Regulatory Express_Oct. 2024

The World Health Organization published a guidance for best practices for clinical trials.

世界卫生组织发布了临床试验最佳实践指南。

This document is intended to guide WHO's Member States and any staff members of non-state actor organizations whose work is related to clinical trials in any way, including the planning, conduct, analysis, oversight, interpretation, and funding of all clinical trials to assess the effects of any health intervention for any purpose in any setting.

本文件旨在指导WHO成员国和任何与临床试验相关的非国家参与者组织工作人员，包括所有临床试验的计划、实施、分析、监督、解释和资助，以评估在任何情况下出于任何目的进行的任何健康干预的效果。

This document aims to complement other guidance in order to support the implementation of universal ethical and scientific standards in the context of clinical trials, with a focus on under-represented populations.

本文件旨在补充其他指南，以支持在临床试验背景下实施普遍的伦理和科学标准，重点关注代表性不足的人群。

The US FDA has released a new draft guidance titled: Integrating Randomized Controlled Trials for Drug and Biological Products Into Routine Clinical Practice.  Traditional randomized controlled drug trials typically capture a large amount of patient information at baseline and over the course of the trial. Health care professionals may also collect this data in routine clinical practice interactions with patients. Researchers may be able to use that data to satisfy trial data requirements, reducing the need for dedicated trial sites and duplicative data entry. This may improve convenience and accessibility for participants and allow for enrollment of more representative populations, resulting in more generalizable trial results.

美国FDA发布了一份新的指南草案，标题为：将药物和生物制品的随机对照试验整合到常规临床实践中。传统的随机对照药物试验通常在基线和整个试验过程中采集大量的患者信息。而医疗保健专业人员可能在与患者的常规临床实践互动中也收集这些数据。研究人员可能能够使用这些数据以满足试验数据要求，减少对专用试验中心和重复数据录入的需求。这可能会提高研究参与者的便利性和可及性，并允许入组更有代表性的人群，从而产生更普遍的试验结果。

As part of FDA's Real-World Evidence (RWE) Program, this draft guidance is intended to support the conduct of randomized controlled drug trials with streamlined protocols and procedures that focus on essential data collection, allowing integration of research into routine clinical practice.

作为FDA真实世界证据（RWE）计划的一部分，本指南草案旨在支持采用精简方案和程序进行随机对照药物试验，重点关注基本数据收集，允许将研究整合到常规临床实践中。

As part of a broader push to modernize clinical research methods, the FDA published a new draft guidance focused on ways that certain drug product clinical trials can be integrated into "routine clinical practice." The initial draft guidance provides some high-level information on these methods, including both decentralized elements of a trial and the use of real-world data (RWD) from clinical practice.

作为更广泛推动临床研究方法现代化的一部分，FDA发布了一份新的指南草案，重点关注某些药品临床试验可以整合到“常规临床实践”中的方式。指南初稿提供了关于这些方法的一些概要信息，包括试验的去中心化元素和临床实践中真实世界数据（ RWD）的使用。

The US FDA has released a final guidance titled: Conducting Clinical Trials With Decentralized Elements.  The agency defines DCTs as occurring at non-traditional clinical trial locations, such as a participant's home or in a local healthcare facility.  The final guidance provides clarity on what roles and responsibilities fall to what stakeholder or partner in the study process and protocol. This includes clarifications about what local health care providers (HCPs) may be best equipped to do, the way these entities can submit their data (and the investigator's responsibility to review their data), and documentation.

美国FDA发布了一份最终指南，标题为：使用去中心化（DCT）元素开展临床试验。该机构将DCT定义为发生在非传统临床试验地点，如研究参与者的家中或当地医疗机构。最终指南明确了研究过程和方案中的哪些利益相关者或合作伙伴的角色和责任。这包括阐明当地医疗保健提供者（ HCP）可能最适合做什么、这些实体提交数据的方式（以及研究者审查其数据的责任）和文件。

The final guidance provides recommendations for using decentralized components in clinical trials. This includes elements like such as use of decentralized health technologies and software, roles and responsibilities for sponsors and investigators, using local healthcare providers as well as remote clinical trial visits, and trial design, conduct, and oversight.

最终指南提供了在临床试验中使用去中心化成分的建议。这包括诸如使用去中心化的医疗技术和软件、申办方和研究者的角色和职责、使用当地医疗保健提供者以及远程临床试验访视、试验设计、实施和监督等要素。

It also outlines informed consent and institutional review board oversight, what investigational products can use a DCT, how to package and ship investigational products, and patient safety processes and procedures.

它还概述了知情同意和机构审查委员会的监督、哪些研究产品可以使用DCT、如何包装和运输研究产品以及患者安全流程和程序。

This guidance is a part of a multifaceted FDA effort to help modernize clinical trial design and conduct to improve efficiency and reduce burden on participants and on those conducting the trial.

本指南是FDA多方面努力的一部分，旨在帮助实现临床试验设计和实施的现代化，以提高效率并减轻参与者和试验实施人员的负担。

By allowing remote participation and reducing the need to travel for face-to-face visits, DCTs may enhance convenience for study participants, facilitate research on diseases affecting populations with limited mobility, and reduce the burden on caregivers.

通过允许远程参与和减少面对面访视随访的需要，DCT可以提高研究参与者的便利性，促进对影响活动受限人群的疾病开展的研究，并减轻护理人员的负担。

The US FDA has released a draft guidance titled: Incorporating Voluntary Patient Preference Information over the Total Product Life Cycle.  The FDA is issuing this draft guidance to propose revisions to the 2016 guidance to reflect the current scope of FDA's benefit-risk paradigm, which may under appropriate circumstances include PPI, and to provide additional considerations and practical recommendations based on additional experience evaluating patient preferences regarding devices.  

美国FDA发布了标题为“在整个产品生命周期中纳入自愿患者偏好信息”的指南草案。FDA发布本指南草案的目的是对2016年指南进行修订，以反映当前FDA获益-风险范式的范围（在适当情况下可能包括PPI），并根据评价患者对器械偏好的其他经验提供额外的考量和实际建议。

FDA is issuing this draft guidance to communicate when and what methods could be used to collect and submit patient preference information (PPI) across the total product life cycle.

FDA发布本指南草案的目的是沟通在整个产品生命周期内何时以及采用何种方法收集和提交患者偏好信息（PPI）。

This will include helping explain when PPI may be helpful, and in what context. Without this re-issuance, sponsors and other patient preference study developers will not be aware of updated methodologies and considerations, which could result in costly studies that may not be appropriate to inform benefit-risk decision making.

这将包括帮助解释PPI何时以及在何种情况下可能有帮助。如果不重新发布，申办方和其他患者偏好研究开发人员将不了解最新的方法和考虑点，这可能导致成本高昂的研究，而这些研究可能不适合为获益-风险决策提供信息。

This update, when finalized, will provide more clarity in when and in what contexts different methods are best applied.

该更新在定稿时将更清楚地说明何时以及在什么情况下最好地应用不同的方法。

The US FDA has released a final guidance titled: Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases.  This guidance finalizes the Draft Guidance for Industry: Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases, Jan-2023.

美国FDA发布了一份标题为：优化治疗肿瘤疾病的人用处方药和生物制品的剂量。本指南于2023年1月定稿了行业指南草案：优化治疗肿瘤疾病的人用处方药和生物制品的剂量。

The guidance aims to move away from the traditional maximum tolerated dose (MTD) paradigm, which was developed for cytotoxic chemotherapies, to a more nuanced approach suitable for modern oncology drugs like kinase inhibitors and antibodies.

该指南旨在从细胞毒性化疗开发的传统最大耐受剂量（MTD）范例转变为更细致入微的方法，适用于现代肿瘤药物，如激酶抑制剂和抗体。

These drugs often have different dose-response relationships and may achieve similar efficacy at doses below the MTD with fewer toxicities.

这些药物通常具有不同的剂量-反应关系，在低于MTD的剂量下可能达到相似的疗效，且毒性较少。

The US FDA has released a draft guidance titled: M14 General Principles on Plan, Design, and Analysis of Pharmacoepidemiological Studies That Utilize Real-World Data for Safety Assessment of Medicines.  

美国FDA发布了标题为“M14利用真实世界数据进行药物安全性评估的药物流行病学研究的计划、设计和分析的一般原则”的指南草案。

This guideline provides harmonized recommendations for post-authorization observational pharmacoepidemiological studies based on existing national guidelines.

本指南根据现有的国家指南，为上市后观察性药物流行病学研究提供了统一的建议。

It outlines general considerations and recommendations for use of RWD for drug, vaccine and other biologic product safety assessments, including defining the research question, data source selection/generation, study design, definitions of target populations, exposure and outcome(s), covariates, data source fit-for-purpose evaluation, sources of and methods to address confounding and bias, analytic approaches, and format and content of reporting.

概述了关于使用RWD进行药物、疫苗和其他生物制品安全性评估的一般考虑因素和建议，包括研究问题的定义、数据来源选择/生成、研究设计、目标人群的定义、暴露和结局、协变量、符合目的的数据来源评价、解决混杂和偏倚的方法、分析方法以及报告的格式和内容。

The US FDA has issued a final guidance titled: Real-World Data: Assessing Electronic Health Records and Medical Claims Data To Support Regulatory Decision-Making for Drug and Biological Products.

美国FDA发布了标题为“真实世界数据：评估电子健康记录（EHR）和医疗索赔数据以支持药品和生物制品的监管决策”的最终指南。

This guidance discusses the following topics related to the potential use of EHR and medical claims data in clinical studies to support regulatory decisions:

1. Selection of data sources that appropriately address the study question and sufficiently characterize study populations, exposure(s), outcome(s) of interest, and key covariates.

2. Development and validation of definitions for study design elements (e.g., exposures, outcomes, covariates).

3. Data traceability and quality during data accrual, data curation, and incorporation into the final study-specific dataset.

本指南讨论了以下与临床研究中EHR和医疗索赔数据的潜在使用相关的主题，以支持监管决策：

1. 选择适当解决研究问题并充分描述研究人群、暴露量、关注结局和关键协变量特征的数据来源。

2. 研究设计要素（例如，暴露量、结局、协变量）定义的制定和验证。

3. 在数据收集、数据整理以及纳入最终研究特定数据集期间的数据可追溯性和质量。

FDA finalized its initial guidance on expectations for drug product sponsors seeking to use real-world data (RWD) from claims, administrative billing, and electronic health record data – together termed "electronic health data" – for regulatory use.

FDA最终确定了药品申办方希望通过索赔、行政账单和电子健康记录数据（统称为“电子健康数据”）使用真实世界数据（RWD）用于监管用途的初始指南。

The guidance provides a robust framework for the use of RWD from EHRs and medical claims data in regulatory decision-making and is a stepping-stone towards the ongoing efforts to leverage RWE to bring innovations to patients more efficiently.

该指南为EHR的RWD和医疗索赔数据用于监管决策提供了一个强大的框架，是利用RWE为患者带来更有效创新的持续努力的基石。

The EMA has adopted the ICH E11A guideline on pediatric extrapolation.  

EMA采纳了ICH E11A儿科外推指南。

The guideline provides recommendations and promotes international harmonization of pediatric extrapolation to support the development and authorization of pediatric medicines. The E11A guideline provides a framework for using extrapolation to support pediatric drug development. The framework describes an iterative process for understanding the existing information available, the gaps in information needed to inform development, and ways to generate additional information when required and recommends approaches to assessing factors that influence the determination of similarity of disease, drug pharmacology and response to treatment between a reference and pediatric target population.

该指导原则提供了建议，并促进了儿科外推、以支持儿科药物的开发和批准的国际协调。E11A指南提供了使用外推法支持儿科药物开发的框架。该框架描述了一个迭代过程，用于理解现有信息、研发所需信息的差距以及在需要时生成额外信息的方法，并推荐了评估影响确定参考人群和儿科目标人群之间疾病相似性、药物药理学和治疗反应的因素的方法。

The purpose of this guideline is to provide recommendations for, and promote international harmonization of, the use of pediatric extrapolation to support the development and authorization of pediatric medicines.

本指导原则的目的是为儿科外推法的使用提供建议，并促进国际协调，以支持儿科药物的开发和批准。

Harmonization of the approaches to pediatric extrapolation should reduce the likelihood of substantial differences between regions.

儿科外推法的协调统一可以降低地区间实质性差异的可能性。

Harmonization should also reduce the exposure of pediatric populations to unnecessary clinical trials and facilitate more timely access to pediatric medicines globally. 

协调统一还应减少不必要的临床试验中儿科人群的暴露，并促进更及时地获得全球儿科药物。

The EMA has adopted the ICH M13A Guideline on bioequivalence (BE) for immediate-release (IR) solid oral dosage forms, as well as the associated Q&A document.  The effective date for this document is 25Jan2025.  The M13A Guideline represents the first ICH guideline ever created explicitly in support of developing and approving generic drugs.  It is intended to reduce the need for multiple different sets of data and information from duplicative BE studies to support marketing authorization in more than one jurisdiction.  ICH hopes this will result in the harmonization of current regional guidelines/guidances, reduce the need for additional in vivo BE studies, and support streamlined global drug development.

EMA采纳了ICH M13A速释（IR）固体口服剂型生物等效性（BE）指导原则以及相关的问答文件。本文件的生效日期为2025年1月25日。M13A指导原则代表了有史以来首次为支持仿制药开发和批准而制定的ICH指导原则。其目的是减少来自重复BE研究的多种不同数据和信息集的需求，以支持多个辖区的上市许可。ICH希望这将导致当前区域指导原则/指南的协调，减少额外体内BE研究的需要，并支持简化的全球药物开发。

This guideline is intended to provide recommendations on conducting bioequivalence (BE) studies during both the development and post-approval phases for orally administered immediate-release (IR) solid dosage forms designed to deliver drugs to the systemic circulation, such as tablets, capsules, and granules/powders for oral suspension.

本指导原则旨在提供设计用于将药物递送至体循环的口服速释（IR）固体剂型在开发和批准后阶段进行生物等效性（BE）研究的建议，如口服混悬剂的片剂、胶囊和颗粒/粉末。

In response to questions posted to ICH M13A comment period, several Questions and Answers have been developed to provide clarity around some of the concepts related to bioequivalence study design and data analysis covered in the Guideline.

针对ICH M13A评论期提出的问题，制定了几个问答，以阐明指导原则中涵盖的与生物等效性研究设计和数据分析相关的一些概念。

This document is intended to provide additional clarification and improve the harmonization of bioequivalence study design and data analysis.

本文件旨在提供额外说明，并改善生物等效性研究设计和数据分析的协调。

ICH has released a reflection paper on pursuing opportunities for harmonization in using real-world data to generate real-world evidence, with a focus on effectiveness of medicines.

ICH发布了一份反思文件，旨在寻求通过使用真实世界数据生成真实世界证据的协调机会，重点关注药物的有效性。

The objectives of this Reflection Paper are:

• To engage ICH on convergence of terminology for RWD and RWE, on the format for protocols and reports of study results submitted to regulatory agencies throughout the lifecycle of medicinal products, and on promoting registration of protocols and reports;

• To inform the assessment of RWD and RWE for regulatory purposes.

本反思文件的目的是：

• ICH就RWD和RWE术语的一致性、药品整个生命周期内提交给监管机构的研究结果的方案和报告格式，以及促进方案和报告的注册等问题的合作；

• 为监管目的，提供RWD和RWE的评估信息。

This Reflection Paper represents the initial step of an incremental approach towards harmonization of regulatory RWE guidance.

本反思文件代表了逐步协调RWE监管指南的初步步骤。

The aim of this paper is expected to be higher quality of RWE that can substantively contribute to the body of evidence supporting the benefit and risk of medicines whilst maintaining evidentiary standards in regulatory decision-making.

本文的目的预期是更高质量的RWE，可实质性地有助于支持药物获益和风险的大量证据，同时在监管决策中维持证据标准。

ICH has released a Final Concept Paper E22 EWG: General Considerations for Patient Preference Studies Dated 27 May 2024.  A new ICH efficacy guideline is proposed about general considerations for patient preference studies (PPS) to inform drug development and related decisions for medical products. The guideline aims to optimize the use of patient preference information as input to pharmaceutical product development using a globally harmonised framework and allow regulatory authorities and the pharmaceutical industry to benefit from harmonised approaches for PPS throughout drug development including, where applicable, submission to different regulatory agencies.

ICH发布了最终概念文件E22 EWG：2024年5月27日的患者偏好研究的一般考虑。  针对患者偏好研究（PPS）的一般考虑，拟定了一个新的ICH疗效指南，以指导药品开发和相关决策。本指导原则旨在使用全球协调框架优化将患者偏好信息作为药品开发的输入信息，并允许监管机构和制药行业在整个药物开发过程中从PPS协调方法中获益，包括向不同监管机构的申报（如适用）。

The new guidance will help identify situations where PPS can have greater impact, recommending suitable approaches depending on the study objectives.

新指南将有助于确定PPS可能产生更大影响的情况，根据研究目的推荐适当的方法。

The activation of this ICH project is likely to create momentum and benefit to the field already during drafting and after publication of the Step 2a/b document (foreseen after 18 months from initiation of EWG activities). 

本ICH项目的启动可能会在起草期间和步骤2a/b文件发表后（预计在EWG活动启动18个月后）为该领域带来势头和益处。