当前，药物临床试验面临着两大难题：数据真实性及相关人员操作规范性。现阶段国内外在药物临床试验方面的监管主要以事后监查为主，在数据质量管理以及操作规划标准的监查方面存在一定的时延性。而区块链通过非对称加密、哈希算法及智能合约等技术，可以在保证受试者隐私信息的前提下，提高政府相关监督机构的监管效率，提升药物临床试验数据管理的透明度；同时，与物联网的紧密结合可以实现对标准操作规范的进一步核查，与人工智能的结合有望实现受试者的自动招募。
Clinical drug trials are confronted with two major issues: first, data authenticity, for instance, if any data falsification is conducted during the whole trial; second, whether the standard of procedure is accordingly conducted throughout the whole trial or not. Currently, both domestic and overseas clinical drug trials are not supervised without delay (ex-post inspection). Blockchain technology can improve the efficiency of Food and Drug Administration and the transparency of trials while the rights and safety of human research subjects are guaranteed by the integrated technology such as chained structure, asymmetry key algorithm, hash algorithm, and smart contract. Furthermore, with the assistance of internet of things (IoT) and artificial intelligence (AI), the actual supervision over the whole trial and automatic recruitment of human research subjects are expected to achieve.
目的：宏观了解2015—2020年中国眼科药物临床试验情况，为我国眼科药物的研发和临床研究提供最新数据参考，为相关决策提供依据。方法：自国家药品监督管理总局药物临床试验登记与信息公示平台登记数据库提取2015—2020年登记的眼科药物临床试验和相关试验药物信息，汇总分析眼科药物临床试验数量、试验分期、试验范围、适应证、药物类型等。结果：2015年1月1日至2020年12月31日共登记98项眼科临床试验。统计每年眼科药物临床试验登记数量，2020年登记的数量最多(28项，占28.57%)；申办方类型中，国内制药企业(75项，占76.53%)发起的眼科药物临床试验数量远高于外资制药企业(23项，占23.47%)；试验分期中，I期临床试验最多(35项，占35.71%)，III期次之(30项，占30.61%)；药物类型中，生物制品数量最多(55项，占56.12%)，化学药物次之(36项，占36.73%)。结论：近6年来，我国眼科药物临床试验进入蓬勃发展时期，尤其是眼底科领域，近2年发展迅速。在创新药领域，国内制药企业已成为眼科新药研发的中坚力量。但创新药大部分集中在眼底科领域，在青光眼、干眼等领域仍需要继续创新。
Objective: To get a macro understanding of the clinical trials of ophthalmic drugs in China from 2015 to 2020, provide the latest data reference for development of ophthalmic drugs and clinical research in China, and provide the basis for relevant decision-making. Methods: The number of clinical trials and related investigational products from 2015 to 2020 were acquired in the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies. Characteristics on number, stage, scope, indications, type were summarized and depicted. Results: There were 98 ophthalmic clinical trials registered in China from January 1, 2015 and December 31, 2020. The year of 2020 hit the highest record of registered ophthalmic clinical trials for 28, accounting for 28.57%. Among sponsor, 75 (accounting for 76.53%) were initiated by domestic pharmaceutical enterprises, much higher than initiated by foreign pharmaceutical enterprises (23, accounting for 23.47%). Among stage, the quantity of phase I (35, accounting for 35.71%) was the largest, followed by phase III (30, accounting for 30.61%). Among type, the quantity of biological product was the largest (55, accounting for 56.12%), followed by chemical product (36, accounting for 36.73%). Conclusion: The past 6 years have seen vigorous growth of ophthalmic clinical trials, particularly in the last 2 years in the field of fundus. Domestic pharmaceutical enterprises have become the central pillar of ophthalmic drugs renovation. However, their focus is limited to fundus, innovation is still needed in areas such as glaucoma xerophthalmia.
目的：分析眼科超说明书用药使用情况，为眼科临床合理用药提供有效、安全的循证参考依据。方法：考察并收集21家爱尔眼科医院集团眼科中心城市及省会级医院备案的超说明书用药情况，同时抽查处方、医嘱用药，对超说明书用药情况进行充分论证评估，参考广东省、山东省等超说明书用药共识、文献，进行统计、分析和归纳，并征求相关眼科临床专家意见。结果：梳理指南、共识及期刊论文等循证医学证据，得出超说明书用药推荐级别1级8项、2级29项、3级24项，并编写了供集团内使用的《眼科医院眼科超药品说明书用药参考目录(2021年版)》，便于临床参考使用。在眼科常用有32种超说明书药品，61项超说明书用药，其中超给药途径32项(52.5%)、超适应证用药13项(21.3%)、超适应证合并超给药途径14项(23.0%)。超说明书品种及超说明用药项目数均以抗菌药物最多，分别为13个(40.6%)品种，26项(42.6%)。结论：眼科因特殊的给药途径，超说明书用药比较普遍，而如抗菌药物注射剂使用眼内注射或滴眼等超说明书用药方式对某些急性眼内感染性疾病起到了很好的治疗效果。规范眼科超说明书用药，是防范医疗风险的必要措施。
Objective: To investigate off-label ophthalmic medications, and provide an effective and safe evidence-based reference for the rational use of ophthalmic drugs. Methods: On the basis of collecting the off-label drug use recorded in 21 Aier Eye Hospital Group which including ophthalmic central cities and provincial capital level hospitals, and spot checking the prescription and doctor’s order drug use, this article conducted full demonstration and evaluation of off-label drug use which referred to the off-label drug used consensus of Guangdong and Shandong, and other literature on the off-label drug use in ophthalmology. The paper conducted statistics, analysis and induction, and solicited the opinions of relevant ophthalmology clinical experts. Results: Sorting out the evidence of the guides,consensus, journal papers and other evidence-based medicine in ophthalmic medication, recommending 8 items of level 1, 29 items of level 2, and 24 items of level 3, we compiled the “Reference catalogue for the off-label drug use in ophthalmic hospital (2021 edition)” within the group which can providing reference for clinical use. There were 61 off-label drugs commonly used in ophthalmology, involving 32 drugs. Among them, 32 items (52.5%) were used by over administration route, 13 items (21.3%) were used by over indication, and 14 items (23.0%) were used by over indication and administration route. Antibacterial drugs were the most frequently used in the varieties and items of off-label drug use, accounting for 13 (40.6%) and 26 (42.6%) respectively. Conclusion: Ophthalmic off-label medications are common owing to the special route of administration. Such as intraocular injection or eye drop have played a good role in the treatment of some ocular infectious diseases. Standardizing the off-label drug use of ophthalmology is an effective measure to reducing medical risks.
近年来随着人类生活方式的改变、用眼频率的增加，眼科药物的市场需求持续增长，但是目前眼病治疗仍面临“缺医少药”的困境。由于新药研发面临成本高、周期长、成功率低的风险，眼科药物创新迭代的进程日趋缓慢。人工智能(artificial intelligence，AI)作为一种全新的技术手段，有望赋能眼科药物研发的全过程，包括药物靶点发现、化合物筛选、药物动力学模型创新与临床试验开展等，以期为眼科药物研发“降本增效”。且随着大数据体系的完善、硬件计算力的提升以及生命科学与智能科学的深度融合，AI在眼科药物研发中的作用将进一步得到提升，助力眼科药物研发实现从精准化到智能化的跨越。
With the change of human lifestyle and overuse of eyes in recent years, the market demand for ophthalmic drugs continues to grow. However, the ocular therapy is still facing the shortage of doctors and drugs. Due to the risk of high cost, long lead time and low success rate, the process of novel ophthalmic drug innovation and iteration is getting slower. As an emerging technology, artificial intelligence is expected to enable the whole process of ophthalmic drug discovery and development, including drug target discovery, compound screening, pharmacokinetic model innovation and clinical trials, thus reducing R&D costs and increase efficiency for ophthalmic drug discovery and development. In addition, with the improvement of big data, hardware calculation and the deep integration of life science and intelligent science, the role of artificial intelligence in ophthalmic drug discovery and development will be significant improved , contributing to achieve the leap from precision to intelligence.
单纯疱疹病毒基质型角膜炎是引起角膜盲的主要原因之一，目前以局部使用糖皮质激素联合口服抗病毒药物治疗为主。传统治疗存在生物利用度低、药物不良反应等缺点，因此亟需寻找替代药物、开发新剂型。环孢素A和他克莫司等免疫抑制剂疗效明显、不良反应少，可能是糖皮质激素的潜在替代品。α干扰素联合阿昔洛韦可缩短病程，而单独使用效果有限。基质再生剂具有新的抗病毒机制，值得进一步研究。此外，纳米载体递送系统，如脂质体、纳米胶束、立方液晶纳米粒，由于能够增强药物角膜穿透性和延长药物释放，在治疗基质型单纯疱疹性角膜炎方面具有巨大潜力。
Herpes simplex virus stromal keratitis is one of the leading causes of corneal blindness. A topical corticosteroidagent in conjunction with an oral antiviral agent is the preferred treatment, which has the disadvantages of low bioavailability and drug side effects. Therefore, there is an urgent need to find alternative drugs and develop new dosage forms. Immunosuppressants such as cyclosporine A and tacrolimus have obvious curative effects and few side effects, and may be potential substitutes for glucocorticoids. Interferon-α combined with acyclovir can shorten the course of disease, but the effect is not obvious when used alone. Matrix regenerating agents have new antiviral mechanisms and deserve further study. In addition, nanocarriers delivery systems, such as liposomes, nanomicelles and cubosomes, have great potential in the treatment of herpes simplex virus stromal keratitis due to their ability to enhance drug corneal penetration and prolong drug release.
