大腸激躁症實證果效暨台灣大腸激躁症之醫療利用及生活品質初探

Evidence-based Efficacy and the Preliminary Study of Medical Utilization and Quality of Life on Taiwanese Irritable Bowel Syndrome Patients

徐啟千(Chi-Chien Hsu)

指導教授 ： 溫燕霞

高雄醫學大學/藥學院/臨床藥學研究所/碩士(2011年)

https://doi.org/10.6832/KMU.2011.00096

摘要

研究目標：大腸激躁症為一種慢性，且不斷復發而引起病人腹部不適或疼痛的症狀。本研究以系統性文獻回顧暨整合分析，整合探討目前藥物治療對於大腸激躁症之臨床治療效益及經濟學效用的評估指標和方法。透過健保申報資料庫的分析，探討台灣大腸激躁症病人疾病狀態、醫療利用型態及藥物使用評估。最後，藉由對大腸激躁症病人進行訪談，以進一步深入了解大腸激躁症病人生活上的困擾。
研究方法：研究方法分成四部分：第一部分為系統性回顧，檢索實證醫學相關資料庫，搜尋大腸激躁症藥物治療相關臨床試驗及經濟學評估文獻，評估文獻的研究品質，並整合文獻中藥物治療臨床果效及經濟學評估的結果。第二部分以橫斷性研究設計，採用2004年至2008年「全民健康保險學術資料庫之2005年百萬人承保抽樣歸人檔」之資料分析。研究對象為在研究期間（2004年至2008年）具大腸激躁症門診診斷紀錄，且曾接受過大腸激躁症藥物治療的成年病人，以描述性統計及簡單線性迴歸分析台灣大腸激躁症病人的醫療利用及花費。第三部分為質性研究，自2010年7月至2010年12月，訪談南臺灣某地區醫院的大腸激躁症病人，以探討大腸激躁症對受訪者生活品質的影響，並採用歐洲生活品質量表與標準賭博法測量受訪者的生活品質。
結果：依搜尋策略及文獻篩選原則，最後納入臨床治療果效整合性分析之文獻共有11篇，病人總數為8,512人，總計所有藥物治療均顯著地改善大腸激躁症的症狀（RR: 1.45; 95%CI: 1.28, 1.69; p< 0.0001）及腹部疼痛（RR: 1.35; 95%CI: 1.35, 1.51; p< 0.0001）。
依搜尋策略搜集文獻篩選原則，最後收納5篇經濟學評估研究文獻進入系統性文獻回顧。分別為：成本效果分析、預算衝擊分析及成本結果分析各一項，其餘2項研究為成本效用分析。經濟學資料來源是以隨機控制臨床試驗為主，受試者以女性為主（80%至100%間）。僅一項研究，同時考量包含直接醫療成本、直接非醫療成本及間接成本。所有5項研究皆有進行遞增分析以及報告敏感性分析方式及數據。
研究期間共計有40,890位大腸激躁症病人，1,451位持續接受藥物治療者。大腸激躁症病人主要為女性，年齡主要介於18至44歲；持續接受藥物治療者則以男性為主，以大於65歲者居多。兩族群的就醫人次及總就醫申報點值皆逐月漸增。開立處方藥品分類以解痙劑及促進腸胃蠕動劑居多，且總藥品的耗用量也逐月增加。
研究期間內共訪談29位受訪者，女性（18位）佔多數，年齡為45.8±16.5歲（在18至80歲之間）。以日本的方式加權換算EQ-5D效用之平均值（0.79±0.15）較標準賭博法測得之平均效用值 （0.85±0.16）為低。質性研究結果發現，長期不斷且反覆發生的大腸激躁症症狀使工作或學習上的效率降低、參與社交行為的意願低落、並造成憂慮及緊張、更進一步引發症狀的發生或惡化，成為一種惡性循環。由於顧忌藥物的副作用或是毒性，使病人未依據指引持續服藥，僅會在無法自行緩解或難以忍耐時，才會求助進一步的治療或使用藥品。
結論：大腸激躁症藥物治療研究，目前仍主要以新開發的用藥（第三型血清張力素拮抗劑、第四型血清張力素致效劑）與安慰劑相比的臨床試驗為主，有正向報告之偏誤、且仍缺乏比較性效益研究、以及對於病人生活品質的改善、長期治療的追蹤的研究。僅有少數符合定義且品質良好的大腸激躁症藥物治療相關的經濟學評估研究，且所使用的研究設計及定義皆莫衷一是。台灣大腸激躁症病人僅有少數接受持續藥物治療，然而醫療利用、花費及藥品已逐月漸增，且流行病學型態也不同於歐美國家。對於中重度且持續接受藥物治療的大腸激躁症病人，尚能容忍症狀對生理功能的影響，但對疾病得焦慮或擔憂和社會壓力卻可能對病人生活品質有較大影響。建議未來在進行台灣大腸激躁症治療藥物的經濟評估分析前，應先建立適當的治療果效及生活品質評估指標，並採用台灣大腸激躁症病人流行病學、疾病型態及醫療利用數據進行分析。

關鍵字

大腸激躁症 ； 系統性回顧及整合分析 ； 醫療利用 ； 生活品質 ； 標準賭博法

並列摘要

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic, relapsing, functional gastrointestinal disorder and causing long-term disturbances to patients. However, the impacts of IBS on patients' quality of life (QoL) and social and economic costs are generally nelegected in health care systm. This study aimed to assess the current best evidence on the efficacy of drug treatments for IBS, evaluate medical utilization of Taiwanese irritable bowel syndrome patients, and to explore the impacts of IBS on patients and underlying attributes to QoL.
METHODS: This study can be divided into three parts. The first part is a systematic review on clincail efficacy and economic evaluations. An electronic database search on PubMed, EMBASE and the Cochrane Controlled Trials Register (up to Jan 2010) were conducted to include double blind, randomized clinical trials (RCT) and economic evaluation studies of drug treatment on IBS. Quality of included studies were evaluations and data were extracted for futher meta-anlaysis. The second part is a cross-sectional study conducted from 2004 to 2008 using a nationwide sampled, longitudinal claim-based database (LHID2005) constituting of a million beneficiaries randomly sampled in 2005. Adult IBS outpatients who have recived drug treatments were identified by diagnosis codes and ATC codes. The medical and drug utilization were analyzed by descriptive statistic, and monthly trends were analyzed by simple linear regression. The third part is a qualitative study; semi-structure interviews were conducted at a reginal hospital in southern Taiwan from July 2010 to December 2010. A topic guide was used to ensure a systematic coverage of attributes related to QoL during the interview. Meanwhile, health-related quality of life was measured by standard gamble (SG), EuroQol (EQ-5D) questionnaire and visual analogue scale (EQ-5D VAS) during the interview.
RESULTS: There are 11 included placebo-control RCTs (8,512 patients). Overall, a significantly higher proportion of patients with drugs treatment achieved relief in disease-related symptoms (RR: 1.45; 95%CI: 1.28, 1.69; p<0.0001) and abdominal pain or discomfort (RR: 1.35; 95%CI: 1.35, 1.51; p<0.0001) comparing against placebo.
There are 5 economic evaluation studies identified, including cost-effectiveness analysis (n=1) , budget impact analysis (n=1) and cost-consequences analysis (n=1) and cost-utility analysis (n=2). Data source for economic evlautions mainly came from randomized, controlled clinical trials (n=3), and most research subjects were female (80% to 100%). Only one study has included a detail cost category other than direct medical costs, i.e. direct medical costs, direct non-medical costs and indirect costs. All of the five studies have conducted and reported sensitivity analysis and incremental analysis.
Of all, 40,890 IBS outpatients (mean age 49.8±17.6 years; 55.0% female) and 1,451 IBS outpatients receiving long-term drug treatment were identified from LHID2005. The overall number of visits and total outpatient medical expenditure significantly increased (p<0.05) during study period. Antispasmodics and propulsive agents were the most frequently prescribed. Defined daily doses of all classes of drugs for IBS symptom control also significantly increased (p<0.05).
Twenty-nine adult IBS outpatients (mean age 45.8±16.5 years; 62.1% female) were successfully interviewed during study period. The utility measured in standard gamble (0.85±0.16) was higher than EQ-5D index (0.79±0.15). The long-term and recurrent abdominal pain or discomfort affected participants’ efficiency of work or study and reduced their willingness to participate in social activities. In addition, these symptoms also raised their further worries and stress. However, due to the worries about the adverse drug reactions, the participants only took medicine when their symptoms were not controled.
CONCLUSIONS: Currently clinical studies for IBS treatments mainly focus on newly developed agents (5-HT3 antagonists and 5-HT4 agonists). However, head-to-head studies and the evidence of treatment effects on long-term functions or quality of life are still lacking and subject to further research. Only a few well-defined and good quality economic evaluations were found associated with IBS drug treatment. However, there was still no consistence on the study designs and definitions. In Taiwan, only a few of patients with IBS receiving long-term drug treatment, but medical and drug utilization of IBS patients have been increasing. The IBS epidemiological characteristics in Taiwan are different from European countries and United States. For patients with potentially moderate to severe IBS and consistent medical treatments, the functional impairment was still tolerable yet intangible (anxiety, worries) and social stress may had greater impacts on QoL. To conduct economic evaluation studies on Taiwanese IBS patients in the future, appropriate and feasible measures to assess the effective and QoL, is and using real life individual patient data are necessary.

並列關鍵字

Irritable bowel syndrome ； systematic review and meta-analysis ； medical utilization ； quality of life ； standard gamble

參考文獻

1. Lu, C. L., Chen, C. Y., Lang, H. C., et al. Current patterns of irritable bowel syndrome in Taiwan: the Rome II questionnaire on a Chinese population. Alimentary Pharmacology & Therapeutics 2003;18(11-12):1159-69.

2. Spiller, R., Aziz, Q., Creed, F., et al. Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut 2007;56(12):1770-98.

3. Dalrymple, J. and Bullock, I. Diagnosis and management of irritable bowel syndrome in adults in primary care: summary of NICE guidance. British Medical Journal 2008;336(7643):556-8.

4. Manning, A. P., Thompson, W. G., Heaton, K. W., et al. Towards positive diagnosis of the irritable bowel. British Medical Journal 1978;2(6138):653-4.

5. Longstreth, G. F., Thompson, W. G., Chey, W. D., et al. Functional bowel disorders. Gastroenterology 2006;130(5):1480-91.