.56 123 1.38 0.06 4.52 123 4.95 0.4 8.07 123 1.44 0.1 6.77 Tosoh 3 4.13 0.15 3.57 3 1.37 0.1 7.33 4 3.9 0.13 3.44 4 1.33 0.14 10.46 LUMIPULSE G1200 11 2.58 0.12 4.71 11 1.14 0.04 3.5 11 2.6 0.16 6.01 11 1.14 0.05 4.1 Other 2 4.82 0.16 3.38 2 1.19 0.3 25.66 3 4.29 1.47 34.21 3 1.11 0.33 29.89 ADVIA Centaur Ultra 1 3.37 1 1.27 Total 641 641 625 625 Mean, SD, and %CV are of peer group (no.). 15-IA-3 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 3 specimen. www.jlmqa.org J Lab Med Qual Assur 2016;38:194-213 207

Table 16. Immunoassays conducted using thyroglobulin (ng/ml) 15-IA-3 15-IA-4 15-IA-11 15-IA-12 Chemiluminescence 10 38.73 12.42 32.07 10 7.05 3.77 53.43 10 37.24 11.2 30.08 10 5.82 2.74 47.04 Electrochemiluminescence 63 52.15 7 13.43 63 14.17 1.05 7.43 64 44.92 1.87 4.15 64 9.59 0.38 3.94 Total 73 73 74 74 Architect series 1 61.83 1 14.36 ADVIA Centaur XP/classic 1 26.64 1 138.6 Beckman DXi 6 42.6 2.45 5.75 6 7.61 0.48 6.29 7 44.01 2.75 6.24 7 7.48 0.55 7.29 Immulite, Immulite 200 2 21.6 1.41 6.55 2 1.71 2 22.6 2.26 10.01 2 2.34 0.07 3.02 Liason 1 19.1 1 1.12 E170/e601/e602 30 57.99 2.81 4.84 30 14.86 0.65 4.36 53 44.64 1.12 2.52 53 9.62 0.26 2.7 Elecsys 2010/e411 10 48.73 2.85 5.85 10 11.97 0.91 7.64 10 46.01 7.79 16.94 10 9.2 1.38 15.03 TG G2 23 46.85 5.95 12.71 23 13.9 0.8 5.73 1 44.39 1 9.02 Total 73 73 74 74 Mean, SD, and %CV are of peer group (no.). 15-IA-3 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 3 specimen. Table 17. Immunoassays conducted using troponin-i (ng/ml) 15-IA-5 15-IA-6 15-IA-13 15-IA-14 Fluorescent immunoassay 47 4.28 0.22 5.15 47 0.12 0.02 19.46 54 5.56 0.31 5.61 54 0.09 0.02 22.85 Chemiluminescence 28 2.73 0.19 7.02 26 0.07 0.01 13.69 28 3.95 0.29 7.29 28 0.23 0.02 9.34 Electrochemiluminescence 91 2.71 0.19 7.06 91 0.08 0.01 15.5 100 3.44 0.22 6.35 100 0.1 0.01 8.26 Other 4 3.29 0.76 23.02 4 0.08 0.02 23.22 3 4.81 0.91 18.88 3 0.16 0.1 63.94 Total 170 168 185 185 ADVIA Centaur CP 1 2.76 1 0.06 27 3.97 0.26 6.62 27 0.23 0.02 9.34 ADVIA Centaur XP/classic 25 2.68 0.14 5.4 24 0.07 0.01 12.88 VIDAS 48 4.26 0.23 5.45 48 0.12 0.02 19.25 54 5.56 0.31 5.61 54 0.09 0.02 22.85 Liason 1 3.14 1 3.32 1 0.1 E170/e601/e602 54 2.76 0.16 5.81 54 0.08 0.01 11.44 58 3.49 0.23 6.48 58 0.1 0.01 8.74 Elecsys 2010/e411 37 2.63 0.21 7.9 37 0.08 0.01 14.53 42 3.36 0.18 5.44 42 0.1 0.01 6.8 Other 4 3.29 0.76 23.02 4 0.08 0.02 23.22 3 4.81 0.91 18.88 3 0.16 0.1 63.94 ADVIA Centaur Ultra 1 3.06 1 0.09 Total 171 169 185 185 Mean, SD, and %CV are of peer group (no.). 15-IA-5 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 5 specimen. 208 J Lab Med Qual Assur 2016;38:194-213 www.jlmqa.org

Table 18. Immunoassays conducted using troponin-t (ng/ml) 15-IA-7 15-IA-8 15-IA-15 15-IA-16 Chemiluminescence 2 0.01 2 0 Turbidimetry 1 1.95 1 0.03 Electrochemiluminescence 77 1.82 0.22 12.02 77 0.03 0 9.7 84 0.01 0 14.71 84 0 0 38.85 Other 1 0.01 1 0.01 Total 78 78 87 87 ADVIA Centaur XP/classic 2 0.01 2 0 Hitachi Chemstry 1 1.95 1 0.03 E170/e601/e602 37 2 0.17 8.45 37 0.03 0 6.78 42 0.02 0 13.34 42 0.01 0 36.83 Elecsys 1010 1 1.58 1 0.02 Elecsys 2010/e411 39 1.65 0.07 4.34 39 0.02 0 5.05 42 0.01 0 14.43 42 0 0 34.19 Other 1 0.01 1 0.01 Total 78 78 87 87 Mean, SD, and %CV are of peer group (no.). 15-IA-7 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 7 specimen. www.jlmqa.org J Lab Med Qual Assur 2016;38:194-213 209

Table 19. Immunoassays conducted using procalcitonin (ng/ml) 15-IA-7 15-IA-8 15-IA-15 15-IA-16 Fluorescent immunoassay 22 2 0.13 6.56 22 0.13 0.01 8.33 20 0.01 0 0 20 0.01 0 0 Turbidimetry 1 18.5 1 0.95 1 0.1 1 0.1 Chemiluminescence 175 9.02 4.7 52.12 175 0.34 0.19 56.98 184 0.01 0.01 97.19 182 0 0 93.1 Electrochemiluminescence 56 18.06 1.54 8.53 56 0.94 0.08 8.7 47 0.1 47 0.1 0 3.37 Other 5 3.24 2.44 75.31 5 0.12 0.1 83.98 5 0.03 0.02 91.56 5 0.03 0.02 91.56 Total 259 259 257 255 Architect series 56 4.6 0.41 8.84 56 0.14 0.01 7.31 66 0.01 0.01 83.21 65 0.01 0 36.55 ADVIA Centaur CP 4 11.19 1.75 15.61 4 0.49 0.06 12.96 3 0.01 0.01 112.02 3 0.01 0.01 173.21 ADVIA Centaur XP/classic 44 14.09 1.13 8 44 0.53 0.05 9.07 43 0 0 72.02 43 0 0 118.07 Access, Access II 5 12.55 0.37 2.97 5 0.49 0.03 6.16 4 0.01 0.01 53.02 4 0 0 120 Beckman DXi 22 14.58 0.58 3.95 22 0.58 0.02 4.01 30 0.01 0 63.57 30 0 0 113.95 VIDAS 21 2.02 0.12 5.88 21 0.13 0.01 7.21 19 0.01 0 0 19 0.01 0 0 Immulite, Immulite 200 1 24.3 1 0.95 1 0.2 1 0.2 Vitros ECi/Vitros3600 3 11.63 0.51 4.41 3 0.39 0.02 3.83 3 0.01 0 4.68 3 0.01 0 4.68 E170/e601/e602 21 17.12 0.64 3.71 21 0.9 0.04 4.57 16 0.1 0 0 16 0.1 0 0 Elecsys 2010/e411 35 18.84 1.78 9.45 35 0.97 0.1 10.3 31 0.1 0 0 31 0.1 0 4.17 Tosoh 1 8.39 1 0.32 1 0.05 1 0.05 VISTA 7 4.38 0.17 3.81 7 0.15 0 1.57 7 0.02 7 0.02 Dimension 2 2.65 1.58 59.76 2 0.07 0.06 84.47 1 0.02 1 0.02 Other 3 3.63 3.17 87.35 3 0.16 0.12 79.77 4 0.03 0.03 95.63 4 0.03 0.03 95.63 ADVIA Centaur Ultra 1 14.48 1 0.54 1 0.01 1 0.01 cobas c702 1 18.5 1 0.95 1 0.1 1 0.1 Dimension EXL 6 4.03 0.28 6.9 6 0.13 0.02 12.22 4 0.01 0.01 75.61 4 0.01 0.01 75.61 PATHFAST 22 5.31 0.62 11.71 22 0.22 0.02 11.39 21 0 0 102.6 20 0 0 91.01 DXi(TnI+3) 5 11.75 0.34 2.86 5 0.45 0.02 3.41 1 0.01 1 0 Total 260 260 257 255 Mean, SD, and %CV are of peer group (no.). 15-IA-7 represents the specimen number used in the trial; it stands for 2015-immunoassay-no. 7 specimen. 210 J Lab Med Qual Assur 2016;38:194-213 www.jlmqa.org

것은권장되지않지만우리나라에서는흔히건강검진등에포함되기때문에검사를실시하는기관수가많은것으로생각된다. 특히남성종양표지자로흔히사용되는 PSA와여성종양표지자로볼수있는 CA 125 등을실시하는기관들을살펴보면, 이종목들이검진목적으로사용되고있는것으로생각되었다. 참고로이때다른여성종양표지자라고할수있는 HCG 나 β-hcg를실시하는기관은비교적많지않았다. 특히장비에따라 β-hcg가아니라 HCG로측정하는기관수가현저히많아진것으로생각된다. 그리고각종양표지자종목들의통계분석결과가서로다른종양표지자종목들이라도비슷하였는데, 그이유는각기관에서어떤장비든지동일한자동면역분석기를이용하여종양표지자검사들을실시하기때문에장비의특성에따라비슷하게나타난것으로생각되었다. 전년도에이어 2015년도에도과거 10여년간혈청면역단백카테고리의외부정도관리사업의문제점을보완하고자새로도입된종목들을시도하였다. 참여도가높지않은 CTX 대신 procalcitonin 등새로운염증및항균제모니터링검사등을시도하였다. Procalcitonin의경우심장표지자보다는많이실시하지않고있었지만골흡수표지자보다는훨씬많은 185기관에서결과를회신하였다. 아직도각기관에서결과입력을마친후그입력된전체결과를다시검토하거나확인하지않기때문에생기는것으로생각되는사무오류들이역시제일많았다 [12]. 단위까지확인하는정확한결과입력등좀더세심하게사무적착오에대해확인할필요가있을것으로생각된다. 따라서아직도결과분석전에우리분과담당자들이일일이전화를하여확인할필요가있다는것이문제점으로파악된다 [13-15]. 각회원기관들에서외부정도관리물질로검사를실시하고나서그결과를인터넷에입력또는회신하기전에각담당자또는책임자들이재검토하고정확히확인하여각기관의결과를입력 / 회신하여준다면전체결과개선에크게도움이될것이다. 그리고자신이입력한결과를다시한번꼼꼼이재확인하여사무적오차를줄일수있으면정확하고표준화된외부정도관리사업이가능할것으로생각된다 [16-18]. 2008년부터는전체병원의통계는우리협회홈페이지에서내려받거나출력할수있게되었으며, 따라서보고서송부시에두꺼운전체기관통계자료를같이보내지않게되었고각기관에서도필요할때마다인터넷에서확인할수있다. 뿐만아니라 2010년부터는각기관의결과지까지도수시로협회인터넷홈페이지에서출력할수있도록협회차원에서전산화가구축되었기에각참여기관들도훨씬편리하고수시로확인해볼수있었다. 분과별외부정도관리사업이그동안진행되면 서참여기관들의정도관리에대한인식이많이높아졌고, 무엇보다전국적인검사결과신뢰도에대한관심이커졌다고생각된다. 특히시약제조 / 수입회사나장비회사에서도해당장비및시약에대한유지보수및정도관리에대한관심이높아졌다. 따라서우리나라임상검사실의수준이우리협회의외부정도관리사업을통해진일보하고있으며, 의료수준도업그레이드되었다고생각된다. 또하나사회적으로비용효율을중요시하는트렌드를읽을수있었는데, 즉 2015년도 2차에참여기관이 730기관에관리물질을보냈지만 693기관만이회신해옴으로써 1차의 710기관회신보다도다소참여기관수가적어진것이눈에띄었는데, 이는각시도별건강관리협회가각기관에서검사실을운영하던것을통합운영하게되었기때문인것으로밝혀졌다. 즉제대로검사실을운영하는것을원칙으로하되효율적인면을중시하여필요한경우다른검사실로의뢰하는것도적극적으로고려하고있음을알수있었다. 감사의글 본 Immunoassay 분과외부정도관리사업을위해서자가제조용관리물질검체를농도별로수집하고우송, 안정성검사과정에서헌신적으로도와주신연세의료원진단검사의학과교직원여러분과우리협회 Immunoassay 분과위원들께깊이감사드린다. Immunoassay 분과위원회위원 (2015) 김현숙 ( 위원장, 연세대학교의과대학세브란스병원 ), 김영란 ( 간사, 연세의료원세브란스병원 ), 심정은 ( 연세의료원세브란스병원 ), 임환섭 ( 가톨릭관동대학교의과대학 ), 원동일 ( 경북대학교병원 ), 박정용 ( 연세의료원세브란스병원 ), 정순호 ( 연세대학교의과대학강남세브란스병원 ), 장호은 ( 분당서울대학교병원 ), 임승택 ( 서울아산병원 ), 조윤정 ( 고려대학교의과대학안암병원 ), 남정현 ( 인하대학병원 ) REFERENCES 1. Kim HS, Kim YL; Immunoassay Subcommittee, Korean Association of External Quality Assessment Service. Annual report on external quality assessment scheme for immunoassay tests in Korea (2014). J Lab Med Qual Assur 2015;37:190-208. www.jlmqa.org J Lab Med Qual Assur 2016;38:194-213 211

2. Kim HS, Kim YL; Immunoassay Subcommittee, The Korean Association of Quality Assurance for Clinical Laboratories. Annual report on external quality assessment of immunoassay testing in Korea (2013). J Lab Med Qual Assur 2014;36:171-89. 3. Kim HS, Kim YL, Park J, Kwon OH, Kim DA, Kim JQ, et al. Immunoassay external quality assessment of immunoassay subcommittee (2010). J Lab Med Qual Assur 2011; 33(Suppl):S91-114. 4. Kim HS, Kim YL, Park J, Kwon OH, Kim DA, Kim JQ, et al. Annual report on external quality assessment in immunoassay in Korea (2009). J Lab Med Qual Assur 2010;32:103-14. 5. Cha YJ, Kwon SY, Kim TY, Kim JR, Kim HS, Park MH, et al. Annual report on external quality assessment in immunoserology in Korea (2008). J Lab Med Qual Assur 2009;31:49-72. 6. Kim HS, Kim YL, Lim HS, Park J, Chun HS, Shin S, et al. Annual report on external quality assessment of Immunoassay Subcommittee in Korean Clinical Laboratory Survey (2007). J Lab Med Qual Assur 2008;30:111-32. 7. Kim HS, Kim YL, Lim HS, Chun HS, Shin S, Jung YS, et al. Annual report on external quality assessment of Immunoassay Subcommittee in Korean Clinical Laboratory Survey (2006). J Lab Med Qual Assur 2007;29:99-119. 8. Kim HS. Immunoassay external quality control of immunoassays. J Lab Med Qual Assur 2003;25(S2):S387-91. 9. Kim HS, Lim HS, Kwon OH, Kim DA, Kim YK, Kim YR, et al. Annual report on external quality assessment of immunoassay in Korea (2001). J Clin Pathol Qual Control 2002;24:83-94. 10. Kwon OH, Lim HS, Kim HS, Kim DA, Kim YK, Kim JQ, et al. Annual report on external quality assessment in immunoassay in Korea (2000). J Clin Pathol Qual Control 2001;23:111-44. 11. Kim HS. Future trends of immunoassay EQA. J Clin Pathol Qual Control 2001;23:S275-6. 12. Jenny RW, Jackson-Tarentino KY. Causes of unsatisfactory performance in proficiency testing. Clin Chem 2000; 46:89-99. 13. Kwon OH, Lim HS, Kim HS, Kim DU, Kim YK, Kim JQ, et al. Annual report on external quality assessment in immunoassay in Korea (1995). J Clin Pathol Qual Control 1996;18:95-117. 14. Kim HS. Internal quality control of immunochemistry tests. J Clin Pathol Qual Control 1993;15:S147-51. 15. Feldkamp CS, Carey JL. Standardization of immunoassay methodologies. In: Rose NR, Hamilton RG, Detrick B, editors. Manual of clinical laboratory immunology. 6th ed. Washington (DC): ASM Press, 2002:1215-26. 16. Bock JL. The new era of automated immunoassay. Am J Clin Pathol 2000;113:628-46. 17. College of American Pathologists. Standards for laboratory accreditation: Laboratory Accreditation Program 1998 edition. http://www.cap.org (Accessed December 2, 2015). 18. Miyai K, Price CP. Problems for improving performance in immunoassay. J Int Fed Clin Chem 1992;4:154-63. 212 J Lab Med Qual Assur 2016;38:194-213 www.jlmqa.org

Immunoassay 분과외부신빙도조사결과보고 (2015) 김현숙 김영란 심정은 대한임상검사정도관리협회 Immunoassay 분과위원회연세대학교의과대학세브란스병원진단검사의학과 2015 년도 Immunoassay 분과에서는 2 회에걸쳐각 8 종씩, 총 16 종의관리물질을 1 차 719 기관, 2 차 730 기관에보내어외부신빙도조사를실시하였다. 1 회와 2 회째모두갑상선호르몬검사용관리물질과심근표지자 troponin 은높은결과치를보이는혈청을수집하기어려웠기때문에상품화된제품을구입하여사용하였고, 그외의관리물질은자가제조하였다. 결과회신율은 1 차 98.7% 와 2 차 94.9% 였다. 검사결과의분석및보고방법은평균, 표준편차, 변이계수등으로분석하였으며, 참여기관에서사용하고있는방법과장비에따라각기기별로분류하여 peer group 결과를분석하였다. 협회에전산화가잘되어있어서우리분과의외부신빙도조사결과입력은물론, 전체방법과기기별통계, 그리고협회홈페이지에서인터넷을이용하여각기관의결과지출력까지할수있었다. 현재참여기관들에서가장많이사용되는면역측정법은자동화된화학발광면역장비들이었는데, 이들자동화장비들이대개고유원리와시약을사용하고있어서서로결과치가다를수있다. 따라서정확한결과를위해서는장비와사용자에따른내부정도관리뿐아니라외부정도관리가지속적으로필요한것으로판단되었다. 또한지금까지와마찬가지로전국적인신빙도조사사업참여를통해검사의질을높여나가야할것으로생각되었다. (J Lab Med Qual Assur 2016;38:194-213) 교신저자 : 김현숙우 )03722 서울시서대문구연세로 50-1, 연세대학교의과대학진단검사의학교실 Tel: 02)2228-2443, Fax: 02)364-1583, E-mail: kimhs54@yuhs.ac www.jlmqa.org J Lab Med Qual Assur 2016;38:194-213 213