Committee For the Protection of Human Subjects

个体患者扩大访问权限Investigational Drugs and Biological Products

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政策

扩展的访问对于患有严重或立即威胁生命的疾病或疾病的患者，可以使用研究药物或生物学产品（即未经FDA批准或清除的产物），这是一种潜在的途径。可用；潜在的患者受益于患者的潜在风险；所要求的使用不会干扰可以支持营销批准的临床调查（21 CFR 312.305（a））。

必须在扩大使用研究药物或生物学产品之前获得IRB（由全额董事会或IRB主席同意）以及FDA的批准或授权，并获得FDA的批准或批准非紧急使用）。

关键术语

扩展的访问对于患有严重或立即威胁生命的疾病或疾病的患者，可以使用研究药物或生物学产品（即未经FDA批准或清除的产物），这是一种潜在的途径。可用；潜在的患者受益于患者的潜在风险；所要求的使用不会干扰可以支持营销批准的临床调查（21 CFR 312.305（a））。The primary purpose of individual patient expanded access is to diagnose, monitor, or treat a patient’s disease or condition, and expanded access use is outside of clinical trials and is not intended to obtain information about the safety or effectiveness of the drug, biological product, or medical device. Expanded access is sometimes informally called “compassionate use”; however, this term is not defined or described in the FDA regulations.

Immediately life threatening疾病或状况for the purposes of 21 CFR 312 Subpart I (the regulation on expanded access to investigational drugs for treatment use) means a stage of disease in which there is reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment (21 CFR 312.300).

Serious disease or conditionfor the purposes of 21 CFR 312 Subpart I means a disease or condition associated with morbidity that has substantial impact on day-to-day functioning. Short-lived and self-limiting morbidity will usually not be sufficient, but the morbidity need not be irreversible, provided it is persistent or recurrent (21 CFR 312.300). Whether a disease or condition is serious is a matter of clinical judgment, based on its impact on such factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one (21 CFR 312.300).

扩大紧急使用的访问is a subset of expanded access where there is an emergency that requires the patient to be treated with an investigational drug before a written submission can be made to FDA (21 CFR 312.310(d)).

Emergency usefor the purposes of 21 CFR 56.104(c) (the regulation on exemption from prior IRB approval for emergency use) means the use of an investigational drug or biological product in a human subject in a life-threatening situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval (21 CFR 56.102(d)). Life-threatening for the purposes of 21 CFR 56.104(c) includes the scope of both life-threatening and severely debilitating. Note that this policy requires that the physician receive IRB approval (by full board or by concurrence of an IRB chairperson) before starting emergency use expanded access treatment.

Life-threatening出于21 CFR 56.104（c）和21 CFR 56.102（d）的目的是指死亡可能性很高的疾病或状况，除非疾病的病程被中断，并且具有潜在致命结果的疾病或状况。这种情况无需立即威胁生命或立即导致死亡。相反，受试者必须处于威胁生命的情况下，需要在IRB能够在召集会议上审查使用之前进行干预。

Severely debilitatingfor the purposes of 21 CFR 56.104(c) and 21 CFR 56.102(d) means diseases or conditions that cause major irreversible morbidity. Examples of severely debilitating conditions include blindness; loss of arm, leg, hand or foot; loss of hearing; paralysis; or stroke.

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程序

如果出现了在单个患者中需要在单个患者中使用研究药物的情况，则优先使用患者作为临床试验的研究性医疗产品的使用，并且治疗医师应确定是否有活性方案并且是否可用，并且如果患者符合资格标准。但是，如果无法进行临床试验的患者入学（例如，患者不符合任何正在进行的临床试验，或没有进行临床试验）时，患者可能能够通过扩展而接受研究产品。使用权。治疗医师应与研究药物或生物产品的制造商联系，以确定是否可以通过扩展的访问提供产品。

扩展的访问类别是个人患者（也称为单身患者）扩大了急诊或非紧急情况使用，中级患者人群扩展的访问权限以及治疗扩展的访问途径，以供广泛使用。中等大小的患者人数扩大了访问和治疗方案，并通过初步审查的政策中概述的常规IRB程序进行了审查。在本政策中描述了IRB审查单个患者扩大使用研究药物或生物产品（用于紧急或非紧急使用）的程序。

FDA对个别患者的评论扩大了对研究药物或生物学产品的访问：There are two mechanisms for submission to FDA:

1. an expanded access protocol submitted as a protocol amendment to an existing IND (i.e., an expanded access protocol). An expanded access protocol submission should be used only if the person or entity seeking the expanded access has an existing IND in effect.
2. a new IND submission, which is separate and distinct from any existing INDs and is intended only to make a drug available for treatment use (i.e., an expanded access IND). A new expanded access IND submission should be used when there is no existing IND in effect for the drug or, more commonly, there is an existing IND in effect for the drug, but the sponsor of the existing IND declines to be the sponsor of the expanded access use (that is, for an individual patient use, the sponsor of the existing IND may prefer that a patient’s physician submit a separate individual patient IND).

FDA在他们的综述中确定要治疗的患者患有严重或立即威胁生命的疾病或病情，并且没有可比或令人满意的替代疗法可以诊断，监测或治疗疾病或病情；潜在的患者利益证明了治疗使用的潜在风险，而在要治疗的疾病或病情的背景下，这些潜在的风险并不是不合理的。患者无法根据其他IND或方案获得该药物；并且提供调查药物以供要求使用的药物不会干扰临床调查的启动，行为或完成，以支持扩大访问使用的营销批准，或者以其他方式损害了扩展的访问使用的潜在发展。

个体患者扩大访问权限IND：除非FDA通知患者的医生或赞助商可能会早些时候开始治疗，否则从FDA开始在使用药物治疗之前收到IND申请之日起有30天的时间（除非将IND放置在临床上）。FDA需要在扩大访问使用开始之前需要审查和批准。

个体患者扩大了紧急使用的访问IND（有时称为“ Eind”）：最初是通过电话（或其他快速通信手段）要求和授权的治疗，并且可能会在FDA授权后立即开始，并且医师或赞助商必须同意在初始授权后的15个工作日内提交书面提交（IND）。

个别患者扩大访问协议：没有30天的时间开始使用该药物的治疗，但是该方案必须提交FDA，并在扩大访问治疗开始之前获得IRB批准。

个人患者扩大了紧急使用的访问协议：Treatment is initially requested and authorized by telephone (or other rapid means of communication) and may start immediately upon FDA authorization, with a requirement for a written submission (protocol) to FDA within 15 working days of the initial authorization.

IRB对个别患者的评论扩大了对研究药物或生物学产品的访问：使用表格FDA 3926提交单个患者扩展访问IND的医师可以在该表格上选择适当的盒子，以要求根据完整IRB审查的要求豁免。当医生在开始使用治疗之前，医生获得IRB主席或其他指定的IRB成员的同意时，这种豁免适用于个人患者扩大访问IND。使用表格FDA 1571提交单个患者扩展访问IND的医师可能包括与该申请的单独的豁免请求。

IRB审查的信息必须足以评估患者的风险是否已被最小化，并且与预期的福利有关此类风险是合理的。在个人患者扩大访问请求的情况下。治疗医师应通过电子邮件将以下信息提交给IRB办公室cphs@uth.tmc.edu对新兴市场ergency use and via iRIS for non emergency use:

1. 填写表格FDA 3926或字母（或协议（如果有）），其中包括支持确定患者处于严重或威胁生命的情况需要立即治疗的条件的情况下，没有可比或令人满意的替代治疗，并且来自研究药物的人的可能风险不高于疾病或病情的可能风险，并要求放弃全面IRB审查的要求）。以下信息应包括在FDA 3926或单独的字母中：
   1. 彻底的患者病史和治疗计划。
   2. 拟议的每日剂量、路由和频率dministration, duration of planned treatment, criteria for discontinuation of treatment, and planned dose modifications for adverse events;
   3. 计划对不良事件，对治疗的反应以及临床状况的变化以及对治疗计划的修改，以减轻患者的风险；
   4. The key details of the patient’s history, including diagnosis and summary of prior therapy (including response to such therapy), as well as information regarding a patient’s relevant clinical characteristics (such as comorbid conditions and concomitant medications) that are necessary to assess the potential for increased risks of the drug; and
   5. 该药物的已知风险摘要。
2. A simple informed consent document or justification for waiver of consent.
3. 赞助商或制造商的授权书允许治疗医生扩大研究药物或生物产品的使用。
4. Documentation of an FDA-approved Individual Patient Expanded Access IND, if available.

IRB董事将将提交材料的审查分配给IRB主席或其他指定的IRB成员进行审查。IRB审稿人可以从治疗医师那里寻求其他信息或澄清。在审查个人患者扩大有关研究药物和生物产品的访问请求时，IRB主席或指定的审查将考虑以下内容：

• Focus the review of an expanded access request for an individual patient on assessing the risks and benefits of treatment with the investigational drug or biological product for the patient involved.
• Assess the qualifications of the physician submitting the individual patient expanded access request.
• 当该请求是针对儿科患者的请求时，请确认包括适当的规定，以征求儿童的适合年龄同意和父母或监护人的许可。
• Confirm that the informed consent document contains the information required under the policy on informed consent. The consent form should contain a statement indicating that although the primary use of the drug is for treatment, the drug is investigational and FDA has not determined that the drug is safe or effective.

If the IRB chairperson agrees with the treating physician’s determination that treatment of the patient with the investigational drug or device is warranted, then the IRB office will issue a letter with the determination that the situation meets the FDA regulatory requirements for individual patient expanded access use of the investigational drug or biological product.

Informed Consent:除非放弃，否则治疗医师必须获得对受试者或受试者合法授权代表的知情同意。如果满足了以下标准，则IRB主席可以免除知情同意的要求。不再参加受试者治疗的医生和医生应以书面形式证明以下标准：

1. 患者面临着威胁生命和/或严重使人衰弱的情况，需要使用研究药物或生物产品；
2. 由于无法与患者沟通或获得法律有效的同意，因此无法获得知情同意；
3. 时间不足以从患者的法律代表中获得同意；和
4. No alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the patient’s life.

If, in the treating physician’s opinion, immediate use of the test article is required to preserve the patient’s life, and if time is not sufficient to obtain an independent physician’s determination that the four conditions listed above apply, then the treating physician should make the determination and, within five working days after the use, have the determination reviewed and evaluated in writing by a physician who is not otherwise participating in the treatment of the subject.

报告：

• IRB Reporting:The treating physician must submit a written follow-up report to the IRB within 2 weeks of use of the investigational product. This report should include:
  • 研究药物的名称；
  • 施用研究药物的条件；
  • 管理日期和时间；
  • 对接收者或其他人的任何不利事件或意外问题；和
  • 结果，如果已知。
• FDA Reporting:与任何IND一样，扩展的访问权限持有人必须向FDA提交安全报告和年度报告（当扩展的访问或协议持续1年或更长时间时）。对于个人患者的扩大访问，在治疗结束时，扩展的访问率必须为FDA提供有关扩展访问使用结果的书面摘要，包括不良效果。关于在FDA IND安全报告中报告严重和意外的不良反应，扩展的访问IND持有人只有在有证据表明该药物与不良事件之间存在因果关系的情况下，才能报告不良反应。

适用的法规和指导

1. 21 CFR 312 I子I：扩大对治疗的研究药物的访问
2. 21 CFR 56.104 - 免除IRB紧急使用要求
3. FDA Guidance - Expanded Access to Investigational Drugs for Treatment Use-Questions and Answers - Oct 2017
4. FDA Guidance - Institutional Review Board (IRB) Review of Individual Patient Expanded Access Requests for Investigational Drugs and Biological Products During the COVID-19 Public Health Emergency. June 2020
5. FDA指南：紧急使用研究药物或生物学
   1. 个人患者扩展访问应用程序：FDA表格3926
   2. 扩展访问如何提交请求（表格）
   3. 紧急协定时间表
   4. 扩大药物的访问类别（包括生物制剂）– Jan 2018

REFERENCES TO OTHER POLICIES

1. 初步审查

REFERENCES TO OTHER SOP

1. None

ATTACHMENTS

1. None

如果您在本文档中发现错误，请联系clinicals@uth.tmc.edu

文件号码：	101-D04
Document Name:	个体患者扩大访问权限
Reviewed by:	研究合规执行董事beplay苹果手机能用吗
Effective:	1 Aug 2008
修订记录：	2011年8月1日，2016年6月1日，2019年1月21日，2021年6月1日