TBPE 검사 (TetraBromoPhenolphthalein Ethylester)

Abstract

평가 배경 TBPE (TetraBromoPhenolphthalein Ethylester) 검사는 마약류 선별을 목적으로 수행되는 체외진단검사로, 약물의 특정한 구조(amines 등)에 결합하는 TBPE 시약을 첨가하여 색의 변화를 육안으로 판독하는 비색법(colorimetric screening test)이다. 해당 의료기술은 내부 모니터링을 통해 개발된 주제로, 대한진단검사의학회의 의견 수렴을 통하여 저가치 혹은 쇠퇴기술로 간주된 바 있다. 2020년 제6차 의료기술재평가위원회(2020.06.12.~19., 서면검토)에서 의료기술재평가 안건으로 선정되었고, 2020년 제10차 의료기술재평가위원회(2020.10.16.)에서 TBPE 검사의 안전성 및 유효성 평가결과를 최종 심의하였다.

평가 방법 TBPE 검사에 대한 안전성 및 유효성 평가는 체계적 문헌고찰을 통해 수행하였다. 모든 평가방법은 연구목적을 고려하여 “TBPE 검사 소위원회(이하 ‘소위원회’라 한다)”의 심의를 거쳐 확정하였다. 평가의 핵심질문은 “TBPE 검사는 마약류(methamphetamine 등)를 선별하는데 임상적으로 안전하고 유효한가?”였다. 체계적 문헌고찰은 한국보건의료연구원에서 출판된 매뉴얼에 따라 문헌검색, 문헌선정, 자료추출, 비뚤림 위험 평가, 자료분석이 수행되었다(김수영 등, 2011).

평가 결과 문헌선정 결과 TBPE 검사의 안전성과 유효성은 총 1편에 근거하여 평가하였다. 선정된 1편의 문헌(Choi 등, 1993)은 국내에서 수행된 연구로, 1993년도에 출판되었으며 새롭게 개발된 TBPE 현장검사(on-site test) 기기를 평가하기 위하여 도핑 검사를 받은 운동선수 및 경찰서의 약물 남용 용의자로부터 획득한 442개의 소변 검체를 대상으로 선별검사를 수행하고 진단정확도를 보고하였다.

안전성 선택된 1편의 연구에서는 TBPE 검사의 안전성과 관련된 연구결과를 보고하고 있지 않았다.

유효성 선택된 1편의 연구에서는 진단정확도 관련 일부 결과를 보고하고 있었다. 형광편광면역측정법의 위양성은 2.0%인데 반해 TBPE 검사법의 위양성은 10-15%에 달했다. 또한 TBPE 검사에서 음성인 검체를 확정검사(GC/NPD)로 확인해 보았을 때, methamphetamine, amphetamine을 포함한 검체는 없었다(위음성 0%).

결론 및 제언 체계적 문헌고찰을 통해 최종 선정된 문헌은 1편이었다. 마약류 선별 목적의 TBPE 검사는 안전성과 관련된 근거를 확인할 수 없었으나 체외진단법으로 안전성에는 문제가 없을 것으로 보았다. 유효성에 있어서 TBPE 검사의 위양성은 15%, 위음성은 0%였으나 형광편광면역측정법의 위양성은 2%에 그쳐 비교검사보다 진단정확도가 낮은 것으로 확인되었다. 추가적으로, TBPE 검사는 검출한도, 정확도 등이 검증되지 않았고 개발된 지 20년 이상된 검사로 선진국에서는 거의 사용하지 않고 있는 것으로 확인되었다. 국내에서도 진료 목적이 아닌 채용신체검사를 목적으로 사용되는 것으로 확인되었다. 이에, 마약류 선별 목적의 TBPE 검사는 체외진단법으로 안전성에는 문제가 없을 것으로 보았으나 진단정확도가 낮아 유효성이 제한적인 검사법이라고 평가하였다. 의료기술재평가위원회는 “TBPE 검사”에 대해 소위원회 검토결과에 근거하여 다음과 같이 심의하였다(2020.10.16.). 의료기술재평가위원회는 마약류 선별을 목적으로 TBPE 검사를 권고하지 않음(권고등급 Ⅱ)으로 심의하였다.

주요어 마약류, 선별검사, TBPE 검사

Background of Assessment TBPE (TetraBromoPhenolphthalein Ethylester) assay is an in vitro diagnostic test performed for the purpose of screening narcotics. It is a colorimetric screening test that visually reads color changes by adding a TBPE reagent, which binds to specific structures (amines, etc.) of drugs. The relevant health technology is a topic developed through internal monitoring and was regarded as a low-value or obsolete technology through the gathering of opinions of the Korean Society for Laboratory Medicine. It was selected as a Health Technology Reassessment agenda at the 6th Health Technology Reassessment Committee (2020.06.12.-19., written review) in 2020, and the safety and effectiveness evaluation results of the TBPE assay were finally reviewed at the 10th Health Technology Reassessment Committee (2020.10.16.) in 2020.

Assessment Method Safety and effectiveness evaluation of the TBPE assay was performed through a systematic literature review. All evaluation methods were determined after deliberation by the “TBPE assay sub-committee (hereinafter referred to as ‘subcommittee’) in consideration of the research purpose. A key question in the evaluation was “Is the TBPE assay clinically safe and effective for screening narcotics (methamphetamine, etc.)?”. For the systematic literature review, the literature search, literature selection, data extraction, risk of bias assessment, and data analysis were performed according to the manual published by the National Evidence-based Healthcare Collaborating Agency (Soo-young Kim et al., 2011).

Assessment Results Selection result of literature The safety and effectiveness of the TBPE assay were evaluated based on a total of one literature. One selected document (Choi et al., 1993) is a study conducted in Korea and published in 1993. It performed screening tests and reported diagnostic accuracy on 442 urine samples obtained from athletes and police station drug abuse suspects who had been tested for doping to evaluate the newly developed TBPE on-site test device.

Safety The one selected document did not report the study results related to the safety of the TBPE assay.

Effectiveness One selected study reported some results related to diagnostic accuracy. The false-positive rate of the fluorescence polarization immunoassay was 2.0%, whereas it was 10-15% for the TBPE assay. Also, when a negative sample in the TBPE assay was confirmed by a definitive test (GC/NPD), there was no sample containing methamphetamine or amphetamine (false negative 0%).

Conclusion and Suggestions One document was finally selected through a systematic literature review. The TBPE assay for the screening narcotics could not confirm the evidence related to safety, but it was assumed that there would be no safety problem as an in vitro diagnostic method. In terms of effectiveness, the false positives of the TBPE assay were 15% and the false negatives were 0%, but the false positives of the fluorescence polarization immunoassay were only 2%. It was confirmed that the diagnostic accuracy was lower than that of the comparative test. Additionally, the detection limit and accuracy of the TBPE assay were not verified, and it was confirmed that this test was developed more than 20 years ago and is rarely used in developed countries. In Korea, it has been confirmed that it is used for recruitment physical examination, not for medical treatment. Therefore, it was considered that there would be no problem in the safety of the TBPE assay for the screening narcotics as an in vitro diagnostic method, but it was evaluated as a test method with limited effectiveness due to low diagnostic accuracy. The Health Technology Reassessment Committee reviewed the “TBPE assay” as follows based on the subcommittee review results (2020.10.16.). The Health Technology Reassessment Committee deliberated that the TBPE assay was not recommended (Recommendation Grade Ⅱ) for the purpose of screening narcotics.

Key Words: Narcotics, Screening test, TetraBromoPhenolphthalein Ethylester, TBPE