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Study of the Current Situation of Clinical Trials of Rare Diseases in China over One Decade: Based on the Chinese First List of Rare Diseases
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摘要: 目的 基于我国《第一批罕见病目录》，分析近10年我国罕见病药物临床试验现状及特点，探讨我国罕见病药物研发面临的问题与挑战。 方法 登录我国国家食品药品监督管理总局药物临床试验登记与信息公示平台（ http://www.chinadrugtrials.org.cn），收集自2012年11月1日（开放注册）至2021年11月28日我国《第一批罕见病目录》涵盖的121种罕见病药物临床试验信息，从研究数量、主要研究者地域分布、研究领域、研究设计和受试者规模等多个角度分析罕见病药物临床试验现状和特点。 结果 共235项罕见病药物临床试验纳入分析，其中Ⅰ期41项，Ⅱ期22项，Ⅲ期74项，Ⅳ期15项，生物等效性试验77项，其他6项。10年间，我国罕见病药物临床试验数目整体呈逐年增长趋势，年平均增长率约为54%。早期（Ⅰ/Ⅱ期）临床试验共涉及16种罕见病，主要集中于血友病、特发性肺纤维化、多发性硬化症和视神经脊髓炎谱系疾病；研究者主要集中于北京、天津、上海等城市；Ⅰ期临床试验以单中心（61%，25/41）平行对照（46%，19/41）研究为主，Ⅱ期临床试验以多中心（96%，21/22）平行对照（65%，13/22）研究为主，Ⅲ期临床试验以多中心（99%，73/74）单臂试验（64%，47/74）研究为主；临床试验受试者规模随研究分期增加而增大，Ⅰ期主要集中于11～50例（85%，34/41），59%（13/22）的Ⅱ期临床试验大于50例，52%（39/74）的Ⅲ期临床试验为51～500例。 结论 我国罕见病药物研发尚处于起步阶段，涉及《第一批罕见病目录》中罕见病病种较少，但呈迅速增长趋势。目前我国罕见病药物研发仍以传统临床试验设计为主，未来需根据疾病及药物作用机制，探索更多新的临床研究策略，助力罕见病药物研发蓬勃发展。
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关键词:
- 罕见病 /
- 临床试验 /
- 药物临床试验登记与信息公示平台 /
- 中国
Abstract: Objective: To explore the current situation and characteristics of clinical trials of 121 rare diseases in Chinese First List of Rare Diseases over the past 10 years and to provide reference for promoting the research and development of orphan drugs in China. Methods: A total of 121 rare diseases covered in Chinese First List of Rare Diseases and Guidelines for Diagnosis and Treatment of Rare Diseases published in 2019 were retrieved as keywords on the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies (chinadrugtrials.org.cn) from November 1st, 2012 (Platform registration open time) to November 28th, 2021. The current status and characteristics of rare disease clinical trials were analyzed from the perspectives of the number of registrations, geographical distribution, research fields, research design, and sample size. Results : A total of 235 clinical trials The Drug Clinical Trial Registration and Information Publication Platform has registered from November 1st, 2012 to November 28th, 2021, including 41 items of phase I, 22 tiems of phase II, 74 items of phase III, 15 items of phase IV, 77 items of bioequivalence clinical trials, and the other 6 clinical trials. During the ten years, the number of rare diseases clinical trials in China showed an increasing trend year by year, with an annual average growth rate of about 54%. A total of 16 kinds of rare diseases were involved in the Chinese First List of Rare Diseases in early phase (phase I and phase II) clinical trials, mainly focusing on hemophilia, idiopathic pulmonary fibrosis, multiple sclerosis, and neuromyelitis optica. The main researchers of rare disease clinical trials were mainly in Beijing, Tianjin, Shanghai, and so on; In phase I clinical trials of rare diseases listed in Chinese First List of Rare Diseases in China, there were mainly Single-center parallel control studies (46%, 19/41), Phase II clinical trials were mainly multi-center paralleled studies (65%, 13/22), and phase III clinical trials were mainly multi-center (99%, 73/74) single-arm trials (64%, 47/74); The sample size in clinical trials increases with study stage. The sample size of phase I clinical trials was mainly restricted in 11 ~ 50 cases (85%, 34/41).59% (13/22) of phase II clinical trials were more than 50 cases, and 52% (13/22) of phase III clinical trials were in the range of 51~500. Conclusions: The research and development of orphan drugs in China is still at an early stage. There are few rare diseases involved in the Chinese First List of Rare Diseases in China, but it has shown a rapid growth trend in recent years. At present, the development of rare disease drugs is still based on traditional clinical trial design. It is necessary to explore more new clinical research strategies according to the disease and drug mechanism of action to promote the development of rare disease drugs. -
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