全民健康保險制度下採用標靶新藥於非小細胞肺癌病患之處方型態分析

Abstract

研究背景： 創新新藥gefitinib和erlotinib這兩個標靶藥物對於末期非小細胞肺癌病人的臨床療效，在隨機性臨床試驗中已被證實。然而，過去研究指出新藥自上市後到被病人所廣泛地使用，仍因各種層面的阻礙，而可能延遲一段相當長的時間，使得病患無法及時接受到最新的治療。 研究目的： 本觀察性研究的目的在於探討在台灣健康保險制度下，非小細胞肺癌病人接受標靶藥物治療在各層面的影響因素，並進一步分析早中晚三期接受者之間的不同，以及其影響程度。 研究方法： 使用台灣健保資料庫承保抽樣檔和癌症登記檔作為資料來源，篩選出2004年到2009年間1,555位新診斷為非小細胞肺癌且接受藥物治療的病患。根據病患是否接受標靶藥物的治療，將病患分為新藥接受組與未接受組；其中的新藥接受組，進一步依照病患接受標靶藥物的時間點先後，依序分組為早期(小於140天)、中期(140-390天)和晚期接受者(大於390天)，並分別利用邏輯式迴歸以及多分類邏輯式迴歸分析上述不同接受者之間的影響因素。 研究結果： 研究期間接受標靶藥物(新藥接受組)的病患共計562人(36.1%)，而未接受組為993人(63.9%)。而新藥接受組的病患依照得到標靶藥物的時間點，可進一步區分為早期接受者(n=141,25%)、中期接受者(n=277,50%)和晚期接受者(n=144人,25%)。 邏輯式迴歸分析發現病患接受到標靶藥物的治療，顯著受到下列因素影響。年齡越大(OR=0.42; 95%CI: 0.29-0.61)及男性病患(OR=0.75; 95%CI: 0.59-0.96)，接受到標靶藥物治療的機會較低；若病患罹患的是末期癌症(OR=1.44; 95%CI: 1.14-1.81 )和腺肺癌(OR=2.95; 95%CI: 2.10-4.16)，則接受到標靶藥物治療的機會較高。若病患的就診醫院為私立醫院(OR=1.35; 95%CI: 1.03-1.78)且經濟規模愈大(OR=2.67; 95%: 1.79-3.98)時，則病患接受到標靶藥物治療的機會較高。 多分類邏輯式迴歸分析發現，比起中期(OR=0.40; 95%CI: 0.25-0.63)和晚期接受者(OR=0.21; 95%CI: 0.12-0.36)，早期接受者受到放寬新藥給付規範的更動影響最大。除了健保給付規定的影響外，比起中期(OR=0.28; 95%CI: 0.11-0.68)和晚期接受者(OR=0.21; 95%CI: 0.08-0.55)，腺肺癌的病患傾向於在早期得到標靶藥物的治療，此符合現下非小細胞肺癌的國際臨床治療準則。 研究結論： 本研究結果顯示非小細胞肺癌病患是否接受到標靶藥物的治療，與病患/腫瘤、醫師、醫院和政策各層面的影響因素有關。而病患接受到標靶藥物治療的時間點早晚，則會受到病患基本性質、疾病嚴重程度以及健保給付規範更動的影響。

Background: Molecular targeted drugs (MTD), gefitinib and erlotinib, have been proven to provide clinical benefit to end-stage non-small cell lung cancer (NSCLC) patients in randomized clinical trials (RCTs). Although RCTs are generally regarded as the highest level of evidence, studies have shown substantial lag time before results are incorporated into clinical practice. Therefore, access to such medical innovation in time is critical for patients who need it. Objectives: The aim of this population-based observational study is to explore multi-aspect determinants of adoption of MTD among NSCLC patients, analyze the likelihood of different users under Taiwan’s National Health Insurance (NHI) system. Methods: Using Taiwan's Longitudinal Health Insurance Database and Cancer Registry as data source, we identified 1,555 newly diagnosed NSCLC patients who initiated their cancer treatment between 2004 and 2009. Patients were categorized into 'non-MTD' and 'MTD' based on the cancer treatment they received. 'MTD' were further categorized as 'early ', 'mid-term' and 'late' users if they receive their MTD within 140 days, during 140-390 days, and after 390 days after the initial cancer treatment of NSCLC, respectively. Logistic regression and multi-nominal logistic regressions were conducted to explore potential determinants associated with the adoption pattern of MTD. Results: During the study period, 562 (36.1%) NSCLC patients adopt MTD, as 'MTD', and 993 (63.9%) patients were 'non-MTD'. Owing to strict reimbursement criteria, 348 (62%) 'MTD' were involved in the second-line and third-line MTD therapy. Among 562 cancer patients who received MTD, early user takes up 141 (25%), mid user takes up 277 (50%) and late user takes up 144 (25%). Logistic regression shows that patients receiving MTD is significantly associated with older age (OR=0.42; 95%CI: 0.29-0.61), male (OR=0.75; 95%CI: 0.59-0.96), end stage (OR=1.44; 95%CI: 1.14-1.81 ), adenocarcinoma (OR=2.95; 95%CI: 2.10-4.16), private hospital (OR=1.35; 95%CI: 1.03-1.78) and bigger economic scale (OR=2.67; 95%: 1.79-3.98). Compared with early users, multi-nominal logistic regression model shows mid-term users (OR=0.40; 95%CI: 0.25-0.63) and late users (OR=0.21; 95%CI: 0.12-0.36) are less influenced by policy intervention. In addition, patients with adenocarcinoma adopted MTD at early stage compared with mid users (OR=0.28; 95%CI: 0.11-0.68) and late users (OR=0.21; 95%CI: 0.08-0.55). The result is consistent with the current international clinical guideline of NSCLC. Conclusions: Our findings suggest that patient/tumor-, physician-, hospital- and policy-level impact factors significantly deterred the adoption of MTD among NSCLC patients. When it comes to the timing of adopting MTD, we found that it was influenced mostly by policy intervention and patient characteristics.