藥物經濟學在臨床藥學之應用硏究

Application of pharmacoeconomics in clinical pharmacy

陳麗芳(Li-Fang Chan)

指導教授 ： 林双金

高雄醫學大學/醫學院/醫學研究所/博士(2009年)

摘要

硏究背景：藥師的執業專業功能已從傳統的藥品調製及調劑工作漸走向提供個別病患專業藥事照顧服務及監測服務品質的工作，前者包括針對評估醫師處方的適當性、療效監測及對病患持續追蹤等服務，後者則包括選擇適當品質的藥物、藥品採購庫存管理、調劑疏失的預防與通報和藥物不良反應的監測與通報等工作。這些工作都可以節省成本，提升病患用藥安全，進而減少健保藥費與醫療費用的支出。面對醫療費用不斷上升的環境，應用經濟學分析來探討藥物的使用已是全球的趨勢，希望將有限的醫療資源發揮極大的價值。本硏究之目的是應用藥物經濟學的原理與方法學於醫院臨床藥學硏究，包括監測服務品質的工作以及探討藥事照顧的成本效益。
硏究架構：本硏究共分兩部分，第一部分為藥師對服務品質的監測，分二子題，第一子題是台灣住院病患藥物不良反應(ADR)之成本評估；第二子題是運用Rasch模式分析藥師介入氣喘病患用藥教育的過程中發展簡易版的生活品質問卷的信效度；第二部分是探討藥事照顧服務的成本效益，也分二子題，第一子題是藥師介入活性蛋白Ｃ治療嚴重敗血症對臨床與經濟成果的影響；第二子題是運用系統性回顧方法評估Trastuzumab用於早期乳癌輔助治療之成本效果。
硏究方法：第一部分ADR之成本評估是觀察性硏究，自2002年至2004年間，病患因ADR住院或於住院期間發生ADR，使用Naranjo algorithm評估發生ADR之可能性，因住院期間發生ADR所致之直接醫療成本不易辨識而不列入計算，僅計算因ADR住院所致之直接醫療成本。第二子題是想建構一個信效度高的療效測量工具來測量藥師介入門診氣喘病患教育是否能改善病患療效，所探討之工具是常用於測量氣喘病患自覺性氣喘生活品質問卷(AQLQ)，評估氣喘對病患生活品質的影響，並以Rasch模式(1960)分析及簡化原版AQLQ發展為TAQLQ，探討二版問卷之信效度是否有差異。第二部分第一子題是回溯性case-control 硏究，評估2003至2007年因敗血症住院之病患病歷，比較臨床藥師介入與沒有臨床藥師介入，對使用活性蛋白C之成效及直接醫療成本分析；第二子題是因應藥師在醫院藥事委員會進藥前的準備能力，增強藥師執行成本效果研究文獻之查詢與分析能力，故利用實證醫學之系統性回顧方法，分析1998年至2008年發表有關運用經濟學模型或臨床試驗探討癌症標靶藥Trastuzumab用於早期乳癌HER+2病患輔助治療之英文文獻，依藥物經濟學文獻評讀指引，評估該類文獻之品質及其發表之成本效果數據，藉此硏究培養藥師能力並推廣到其他藥品之成本效果文獻資訊的查詢、評估與使用。
硏究結果：本硏究初步認為藥師在監測服務品質的成果是具有成本效益的，藥師監測ADR並分析估算因此導致住院的直接醫療成本為美金$3489.00元，如果臨床藥師或醫師能預防一個ADR的發生，即可節省許多的額外花費；又藥師介入對門診氣喘病患進行教育，對誘發氣喘過敏原的認識及用藥知識與技巧後，病患對氣喘認知及用藥知識與技巧是有改善的，此研究結果已發表於2004年Clin Drug Investig雜誌。本硏究僅對執行上述研究的同時所採用之自覺性氣喘生活品質問卷AQLQ，做信效度之分析，以確認此療效工具能反映真實的結果。以Rasch模式(1960)分析的結果初步認為中文翻譯版AQLQ問卷題目有閾階難度失序現象，即氣喘病患對翻譯過的7分問卷存在辨識上不明確，刪除失序項目後發展的簡易版5分的TAQLQ問卷較原版更具結構的效度(infit與outfit MNSQ為0.5-1.5)及信度(person separation index 0.92)。第二部分的二個子題結果顯示藥事照顧也是具有經濟效益的。藥師介入評估活性蛋白C (APC)治療加護病房敗血症病患是可以提醒醫師及早使用APC，而節省住院天數及直接醫療成本。藥師利用實證醫學方法發現治療乳癌標靶藥物trastuzumab對HER+2，年齡55歲以下的乳癌病患一年期及長期治療之遞增成本效果比值(ICERs)是在目前共識的閾值之內，顯示具有成本效益的；但若使用於早期具有HER2+ 的乳癌患者年齡超過75歲且治療時間少於10年之輔助治療，則所產生的遞增成本效果比值(ICERs) 顯示不具有成本效益。
硏究結論：由本論文各子題所得的結果初步建議：藥師運用藥物經濟學原理於臨床硏究，不但可提供醫師選擇較具成本效益的治療方案，同時可發現應用藥師的專業執業功能，包括藥事照顧服務及監測服務品質的工作上可以減少直接醫療成本。期盼未來在醫院藥學管理上，能探討更多藥師執行藥事照顧及服務品質管理的成本效益議題，譬如說：DRG管理、同一類藥品如何選出最適當者使用、藥師開設慢性病諮詢門診等，以提供醫院更多實證資料，讓醫院決策者重用藥師的專業知識與技能，更期盼能提供健保局修改藥事服務費給付項目的參考。

關鍵字

藥物經濟學 ； 藥物不良反應 ； 系統性回顧 ； 臨床藥學

並列摘要

Background: The functions of pharmacist professional practice have been changed from the traditional compounding and dispensing to providing individual patients with pharmaceutical care and its quality management. Pharmaceutical care includes assessment of the prescription appropriateness, drug effectiveness monitoring and follow-up evaluations. The quality management includes selection of appropriate drugs, management of drug purchase and inventory, preventing and reporting medication error, adverse drug monitoring and reporting. All those services are most likely to improve patients’ drug safety and reduce drug expenditure and health care cost reimbursed by Bureau of National Health Insurance Company (BNHI). In order to cope with the continuously increase of health care expenditure, the application of economic analysis to explore the consumption of pharmaceuticals is part of a larger global trend to maximize the value received for money spent on healthcare services. The aim of this study was to apply the pharmacoeconomic methodologies and principles to pharmaceutical services which included pharmaceutical care quality management, such as the costs of adverse drug monitoring and reporting; pharmacist intervention to educate asthma patients and develop shortened version of quality of life questionnaire (AQLQ), validity and reliability measuring. The evaluation on cost-effectiveness of pharmaceutical care included pharmacist intervention in the use of activated protein C (APC) for the treatment of severe sepsis; evaluation on Trastuzumab for HER-2(+) early breast patients by using systematic review methodology.
Study design: This study included two parts. The first part was pharmacist monitoring on the quality of pharmaceutical care services, two sub-studies were included. The first was the cost evaluation of adverse drug reactions (ADRs) caused hospitalization; the second sub-study was pharmacist intervention in educating asthmatic patients and measuring the validity and reliability of shortened asthma quality of life questionnaire by Rasch model. The second part was to explore the economic effictiveness of pharmaceutical care, included pharmacist intervention in APC therapy for severe sepsis: influence on clinical and economic outcome and the cost-effectiveness ratio of trastuzumab as an adjuvant therapy for early breast cancer.
Study methods: The first sub-study of the first part was an observational study, patients who were admitted into the hospital due to ADRs or experienced ADRs during hospitalization from January 2002 to December 2004 were identified actively through high-intensity ADR monitoring by clinical pharmacists and passively by physicians and nurses told to report ADRs. The WHO definition of ADR severity was adopted, and degrees of probability for each ADR were determined using the Naranjo algorithm. The direct medical cost incurred by ADRs during hospitalization was excluded to calculate because of uneasy identification; therefore, only direct medical cost of ADRs caused admission was calculated. The second sub-study was educating asthma outpatients about the skill of using inhaler and then administered the asthma knowledge questionnaire to measure the improvement of asthma knowledge. In addition, the original 32-item AQLQ was also administered to the patients and evaluate the impact of asthma on their quality of life. The validity and reliability of two versions was assessed using Rasch model. The first sub-study of the second part was a retrospective case-control study. We reviewed the medical records of patients aged 18 years and older who were admitted to research hospital for severe sepsis from Jan 1, 2003 to Dec 31, 2007. The influence of pharmacist intervention on clinical and economic outcomes was evaluated. The second sub-study was using the systematic review methology to analyze the cost-effectiveness ratio of trastuzumab as an adjuvant therapy for early breast cancer by using modeling or clinical trials. The quality and cost-effectiveness reported in studies retrieved were appraised according to the pharmacoeconomic appraisal guideline. By virtue of the search strategy practiced in this study, we anticipate that the experience in searching evidence-based medicine data may extend to search EBM data of cost-effectiveness of other anti-cancer drugs.
Study results: The results indicated that pharmacist intervention in quality monitoring of pharmaceutical care services is cost-effective, including ADRs monitoring and estimated the direct medical cost of ADRs caused hospitalization was US$ 3489.00, which is the direct medical cost to be saved as pharmacist or physician can prevent the occurrence of one ADR. The asthma outpatients’ recognization of asthma allergen and skill of using inhaler showed improvement. The results of this part have already published in Clin Drug Investig. 2004: 24(10):603-9. This study was only assessed the influence on asthma patients’ quality of life. Rasch model was used to assess and shorten the original AQLQ. The preliminiary results showed that there was differential item functioning (DIF) in the original Chinese AQLQ, i.e. some items in Chinese AQLQ exhibited difficulty for asthma patients’ in answering the questionnaire. The constructive validity (infit and outfit MNSQ were 0.5-1.5) and the person separation index (0.92 Conbach’s α) of the simplied version of 5-scale TAQLQ was better than the original AQLQ. The second parts, the first sub-study showed that the pharmaceutical care is cost-effective. The pharmacist intervention in the use of APC for patients with septic shock in ICU can remind physician to use APC earier which resulted in shortened hospital’s length of stay and reduced direct medical cost; pharmacist using systematic review method indicated that the incremental cost-effectiveness ratios threshold for trastuaumab as an adjunvant treatment for HER+2 early breast cancer patients aged below 55 for one year or long term therapy is appropriate. However, it is not cost-effective for HER+2 breast cancer patients aged over 75 and less than 10 year.
Conclusion: The results showed that the application of pharmacoeconomic in clinical pharmacy is not only providing physicians with a cost-effective drug regimen, the function of pharmacist professional practice, including pharmaceutical care and its quality management monitoring are also likely to reduce direct medical cost. We therefore anticipate that the application of pharmacoeconomic methodology in clinical research on cost-effectiveness of pharmaceutical care and quality management will be continued in order to provide the health care decision maker with more evidence-based data for cost containment and physician to select more cost-effective drug regimens. In addition, we also hope that BNHI may consider adjusting the reimbursement of pharmacist service.

並列關鍵字

Pharmacoeconomic ； ADRs ； Clinical Pharmacy ； Systematic review

參考文獻

1.行政院衛生署 國民醫療保健支出統計 http://www.doh.gov.tw/CHT2006/DM/DM2_2.aspx?now_fod_list_no=10238&class_no=440&level_no=1. Accessed on 2008 Sept, 30

2 中央健康保險局http://www.nhi.gov.tw/webdata/webdata.asp?menu=5&menu_id=412&webdata_id=2248&WD_ID. Accessed on 2008 Sept, 30

3.行政院衛生署醫療資訊網http://consumer.doh.gov.tw/fdaciw/pages/public_content.jsp?typeSn=2&sn=142&year=95&month=5&pageNo=1. Accessed on 2008 Sept, 23.

4. Marshall DA, Douglas PR, Drummond MF, Torrance GW, Macleod S, Manti O, Cheruvu L, Corvari R. Guidelines for conducting pharmaceutical budget impact analyses for submission to public drug plans in Canada. Pharmacoeconomics. 2008; 26(6):477-95.

5. Anis AH, Gagnon Y. Using economic evaluations to make formulary coverage decisions. So much for guidelines. Pharmacoeconomics. 2000; 18(1):55-62.