Contents

Part 4: Investigational New Drugs Responsibilities

Part 5: Summary of Key Points

Part 4: Investigational New Drugs Responsibilities   新药研究责任

Responsibilities of Sponsor   发起人的责任

Both sponsors and investigators who are involved in conducting a clinical trial under an IND filed with the FDA must accept and fulfill certain responsibilities.

参与根据向FDA提交的IND进行临床试验的发起人和研究者必须接受并履行某些责任。

Sponsors' responsibilities include:

Ⅰ、Selecting qualified investigators.

Ⅱ、Providing investigators with the information they need to conduct the investigation.

Ⅲ、Ensuring proper monitoring of the trial.

Ⅳ、Ensuring the trial is conducted according to the plan and protocols contained in the IND.

Ⅴ、Informing the FDA and all investigators of significant new adverse effects or risks that are reasonably likely to be caused by the investigational new drug.

Ⅵ、Maintaining proper records.

Ⅶ、Disposing of unused supplies of the investigational new drug.

发起人的责任包括：

1、选择合格的调查人员。

2、向调查人员提供开展调查所需的信息。

3、确保对试验进行适当的监督。

4、确保试验按照IND中包含的计划和方案进行。

5、告知FDA和所有研究人员试验新药合理可能引起的重大新不良反应或风险。

6、保持适当的记录。

7、处置未使用的研究新药供应。

Unless the sponsor is a sponsor-investigator, the sponsor does not actually conduct the investigation.

除非发起人是发起人调查人，否则发起人实际上不进行调查。

Based on GCP guidelines, other Sponsor responsibilities include (ICH GCP E6, 5.12; 5.13; 5.14):

Ⅰ、Ensuring that the Investigational Product is manufactured in accordance with Good Manufacturing Practices.

Ⅱ、Ensuring that Investigational Product is packaged in a way that prevents contamination and unacceptable deterioration during transport and storage.

Ⅲ、Supplying investigators/institutions with the Investigational Product.

Ⅳ、Having written procedures that include instructions on the handling and storage of Investigational product that sites should follow.

Ⅴ、Maintaining sufficient quantities of the Investigational Product used in the trial to reconfirm specifications should the need arise.

根据GCP指南，其他赞助商责任包括（ICH GCP E6，5.12；5.13；5.14）：

1、确保试验产品的生产符合良好的生产规范。

2、确保试验产品的包装方式能够防止运输和储存过程中的污染和不可接受的变质。

3、向调查人员/机构提供试验药物。

4、具有书面程序，包括现场应遵循的试验药物处理和储存说明。

5、保留试验中使用的足够数量的试验药物，以在需要时重新确认规范。

The above represent good examples of responsibilities the Sponsor may transfer to a Contract Research Organization (CRO), such as a clinical coordinating center. However, the ultimate responsibility for Investigational Product resides with the Sponsor. Any Investigational Product-related duties and functions that are transferred to and assumed by a CRO are specified in writing.

例如，一个好的研究中心（CRO）的临床责任可能会转移到上述的研究中心。然而，研究药物的最终责任在于申办方。移交给首席风险官并由首席风险官承担的任何与试验药物相关的职责和职能均以书面形式规定。

Responsibilities of Investigators   调查员的责任

Investigators' responsibilities include:

Ⅰ、Providing the sponsor with a completed, signed Statement of Investigator. (Form FDA 1572. Click here for instructions on completing this form.)

Ⅱ、Conducting the trial in accordance with the signed investigator statement, protocol, and applicable regulations.

Ⅲ、Protecting the rights, safety, and welfare of trial participants.

Ⅳ、Obtaining informed consent from all trial participants.

Ⅴ、Maintaining proper records.

Ⅵ、Furnishing all required progress reports, safety reports, financial disclosure reports, and a final report.

Ⅶ、Complying with Institutional Review Board review. and

Ⅷ、Ensuring the proper handling of controlled substances.

调查人员的职责包括：

1、向申办方提供一份完整、签字的研究人员声明。（FDA 1572表格。点击此处获取填写此表格的说明。）

2、根据签署的研究者声明、方案和适用法规进行试验。

3、保护试验参与者的权利、安全和福利。

4、获得所有试验参与者的知情同意。

5、保持适当的记录。

6、提供所有要求的进度报告、安全报告、财务披露报告和最终报告。

7、遵守机构审查委员会的审查。和

8、确保受控物质的正确处理。

This topic is also discussed in the Roles and Responsibilities module.

角色和职责模块中也讨论了此主题。

Based on GCP guidelines, other Investigator responsibilities include (ICH GCP E6, 4.6):

Ⅰ、Ensuring Investigational Product accountability

Ⅱ、Assigning duties for Investigational Products to a pharmacist or an appropriate individual who has the necessary license for dispensing

Ⅲ、Maintaining records of the Investigational Product from delivery at the site to dispensing to the participant as well as use by the participant, return by the participant, and reconciling all product prior to destruction.

Ⅳ、Ensuring that the Investigational Product is used in accordance with the approved protocol 

Ⅴ、Explaining the correct use of the Investigational Product to each participant and checking at intervals that each participant is following instructions properly.

根据GCP指南，其他研究者职责包括（ICH GCP E6，4.6）：

1、确保试验产品的责任

2、将试验药物的职责分配给药剂师或具有必要配药许可证的适当个人

3、保存试验药物从现场交付到分配给参与者以及参与者使用、参与者返还以及销毁前核对所有药物的记录。

4、确保试验产品的使用符合批准的方案

5、向每位参与者解释试验药物的正确使用，并每隔一段时间检查每位参与者是否正确遵守说明。

Click to view Clinical Trial Network（CTN） related content

Why is the regulation of investigational new drugs relevant to the Clinical Trials Network?   为什么研究新药的监管与临床试验网络相关？

Studies performed within the NIDA Clinical Trials Network (CTN) that involve an investigational drug must be carried out in accordance with the investigational new drug regulations.

在NIDA临床试验网络（CTN）内进行的涉及研究药物的研究必须按照研究新药条例进行。

The investigational new drug regulations are enacted to:

Ⅰ、Protect the safety of research participants,

Ⅱ、Ensure that participants are not exposed to experimental drugs or procedures unnecessarily, and

Ⅲ、Protect participants' rights.

制定新药研究条例的目的是：

1、保护研究参与者的安全，

2、确保参与者不会不必要地接触实验药物或程序，以及

3、保护参与者的权利。

It is important, however, that all members of the CTN — not only those involved with studies of investigational new drugs — understand the basics of these important regulations because the reasoning behind the investigational drug regulations applies to all research involving human participants, including the International Council for Harmonization Good Clinical Practice guidelines.

然而，重要的是CTN的所有成员——不仅仅是那些参与实验性新药研究的成员了解这些重要法规的基础知识，因为研究药物法规背后的理由适用于所有涉及人类参与者的研究，包括国际协调理事会良好临床实践指南。

These principles are equally applicable to behavioral research, or to medication studies not requiring an IND, even though these studies do not involve an investigational new drug. Research participants should not be exposed to any experimental intervention unnecessarily, in an unsafe manner, or in a manner that fails to protect their rights.

这些原则同样适用于行为研究，或不需要IND的药物研究，即使这些研究不涉及研究新药。研究参与者不应以不安全的方式或无法保护其权利的方式不必要地接受任何实验干预。

Although behavioral studies and IND-exempt medication studies conducted in the CTN are not subject to the requirement to submit IND safety reports to the FDA, CTN members who conduct such studies must submit Adverse Event/Serious Adverse Event information and reports to the DSMB Medical Monitor at NIDA. All CTN members should be familiar with the similarities and differences in terminology and reporting requirements between reports required by NIDA and those required by the FDA.

尽管在CTN中进行的行为研究和非抗IND药物研究不受向FDA提交IND安全性报告的要求，但进行此类研究的CTN成员必须向NIDA的DSMB医疗监测机构提交不良事件/严重不良事件信息和报告。所有CTN成员应熟悉NIDA要求的报告与FDA要求的报告在术语和报告要求方面的异同。

Guidance Documents   指导文件

The FDA has incorporated the concept of Good Clinical Practice (GCP) into agency guidance documents, which are intended to help researchers comply with GCP regulations. Guidance on Good Clinical Practice may be found in the following documents:

FDA已将良好临床实践（GCP）的概念纳入机构指导文件，旨在帮助研究人员遵守GCP法规。关于良好临床实践的指导可在以下文件中找到：

Ⅰ、FDA’s Good Clinical Practice: Consolidated Guideline (April 1996)

Ⅱ、Clinical Investigation of Medicinal Products in the Pediatric Population

Ⅲ、Choice of Control Group and Related Issues in Clinical Trials (May 2001)

Ⅳ、Investigational New Drug Applications Prepared and Submitted by Sponsor-Investigators (2015)

1、FDA的良好临床实践：综合指南（1996年4月）

2、儿科人群中药品的临床调查

3、临床试验中对照组的选择及相关问题（2001年5月）

4、赞助研究者准备和提交的研究性新药申请（2015年）

Although these guidance documents are not binding, they reflect the FDA’s current thinking about the interpretation of the regulations. Many guidance documents are available on the FDA’s Website. (Click here for a list of available guidance documents.) Guidance documents are also published in the Federal Register.

尽管这些指导文件没有约束力，但它们反映了FDA目前对法规解释的想法。FDA网站上提供了许多指导文件。（单击此处查看可用指导文件的列表）指导文件也发表在《联邦公报》上。

Guidance documents used internationally include both the:

Ⅰ、International Conference on Harmonization Good Clinical Practice guidelines E6, and

Ⅱ、International Conference on Harmonization Good Clinical Practice guidelines E8.

国际上使用的指导文件包括：

1、国际协调会议良好临床实践指南E6，以及

2、国际协调会议良好临床实践指南E8。

Interactive: Investigational New Drugs   研究新药

Users are instructed as follows:   用户须知如下：

The three investigators below are planning clinical trials that involve substance abuse treatment. Read about each of their trials, and then make a decision: Which Investigator needs to file an Investigational New Drug Application prior to initiating the study? Then, consider the feedback.

下面的三位研究人员正在计划进行涉及药物滥用治疗的临床试验。阅读他们的每项试验，然后做出决定：哪位研究者需要在开始研究之前提交一份研究性新药申请？然后，考虑反馈。

A) Dr. Alvin

Marketed drug with a change in the indication

Dr. Alvin’s trial will see if participants taking a marketed drug, currently used to treat anxiety, will have any use for relapse prevention in adults with cocaine dependence. Dr. Alvin is planning a small pilot study first, using the drug at doses currently used clinically, but with a reduction in dosing frequency. If the results are good, a larger study will be planned.

A）阿尔文博士

有适应症改变的上市药物

阿尔文博士的试验将看看，服用一种目前用于治疗焦虑的上市药物的参与者，是否对有可卡因依赖的成年人预防复发有任何作用。阿尔文博士计划先进行一项小规模的初步研究，按照目前临床使用的剂量使用该药物，但降低了给药频率。如果结果良好，将计划进行一项更大规模的研究。

B) Dr. Bluth

Two marketed drugs in a head to head comparison for the same condition

Dr. Bluth has been approached by a small pharmaceutical company to run a comparison study of two products, both currently marketed to help adults quit smoking. The company has just gained FDA approval of their drug and want to use the data from Dr. Bluths study in advertisements and in a journal article.

B）布卢斯博士

两种上市药物在相同条件下的头对头比较

一家小型制药公司与布卢斯博士接洽，对两种产品进行了对比研究，这两种产品目前都是为帮助成年人戒烟而上市的。该公司刚刚获得FDA对其药物的批准，并希望在广告和杂志文章中使用来自Bluths博士研究的数据。

C) Dr. Carey

Combination drug treatment for tobacco and stimulant dependence

Dr. Carey is planning a trial to determine if smokers who are currently receiving FDA-approved treatment for stimulant dependence can benefit from taking an FDA-approved treatment to help them stop smoking. The goal is to see if stopping a patient from smoking helps with their stimulant dependence. Dr. Carey is drafting a grant for NIH to hopefully support this study.

C） 凯里博士

烟草和兴奋剂依赖的联合药物治疗

凯里博士正计划进行一项试验，以确定目前正在接受FDA批准的兴奋剂依赖治疗的吸烟者是否能从FDA批准的帮助他们戒烟的治疗中获益。目的是观察阻止患者吸烟是否有助于缓解他们对兴奋剂的依赖。Carey博士正在为NIH起草一份补助金，希望能支持这项研究。

Feedback: Which Investigator needs to file an Investigational New Drug Application prior to initiating the stud: (A) Dr. Alvin, (B) Dr. Bluth, or (C) Dr. Carey?

反馈：哪位研究者需要在开始研究前提交研究性新药申请：（A）阿尔文博士，（B）布卢斯博士，或（C）凯里博士？

A) Dr. Alvin

Feedback: Dr. Alvin is exempt from the IND application because the trial involves 1) a product lawfully marketed in the US 2) not intended to be reported to FDA as a well-controlled study in support of a label change 3) not intended to support a change in advertising for the drug 4) the study does not increase the risk associated with the use of the drug. Dr. Alvin will still need approval by the local IRB and ensure patients are consented. Dr. Bluth’s trial requires an IND application because it is conducting a ‘head to head’ comparison study which, although within the approved labels for both drugs, will be used to make a significant change to the advertising for the drug. Therefore, A is an incorrect response.

A） 阿尔文博士

反馈：Alvin博士免于IND申请，因为该试验涉及1）在美国合法销售的产品2）不打算作为支持标签变更的良好对照研究报告给FDA 3）不打算支持药物广告变更4）该研究不会增加与药物使用相关的风险药物。阿尔文医生仍需获得当地IRB的批准，并确保患者同意。Bluth博士的试验需要IND申请，因为它正在进行一项“头对头”对比研究，尽管这两种药物的标签都在批准的范围内，但将用于对该药物的广告进行重大改变。因此，A是不正确的响应。

B) Dr. Bluth

Feedback: Dr. Carey is exempt from the IND application because the trial involves 1) two products lawfully marketed in the US 2) not intended to be reported to FDA as a well-controlled study in support of a label change 3) not intended to support a change in advertising for the drug 4) the study does not increase the risk associated with each use of the drug. Dr. Alvin will still need approval by the local IRB and ensure patients are consented. Dr. Bluth’s trial requires an IND application because it is conducting a ‘head to head’ comparison study which, although within the approved labels for both drugs, will be used to make a significant change to the advertising for the drug. Therefore, C is an incorrect response.

B） 布卢斯博士

反馈：Carey博士免于IND申请，因为该试验涉及1）两种在美国合法销售的产品2）不打算作为支持标签变更的受控研究报告给FDA 3）不打算支持药物广告变更4）该研究不会增加每次使用的相关风险药物的作用。阿尔文医生仍需获得当地IRB的批准，并确保患者同意。Bluth博士的试验需要IND申请，因为它正在进行一项“头对头”对比研究，尽管这两种药物的标签都在批准的范围内，但将用于对该药物的广告进行重大改变。因此，C是一个不正确的响应。

C) Dr. Carey

Feedback: Dr. Bluth must submit an IND application because, although the trial involves testing two legally marketed drugs within the approved label, the goal of the study is to make a significant change to the advertising materials used from the drug, by, hopefully, saying that drug X is better or safer than drug Y in helping patients stop smoking. Therefore, the correct response is B.

C） 凯里博士

反馈：Bluth博士必须提交IND申请，因为尽管该试验涉及在批准标签内测试两种合法上市的药物，但该研究的目标是对该药物使用的广告材料进行重大改变，希望，说X药在帮助病人戒烟方面比Y药更好或更安全。因此，正确的回答是B。

Part 5: Summary of Key Points

Ⅰ、ICH GCP refers to an Investigational Product as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial.

1、ICH GCP是指作为活性成分或安慰剂的药物形式的试验产品，在临床试验中被测试或用作参考。

Ⅱ、In FDA regulations, an investigational new drug is any substance (such as a drug, vaccine, or biological product) for which FDA approval is being sought.

2、在FDA法规中，试验新药是指寻求FDA批准的任何物质（如药物、疫苗或生物制品）

Ⅲ、A drug may be considered “new” even if it has been in use for years if a change is proposed in its use, formulation, route of administration, or packaging.

3、如果建议改变药物的用途、配方、给药途径或包装，即使药物已使用多年，也可能被视为“新的”。

Ⅳ、A sponsor who wishes to conduct a clinical trial that involves an investigational new drug must submit an Investigational New Drug application (IND) to the FDA. Lawfully marketed drugs are exempt from the IND regulations if they meet certain criteria.

4、希望进行涉及研究新药的临床试验的赞助者必须向FDA提交研究新药申请（IND）。如果合法销售的药物符合某些标准，则可免于遵守IND法规。

Ⅴ、Behavioral studies (like the ones conducted in the CTN) are not subject to investigational new drug regulations. Moreover, certain medication studies may be IND-exempt. It is important, nonetheless, that all researchers understand these regulations. The principle that research participants should not be exposed to experimental interventions unnecessarily, in an unsafe manner, or in a manner that fails to protect their rights is equally applicable to all studies involving human participants.

Ⅴ、行为研究（如在CTN中进行的研究）不受新药研究条例的约束。此外，某些药物研究可能是免税的。然而，重要的是，所有研究人员都了解这些规则。研究参与者不应以不必要、不安全的方式或无法保护其权利的方式接触实验干预的原则同样适用于所有涉及人类参与者的研究。