디지털 유방단층촬영술의 안전성 및 유효성 평가

Abstract

평가배경 디지털 유방단층촬영술(Digital breast tomosynthesis)은 여성에게서 유방암을 조기에 발견하기 위해 많은 각도로부터 X-선 영상들을 만들어내서 3차원 이미지를 구현하여 유방암을 선별 및 진단 할 수 있는 검사 방법이다. 해당 의료기술은 2012년 신의료기술평가를 통해 유방촬영술 결과 유소견자 및 추적환자를 대상으로 유방암을 선별 또는 진단하기 위한 검사로 사용이 인정되었으며, 2014년 비급여 항목으로 등재되었다. 보건복지부는 비급여 항목의 급여화를 진행 중에 있기에, 동 기술의 치료효과성을 업데이트 하여 2020년 급여 의사결정을 위한 근거자료로 제공하고자 한다.

위원회 운영 임상전문 학회의 추천을 받아 총 5인으로 구성된 소위원회는 2019년 8월 31일까지 약 4개월간 총 3회의 소위원회 운영을 통해 체계적 문헌고찰 프로토콜 검토, 문헌 선택 및 배제기준, 문헌추출, 결과합성 및 비뚤림 위험평가, 결론도출 등 모든 평가에 참여하여 자문을 수행하였다. 2019년 의료기술재평가위원회(2019.10.11.)에서는 디지털 유방단층촬영술의 임상적 안전성 및 유효성 평가 결과를 최종 심의하였다.

평가 목적 및 방법 디지털 유방단층촬영술의 안전성 및 유효성평가는 기 평가된 신의료기술평가의 체계적문헌고찰 프로토콜을 준용하되 소위원회의 합의를 도출하여 범위 및 내용을 확정하였다. 체계적문헌고찰은 국외 3개, 국내 5개 데이터베이스에서 검색하였으며, 문헌선정 및 배제기준에 따라 두 명의 검토자가 독립적으로 선별하고 선택하였다. 문헌의 비뚤림 위험 평가는 QUADAS-2를 사용하여 두 명의 검토자가 독립적으로 수행하여 의견합의를 이루었다. 자료추출은 미리 정해놓은 자료추출 양식을 활용하여 두 명의 검토자가 독립적으로 수행하였으며, 의견 불일치가 있을 경우 제 3자와 함께 논의하여 합의하였다. 자료 분석은 정량적 분석(quantitative analysis)이 가능할 경우 메타분석을 수행하고 불가능할 경우 정성적(qualitative review) 분석을 적용하였다.

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Assessment background Digital breast tomosynthesis (DBT) is a test method for screening and diagnosing breast cancer by synthesizing 3D images based on X-ray images from multiple angles for early detection of breast cancer in women. This health technology was recognized as a test for screening or diagnosing breast cancer in follow-up patients and patients with abnormal findings on mammography through new health technology assessment in 2012 and was subsequently registered as a non-coverage item in 2014. The Ministry of Health and Welfare is the process of changing non-coverage items into items covered by insurance and providing evidence data for 2020 insurance coverage decision-making by updating the treatment efficacy of this technology.

Committee operation The subcommittee, consisting of a total of five members recommended by clinical professional academies, held three subcommittee sessions over approximately four months up to August 31, 2019 and played an advisory role by participating in all assessments, including review of systematic literature review protocol, article selection and exclusion criteria, results synthesis, risk of bias assessment, and derivation of conclusions. In 2019 (October 11), the Health Technology Reassessment Committee conducted the final review on the clinical safety and efficacy assessment results of DBT.

Assessment objectives and methods DBT safety and efficacy assessment followed the systematic literature review protocol for new health technology assessment previously assessed, but the scope and content were confirmed by reaching a consensus of the subcommittee. For systematic literature review, five Korean and three foreign databases were searched. Two reviewers independently screened and selected the articles according to the selection and exclusion criteria. Risk of bias assessment was performed independently by two reviewers using QUADAS-2 until an agreement was reached. Data were extracted independently by two reviewers using pre-determined format. If there was a disagreement between the reviewers, such cases were discussed with a third party to reach an agreement. Meta-analysis was performed when quantitative analysis was possible and qualitative review was applied when otherwise

.............................................ellipsis................................................... Assessment results As a result of updated systematic literature review for reassessment of DBT safety and efficacy, a total of 32 articles were selected. The safety of the same test was assessed by the amount of radiation exposure identified in four studies as a major indicator and the difference with the comparator test was –2.30mGy~1.68mGy, showing that the average amount of radiation exposure was similar between the two tests. The efficacy of the same test was assessed by diagnostic accuracy, recall rate, and disease detection rate in 31 articles and the results were compared to those of digital mammography. The pooled sensitivity and specificity of this test identified in 24 articles included in the meta-analysis were 0.92 (95%CI 0.88-0.94) and 0.85 (95%CI 0.77-0.91), respectively, which showed statistically significant differences with the comparator test showing pooled sensitivity and specificity of 0.82 (95%CI 0.74-0.87) and 0.83 (95%CI 0.73-0.90), respectively (p=0.01). Moreover, the levels of pooled likelihood ratio and diagnostic odds ratio were high. When diagnostic accuracy was identified by varying the patient characteristics and characteristics of the interventional tests, the results were similar to the overall diagnostic accuracy and there were no factors that affected heterogeneity. Moreover, the results of sensitivity analysis with consideration for the sample size, patient group exclusion, level of diagnostic accuracy, and positive test criteria were consistently similar. The disease detection rate of the same test identified in 24 articles was statistically significantly higher by 9% than the comparator test (RR=1.09, 95% CI 1.04-1.15, I2=20.0%). The recall rate calculated by 24 articles did not show statistically significant difference as compared to the comparator test, but heterogeneity among the articles was very high (I2=91.0%).

Conclusions The DBT subcommittee proposed the following based on currently available assessment results. When the safety and efficacy of DBT in follow-up patients and patients with abnormal findings on mammography were assessed based on 32 articles, there was no evidence that the safety of the same test is more harmful than digital mammography, the comparator test. Meanwhile, the diagnostic accuracy and disease detection rate were consistently high and there was no difference in recall rate. Such findings were consistent with results reported in existing literature. Based on such literary evidence, the subcommittee determined that DBT is a safety and effective technology with higher diagnostic accuracy and disease detection rate than digital mammography, the conventional test method, for screening and diagnosing breast cancer in follow-up patients and patients with abnormal findings on mammography. The Health Technology Reassessment Committee reviewed and determined that the findings of the subcommittee on DBT are valid (October 11, 2019).