Mishra Sangita, Venkatesh M P
Dept. of Pharmaceutics, Centre of Excellence in Regulatory Sciences, JSS College of Pharmacy, JSS Academy of Higher Education and Research, SS Nagara, Mysore, Karnataka, 570015, India.
Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia.
Orphanet J Rare Dis. 2024 Jul 31;19(1):285. doi: 10.1186/s13023-024-03146-5.
Clinical development for orphan drugs presents significant difficulties and challenges. There is no unique or standard design, conduct, and outcome assessment methodology and it is sometimes impractical to fit design models of rare disease trials in any practiced and well-known framework. In the European Union (EU) these challenges encompass a broad array of subjects, including trial design, study outcomes, patient recruitment, trial conduct ethics, trial cost, and chances of success. This literature-based review study aims to provide a thorough overview of the critical aspects of rare disease trials in the EU by analyzing the current landscape of rare disease trials, highlighting key challenges, delving into regulatory and research initiatives and innovation in trial designs, and proposing multi-faceted solutions to implement effective rare disease clinical trials in the region.
Traditional clinical trial designs, validation, and evaluation methodologies used for nonorphan drugs often prove unsuitable for orphan drugs, given the small patient populations, sometimes fewer than 1000 cases. There is an increasing need for accessible therapies and both regulators as well as industry are trying to develop affordable and effective drugs to address this need. Despite several steps that have been taken, the timely development of drugs remains a challenge. One of the reasons behind the long development timeline is the recruitment, retention, and conduct of rare disease trials. To optimize the development timelines of orphan drugs in the EU, it is important to ensure that the safety and efficacy of the product is not compromised. Industry and regulatory agencies must implement innovative trial designs, devise flexible policies, and incorporate real-world data for assessing clinical outcomes.
Collaboration among academic institutions, pharmaceutical companies (both small and major), patient groups, and health authorities is crucial in overcoming obstacles related to clinical trials and providing assistance and creative ideas. The ultimate objective of granting rare disease patients timely and affordable access to medications with a positive balance between benefits and risks is to be met.
罕见病药物的临床开发面临重大困难和挑战。不存在独特或标准的设计、实施及结果评估方法，而且在任何成熟且广为人知的框架内采用罕见病试验的设计模型有时并不实际。在欧盟（EU），这些挑战涵盖广泛主题，包括试验设计、研究结果、患者招募、试验实施伦理、试验成本及成功几率。这项基于文献的综述研究旨在通过分析罕见病试验的当前状况，突出关键挑战，深入探讨监管和研究举措以及试验设计方面的创新，并提出多方面解决方案以在该地区开展有效的罕见病临床试验，从而全面概述欧盟罕见病试验的关键方面。
鉴于患者群体规模小，有时病例数不足1000例，用于非罕见病药物的传统临床试验设计、验证和评估方法往往不适用于罕见病药物。对可及性治疗的需求日益增加，监管机构和行业都在努力开发负担得起且有效的药物以满足这一需求。尽管已经采取了若干措施，但药物的及时开发仍然是一项挑战。开发时间表长的原因之一是罕见病试验的招募、留存和实施。为优化欧盟罕见病药物的开发时间表，确保产品的安全性和有效性不受影响很重要。行业和监管机构必须采用创新的试验设计，制定灵活的政策，并纳入真实世界数据以评估临床结果。
学术机构、制药公司（包括小型和大型公司）、患者群体及卫生当局之间的合作对于克服与临床试验相关的障碍并提供帮助和创新想法至关重要。要实现让罕见病患者及时且负担得起地获得益处与风险平衡良好的药物这一最终目标。
