혈액점도검사 [상대점도측정법]

Abstract

평가 배경 혈액점도검사 [상대점도측정법]은 수축기 및 이완기 환경에서 혈액점도를 측정하여 질병 치료 및 예후를 예측하는 검사로서 신의료기술평가 후 2019년 제7차 의료행위전문평가위원회에서 선별급여 본인부담률 80%로 심의하였다(보건복지부 고시, 제2019-198호(2019.7.15.)). 의료행위전문평가위원회에서 기존검사인 혈액점도검사 [스캐닝 모세관법, 콘플레이트회전법]보다 혈액점도의 변화를 미세한 부분까지 측정이 가능하여 구체적인 치료방향 설정에 도움이 되고 소량의 혈액으로도 검사가 가능하다는 장점이 있으나 신의료기술평가에서 국내문헌 1편만 검토하였고 교과서 및 제 외국 행위분류 등에서 확인되지 않으며, 기존 검사도 근거자료 축적과 모니터링이 필요하다는 점들을 감안하여 선별급여로 결정하였다. 혈액점도검사 [상대점도측정법]은 선별급여 적합성 평가주기를 고려하여 내부 모니터링을 통해 재평가 주제로 발굴되었으며, 의료기술의 적정사용 및 관련 정책결정을 지원하기 위해 체계적 문헌고찰을 통해 임상적 안전성 및 효과성에 대한 최신 근거를 확인하고자 재평가를 수행하였다.

평가 방법 혈액점도검사 [상대점도측정법]에 대한 안전성 및 효과성을 평가하기 위해 체계적 문헌고찰을 수행하였다. “혈액점도검사 소위원회(이하 ‘소위원회’라 한다)”는 총 6인(순환기내과, 혈액종양내과, 신경과, 진단검사의학과, 근거기반의학)으로 구성하였으며, 모든 평가방법은 평가목적을 고려하여 소위원회의 검토를 거쳐 확정하였다. 평가의 핵심질문은 ‘혈액점도검사 [상대점도측정법]은 심혈관질환, 말초혈관질환에서 혈액점도를 측정하여 질병 치료와 예후를 예측하는데 임상적으로 안전하고 효과적인가?’이었다. 안전성은 부작용 및 이상반응을 결과지표로 설정하였고 심혈관질환과 말초혈관질환에서 효과성은 주요 심혈관질환, 전체 심혈관질환, 후속 질환의 발생 및 재발과 사지절단을 결과지표로 설정하여 질병치료적 관점에서 예후 예측에 중점을 두고 평가하였다. 체계적 문헌고찰은 핵심질문을 토대로 국외 3개, 국내 5개 데이터베이스를 검색하여 문헌선정 및 배제기준에 따라 두 명의 검토자가 독립적으로 선별하고 선택하였으며, 소위원회의 검토를 진행하였다. 또한, 소위원회의 평가결과를 토대로 의료기술재평가위원회에서 권고등급을 결정하였다.

평가 결과 혈액점도검사 [상대점도측정법]의 선별급여 인정기준에 따라, 심혈관질환, 말초혈관질환을 대상으로 체계적 문헌고찰을 수행한 결과, 최종 선택문헌은 없었으며, 신의료기술평가에 활용된 선택문헌도 수기검색으로 포함하여 검토하였으나 연구대상자, 목표질환, 대조군 및 결과변수, 연구설계 등의 차이로 배제하였다.

안전성 혈액점도검사 [상대점도측정법]은 대상자의 체외에서 이루어지는 혈액검사로서 혈액채취과정 이외 인체에 직접적인 위해가능성은 없어 안전성에 대한 우려는 없을 것으로 판단하였다. 또한, 동 검사는 질환을 확진하거나 진단검사로 활용하지는 않아 진단검사 결과의 오류로 인한 치료 및 처치 등의 위해가능성은 낮을 것으로 판단하였으나, 최종 선택문헌이 없어 안전성을 확인할 수는 없었다.

효과성 혈액점도검사 [상대점도측정법]의 효과성은 질병 치료적 관점에서 예후 예측을 결과지표로 설정하고 임상적 문헌을 근거로 평가하였다. 혈액점도검사 [상대점도측정법]을 이용하여 혈액점도의 수준에 따른 주요 심혈관질환, 전체 심혈관질환의 발생 위험도, 후속질환 발생 위험도, 절단 등의 예후 예측에 대한 연구문헌이 한 편도 없었으며, 의료결과에 미치는 영향, 치료 모니터링을 보고한 문헌도 없어 임상적 효과성을 확인할 수 없었다.

결론 및 제언 소위원회에서는 현재의 문헌적 근거를 바탕으로 혈액점도검사 [상대점도측정법]의 안전성 및 효과성에 대한 평가결과를 다음과 같이 제시하였다. 혈액점도검사 [상대점도측정법]은 체외혈액검사로 임상적 판단기준(임계값)이 불명확하고 주요 심혈관질환의 발생위험도, 전체 심혈관질환 관련 사망위험도, 후속 질환의 발생 및 재발위험도, 사지절단 위험도와 같은 주요 임상결과지표를 확인할 만한 문헌적 근거가 부족하여 안전성과 효과성을 판단할 수 없다는 의견을 제시하였다. 또한, 소위원회는 환자의 기저상태와 치료과정에서 각종 수액 및 병용요법에 따른 혈액점도수치의 변화 등으로 연구수행의 제한점들이 있지만 혈액점도검사 [상대점도측정법]의 효과성을 확인하기 위해서는 다양한 교란변수들을 통제하고 비뚤림 위험의 가능성을 최소화하여 근거수준이 높은 전향적 임상연구에서 객관적이고 일관성있는 연구결과의 도출이 필요하다고 제언하였다. 2023년 제1차 의료기술재평가위원회(2023.1.13.)에서는 소위원회의 검토 결과에 근거하여 의료기술재평가사업 관리지침 제4조제10항에 의거 “혈액점도검사 [상대점도측정법]”에 대해 다음과 같이 심의하였다. 혈액점도검사 [상대점도측정법]은 심혈관질환, 말초혈관질환에서 질병 치료 및 예후 예측을 위한 혈액점도의 임상적 판단기준(임계값)이 불명확하고 주요 심혈관질환의 발생위험도, 사망위험도, 후속 질환의 발생 및 재발위험도 등과 같은 각 적응증별 주요 결과지표에 대한 예후를 확인할 만한 문헌이 부족하다고 판단하였다. 따라서, 현 시점에서 동 기술은 혈액점도를 측정하는 안전한 검사이나 질병 치료 및 예후 예측을 위한 임상적 효과성을 판단하기에는 문헌적 근거가 불충분하고 환자 적용에 있어 검사유용성이 부족하다고 평가하였다. 이에 의료기술재평가위원회는 심혈관질환, 말초혈관질환에서 질병 치료 및 예후 예측을 위해 혈액점도검사 [상대점도측정법]을 ‘권고하지 않음’으로 심의하였다(권고등급: 권고하지 않음).

주요어 심혈관질환, 말초혈관질환, 혈액점도검사 [상대점도측정법], 안전성, 효과성

Background The complete blood count (CBC): White blood cell (WBC) count [image analysis] – Handy test (hereafter referred to as the “WBC – Handy test”) is a streamlined screening test for assessing WBC counts, plays a pivotal role in identifying fluctuations in WBC counts in patients requiring regular monitoring. Endorsed for its safety and efficacy by the New Health Technology Assessment Committee in February 2016, this test gained recognition as a selective benefit item with a 90% co-payment (Nuh-000rah) in July 2019, as per the Ministry of Health and Welfare Notice No. 2019-110 dated June 14, 2019. Its integration into clinical practice has been sustained since then. The technology underwent a reassessment in 2022, driven by internal monitoring and the need to reevaluate its conformity as a selective benefit item. This reassessment, conducted during the eleventh session of the Committee of Health Technology Reassessment in 2022, aimed to thoroughly reassess the clinical safety and effectiveness of the WBC – Handy test, thereby informing policy decisions for its optimal utilization in healthcare settings.

Methods A rigorous systematic review was conducted to evaluate the WBC – Handy test's safety and effectiveness. This process was meticulously structured following extensive deliberations by the “WBC – Handy test subcommittee (hereafter referred to as “Subcommittee”). The primary question of the assessment was, “Is WBC – Handy test clinically safe and effective as a screening tool for patients requiring WBC count evaluations?” Safety outcomes were gauged based on the occurrence of complications and adverse events (AEs), while effectiveness was measured through comparisons with other tests, impact on health outcomes, and testing convenience. For the literature review, a thorough search was conducted across three international and five domestic databases. Two independent reviewers were tasked with screening and selecting relevant articles based on predefined inclusion and exclusion criteria. The agenda's lead conducted a risk of bias (RoB) assessment using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), which was then reviewed by the Subcommittee for consensus. Data extraction followed a structured format, and due to the limitations in quantitative analysis, a narrative review approach was employed to synthesize and describe the findings. Additionally, the Committee of Health Technology Reassessment formulated the grade of recommendation based on the insights gleaned from the Subcommittee's review.

Results The systematic review, focusing on patients eligible for the current selective benefit criteria who require WBC count monitoring, resulted in the selection of eight diagnostic test evaluation studies and one cohort study. In the RoB assessment utilizing QUADAS-2, instances of ambiguous patient selection descriptions led to a “high” (44.4%) RoB and concern about applicability. Similarly, when study populations did not exclusively comprise patients suspected of having abnormal WBC counts, the concern about applicability was deemed “uncertain” (44.4%). However, the RoB and concern about applicability in the index test and reference standard domains were assessed as “low”, reflecting the use of comparison to established reference standards, application of clinical thresholds, and adherence to internationally recognized measurement methods and normal ranges. The RoB in the flow and timing domain was marked as “uncertain” (33.3%) due to ambiguities in including some patient test results in the analysis.

Safety In the systematic review which encompassed nine selected articles, there were no reports concerning the safety of the WBC – Handy test.

Effectiveness The effectiveness of the WBC – Handy test was examined through a comprehensive evaluation based on three critical aspects: correlation with comparator (n=6) tests, impact on health outcomes (n=1), and testing convenience (n=3). Correlation with Comparator Tests: The studies that assessed the correlation between WBC counts from the WBC – Handy test and automated hematology analyzers varied in their findings. Five studies reported correlation coefficients (r) ranging from 0.864 to 0.997, while one study reported a coefficient of determination (r2) of 0.798. However, two studies indicated some discrepancies compared to the reference standard, particularly in patients with decreased WBC counts or blood disorders. This led to suggestions that the WBC – Handy test should primarily serve as a screening tool or be used in settings where automated hematology analyzers are not accessible. Impact on Health Outcomes: In a study involving 120 pediatric patients with suspected acute disease, the results revealed that 32 patients (27%) were prescribed antibiotics, with only one patient (3%) revisiting the hospital for follow-up treatment. In contrast, among the 88 patients (73%) who were not initially prescribed antibiotics, three (3%) revisited the hospital within 30 days for antibiotic prescriptions. These findings suggest that the WBC – Handy test can be instrumental in facilitating timely decisions regarding antibiotic prescriptions. Testing Convenience: The convenience offered by the WBC – Handy test was noted in three studies. The test's capability to provide results within a five-minute timeframe was particularly emphasized. Other advantages included the simplicity of the finger capillary sampling method, making self-measurement easy and convenient (n=1); the provision of consistent and timely information to patients and guardians in emergency room settings (n=1); and the feasibility of on-site, real-time measurements in challenging scenarios, such as for critically ill patients in intensive care units and transporting the samples.

Conclusions and recommendations The Subcommittee conducted a thorough review of the available literature to assess the safety and effectiveness of the WBC – Handy test, leading to several key observations and recommendations. The WBC – Handy test demonstrated a significant correlation with CBC using an automated hematology analyzer, which serves as the reference standard. However, notable differences in results were reported in patients with abnormal WBC counts. This discrepancy, coupled with the test's low acceptance in medical institutions due to insufficient evidence of its impact on health outcomes, led the Subcommittee to suggest that the WBC – Handy test should be primarily employed for rapid testing scenarios or when constraints prevent the use of the reference standard. Furthermore, considering the widespread use, timeliness, and accuracy of CBC via automated hematology analyzers in Korean clinical settings, the test was deemed to have limited clinical utility. The practice of using this test for WBC count screening was also seen as potentially leading to the misuse of medical resources. There is a pressing need for more clinical evidence to determine the effectiveness of using the WBC – Handy test in treatment decision-making or in predicting disease prognosis, especially when used initially in patients suspected of having abnormal WBC counts, followed immediately by the reference standard test. In the first session of the Committee of Health Technology Reassessment in 2023 (on July 14, 2023), the following conclusions were reached based on the Subcommittee's findings in accordance with Article 4-10 of the Guidelines for Management of Health Technology Reassessment. The WBC – Handy test is acknowledged as a safe health technology, akin to an in vitro diagnostic test, employing a sample collection method similar to a blood glucose meter. This test showed a high correlation with CBC using an automated hematology analyzer (reference standard). However, given the disparities in results compared to the reference standard in cases of abnormal WBC counts and the lack of robust evidence on its impact on health outcomes, the Subcommittee determined that the test has limited clinical utility. It is advised to be used either as a screening test or only under circumstances where the reference standard is not applicable. The practice of conducting retests due to uncertainties in clinical decisions based on the WBC count measured by this test could be seen as an inappropriate use of medical resources in the clinical settings of Korea. Accordingly, the Committee of Health Technology Reassessment “does not recommend” the use of the WBC – Handy test as a screening method for patients needing WBC count checks in Korea. This recommendation is based on a comprehensive consideration of the evidence of its clinical safety and effectiveness, alongside other assessment criteria (Grade of recommendation: Not recommended).

Keywords: WBC count [image analysis]- Handy test, Safety, Effectiveness