Clinical Trials Consulting & Training Limited, 53 Portway, North Marston, Buckingham, Buckinghamshire, MK18 3PL, UK.
IRDiRC Scientific Secretariat, Inserm US-14, Paris, France.
Orphanet J Rare Dis. 2018 Nov 6;13(1):195. doi: 10.1186/s13023-018-0931-2.
Orphan drug development faces numerous challenges, including low disease prevalence, patient population heterogeneity, and strong presence of paediatric patient populations. Consequently, clinical trials for orphan drugs are often smaller than those of non-orphan drugs, and they require the development of efficient trial designs relevant to small populations to gain the most information from the available data. The International Rare Diseases Research Consortium (IRDiRC) is aimed at promoting international collaboration and advance rare diseases research worldwide, and has as one of its goals to contribute to 1000 new therapies for rare diseases. IRDiRC set up a Small Population Clinical Trials (SPCT) Task Force in order to address the shortcomings of our understanding in carrying out clinical trials in rare diseases.
The IRDiRC SPCT Task Force met in March 2016 to discuss challenges faced in the design of small studies for rare diseases and present their recommendations, structured around six topics: different study methods/designs and their relation to different characteristics of medical conditions, adequate safety data, multi-arm trial designs, decision analytic approaches and rational approaches to adjusting levels of evidence, extrapolation, and patients' engagement in study design.
Recommendations have been issued based on discussions of the Small Population Clinical Trials Task Force that aim to contribute towards successful therapy development and clinical use. While randomised clinical trials are still considered the gold standard, it is recommended to systematically take into consideration alternative trial design options when studying treatments for a rare disease. Combining different sources of safety data is important to give a fuller picture of a therapy's safety profile. Multi-arm trials should be considered an opportunity for rare diseases therapy development, and funders are encouraged to support such trial design via international networks. Patient engagement is critical in trial design and therapy development, a process which sponsors are encouraged to incorporate when conducting trials and clinical studies. Input from multiple regulatory agencies is recommended early and throughout clinical development. Regulators are often supportive of new clinical trial designs, provided they are well thought through and justified, and they also welcome discussions and questions on this topic. Parallel advice for multiregional development programs should also be considered.
孤儿药的开发面临着许多挑战，包括疾病的低流行率、患者人群的异质性以及儿科患者人群的存在。因此，孤儿药的临床试验通常比非孤儿药的临床试验规模小，需要开发针对小人群的高效试验设计，以便从可用数据中获得最多信息。国际罕见病研究联盟（IRDiRC）旨在促进全球罕见病研究的国际合作，并推进全球罕见病研究，其目标之一是为 1000 种新的罕见病疗法做出贡献。IRDiRC 成立了一个小人群临床试验（SPCT）工作组，以解决我们在开展罕见病临床试验方面理解不足的问题。
IRDiRC SPCT 工作组于 2016 年 3 月举行会议，讨论了在设计罕见病小研究中面临的挑战，并提出了建议，这些建议围绕六个主题展开：不同的研究方法/设计及其与医疗状况不同特征的关系、充分的安全性数据、多臂试验设计、决策分析方法和合理调整证据水平的方法、外推以及患者参与研究设计。
根据小人群临床试验工作组的讨论，提出了建议，旨在为成功的治疗开发和临床应用做出贡献。虽然随机临床试验仍被认为是金标准，但建议在研究罕见病治疗方法时系统地考虑替代试验设计方案。结合不同来源的安全性数据对于更全面地了解治疗方法的安全性概况非常重要。多臂试验应被视为罕见病治疗开发的机会，并鼓励资助者通过国际网络支持这种试验设计。患者参与是临床试验设计和治疗开发的关键，鼓励赞助商在进行试验和临床研究时将这一过程纳入其中。建议在临床开发的早期和整个过程中从多个监管机构获得意见。监管机构通常支持新的临床试验设计，只要它们经过深思熟虑并合理，他们也欢迎就这一主题进行讨论和提问。还应考虑为多区域开发计划提供平行建议。
