The State of Infectious Diseases Clinical Trials: A Systematic Review of ClinicalTrials.gov

Background
There is a paucity of clinical trials informing specific questions faced by infectious diseases (ID) specialists. The ClinicalTrials.gov registry offers an opportunity to evaluate the ID clinical trials portfolio.
Methods
We examined 40,970 interventional trials registered with ClinicalTrials.gov from 2007–2010, focusing on study conditions and interventions to identify ID-related trials. Relevance to ID was manually confirmed for each programmatically identified trial, yielding 3570 ID trials and 37,400 non-ID trials for analysis.
Results
The number of ID trials was similar to the number of trials identified as belonging to cardiovascular medicine (n = 3437) or mental health (n = 3695) specialties. Slightly over half of ID trials were treatment-oriented trials (53%, vs. 77% for non-ID trials) followed by prevention (38%, vs. 8% in non-ID trials). ID trials tended to be larger than those of other specialties, with a median enrollment of 125 subjects (interquartile range [IQR], 45–400) vs. 60 (IQR, 30–160) for non-ID trials. Most ID studies are randomized (73%) but nonblinded (56%). Industry was the funding source in 51% of ID trials vs. 10% that were primarily NIH-funded. HIV-AIDS trials constitute the largest subset of ID trials (n = 815 [23%]), followed by influenza vaccine (n = 375 [11%]), and hepatitis C (n = 339 [9%]) trials. Relative to U.S. and global mortality rates, HIV-AIDS and hepatitis C virus trials are over-represented, whereas lower respiratory tract infection trials are under-represented in this large sample of ID clinical trials.
Conclusions
This work is the first to characterize ID clinical trials registered in ClinicalTrials.gov, providing a framework to discuss prioritization, methodology, and policy.

背景
目前针对感染病科（Infectious Diseases, ID）专科医师所面临的具体临床问题开展的临床试验较为匮乏。ClinicalTrials.gov注册数据库为评估感染病相关临床试验的整体布局提供了契机。

方法
我们检索了2007年至2010年间在ClinicalTrials.gov注册的40970项干预性临床试验，以研究疾病类型与干预措施为切入点筛选感染病相关试验。对每一项经算法初步筛选出的试验，均通过人工核验确认其与感染病学科的相关性，最终纳入3570项感染病相关临床试验与37400项非感染病相关临床试验用于后续分析。

结果
感染病相关临床试验的数量与心血管病学（n=3437）、精神卫生学（n=3695）领域的临床试验数量基本相当。略超半数的感染病相关试验为治疗导向型试验（53%，非感染病相关试验该占比为77%），其次为预防导向型试验（38%，非感染病相关试验仅为8%）。感染病相关临床试验的样本量普遍大于其他专科领域的试验，其中位入组受试者人数为125例（四分位距[IQR]：45~400），而非感染病相关试验的中位入组人数为60例（IQR：30~160）。多数感染病相关研究采用随机分组设计（73%），但多为非盲法试验（56%）。51%的感染病相关试验由企业资助，仅10%的试验主要由美国国立卫生研究院（National Institutes of Health, NIH）资助。人类免疫缺陷病毒-艾滋病（HIV-AIDS）相关试验是感染病相关临床试验中规模最大的亚组（n=815，占比23%），其次为流感疫苗（n=375，占比11%）与丙型肝炎（n=339，占比9%）相关试验。相较于美国及全球的死亡率数据，本次大样本感染病临床试验分析中，HIV-AIDS与丙型肝炎病毒相关试验的占比偏高，而下呼吸道感染相关试验的占比则偏低。

结论
本研究首次对ClinicalTrials.gov注册的感染病相关临床试验进行了系统性特征描述，为后续探讨试验优先级制定、研究方法学优化与政策制定提供了分析框架。