受託研究機構於臨床試驗機構選擇的策略：影響因子的定性研究

Abstract

由於人口老化及治療需求的增加，生物科技藥品行成為各國重要關注的領域，同時全球臨床試驗市值持續處於成長狀態且為利潤豐厚的增長。但是藥物研發及臨床試驗所需時間極長、費用極高、也面臨諸多挑戰，例如，臨床試驗機構的選擇與受試者招募為主要困難之一，有19%試驗受試者招募不足、11%的試驗機構甚至為零招募。許多影響因子會造成試驗延誤，藥物試驗委况方為分散風險與降低成本，越來越頻繁將這些任務外包給受託臨床研究機構 (CRO)。 本研究整理了全球及台灣臨床試驗的數據資料。探討美國FDA及Duke大學帶領的臨床試驗轉型計劃，目的為透過80個會員間的合作，來大範圍的由上游開始產生影響，減少下游障礙的潛力，並改變臨床試驗的生態鏈。介紹文獻於業界的可行性評估流程，如何找到合適的試驗機構參與試驗以達成受試者招募目標。同時，網羅了文獻的45個試驗影響因子，選取其中部份因子加上實務操作考量因子，採用深度訪談法及問卷調查，了解臨床試驗醫師、受託臨床研究機構的試驗專員及醫院端協助受試者招募的護理專業人員，在不同的工作職位上，對不同影響因子的看法，透過訪談及問卷調查，本研究發現文獻以外的影響因子及建議。 數據資料顯示過往十六年的全球臨床試驗案件數量增加2.6倍，台灣成長3.2倍，其中85%為多國多中心、15%為台灣單國試驗，且台灣PI擔任試驗重要角色的比例為13%，台過去八年，藥廠/生技公司為臨床試驗申請者由51%增加至62%，CRO則從42%降至35%，此部份台灣和國際增加委託CRO的趨勢呈反向發展。生物製藥行業贊助的臨床試驗開始轉向新興地區，以降低成本及擴大受試者招募，而臨床試驗的可行性評估流程是利用內外部多種資訊來源，幫助試驗找到合適的區域 (國家)及試驗機構參與試驗，其文獻的評估步驟為找出初步合適PI名單、製作可行性評估問卷、問卷回收評分、電話訪談、最終名單確認。評估目的可擴張至確認試驗未來可能遇到的挑戰，協助試驗控制預算及時程，並產生高品質的試驗資料。可行性評估考量因子極多，除了至少包含文獻的45個因子以外，業界根據各國新增的法規如FDA病人多樣性、歐盟EU-CTR、國際國內政局變動、流行病疫情及其他發現，持續增加影響因子，種種顯示臨床試驗是一項日益繁瑣的複雜流程。 透過六位PI訪談，了解PI參與試驗的動機、對試驗計劃書設計的看法、受試者招募的挑戰及其他補充事項，訪談內容經過編碼分析回應文獻因子及區分新發現的因子。線上問卷是使用李克特量(Likert)五分量表，加上開放式補充問題，針對藥廠、CRO有可行性評估經驗的試驗專員，及醫院端有受試者招募的專業人員進行調查，分析影響因子的重要度，開放式的補充問題回答經過編碼分析回應文獻因子及區分新發現的因子，最後於第五章討論，進行各回答內容的重疊因子差異比較、及其他因子討論。 可行性評估流程存在資訊不對稱的問題，而選取不合適的機構參與試驗則可能導至招募不足或是零招募，所以綜合本研究所分析的因子、業界可行性評估流程及美國臨床試驗轉型計劃，提出可行性評估流程優化建議：一、建立可支援多試驗的開放式資料平台，二、國家選擇納入考量至少高重要度的因子，三、試驗機構及PI選擇至少納入考量高重要度的因子，四、及時招募目標病人，包含招募及記錄保留及時間表，並讓各項資料回流至第一個開放式資料庫支援未來數據導導向評估流程的。影響因子極多，此部份不於摘要裡贅述，但需注意的是，即使在本研究為低重要評分的因子，在不同的試驗條件下，皆有可能成為決定影響因子，例如，國際政局在本論文只有61%的重要度，但是觀看烏克蘭2022年戰前的794試驗案件數，到2024年只剩400件，則知國際政局的穩定度是為試驗國家選擇的決定性影響因子。 最後在未來規劃的部份，針對問卷回答提出的試驗四要素RUBI (Risk 風險, Urgency 緊急性, Benefit 利益, Inconvenience 不方便性)，從不同角度提出優化策略。希望藉此研究歸納得到的結果，提供跨國臨床試驗的優勢策略做參考，並協助台灣試驗能由單國試驗拓展由台灣發起的多國多中心的試驗，讓台灣獲得最大的競爭優勢。

Due to aging populations and increasing treatment demands, biotechnology pharmaceuticals have become a significant focus in each country worldwide. Concurrently, the global clinical trial market continues to grow, offering lucrative opportunities. However, drug development and clinical trials are plagued by lengthy timelines, high costs, and numerous challenges. For instance, one of the major difficulties involves selecting clinical trial sites and recruiting participants, with 19% of trials experiencing recruitment issues and 11% even failing to recruit any sites. Many factors contribute to trial delays, prompting pharmaceutical companies to increasingly outsource these tasks to Contract Research Organizations (CROs) to mitigate risks and reduce costs. This study compiled global and Taiwan-specific clinical trial data. It explores the Clinical Trials Transformation Initiative led by the FDA and Duke University, aimed at transforming the clinical trial ecosystem through collaboration among 80 members to address upstream influences and reduce downstream barriers. The literature reviews feasibility assessment processes in the industry, focusing on how suitable trial sites are identified to meet participant recruitment goals. Additionally, it encompasses 45 trial influencing factors identified in literature, with a subset selected for practical operational considerations. Using in-depth interviews and surveys, the study investigates perspectives on these factors across clinical trial physicians, CRO trial specialists, and hospital nursing professionals involved in participant recruitment. Findings reveal factors beyond those covered in literature and propose recommendations. Data indicates a 2.6-fold increase in global clinical trial cases over the past sixteen years, with Taiwan showing a 3.2-fold increase. Of these, 85% are multinational and 15% are single-country trials in Taiwan. Taiwanese Principal Investigators (PIs) play a significant role in 13% of trials. Over the past eight years, pharmaceutical/biotech companies' role as trial sponsors increased from 51% to 62%, while CRO involvement decreased from 42% to 35%, suggesting a reversal trend in outsourcing to CROs in Taiwan and internationally. Clinical trials sponsored by biopharmaceutical industries are shifting towards emerging regions to reduce costs and expand participant recruitment. Feasibility involve utilizing multiple internal and external information sources to select appropriate countries and trial sites, involving steps such as preliminary PI identification, feasibility questionnaire development, scoring, telephone interviews, and final list confirmation. These evaluations also extend to anticipating future trial challenges, assisting with budget and timeline management, and generating high-quality trial data. The feasibility assessment considers numerous factors, expanding beyond the initial 45 from literature to incorporate new factors such as FDA patient diversity regulations, EU-CTR, international/domestic political changes, epidemics, and other discoveries, reflecting the increasing complexity of clinical trial processes. Six PI interviews provide insights into motivations for trial participation, perspectives on trial protocol design, recruitment challenges, and supplementary considerations, analyzed through coding to distinguish between literature-based and newly discovered factors. Online surveys using Likert scales and open-ended questions targeted trial specialists with feasibility assessment experience from pharmaceutical companies/CROs and hospital professionals involved in participant recruitment. Analysis prioritizes factors' importance and contrasts responses between overlapping content and additional factors in Chapter Five.

The feasibility assessment process faces challenges of information asymmetry, potentially leading to inadequate site selection and recruitment. Integrated findings from factor analysis, industry feasibility processes, and the US Clinical Trials Transformation Initiative propose several improvement strategies: establishing open data platforms supporting multiple trials, prioritizing critical factors in country and site selection, ensuring timely patient recruitment, and optimizing data flow back to the initial open database to support future data-driven evaluation processes. Although numerous influencing factors are discussed in detail within the study, even factors with lower initial importance ratings may become decisive under different conditions. For example, international political stability initially rated at 61% importance saw reduced trial activity from 794 cases pre-Ukraine 2022 conflict to 400 in 2024, highlighting its critical role. Finally, the study outlines future planning based on responses from the survey's Trial RUBI (Risk, Urgency, Benefit, Inconvenience) of trial of four elements, providing optimal strategies from various perspectives. The study aims to synthesize these results into strategic advantages for multinational clinical trials and assist Taiwan in expanding from single-country to multi-national trials initiated from Taiwan, maximizing its competitive edge.