Regulatory Express_Q3 2019

5.      FDA Updates Clinical Outcome Assessment Compendium

(FDA Aug 2019)

FDA更新临床结局评估纲要

(FDA 2019年8月）

Summary:

FDA has updated its Clinical Outcome Assessment (COA) Compendium for the first time since the pilot launched in 2016.  This is part of FDA’s efforts to foster patient-focused drug development.

摘要：

自2016年试点启动以来，FDA首次更新了临床结果评估 (COA) 纲要。这是FDA为促进以患者为中心的药物研发所做出的努力。

The COA Compendium is a table that:

·        Describes how certain COAs have been used in clinical trials to measure the patient’s experience (such as disease-related symptoms) and to support labeling claims.

·        Identifies COAs that have been qualified for potential use in multiple drug development programs under CDER’s Drug Development Tool (DDT) Qualification Program.

·        Alphabetically lists conditions or diseases based on each review division’s therapeutic assignment.

o   Shaded rows describe information about a COA DDT qualification project

o   Unshaded rows describe information about COAs from previous labeling

COA纲要以表格形式汇总：

·        描述了在临床试验中如何使用某些COA来评估患者的经历（如疾病相关症状）并支持药品标签上的说明

·        根据CDER的药物开发工具(DDT)资格认证计划，确定在多个药物开发项目中已具备潜在使用资格的COAs。

·        根据每个审查部门的治疗领域分工，按字母顺序列出病症或疾病。

o   阴影行描述有关COA DDT确认项目的信息

o   无阴影行描述以前标签中有关COA的信息

The update is an extension of the original document and includes COAs from three major sources:

·        Labeling of new molecular entity (NME) drugs and biological license application (BLA) drugs approved from 2015 to June 2017

·        Efficacy supplements pertaining to new indication and new population for first and second quarter (January to June) of 2017

·        Qualified measures based on CDER’s COA DDT Qualification Program

本次更新是对先前版本的扩展，包括的COAs来自以下三个主要来源：

·        2015年至2017年6月批准的新分子实体（NME）药物标签和生物许可申请（BLA）

·        2017年第1季度和第2季度（1-6月）针对新适应症和新人群相关的疗效补充

·        基于CDER的 COA DDT资格认证项目的合格措施

Key Takeaways:

·        The COA Compendium is intended to facilitate communication and to provide clarity and transparency to drug developers and researchers by collating and summarizing clinical outcome assessment (COA) information for many different diseases and conditions into a single resource. 

·        CDER suggests using the COA Compendium as a starting point when considering a COA for use in clinical trials.

关键信息：

·        COA纲要旨在通过将许多不同疾病和病症的临床结果评估（COA）信息整理和汇总为单一资源，促进沟通，为药物开发人员和研究人员提供清晰而透明的信息。

·        CDER建议,在考虑将COA用于临床试验时，以COA纲要为起点。

6.      FDA Guidance on Placebos and Blinding in Randomized Controlled Cancer Clinical Trials for Drug and Biological Products

(FDA Aug 2019)

FDA关于药物和生物制品随机对照癌症临床试验中安慰剂和设盲的指南

(FDA 2019年8月）

Summary:

The FDA has released a final guidance entitled Placebos and Blinding in Randomized Controlled Cancer Clinical Trials for Drug and Biological Products.  This guidance finalizes the draft guidance entitled “Hematologic Malignancy and Oncologic Disease: Considerations for Use of Placebos and Blinding in Randomized Controlled Clinical Trials for Drug Product Development” issued August 24, 2018.  Given that using a placebo in randomized controlled clinical trials of therapies to treat hematologic malignancy and oncologic disease for which there is known effective therapy is ethically unacceptable, sponsors should consider using a placebo-controlled design only in selected circumstances (e.g., in trials of adjuvant therapies for which standard of care is surveillance[LH([1] ) or with certain trial design features (e.g., when the trial uses an add-on design).

摘要：

FDA发布了一项名为“药物和生物制品随机对照癌症临床试验的安慰剂和设盲”的指南，定稿了2018年8月24日发布的题为“血液系统恶性肿瘤和肿瘤疾病：药品研发随机对照临床试验中使用安慰剂和设盲的考虑”的指南草案。鉴于在治疗血液恶性肿瘤和已知有效治疗的肿瘤疾病的随机对照临床试验中使用安慰剂在伦理上是不可接受的，申办者应该考虑，仅在特定的情况下使用安慰剂对照设计（例如，辅助疗法临床试验中监测标准护理时）或具有某些试验设计特征（例如，当试验使用附加设计时）。

When considering a placebo control sponsors should provide:

·        The rationale for the trial design.

·        A detailed description in the protocol and in the statistical analysis plan of the proposal for blinding and planned unblinding

在考虑安慰剂对照时，申办者应提供：

·        试验设计的基本原理。

·        在方案和统计分析计划中对设盲和计划揭盲进行详细描述

Continued blinding of patients and investigators at the time of disease progression or occurrence of serious adverse events is usually not acceptable, therefore FDA recommends unblinding only the patient and the investigator in the following instances:

·        At the time of documented disease recurrence or progression by an objective measurement or measurements to ensure optimal patient management, unless there are no available appropriate treatment alternatives.

·        When the patient has an adverse event suspected to be related to the investigational drug product and for which management of the adverse event with one or more drug products with substantial toxicity or invasive procedures is being considered.

在疾病进展或发生严重不良事件时继续对患者和研究者保持盲态通常是不可接受的， 因此FDA建议以下情况下，仅对患者和研究者揭盲：

·        当通过客观测量证实疾病复发或进展时，或为了采取措施来确保最佳的患者管理时，除非没有可用的适当治疗替代方案。

·        当患者发生怀疑与研究药物有关的不良事件，并且考虑用一种或多种具有实质性毒性的药物或采取侵入性操作来处理不良事件时。

Key Takeaways:

·        This guidance provides recommendations to industry about using placebos and blinding in randomized controlled clinical trials in development programs for drug or biological products to treat hematologic malignancies and oncologic diseases. 

·        Sponsors should ensure they have appropriate unblinding procedures in the protocol in circumstances where placebo-controlled trials are conducted in oncology.

关键信息：

·        本指南向制药行业提供关于在药物或生物制品研发项目中使用安慰剂和盲法治疗血液恶性肿瘤和肿瘤疾病的随机对照临床试验的建议。

·        在肿瘤学研究中进行安慰剂对照试验的情况下，申办者应确保在试验方案中有适当的揭盲程序。