以次級資料分析台灣癌症中心非小細胞肺癌末期病人之嗎啡類藥物利用

Abstract

研究目的 本研究欲以台灣癌症中心末期非小細胞肺癌病人為對象，探討癌症治療醫院的特性（服務量、區域別、是否提供安寧緩和醫療服務）與病人嗎啡類藥物利用是否相關。 材料與方法 以台灣癌症中心資料庫（TCDB）93年上半年（1~6月）新診斷為非小細胞肺癌且腫瘤分期為stage IIIB或stage IV之病患，並排除診斷日期不確定、死亡日期在94年1月1日以後、或TCDB首次癌症治療記錄不明者，建立末期非小細胞肺癌之研究樣本。再將此樣本與全民健康保險資料庫93年度資料串聯，回溯自病患死亡日期6個月內之健保申報資料（含門診及住院），分析所有嗎啡類藥物品項，以建立研究樣本嗎啡類藥物利用之資料檔。所有嗎啡類藥物劑量，皆轉換為「口服嗎啡當量」進行分析比較。嗎啡類藥物利用的定義，則包含：病患是否使用嗎啡類藥物、平均每人每日口服嗎啡當量、死亡前26週每日口服嗎啡當量隨時間之變化趨勢。 結果 本研究的研究樣本共包含1042位末期非小細胞肺癌病患。在性別方面，男性714位（68.5%）、女性328位（31.5%）。在年齡方面，65歲以上患者占71.1%，而小於65歲的患者僅占28.9%。在腫瘤分期方面，腫瘤分期為stage IV者占77.7%，stage IIIB者占22.3%。超過半數的病患（56.4%）並未接受腫瘤治癒性治療。 多數病患（80.7%）曾經使用過嗎啡類藥物，然而使用過弱效嗎啡類藥物者比例較低，僅占44.2%。平均每人每日口服嗎啡當量為32毫克，利用的劑型則以「強效」、「非針劑」為主。Fentanyl經皮貼片之利用相當高，占全部嗎啡類藥物口服嗎啡當量三分之一，占非針劑嗎啡類藥物二分之一。Meperidine針劑之利用仍高，占全部嗎啡類藥物口服嗎啡當量十分之一，占針劑嗎啡類藥物三分之一，值得注意。運用混合式模型（Mixed Model）針對從醫囑性較高的病患進行分析，則發現：在適當調整病患特性（年齡、性別、腫瘤分期）與癌症初始治療方式之後，醫院是否提供安寧緩和醫療服務，與死亡前26週口服嗎啡當量隨時間變化之趨勢相關（p=0.034）。醫院若能夠提供安寧緩和醫療居家及病房服務，較諸沒有安寧緩和醫療服務者，病患的嗎啡類藥物利用較多。 結論 本研究顯示台灣癌症中心之末期非小細胞肺癌病患，其死亡前26週口服嗎啡當量隨時間變化之趨勢，與醫院是否提供安寧緩和醫療服務相關，而與醫院服務量、醫院區域別無關。其相關的原因，則有待進一步探討。

Objectives The aim of this study was to explore the association between opioid utilization and hospital characteristics (caseload, geographic variation, and palliative care service) among advanced non-small cell lung cancer (NSCLC) patients in Taiwan cancer centers. Materials and Methods We exploited a retrospective cohort, consisting of all newly diagnosed advanced NSCLC (stage IIIB and stage IV) patients from Taiwan Cancer Center Data Base (TCDB) from Jan 2004 to June 2004, and excluding those who died after Jan 1st 2005 or had no definite data of diagnosis date or initial anti-cancer treatment. We then retrieved the details of opioid utilization of the last six months of each patient by linking this cohort with claimed National Health Insurance Data (NHID). The dosage of each kind of opioid analgesics was transformed to “oral morphine equiavalents” (OMEQ). The definitions of “opioid utilization” were: the experience of taking opioid analgesics (yes or no), the average OMEQ per person per day, and the trend of OMEQ utilization in the last 26 weeks before death. Results Of the 1042 advanced NSCLC patients enrolled in this study, 714 (68.5%) were males and 328 (31.5%) were females. Most of them were above 65 years old (71.7%) and with the diagnosis of stage IV cancer (77.7%). More than a half of them (56.4%) did not receive anti-cancer treatment at the time of diagnosis. Most of these patients (80.7%) had experiences in taking opioid analgesics. However, the proportion of taking weak opioid analgesics was only 44.2%. The average OMEQ per person per day was 32mg, and strong or non-parenteral opiod analgesics accounted for most of the dosage. The utilization of transdermal Fentanyl was quite high, accounting for one-third of total dosage and half of non-parenteral dosage. Noteworthily, the utilization of parenteral Meperidine was still high, accounting for one-tenth of total dosage and one-third of parenteral dosage. We then used a mixed model with patient and patient-time interaction fitted as random. After adjusting all the confounders (sex, age, stage, and initial anti-cancer treatment), we found that the trend of OMEQ utilization in the last 26 weeks before death was higher when the hospital offered palliative care service. (p=0.034) Conclusions Among the advanced NSCLC patients in Taiwan cancer centers, the trend of OMEQ utilization in the last 26 weeks before death was correlated with palliative care service, but not correlated to caseload or geographic variation. The causal relationship needs further investigation.