Description
This documentis intended to provide guidance to those involved in designing clinical studies intended to support pre-market submissions for medical devices and FDA staff who review those submissions. Although the Agency has articulated policies related to design of studies intended to support specific device types, and a general policy of tailoring the evidentiary burden to the regulatory requirement, the Agency has not attempted to describe the different clinical study designs that may be appropriate to support a device pre-market submission, or to define how a sponsor should decide which pivotal clinical study design should be used to support a submission for a particular device. This guidance document describes different study design principles relevant to the development of medical device clinical studies that can be used to fulfill pre-market clinical data requirements. This guidance is not intended to provide a comprehensive tutorial on the best clinical and statistical practices for investigational medical device studies.
Scope & Applicability
Product Classes
10One of two broad categories of medical devices addressed
Medical device being tested in a clinical trial.; Medical devices intended for participants during the trial.
A procedure or another medical product that serves to assess the level of performance of the investigational device.
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
unique issues with adaptive study designs for diagnostic devices; heterogeneous in scope and include devices that may be invasive
Devices intended to change visual appearance; device intended to provide a desired change in visual appearance
rationale for adaptive study may differ from diagnostic devices
IVDs for emerging pathogens during a Section 564 declared emergency
Device studies that may not require an IDE submission to FDA; Devices that do not meet the definition of significant risk
Devices requiring full IDE submission
Stakeholders
8Individuals responsible for monitoring and reporting protocol deviations
Veterinarian responsible for selecting anesthetic regimens and conducting field studies
FDA might present PMAs using PGs to the relevant advisory panel to obtain outside scientific counsel.
Independent individuals recommended to be blinded to intervention assignment
Encouraged for evaluation of serious hepatic events
Bodies responsible for evaluating trial risks and benefits for pregnant participants.; IRBs experienced in this population may advise on compensation.
Entity responsible for submitting applications under section 524B
Governs top dose in clinical studies
Regulatory Context
Attributes
8Evidence of a new intended use based on communications
Statistical parameter requiring strong control when testing multiple endpoints
A PG might be considered for challenging patient populations or if there is no clinical equipoise for any control.
Statistical parameter to be controlled when handling multiplicity issues
Sampling variability controlled by the sample size of the study.
Systematic errors introduced due to sampling or measurement.
Time taken to master device use
Standard for PMA approval
Identified Hazards
Hazards
10Risk factor for diagnostic devices leading to unnecessary treatment
mitigate potential unwanted bias in learning or performance estimation
When comparing two or more diagnostic assessments, the reader's interpretation is affected by memory.
Subjects who are screened with a diagnostic device can falsely appear to benefit from diagnostic testing.
Produced when frequency of application of the clinical reference standard depends on the investigational device results.
A type of bias to be addressed in the study design; Evaluation of any potential biases such as information bias and selection bias.
Incorrect diagnostic result that can lead to subject harm
Incorrect diagnostic result that can lead to inappropriate management
Bias inherent in the use of a historical control since groups are not concurrent
Bias avoided by using a randomized group in a blinded study
Related CFR Sections (12)
- 21CFR812.3§ 812.3 Definitions.
(a) Act means the Federal Food, Drug, and Cosmetic Act (sections 201-901, 52 Stat. 1040 et seq., as amended ( 21 U.S.C. 301-392 )).Read full regulation →
- 21CFR812.25§ 812.25 Investigational plan.
The investigational plan shall include, in the following order:Read full regulation →
- 21CFR812.43§ 812.43 Selecting investigators and monitors.
(a) Selecting investigators. A sponsor shall select investigators qualified by training and experience to investigate the device.Read full regulation →
- 21CFR812.119§ 812.119 Disqualification of a clinical investigator.
(a) If FDA has information indicating that an investigator (including a sponsor-investigator) has repeatedly or deliberately failed to comply with the requirements of this part, part 50 , or part 56 of this chapter , or has repeatedly or deliberately submitted to FDA or to the sponsor false informatRead full regulation →
- 21CFR812.140§ 812.140 Records.
(a) Investigator records. A participating investigator shall maintain the following accurate, complete, and current records relating to the investigator's participation in an investigation:Read 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 →
- 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 →
- 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 →
- 21CFR812.20§ 812.20 Application.
(a) Submission.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 →
- 21CFR814.15§ 814.15 Research conducted outside the United States.
(a) Data to support PMA. If data from clinical investigations conducted outside the United States are submitted to support a PMA, the applicant shall comply with the provisions in § 812.28 of this chapter , as applicable.Read full regulation →
- 21CFR812.2§ 812.2 Applicability.
(a) General. This part applies to all clinical investigations of devices to determine safety and effectiveness, except as provided in paragraph (c) of this section.Read full regulation →
Related Warning Letters (10)
- 2025-09-09
Clinical Investigator
Shirish M. Gadgeel, M.D.
- 2025-07-15
Clinical Investigator
Mark J. Savant, M.D
- 2025-05-20
Bioresearch Monitoring Program/Institutional Review Board (IRB)
United Health Products, Inc.
- 2025-03-25
Clinical Investigator
Americo F. Padilla, M.D.
- 2024-11-05
Institutional Review Board (IRB)
Armstrong County Memorial Hospital
- 2024-10-22
Clinical Investigator
Namita A. Goyal, M.D.
- 2024-10-08
Institutional Review Board (IRB)
Louisiana State University Health Science Center IRB
- 2024-07-16
Bioresearch Monitoring Program/IRB
Massachusetts Institute of Technology MIT
- 2024-06-18
Clinical Investigator (Sponsor)
Angela D. Ritter, M.D.
- 2024-03-26
Institutional Review Board (IRB)
New York State Psychiatric Institute IRB
See Also (8)
- Classification of Products as Drugs and Devices and Additional Product Classification Issues: Guidance for Industry and FDA Staff (Status: Final)
- Devices Used to Process Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps): Guidance for Industry and FDA Staff (Status: Final)
- Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs): Guidance for FDA Reviewers and Sponsors (Status: Final)
- New Contrast Imaging Indication Considerations for Devices and Approved Drug and Biological Products: Guidance for Industry (Status: Final)
- Influenza: Developing Drugs for Treatment and/or Prophylaxis (Status: Final)
- How to Write a Request for Designation (RFD): Guidance for Industry (Status: Final)
- Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee Cartilage: Guidance for Industry (Status: Final)
- Glass Syringes for Delivering Drug and Biological Products: Technical Information to Supplement International Organization for Standardization (ISO) Standard 11040-4: Draft Guidance for Industry and FDA Staff (Status: Draft)