研究成果摘要

計畫編號:DOH94-NH-1017
計畫名稱:用於治療末梢血管循環障礙用藥之口服單方製劑藥品臨床療效經濟效益與健保支付合理性之評估
執行機構:財團法人彰化基督教醫院(藥劑部)
研究人員:簡素玉主任
執行期間:94年12月16日至95年05月15日

中文摘要
臨床上末梢血管疾病常用「末梢循環障礙治療劑」來增加血液循環、改善周邊血管代謝,但多為症狀緩解或輔助治療。由於這類藥品臨床療效或適應症常具爭議性,加上用量多、單價高,故被列為健保醫療審查之重點藥物,且屢見被核刪案例。再加上這類藥品各成份各廠牌間每日藥費相差甚巨,值此健保資源拮据之秋,更須通盤檢討支付價格之合理性,以合乎醫療經濟效益。由於國內目前尚無相關研究,因此本研究之目的為評估本類藥品臨床療效與經濟效益、保險給付與使用限制、檢討現行健保支付價之合理性、分析本類藥品臨床使用情形研究方法及步驟
1.系統性文獻回顧:利用證據醫學(EBM)方法,針對本類藥品之臨床療效、安全性與經濟效益評估等,進行文獻回顧。2.比對分析:搜尋國外相關保險制度對本類藥品支付價格與使用限制,與國內健保給付作比對分析。3.建立比較表:依據國內外適應症、建議劑量、頻次、不良反應、每日藥費、健保支付價與使用規範等,建立比較表,通盤檢討現行健保支付價格之合理性。4.臨床使用分析:利用健保局提供之資料檔為資料來源,分析本類藥品之臨床使用合理性。5.專家會議:邀請醫藥專家學者,共同評估、討論,提出具體可行之建議案。
本研究共納入13項成份,包括ginkgo biloba extract、pentoxifylline、tocopherol nicotinate、inositol、xanthinol niacinate、nicametate、phenoxybenzamine、nicergoline、cyclandelate、buflomedil、cinnarizine、flunarizine、cilostazol等。經系統性文獻回顧,此類藥品在治療末梢循環障礙之療效證據結果顯示:於初級研究文獻中,ginkgo biloba extract、pentoxifylline、buflomedil、cilostazol是具足夠之療效證據;次級研究文獻中,證據最顯著者為cilostazol、buflomedil,次之為pentoxifylline,此外ginkgo biloba extract雖有文獻證據但作者認為臨床應用具不確定性,至於其他成分皆無足夠之證據。在安全性方面,文獻證據顯示本類藥品安全性高。在經濟效益評估上,僅cilostazol及pentoxifylline具經濟效益文獻證據。而在疾病臨床診療指引中,足以作為治療末梢循環障礙之建議藥品為cilostazol、pentoxifylline。綜合以上,本類藥品在治療末梢循環障礙證據性最強的三個成份是cilostazol、pentoxifylline、buflomedil。
13種成份藥品之健保支付價,cilostazol僅一家藥廠收載但具2種內含量,50mg 13.1元;100mg 26.1元,應屬合理;xanthinol、cyclandelate、phenoxybenzamine、inositol等4成份有多家藥廠收載但為單一內含量;其餘8項成份則為多家藥廠收載且具許多不同內含量,此12項成份健保支付價皆差距甚大。在保險給付規範與限制方面,僅國內對buflomedil、cilostazol訂有藥品給付規範。以民國93年健保資料庫分析門診病患申報資料,結果顯示13種成份別共申報7,525,263筆,藥品總量224,886,550粒,總金額1,140,937,222元。申報筆數最多者為nicametate 2,765,716筆(36.8%);申報總量最多者為nicametate 75,287,509粒 (33.5%);申報總金額最多ginkgo biloba extract 368,293,353元(32.3%)。此13項成分臨床使用合理性分析中,「合理」性最高者為buflomedil 佔18.9%,「符合許可證」者flunarizine佔率最高為43.4%,「不符合許可證」者phenoxybenzamine佔率最高為98.6%。
英文摘要
Physicians can use "peripheral disorder drugs" to treat the peripheral vascular disease clinically. Its main function is to increases the blood circulation and improve peripheral blood vessel metabolism. But the role of these agents is on assistance treatment for the symptom. Because the clinical efficacy of these agents is controversial, and the range of daily costs of theses agents is huge. The adjustment of reimbursement price of these agents is important at the pinch of National Health Insurance (NHI) budget. There are little published data on the use of health care resources and costs attributable to peripheral vascular disease. The goal of this study is to suggest the reasonable reimbursement price and criteria according to systemic literatures review and utilization evaluation of profiles of NHI database.
Methods:
1.Systemic literatures review:To assess the efficacy, safety, cost-effectiveness of these agents via the methods of EBM. 2.Comparison assess:To compare the health insurance reimbursement prices and the restriction on use for the domestic and overseas. 3.Establish comparison charts:To establish the comparison charts, include indications, recommended dosage, frequency, adverse effects, daily cost, reimbursement prices and the restriction on use. 4.Evaluate of utilization from profiles of NHI database:To analysis the domestic database of NHI about the clinical utilizations. 5.The meeting of experts:To invite the medicine experts, appraise and discuss together, then they propose specifically the feasible draft resolution.
This study included 13 agents. There were ginkgo biloba extract, pentoxifylline, tocopherol nicotinate, inositol, xanthinol niacinate, nicametate, phenoxybenzamine, nicergoline, cyclandelate, buflomedil, cinnarizine, flunarizine and cilostazol.
The ginkgo biloba extract, pentoxifylline, buflomedil and cilostazol were the modest of clinical efficacy based on primary randomized control trials. From secondary studies cilostazol and buflomedil showed significant positive efficacy in peripheral vascular disease. Pentoxifylline showed may be efficacious. Ginkgo biloba extract showed modest efficacy and uncertain clinical relevance. The other agents were poor evidence. These agents were relative safe in clinical use. Cilostazol and pentoxifylline had cost-effective evidence from literature review. Drug above recommendation IIa of clinical guidelines were cilostazol and pentoxifylline.
Among reimbursement price of 13 agents, cilostazol had 2 kinds of content but only to have one pharmaceutical factory (50mg NTD 13.1; 100mg NTD 26.1). Xanthinol, cyclandelate, phenoxybenzamine, and inositol were the sole content but many pharmaceutical factories. The other 8 agents were the multi- content, many pharmaceutical factories. These reimbursement prices distributed broadly, and the disparity had been really big.
The prescribing pattern of these agents in NHI files was analyzed. The total utilization frequency was 7,525,263. The total prescribing quantities was 224,886,550. The total pharmaceutical expenditure was 1,140,937,222. Among these agents the most of utilization frequency was nicametate 2,765,716 (36.8%). The most prescribing quantities were nicametate 75,287,509 (33.5%). The most pharmaceutical expenditure was ginkgo biloba extract 368,293,353 (32.3%). In analysis most of utilization frequency, we found buflomedil that was 21.0% of rational use. Flunarizine was 43.4% of cohere use with indications. Phenoxybenzamine was 98.6% of incoherent use with indications.
Conclusion and Suggestions
The cilostazol, pentoxifylline, and buflomedil were the most of clinical efficacy based on literatures review of EBM and recommendations of clinical guidelines.
According the findings of our study, we proposed two suggestions. The suggestion one was that the cilostazol, pentoxifylline, and buflomedil can pay reimbursement price and setup drug reimbursement criteria. Cilostazol and buflomedil maintained original reimbursement criteria. Pentoxifylline limited the same as Buflomedil’s criteria. The other agents changed position to no positive efficacy drugs and not paid for indication of peripheral vascular disease. Except cilostazol was rational, the reimbursement price of the other tweleve agents was unreasonable because range too far and disparity too big. The suggestion two was that Bureau of NHI must re-evaluate this agent’s price by identical principle with inquiring the international price.