研究背景
現今各國醫療成本不斷攀升，學名藥因省下龐大研發經費，且能提供與原廠藥等效的臨床品質，故成為公私部門節省醫療成本的治療選擇。禮來股份有限公司生產之「百憂解」fluoxetine自108年4月1日起宣布停止供貨。即使原廠藥退出台灣市場，尚有同成分之藥品可供醫師處方。然而在臨床現況上，部分醫療人員和民眾仍對學名藥的療效和安全性是否與原廠藥相等存有疑慮。
有鑑於此，本研究將從台灣和其他國家的學名藥管理切入。一方面了解各國對於學名藥的態度和科學基礎上的相關法規規範，另一方面欲利用實際臨床資料，評估上市後原廠藥與學名藥之療效相等性，以回應各方對於原廠藥與學名藥療效相等性的疑慮，進一步提升對於學名藥的認識與信心。
研究方法
本研究搜集美國、英國、日本、台灣等國家的學名藥相關法規，彙整各國原廠藥與學名藥之定義、學名藥使用現況和預估市場，再探究各國學名藥上市前審查規範，到上市後監控機制。接著回顧學名藥相關法規演進，隨著各國規範越趨嚴謹，對於相繼推出的學名藥法規進行介紹。
接著，本研究搜尋Pubmed、Embaase和華藝線上圖書館，尋找抗精神病藥物的原廠藥和學名藥療效相等性的研究，並分析研究結果和研究指標之特性。然後，本研究運用2002~2015年健保資料庫兩百萬人抽樣檔，進行回溯性世代研究 (retrospective cohort study)。研究對象為2002年1月1日到2015年12月31日間，曾有憂鬱症診斷且開立fluoxetine之患者，並排除有癌症或曾使用任何抗憂鬱劑者後，依藥品廠牌分為使用原廠藥和學名藥者。主要分析指標為「用藥持續性」(medication persistence)，即病患從開始使用fluoxetine到發生治療改變事件 (停藥、換藥、加藥)的治療天數，以及分析兩組發生治療改變事件的風險比 (hazard ratio, HR); 療效指標設為自殺傾向+死亡+精神科住院或急診的風險比; 安全性指標為兩組併用benzodiazepine (BZD)、Z drug (包含zopiclone, zolpidem, zaleplon, eszopiclone)的比率。
研究結果
總共針對世界上八個國家進行學名藥相關法規文獻回顧，從1790年代專利制度逐漸純熟，到預估2025年學名藥市場發展;從上市前生體相等性藥物動力學參數和試驗設計比較，到學名藥上市後主動稽查、被動通報、源頭管理及製造廠規範進行了詳實探討與比較。最後學名藥法規回顧部分，除敘述相關法規演進，亦針對上述八國豁免生體相等性試驗指引進行公告時間之比較，與美國食品藥物管理局 (US The Food and Drug Administration, US FDA)、歐洲藥品管理局 (European Medicines Agency, EMA)、世界衛生組織 (World Health Organization, WHO)規範異同之整理。
本研究共納入fluoxetine新使用者14392人。進行傾向分數配對後，原廠藥組和學名藥組各有4251人。用藥持續性方面，原廠藥使用者有3802 (89.44%)人停藥、2912 (68.50%)人換藥、116 (2.73%)人加藥。學名藥使用者有3873 (91.11%)人停藥、2740 (64.46%)人換藥、99 (2.33%)人加藥。不論原廠藥組或學名藥組，在觀察的一年中全部都發生了治療改變事件。相較於原廠使用者，學名藥發生治療改變事件的風險比，在以指標年份和醫療層級校正情況下，兩組之間無顯著差異HR 0.97 (95%信賴區間0.92-1.02)。療效指標結果經傾向分數配對後，再經指標年份和醫療層級校正後的風險比1.09 (95%信賴區間0.87-1.04)，無統計學上顯著差異。安全性指標方面，兩組之間併用比率沒有顯著差異。
研究結論
本篇回顧的國家中，學名藥市場都穩健成長，主要原因為學名藥使用率上升、人口老化、慢性疾病負擔加重、原廠藥專利過期等，加上大眾對於學名藥逐漸了解與接受，學名藥市場的發展性值得關注。各國上市前規範方面，在嚴謹的法規與科學基礎上，可以確保生產之原廠藥與學名藥療效與安全性相等。各國上市後監控方面，隨著監控機制漸趨完整成熟，期望能有效提升部分醫療人員和民眾對學名藥的信心。各國推出的豁免生體相等性試驗相關指引，目的為增進民眾醫療可近性，在藥物有效與安全的前提下，盡可能縮減不必要的試驗，加速學名藥的核准與上市。
本研究利用用藥持續性作為同時反應療效與安全性之綜合指標，採用自殺傾向+自殺死亡+精神科住院和急診作為療效指標，另以併用鎮靜安眠藥比率作為安全性指標。整體而言，在三項指標中使用原廠藥與學名藥皆無達到統計學上顯著差異。因此，本研究所得結論不論使用原廠藥和學名藥fluoxetine，藥品本身對療效和安全性造成之影響不大，在臨床應用上應不會有顯著之差異。因此，現行的法規與科學證據下，本研究足以支持學名藥可以做為醫師處方同療效與安全的治療選擇。

The Eli Lilly Co. Ltd. announced that it would withdraw “Prozac” fluoxetine from Taiwan market after April 1, 2019. However, in the current clinical situation, some medical members and general public had doubts about whether the effectiveness and safety of the generic drugs were equal to the brand-name drugs. In view of this, this study reviewed the regulation of generic drugs in Taiwan and other countries. Based on evolving regulations and scientific evidence, various national authorities were accountable for the effectiveness and safety between generic and brand drugs are equal. Meanwhile, we conducted a retrospective cohort study to evaluate the therapeutic equivalence of fluoxetine between the brand-name and the generic drugs. There were both 4251 patients in the brand-name and generic drugs group. Compared with the brand-name users, the results of medication persistence (HR 0.97, 95% CI 0.92-1.02), efficacy index (HR 1.09, 95% CI 0.87-1.04) and safety index (combination rates of BZD and Z drugs) were no significant difference between two groups. It was hoped that by promoting communication with the real world evidence, the medical members and general public would have better understanding about the generic drugs, and increase prescribing experience with confidence.

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