평가배경

경피적 풍선확장 경막외강 신경성형술은 척추성 통증 환자를 대상으로 통증 감소를 위해 수행되는 기술로 경피적으로 풍선확장기능이 있는 신경성형술용 카테터를 경막외강으로 진입시켜 카테터 끝에 달린 풍선의 팽창 및 이완을 통해 경막외강 병변부위의 유착을 박리하거나 추간공을 확장시키고 약물을 투여하는 시술이다.

건강보험 보장성 강화대책이 발표된 후(2017년 8월), 2020년에는 ‘척추·근골격계·통증’분야에 대해 의학적 비급여의 급여화를 추진하게 되면서 신경성형술(내시경적 경막외강 신경근 성형술, 경피적 경막외강 신경성형술, 경피적 풍선확장 경막외강 신경성형술)이 비급여 규모가 크고 급여 전환시 다양한 쟁점이 제기될 것으로 예측됨에 따라 급여 전환 타당성 검토의 필요성이 제시된 바 있다.

이후 보건복지부는 척추 관련 기존 행위 4개 항목(추간판내 고주파 열치료술, 내시경적 경막외강 신경근성형술, 경피적 경막외강 신경성형술, 경피적 풍선확장 경막외강 신경성형술)에 대한 재평가를 한국보건의료연구원에 의뢰하였다(2020년 1월). 이에 따라 경피적 풍선확장 경막외강 신경성형술에 대해 2020년 제2차 의료기술재평가위원회(2020.2.14.)에서 평가계획서 및 소위원회 구성안을 심의한 후 임상적 안전성 및 유효성을 평가하였다.

평가 방법

본 평가는 척추성 통증환자를 대상으로 경피적 풍선확장 경막외강 신경성형술이 임상적으로 안전하고 유효한지 평가하기 위해 체계적 문헌고찰을 수행하였다.

체계적 문헌고찰은 위의 핵심질문을 토대로 국내 데이터베이스 5개(KoreaMed, 의학논문데이터베이스, 학술데이터베이스, 한국교육학술정보원, 과학기술정보통합서비스) 및 국외 데이터베이스 3개(Ovid MEDLINE, Ovid EMBASE, Cochrane Central Register of Controlled Trials)을 이용하여 문헌검색하였으며, 2명의 평가자가 독립적으로 문헌 선정기준 및 배제기준을 적용하여 선택배제를 수행하였다. 자료추출, 비뚤림 위험평가 및 GRADE 적용은 선택문헌이 0편으로 수행되지 않았다.

본 평가를 위해 총 10인(마취통증의학과 2인, 신경외과 2인, 정형외과 2인, 영상의학과 1인, 재활의학과 1인, 근거기반의학 2인)으로 구성된 소위원회에서 체계적 문헌고찰을 통해 동 기술의 안전성 및 유효성에 대한 문헌적 근거를 평가하였고, 2020년 제12차 의료기술재평가위원회(2020.12.11.)에서 경피적 풍선확장 경막외강 신경성형술의 임상적 안전성 및 유효성 평가 결과에 대해 최종심의하였다.

평가 결과

경피적 풍선확장 경막외강 신경성형술 평가에 선택된 문헌은 0편이었다. 비교치료법의 경우 중재시술의 효과를 평가하기 위해 기존 급여권에서 활용되고 있는 치료법을 적절한 치료법으로 보고 해당 비교치료법과 비교된 연구만 선택문헌에 포함하여 평가하기로 하였기 때문에 경피적 풍선확장 경막외강 신경성형술의 전후 연구 혹은 현재 비급여 행위인 경피적 경막외강 신경성형술과 비교된 연구는 확인되었으나 모두 사전에 정의된 비교시술과 비교하지 않은 연구로 배제되었다.

이에 소위원회에서는 경피적 풍선확장 경막외강 신경성형술의 경우 급여권에 등재되어있는 기존기술과 비교된 연구가 확인되지 않아 동 기술에 대한 안전성 및 유효성을 판단할 근거가 부족하여 동 기술의 안전성 및 유효성에 대해 평가할 수 없다는 의견이었다.

결론

경피적 풍선확장 경막외강 신경성형술 소위원회는 현재 평가 결과에 근거하여 다음과 같이 제언하였다.

경피적 풍선확장 경막외강 신경성형술은 현재 급여권내에 있는 기술과 비교된 연구가 없기 때문에 근거가 부족해 평가하기 어려우며, 추후 동 기술의 평가를 위해 경막외강 신경차단술과 같은 급여권내에 있는 기술과 비교한 잘 설계된 연구 결과를 통한 근거 축적이 더 필요하다고 판단하였다.

의료기술재평가위원회는 ‘경피적 풍선화장 경막외강 신경성형술’에 대해 소위원회의 검토결과에 근거하여 다음과 같이 심의하였다(2020.12.11.).

경피적 풍성확장 경막외강 신경성형술은 척추성 통증 환자를 대상으로 통증감소를 위해 수행시 안전성은 수용가능하나 기존의 보존적 치료 및 경막외강 신경차단술과 비교연구가 없었다. 다만 시술 전후 효과를 보고한 문헌이 6편(경피적 경막외강신경성형술과 비교 연구 2편, 전후연구 1편, 증례보고 3편) 확인되었고, 동 기술이 카테터를 경피적으로 삽입하여 경막외강 병변부위의 유착을 제거 또는 박리한다는 점에서 카테터의 종류는 다르지만 경피적 경막외강 신경성형술과 유사한 방법을 이용하고 있어 안전성 및 유효성이 있다고 평가된 경피적 경막외강 신경성형술과 유사한 유효한 기술로 평가하였으며, 추후 현재 급여권에서 활용되고 있는 적절한 시술과 비교한 양질의 근거축적은 필요하다고 제언하였다. 또한 동 기술이 경피적 경막외강 신경성형술과 유사한 안전성을 가지고 있기 때문에 경피적 경막외강 신경성형술과 동일하게 상당한 주의와 감독하에 수행할 필요가 있다는 의견이었다.

이에 의료기술재평가위원회는 척추성 통증 환자를 대상으로 통증 감소를 위해 경피적 풍선확장 경막외강 신경성형술을 권고함(권고등급 Ⅰ-b)으로 심의하였다.

​Background and Purpose of Assessment

TAVR (Transcatheter Aortic Valve Replacement, hereinafter TAVR) is a procedure to percutaneously insert a stent-type artificial valve for the treatment of severe aortic valve stenosis. It was introduced as a selective reimbursement with conditions (80% co-payment rate) from June 2015 as a condition of submitting the limitation of healthcare facilities and procedure data.

The US FDA approved even the low-risk group for surgery (2019), and previous studies in Korea have also reported that a re-assessment is necessary after accumulating evidence in the future for the intermediate-low risk group (Dong-Ah Park et al., 2019). To reflect these changes and needs, the Health Insurance Review & Assessment Service commissioned the Korea Institute of Health and Medical Research to evaluate the safety and effectiveness of 「TAVR」 in patients in the intermediate-low risk group (Preliminary Benefit Evaluation Department-262 Apr. 08. 2020). Therefore, this assessment evaluated the medical and scientific evidence for the clinical safety and effectiveness of TAVR in the intermediate-risk group among patients with severe aortic valve stenosis.

Committee’s Operation

The subcommittee consisted of a total of 7 members and held a total of three subcommittee meetings to evaluate the safety and effectiveness of the technology based on the literature for 4 months from June 26 to September 18, 2020. The final deliberation was conducted on the subcommittee's assessment results of safety and effectiveness at the 10th Health Technology Reassessment Committee (2020.10.16.).

Assessment Method

A systematic literature review was conducted on the safety and effectiveness of TAVR in the intermediate-risk group, and the opinions of the subcommittee were summarized on costs and others. All assessment methods were finalized after discussion of the “TAVR subcommittee (hereinafter referred to as the ‘subcommittee’).

A key question in the systematic review is “Is TAVR safer and more effective than surgical aortic valve replacement in intermediate-risk patients with symptomatic severe aortic valve stenosis?” For the comparative procedure, the surgical aortic valve replacement (hereinafter referred to as SAVR), a standard treatment for severe aortic valve stenosis, was selected. SAVR is a surgical procedure to replace the aortic valve with an artificial valve, and it is difficult to perform SAVR in some high-risk groups, where the risk of surgery increases due to old age and comorbidities. TAVR has begun to be used as an alternative procedure for elderly patients who are difficult to get SAVR or for high-risk surgical groups.

The literature search of a systematic literature review was conducted in three overseas and five domestic databases. The literature selection process was independently performed by two evaluators according to the literature inclusion and exclusion criteria. In case of disagreement, the final articles were decided through consensus among the evaluators. The risk of bias in literature was evaluated using Cochrane's Risk of Bias, and two evaluators independently evaluated the finally selected literature. In case of disagreement, concordant results were drawn through consensus among evaluators. All data were extracted by the research unit, and if the outcome indicators of the same study were reported repeatedly, the latest literature was used for analysis. Based on the results of the systematic literature review conducted in this assessment, the level of evidence was evaluated using the GRADE method, and the recommendation grade was determined based on the assessment results. In addition, the literature reporting the economic outcome index was compiled and domestic TAVR costs and related reports (Dong-ah Park et al., 2019) were summarized.

Assessment Results

The final selected literature for this assessment was 2 studies (6 articles) reporting clinical safety and effectiveness results and 7 publications reporting economic results, for a total of 13 articles. All studies reporting clinical safety and effectiveness results were randomized clinical trials (RCT), and the total number of patients was 3,692. The average of the Society of Thoracic Surgeons Operative Risk Score (hereinafter STS) of subjects was 4.4-5.8%.

Safety Results

Clinical safety outcome indicators were defined as 30-day mortality rate, neurological events such as stroke, myocardial infarction, atrial fibrillation, and endocarditis. As a result of a meta-analysis of safety outcome indicators, TAVR was statistically significantly safer than aortic valve replacement in terms of severe stroke and atrial fibrillation at 1 month. However, there were no differences between the two groups in long-term outcomes of 1 year or longer. 

Effectiveness Results

As a result of meta-analysis on clinical effectiveness outcome indicators, TAVR was statistically significantly more effective than SAVR in terms of life-threatening bleeding* at 1 month, acute renal failure, aortic valve-related readmission, quality of life*, and improvements in New York Heart Association class (hereinafter NYHA class) . On the other hand, SAVR was more effective than TAVR in aortic regurgitation, aortic valve-related reoperation, and permanent pacemaker implantation*. TAVR was statistically significantly more effective than SAVR in terms of occurrence of NYHA class III or higher in the long-term outcome of 1 year or longer. On the other hand, the SAVR group was statistically significantly more effective than the TAVR group in terms of aortic regurgitation at 2 years, aortic valve-related reoperation*, and quality of life change at 1 year (*statistically significant result with >50% heterogeneity).

Economics-Related Results

There were a total of 7 documents reporting economic outcome indicators, with 3 from Canada and 1 each from Japan, France, Australia, and the US by study country. Considering the cost-effectiveness threshold of each country, three studies reported that percutaneous aortic valve insertion was a dominant alternative, which is cheaper and more effective, than aortic valve replacement. 

Considering the cost-effectiveness threshold, Considering the cost-effectiveness criterion, there were three studies that reported the possibility of being cost-effective (moderate to high uncertainty). One study conducted in Japan suggested that TAVR was not cost-effective (Kodera, 2018). Cost-effectiveness was more affected by the cost difference than by the effect difference, and the factor that greatly affected the cost was the valve price of TAVR.

In addition, according to a report by Dong-ah Park et al. (2019) regarding the cost of TAVR in Korea, the out-of-pocket cost of TAVR per patient was KRW 25,914,000 out of KRW 40,981,000 per patient as of 2018, when the co-payment rate for TAVR was 80%. On the other hand, the cost of the single SAVR procedure was 22,874,000 won, which was lower than that of TAVR, and the out-of-pocket cost was 1,344,000 won, which was lower than the patient co-payment rate of TAVR.

Conclusion and Suggestions

As a result of a systematic review of the literature, there was no difference in mortality from TAVR compared to SAVR in the intermediate-risk group for severe aortic valve stenosis. There was no statistically significant difference between the two groups in terms of cardiovascular-related mortality, neurological events such as stroke, major vascular complications, major bleeding (life-threatening or disability). The incidence of aortic valve-related regurgitation and aortic valve-related reoperation was statistically significantly higher in the TAVR group than in the SAVR group. In conclusion, in the intermediate-risk group of severe aortic valve stenosis, TAVR was evaluated as a safe and effective technique because there was no difference in safety and effectiveness compared to SAVR (GRADE reliability Moderate-High).

As a result of the discussion on the reimbursement coverages according to the risk of surgery in the TAVR reassessment subcommittee, there was an opinion that it would be appropriate to apply for the same reimbursement coverages as SAVR in the group where SAVR is impossible or high-risk, to apply 50% co-payment for the intermediate-risk group, and to maintain the current reimbursement coverages for the low-risk group. It is judged that the difference between TAVI cost and SAVR cost in Korea is caused by the difference in reimbursement coverages and treatment material cost. There was a consensus on the need for an increase in the cost of TAVI and SAVR procedures and the need for an expanded reimbursement coverage according to the surgical risk criteria.

The Health Technology Reassessment Committee deliberated as “recommended TAVR for intermediate-risk patients with severe aortic valve stenosis surgery (recommendation grade I-b)” according to Article 4, Paragraph 10 of the Health Technology Reassessment Project Management Guideline (2020. 10. 16). As a result of a systematic literature review on TAVR, the recommendation grade was determined to be 'low (Grade I-b)' because it is difficult to make a strong recommendation based on the current evidence, considering that it is a technology that is not different from SAVR and expensive.

Keywords

TAVR, TAVI, Severe aortic valve stenosis, Intermediate risk, SAVR

요약문 i

Ⅰ. 서론 1

  1. 평가배경 1

  2. 평가목적 4

Ⅱ. 평가 방법 5

  1. 체계적 문헌고찰 5

Ⅲ. 평가결과 9

  1. 문헌선정 결과 9

    1.1 문헌선정 개요 9

Ⅳ. 결과요약 및 결론 11

  1. 평가결과 요약 11

  2. 결론 11

Ⅴ. 참고문헌 13

Ⅵ. 부록 14

  1. 의료기술재평가위원회 14

  2. 소위원회 15

  3. 문헌 검색 전략 16

  4. 배제문헌 목록 및 배제사유 21

  5. 경피적 풍선확장 경막외강 신경성형술과 경피적 경막외강 신경성형술 비교 연구 결과 24

  6. 경피적 풍선확장 경막외강 신경성형술 전후 연구 및 증례보고 요약 28