隨機對照試驗與真實世界證據的銜接

醫療科技評估（HTA）在新藥給付評估中面臨的重大挑戰之一，正是如何銜接隨機對照試驗（RCT）與真實世界證據（RWE）。2026年5月27日，醫藥品查驗中心（CDE）舉辦的醫療科技評估人才培訓課程首日議程，深入探討了這一問題，同時涵蓋健保暫時性支付機制的實務運作。

RCT 的內部效度與外部效度的落差

國家衛生研究院鄒小蕙博士在會中精闢指出，隨機對照試驗雖然是臨床研究的黃金標準，且具有極高的內部效度，但為了嚴格控制偏誤，通常設有嚴謹的納入與排除條件。這導致試驗結果與真實世界中高齡、具有多重共病症病人的實際情況之間，存在外部效度上的落差。

RWE 如何補足證據缺口

HTA 決策不僅重視藥物在理想條件下是否有療效，也更關注藥物在真實醫療體系中，是否具有長期整體存活期效益與安全性。在這方面，真實世界證據正好能補足隨機對照試驗追蹤期間較短的限制，協助驗證長期整體存活期，並發現短期試驗中較難察覺的罕見或延遲性不良事件。

暫時性支付機制下的實務應對

恩慈治療計畫與人體生物資料庫的應用

現場學員在培訓中提出許多切中要點的問題。例如，大家十分關心，在暫時性支付機制下，若樣本數有限，恩慈治療計畫或人體生物資料庫中的資料，是否可以作為真實世界資料的來源。

對此，專家與 CDE 團隊強調，資料的「完整性」與「代表性」是決定證據價值的關鍵。在樣本數有限的情況下，確實可以考慮納入恩慈治療計畫中符合健保給付條件的病人，作為佐證資料。

「符合研究目的」原則與次族群分析

CDE 醫藥科技評估組也分享了暫時性支付再評估計畫書的撰寫重點，也就是「符合研究目的（fit for purpose）」原則。

有學員提問，若廠商蒐集到的真實世界資料未能完全符合現行健保給付條件，應如何處理？CDE 建議，廠商可以估算符合健保給付條件的病人比例，並針對這群病人進行專屬的次族群分析。

期滿時的資料提交標準

此外，若暫時性支付期限屆滿時，仍無法提供最終資料，廠商不能僅提交進度報告，而應至少提供期中分析結果，作為是否繼續給付的決策依據。

展望：高品質 RWE 研究的重要性

這些討論再次提醒我們，設計具備高資料品質、且符合臺灣醫療情境的真實世界證據研究，已成為新藥爭取及維持健保給付不可或缺的一環。隨著醫療科技評估愈趨重視真實世界數據，業界從業者與決策者都應掌握如何整合隨機對照試驗與真實世界證據的方法，以因應未來的給付評估挑戰。

English version below

Bridging Randomized Controlled Trials and Real-World Evidence

One of the major challenges in health technology assessment (HTA) for new drug reimbursement is bridging the gap between randomized controlled trials (RCT) and real-world evidence (RWE). On May 27, 2026, the Center for Drug Evaluation (CDE) hosted a health technology assessment capacity-building program whose first day addressed this critical issue, along with the practical operation of the National Health Insurance’s temporary payment mechanism.

The Internal Validity and External Validity Gap in RCT

Dr. Tzu-Hui Tsou from the National Health Research Institutes made a keen observation: while randomized controlled trials remain the gold standard in clinical research with high internal validity, they typically impose strict inclusion and exclusion criteria to control for bias rigorously. This creates a gap in external validity between trial results and real-world circumstances involving elderly patients with multiple comorbidities.

How RWE Fills Evidence Gaps

HTA decision-making values not only whether a drug is efficacious under ideal conditions, but also whether it delivers long-term overall survival benefits and safety in real healthcare systems. Real-world evidence effectively supplements the limitation of shorter follow-up periods in randomized controlled trials, helping to verify long-term overall survival and detect rare or delayed adverse events that are difficult to observe in short-term trials.

Practical Responses Under Temporary Payment Mechanisms

Application of Compassionate Use Programs and Biobanks

Participants raised numerous pertinent questions during the training. Many were concerned about whether data from compassionate use programs or biobanks could serve as sources of real-world data when sample sizes are limited under temporary payment mechanisms.

Experts and the CDE team emphasized that data “completeness” and “representativeness” are key determinants of evidence value. When sample sizes are limited, it is indeed reasonable to consider including patients from compassionate use programs who meet national health insurance reimbursement criteria as supporting data.

The “Fit for Purpose” Principle and Subgroup Analysis

The CDE’s Medical Technology Assessment Group also shared key points for preparing temporary payment re-evaluation protocols, particularly the “fit for purpose” principle.

When asked what manufacturers should do if the real-world data they collected does not fully comply with current national health insurance reimbursement criteria, CDE recommended that manufacturers can estimate the proportion of patients meeting reimbursement criteria and conduct dedicated subgroup analysis for this population.

Data Submission Standards at the End of Temporary Payment Period

Furthermore, if manufacturers cannot provide final data when the temporary payment period expires, they cannot submit merely a progress report; they must provide at least interim analysis results to serve as evidence for continued reimbursement decisions.

Outlook: The Importance of High-Quality RWE Research

These discussions serve as a timely reminder that designing real-world evidence studies with high data quality tailored to Taiwan’s healthcare context has become indispensable for new drugs seeking and maintaining national health insurance reimbursement. As health technology assessment increasingly prioritizes real-world data, industry practitioners and decision-makers must grasp how to integrate randomized controlled trials with real-world evidence to meet future reimbursement assessment challenges.