研究目的

了解我国呼吸药物临床试验开展情况及发展趋势，了解呼吸专业药物临床试验机构与主要研究者（Principle Investigator, PI）备案现状，以期为呼吸临床研究网络体系建设提供参考，从而助力我国呼吸系统药物研发。

研究方法

通过药物临床试验登记与信息公示平台，以“呼吸”“气道”“肺”“胸”等为关键词对“目标适应症”进行检索，根据ICD-11筛选呼吸药物临床试验；时间范围为建库至2022年12月31日。通过药物临床试验机构备案管理信息平台，以“呼吸”“肺”“胸”“鼻”为关键词对“备案药物专业名称”进行检索，从而确定呼吸专业备案机构及PI；时间范围为建库至2023年3月9日。针对数据分析，描述统计采用频数和构成比，组间比较采用卡方（检验或Fisher’s精确检验；时间趋势采用Mann-Kendall检验；双侧检验，以P<0.05认为差异有统计学意义；年均变化率采用几何平均法计算。

研究结果

截至2022年12月31日，我国共开展3056项呼吸系统疾病治疗药物临床试验，其中生物等效性（Bioequivalence, BE）试验占比46.43%。从药物类型看，化学药物试验占比78.04%，生物制品试验占比14.53%，中药/天然药物试验仅占7.43%。2014～2022年，呼吸药物临床试验数量整体呈上升趋势，但新药试验基本保持平稳；此外，境外申办者发起的试验和国际多中心临床试验（Multi-regional Clinical Trial, MRCT）也未见增长。呼吸药物临床试验目标适应症以呼吸系统感染性疾病（39.89%）和呼吸系统肿瘤（27.29%）较多；在新药试验中，仅呼吸系统肿瘤药物试验呈增长趋势。我国呼吸药物试验以交叉设计（49.74%）和平行分组（35.57%）为主要设计类型；随机化试验占比较高（84.36%），而对于盲法原则，双盲试验占比较低（26.28%）。相较境内企业发起的试验和国内试验，境外企业发起的试验和国际MRCT在设置DMC和为受试者购买试验伤害险方面表现更好。在特殊人群方面，包含儿童人群的试验占3.50%，包含老年人群的试验占70.62%。中国呼吸试验共由310家组长单位牵头开展，其中仅14.84%的组长单位承接过国际MRCT，而40.65%的组长单位只承接过BE试验。

截至2023年3月9日，我国呼吸专业备案机构有771家，占全部机构59.13%；呼吸专业PI有3 133人，占全部PI的9.53%。广东、江苏、河南等备案机构数量排名前5位的省份占全国总数的35.80%。87.03%的备案机构为三甲医院，93.74%的PI集中于三甲医院。结合临床试验承接情况，自备案制实施至2022年底，我国呼吸专业备案机构逐渐增多，但组长单位及其牵头承接试验数量却未见增长。

研究结论

伴随一系列监管法规的完善与落实，我国呼吸药物临床试验数量与质量都稳步提升，但仍存在创新药物研发水平不足、国际试验参与较少、适应症较为集中、方案设计与项目管理能力不足、特殊人群重视不够及资源分配不均衡等短板。因此，以临床需求为导向完善呼吸临床研究网络体系，充分动员可用力量，有助于推动我国呼吸药物临床试验突破瓶颈，对中国呼吸系统疾病新药研发具有重要意义。

Objective

To understand the status and trends of Respiratory drug clinical trials in China, and to understand the current situation of the registration clinical trial institutions and principle investigators (PIs) of Respiratory, with a view to providing references for the construction of the Respiratory clinical research network system, so as to help Respiratory system drug research and development of China.

Methods

Through the Drug Clinical Trial Registration and Information Disclosure Platform, search the "Indication" based on the keywords "Respiratory", "Airway", "Lung", "Chest", etc. to screen Respiratory drug clinical trials according to ICD-11; the timeframe was from the establishment of the database to 31 December 2022. Through the Drug Clinical Trial Institutions Registration Management Information Platform, search the "Registration Drug Specialty Name" based on the keywords "Respiratory", "Lung", "Thorax", "Nose", etc. to identify the registration institutions and the PIs of Respiratory specialty; the timeframe was from the establishment of the database to 9 March 2023. For data analysis, frequency counts and component ratios were used for descriptive statistics, and the chi-square (χ²) test or Fisher's exact test was used for between-group comparisons; the Mann-Kendall test was used for temporal trends; two-sided tests were used, and the difference was considered statistically significant at P<0.05; and the mean annual rate of change was calculated using the geometric mean method.

Results

As of 31 December 2022, a total of 3,056 drug clinical trials for the treatment of Respiratory system diseases have been conducted in China, of which bioequivalence (BE) trials accounted for 46.43%. In terms of drug type, chemical drug trials account for 78.04%, biologics trials account for 14.53%, and traditional Chinese medicine/natural drug trials account for only 7.43%. From 2014 to 2022, the number of drug clinical trials of Respiratory is on an overall upward trend, but the new drug trials basically remain stable; in addition, trials initiated by overseas sponsors and international multi-regional clinical trials (MRCTs) have not seen any growth. The target indications of drug clinical trials of Respiratory are mostly respiratory infectious diseases (39.89%) and respiratory tumors (27.29%); among the new drug trials, only the respiratory tumor drug trials show a growing trend. Respiratory drug trials in China have crossover design (49.74%) and parallel grouping (35.57%) as the main design types; randomized trials account for a relatively high proportion (84.36%), while for the principle of blinding, double-blind trials account for a relatively low proportion (26.28%). Compared to trials initiated by domestic sponsors and domestic trials, trials initiated by overseas sponsors and international MRCTs perform better in setting up DMC and purchasing trial injury insurance for subjects. In terms of special populations, 3.50% of the trials include the child population, and 70.62% of the trials include the elderly population. Respiratory trials in China are led by a total of 310 leader units, of which only 14.84% have undertaken an international MRCT, while 40.65% have only undertaken BE trials.

As of 9 March 2023, there are 771 registration institutions of Respiratory specialty in China, accounting for 59.13% of all institutions; there are 3,133 PIs of Respiratory specialty, accounting for 9.53% of all PIs. Guangdong, Jiangsu, Henan and other top 5 provinces in terms of the number of registration institutions accounted for 35.80% of the country’s total. 87.03% of the registration institutions were tertiary hospitals, and 93.74% of the PIs were concentrated in tertiary hospitals. Combined with the clinical trial undertaking, since the implementation of the registration system to the end of 2022, the number of registration institutions of Respiratory specialty in China has gradually increased, however, the number of leader units and their leading undertakings of trials has not seen any growth.

Conclusion

Along with the improvement and implementation of a set of regulatory laws and regulations, the quantity and quality of Respiratory drug clinical trials in China have been steadily improving, but there are still shortcomings such as insufficient R&D of innovative drugs, less participation in international trials, more concentrated indications, insufficient capacity in protocol design and project management, insufficient attention to special populations, and unbalanced distribution of resources. Therefore, improving the respiratory clinical research network system based on clinical needs and fully mobilizing the available resources will help Respiratory drug clinical trials of China break through the bottleneck, which is of great significance to China's R&D of new drugs for respiratory diseases.