Description
This guidance discusses the roles, responsibilities and operating procedures of Data Monitoring Committees (DMCs) (also known as Data and Safety Monitoring Boards (DSMBs) or Data and Safety Monitoring Committees (DSMCs)) that may carry out important aspects of clinical trial monitoring. This guidance is intended to assist clinical trial sponsors in determining when a DMC may be useful for study monitoring, and how such committees should operate. We recognize that in many clinical trials the sponsor delegates some decision-making regarding the design and conduct of the trial to some other entity such as a steering committee (see Section 3.2) or contract research organization (CRO) (see 21 Code of Federal Regulations (CFR) 312.3(b)). This document, while pertaining primarily to the sponsor with regard to trial management and decision-making, may also be relevant to any individual or group to whom the sponsor has delegated applicable management responsibilities (see Section 3). This guidance finalizes the draft guidance entitled "Guidance for Clinical Trial Sponsors: On the Establishment and Operation of Clinical Trial Data Monitoring Committees" dated November 2001.
Scope & Applicability
Product Classes
2Synonymous with drugs, medicines, medicinal products, vaccines, and biological products.; Product intended to benefit population groups once authorized; The product being tested in the clinical trial.; The product being studied in the clinical trial.; monitoring extent based on the nature of the investigational product; Management, storage, and accountability of the product being tested.; management should be arranged and conducted in accordance with applicable regulatory requirements; The produ
FDA intends to assess device cybersecurity based on a number of factors; demonstrate or maintain its safety and effectiveness; ensuring cybersecurity has become essential to FDA’s ability to protect the public health; Cyber-resiliency capabilities for medical devices
Stakeholders
10Entity responsible for submitting applications under section 524B
Individuals involved in the conduct of the clinical trial at research sites.
The individual or group responsible for designing the trial and managing its conduct.
Responsible for qualifications, training, and trial conduct; Individual responsible for trial conduct and data governance at a site.; May delegate tasks but retains overall responsibility; Person responsible for the conduct of the clinical trial at a trial site; Responsible for trial conduct and participant safety; Responsible for trial conduct, data integrity, and investigational product management.; Individual responsible for trial conduct at a site and informing the institution.; maintaining
Insulated from knowledge of interim data to minimize potential for bias.
Front-line responsibility for identifying adverse effects
Safety oversight body for interpreting adverse events; Safety oversight body for study design
Entity to which obligations may be transferred
Governs top dose in clinical studies
May include investigators and experts to consider trial performance aspects.
Regulatory Context
Attributes
6Protection of data whose disclosure could lead to patient harm
accessing interim data by the sponsor carries many risks
The degree to which DMC members are free from sponsor influence; The degree to which the DMC is separate from the sponsor's influence.
Data that reveals treatment assignments, which can introduce bias if accessed by sponsors.
failing to conclude that a device was effective when it was
Trial design should provide strong control of Type I error
Identified Hazards
Hazards
4Risk of concluding a benefit exists when it does not due to multiple analyses.
Risks associated with the investigational product
Potential for interoperable systems to reveal treatment allocation in blinded studies.
mitigate potential unwanted bias in learning or performance estimation
Related CFR Sections (19)
- 21CFR312.3§ 312.3 Definitions and interpretations.
(a) The definitions and interpretations of terms contained in section 201 of the Act apply to those terms when used in this part:Read full regulation →
- 21CFR314.50§ 314.50 Content and format of an NDA.
NDAs and supplements to approved NDAs are required to be submitted in the form and contain the information, as appropriate for the particular submission, required under this section. Three copies of the NDA are required: An archival copy, a review copy, and a field copy. An NDA for a new chemical enRead full regulation →
- 21CFR812.150§ 812.150 Reports.
(a) Investigator reports. An investigator shall prepare and submit the following complete, accurate, and timely reports:Read full regulation →
- 21CFR312.56§ 312.56 Review of ongoing investigations.
(a) The sponsor shall monitor the progress of all clinical investigations being conducted under its IND.Read full regulation →
- 21CFR812.46§ 812.46 Monitoring investigations.
(a) Securing compliance. A sponsor who discovers that an investigator is not complying with the signed agreement, the investigational plan, the requirements of this part or other applicable FDA regulations, or any conditions of approval imposed by the reviewing IRB or FDA shall promptly either securRead full regulation →
- 21CFR312.66§ 312.66 Assurance of IRB review.
An investigator shall assure that an IRB that complies with the requirements set forth in part 56 will be responsible for the initial and continuing review and approval of the proposed clinical study. The investigator shall also assure that he or she will promptly report to the IRB all changes in thRead full regulation →
- 21CFR56.108§ 56.108 IRB functions and operations.
In order to fulfill the requirements of these regulations, each IRB shall:Read full regulation →
- 21CFR812.35§ 812.35 Supplemental applications.
(a) Changes in investigational plan —Read full regulation →
- 21CFR312.30§ 312.30 Protocol amendments.
Once an IND is in effect, a sponsor shall amend it as needed to ensure that the clinical investigations are conducted according to protocols included in the application. This section sets forth the provisions under which new protocols may be submitted and changes in previously submitted protocols maRead full regulation →
- 21CFR312.32§ 312.32 IND safety reporting.
(a) Definitions. The following definitions of terms apply to this section:Read full regulation →
- 21CFR312.41§ 312.41 Comment and advice on an IND.
(a) FDA may at any time during the course of the investigation communicate with the sponsor orally or in writing about deficiencies in the IND or about FDA's need for more data or information.Read full regulation →
- 21CFR312.23§ 312.23 IND content and format.
(a) A sponsor who intends to conduct a clinical investigation subject to this part shall submit an “Investigational New Drug Application” (IND) including, in the following order:Read full regulation →
- 21CFR312.50§ 312.50 General responsibilities of sponsors.
Sponsors are responsible for selecting qualified investigators, providing them with the information they need to conduct an investigation properly, ensuring proper monitoring of the investigation(s), ensuring that the investigation(s) is conducted in accordance with the general investigational plan Read full regulation →
- 21CFR812.40§ 812.40 General responsibilities of sponsors.
Sponsors are responsible for selecting qualified investigators and providing them with the information they need to conduct the investigation properly, ensuring proper monitoring of the investigation, ensuring that IRB review and approval are obtained, submitting an IDE application to FDA, and ensurRead full regulation →
- 21CFR50.24§ 50.24 Exception from informed consent requirements for emergency research.
(a) The IRB responsible for the review, approval, and continuing review of the clinical investigation described in this section may approve that investigation without requiring that informed consent of all research subjects be obtained if the IRB (with the concurrence of a licensed physician who is Read full regulation →
- 21CFR50.3§ 50.3 Definitions.
As used in this part:Read full regulation →
- 21CFR56.111§ 56.111 Criteria for IRB approval of research.
(a) In order to approve research covered by these regulations the IRB shall determine that all of the following requirements are satisfied:Read full regulation →
- 21CFR314.126§ 314.126 Adequate and well-controlled studies.
(a) The purpose of conducting clinical investigations of a drug is to distinguish the effect of a drug from other influences, such as spontaneous change in the course of the disease, placebo effect, or biased observation. The characteristics described in paragraph (b) of this section have been develRead full regulation →
- 21CFR860.7§ 860.7 Determination of safety and effectiveness.
(a) The classification panels, in reviewing evidence concerning the safety and effectiveness of a device and in preparing advice to the Commissioner, and the Commissioner, in making determinations concerning the safety and effectiveness of a device, will apply the rules in this section.Read full regulation →
Related Warning Letters (10)
- 2025-09-23
Clinical Investigator/Sponsor
Ralph A. DeFronzo, M.D.
- 2025-06-03
Bioresearch Monitoring Program
Amy Lightner, MD
- 2025-05-20
Bioresearch Monitoring Program/Institutional Review Board (IRB)
United Health Products, Inc.
- 2024-10-22
Clinical Investigator
Namita A. Goyal, M.D.
- 2024-03-12
Investigational Review Board (IRB)
Nobles Medical Technology II, Inc.
- 2024-01-09
Clinical Investigator
Jeffrey W. Taub, M.D./Children's Hospital of Michigan
- 2023-09-29
Clinical Investigator
Luis Javier Pena-Hernandez, M.D., FCCP
- 2022-03-15
Clinical Investigator (CI)
Sabine S. Hazan, M.D.
- 2020-04-07
Investigational Device Exemptions (Clinical Investigator)
Kennedy, Philip R.
- 2020-03-10
Clinical Investigator
James R. Corbett, M.D.
See Also (8)
- Safety Reporting Requirements for INDs (Investigational New Drug Applications) and BA/BE (Bioavailability/Bioequivalence) Studies: Guidance for Industry and Investigators (Status: Final)
- PHS Guideline on Infectious Disease Issues in Xenotransplantation: PHS Guideline (Status: Final)
- Investigator Responsibilities — Protecting the Rights, Safety, and Welfare of Study Subjects: Guidance for Industry (Status: Final)
- Frequently Asked Questions – Statement of Investigator (Form FDA 1572): Guidance for Sponsors, Clinical Investigators, and IRBs (Status: Final)
- Postmarketing Studies and Clinical Trials—Implementation of Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act Guidance for Industry (Status: Final)
- FDA Acceptance of Foreign Clinical Studies Not Conducted Under an IND: Frequently Asked Questions: Guidance for Industry and FDA Staff (Status: Final)
- Expanded Access to Investigational Drugs for Treatment Use: Questions and Answers (Status: Final)
- Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers (Status: Final)