1. FDA Releases Final Guidance on Adaptive Design Clinical Trials (Dec 2019)
FDA发布适应性设计临床试验的最终指南
Summary:
The FDA has released a final guidance titled: Adaptive Design Clinical Trials for Drugs and Biologics. This document:
· Provides guidance on the appropriate use of adaptive designs for clinical trials to provide evidence of the effectiveness and safety of a drug or biologic.
· Describes important principles for designing, conducting, and reporting the results from an adaptive clinical trial.
· Advises sponsors on the types of information to submit to facilitate FDA evaluation of clinical trials with adaptive designs, including Bayesian adaptive and complex trials that rely on computer simulations for their design.
摘要：
FDA发布标题为药物和生物制剂的适应性设计临床试验的最终指南。本文件：
· 为临床试验适当使用适应性设计提供指导，以提供药物或生物制剂有效性和安全性的证据。
· 描述了适应性临床试验的设计、实施和报告结果的重要原则。
· 对申办方提交的信息类型给出建议，以帮助FDA评估临床试验的适应性设计，包括依赖计算机模拟进行设计的贝叶斯适应性和复杂试验。
Changes from the October 2018 draft guidance include
1. Reworking the subsection on Bayesian adaptive designs to clarify the Agency's recommendations
2. Clarifying the extent of pre-specification required for the rules governing adaptations.
3. Editorial changes to improve clarity
针对2018年10月的指南草案所作的变更包括：
1. 修改贝叶斯适应性设计章节以澄清FDA的建议
2. 澄清调整规则所需的预先指定的程度
3. 为提高明晰度而进行的编辑修改
Key Takeaways:
· The primary focus of this guidance is on adaptive designs for clinical trials intended to support the effectiveness and safety of drugs.
· The concepts contained in this guidance are also useful for early-phase or exploratory clinical trials as well as trials conducted to satisfy post-marketing commitments or requirements.
关键信息：
· 本指南的主要重点是旨在支持药物有效性和安全性的临床试验的适应性设计
· 本指南中的概念对于早期或探索性临床试验以及满足上市后承诺或要求而开展的试验也是有帮助的
2. EU Remote Decentralized Clinical Trials Project - Trials@Home (Dec 2019)
欧盟远程分散临床试验项目-Trials@Home（2019年12月）
Summary:
Europe’s Innovative Medicines Initiative (IMI) has launched a new project, Trials@Home, to evaluate the use of remote decentralized clinical trials (RDCTs). The Trials@Home project is funded by the IMI, a joint enterprise between the European pharmaceutical industry body EFPIA and the EU’s Horizon 2020 R&D innovation program. It is being run by a consortium of 31 members which includes representatives from regulators, primarily the EMA, payers, health technology appraisal bodies and sponsor. As such there will be ongoing discussion about how trials will meet needs of payers and regulators, which will be reflected in the final guidelines.
摘要：
欧洲创新药倡议（IMI）启动了一个新项目，试验@家庭，评估远程分散临床试验（RDCT）的应用情况。IMI，一家欧洲制药工业机构EFPIA和欧盟Horizon 2020研发创新计划的联合企业，资助了试验@家庭项目。项目由31名成员组成的联盟管理，其中包括来自监管机构的代表，主要是EMA，纳税人，卫生技术评估机构和申办方。因此，关于试验如何满足纳税人和监管机构要求的讨论将持续进行，这将在终版指导方针得以反映。
The project will eventually conduct a pilot comparing an RDCT alongside an RCT and a hybrid model with the aim of establishing a set of guidelines that companies could use to conduct their own research. The project will run for five years. Over that period, they hope to make big strides in using new innovative technologies such as apps and wearable devices to enable trials to be conducted remotely, and “bring them to patients rather than bring patients to the trials.”
该项目最终将RDCT与RCT和混合模型进行尝试性比较，目的是建立一套指导方针，供公司用于开展自己的研究。该项目将运行五年。在这段时间里，他们希望大幅度利用app、可穿戴设备等新型创新技术，以实现远程开展临床试验，“将试验带给患者而不是带患者去试验”。
Phase I: The first phase of the project will explore an inventory of studies that are already conducted using new technologies to better understand how they are used and the possibilities that they lay open. In addition, studies will be evaluated in terms of methodology and the regulations and ethical requirements associated with them.
I期： 该项目的第一阶段将对已经使用新技术进行的试验进行探讨，以更好地理解新技术是如何使用的以及予以公开的可能性。此外，将就方法学以及与之相关的法规和伦理要求对试验进行评估。
Pilot Phase: After Phase I is complete, the project will initiate a pilot comparing a wholly RDCT model with a traditional RCT and a hybrid approach. The pilot will look at the impact of the type of study on the efficiency of trials, the quality of data and how patients and physicians engaged in the studies. The pilot should result in a set of recommendations that companies can use to conduct their own trials.
中试阶段： 第一阶段完成后，该项目将对完全RDCT模型与传统RCT和混合方法进行探索比较。将比较研究试验类型对试验效率，数据质量以及患者和医生如何参与试验的影响。将建立一套公司可以用来开展自己试验的建议。
Key Takeaways:
· The consortium hopes that moving the trials from the traditional clinical setting, RDCTs will be faster and more efficient through the gathering of real-world evidence.
· The project has had a lot of interest and several companies participating in the consortium have put their products forward for the pilot.
关键信息：
· 该联盟希望将试验从传统的临床环境中转移到RDCT，通过收集真实世界的证据而使试验更快，更高效地开展。
· 该项目引起了很多人的兴趣，参与该联盟的几家公司已经申请将他们的产品作为试点。
References:
Remote Decentralized Clinical Trials Could Solve RCT Problems – Pink Sheet
3. Six-Year Review of the EU Signal Management System in Improving Safe Use of Medicines (Dec 2019)
对欧盟信号管理系统在改善药品安全使用六年的回顾（2019年12月）
Summary:
An article was published in Clinical Pharmacology and Therapeutics titled: Improving the Safety of Medicines in the European Union: From Signals to Action. It describes the first six years since the implementation of the 2012 EU pharmacovigilance legislation. The EU network has demonstrated its ability to reliably detect, assess and manage safety signals for medicines, opening a new era for patient protection and transparency in medicines safety. The PRAC has reviewed over 26,000 potential signals, resulting in 453 signals assessed by EMA’s safety committee (PRAC). More than half of the PRAC recommendations resulted in changes to medicine product information supporting the safe and effective use of medicines. The system proved responsive with recommendations for risk minimisation measures made in as few as five days of a signal being confirmed (with a median of five months).
摘要：
一篇发表在Clinical Pharmacology and Therapeutics上的文章，题目为：提高欧盟药品的安全性：从信号到行动。 它描述了自2012年欧盟药物警戒立法实施后六年的情况。欧盟网络已经展示了其在检测、评估和管理药品安全信号方面的可靠能力，为患者保护和药品安全透明度开辟了新的时代。EMA安全委员会（PRAC）审查了超过26,000个潜在信号，其中 453个信号经PRAC评估。超过一半的PRAC建议的结果是对支持安全有效地使用药物的药物产品信息进行变更。事实证明，该系统响应迅速，在确认信号的五天内（中位数为五个月）对风险最小化措施的建议。
The PRAC has made several improvements to the way it works over the years, the article says, including:
1. Setting up of a subgroup, the Signal Management Review Technical Working Group (SMART) review process improvements and foster new detection and management methodologies.
2. The introduction of new statistical methodology for signal detection in Eudravigilance.
3. The EMA’s “continuous effort to enhance the transparency of relevant information on medicines” by publishing the PRAC agendas, highlights, and minutes.
文章说，PRAC多年来的工作方式有了一些改进，包括：
1. 成立了信号管理审查技术工作组（SMART）审查流程改进，并鼓励新的检测和管理方法。
2. 在Eudravigilance中引入新的信号检测统计方法。
3. EMA通过发布PRAC议程、重点和会议纪要来宣传，要“不断努力提高药品相关信息的透明度”。
Several Initiatives are under way to improve the effectiveness and efficiency of signal management, including:
· The use of real-world data
· A focus on challenges such as misuse and abuse of medicines
· Safety in the elderly
· Drug-drug interactions
· The impact on pharmacovigilance systems of non-serious suspected ADRs
目前正在采取若干举措来提高信号管理的有效性和效率，包括：
· 使用真实世界的数据
· 重点关注错用和滥用药物等挑战
· 老年人的用药安全
· 药物间相互作用
· 非严重的可疑ADR对药物警戒系统的影响
Key Takeaways:
· The article describes the signal management process in place in the EU, underpinned by transparency, with specific actions to rapidly communicate reliable information on the safety of medicines to patients and healthcare professionals.
· Recognizing, evaluating, and improving the existing system will ensure a better and more rapid analysis and understanding of safety concerns and highlight areas of missing information, which can be managed through risk management planning.
关键信息：
· 文章描述了欧盟的信号管理过程，以透明度为基础，采取了具体行动，向患者和医疗保健专业人员快速传达有关药物安全性的可靠信息。
· 认识，评估和改进现有系统将确保更好，更快速地分析和理解安全问题，并强调那些可通过风险管理计划进行管理的缺失信息的领域。
References:
EU’s Pharmacovigilance System: A ‘New Era Of Safety & Transparency’ – Pink Sheet
Six-year Review Shows Success of the EU Signal Management System in Improving Safe Use of Medicines - Clinical Pharmacology and Therapeutics.
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