Description
An adaptive design for a medical device clinical study is defined as a clinical study design that allows for prospectively planned modifications based on accumulating study data without undermining the study’s integrity and validity. Adaptive designs, when properly implemented, can reduce resource requirements, decrease time to study completion, and/or increase the chance of study success.This guidanceprovides sponsors and Food and Drug Administration (FDA) staff with guidance on how to plan and implement adaptive designs for clinical studies when used in medical device development programs.
Scope & Applicability
Product Classes
7Special Considerations for Diagnostic Devices
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
rationale for adaptive study may differ from diagnostic devices
unique issues with adaptive study designs for diagnostic devices; heterogeneous in scope and include devices that may be invasive
Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.
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
6Entity responsible for submitting applications under section 524B
Data monitoring committee; Oversight body that may request interim analysis
Safety oversight body for interpreting adverse events; Safety oversight body for study design
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
May access unblinded data as described in the DMC Charter.
Bodies responsible for evaluating trial risks and benefits for pregnant participants.; IRBs experienced in this population may advise on compensation.
Regulatory Context
Attributes
10Bias arising from differences in study conduct.
Probability of a statistically significant treatment effect based on interim results.
Estimated number of people with a disease, used to determine clinical investigation enrollment.
The significance level, typically 0.05.; Each vertex is allocated an initial amount of alpha.
Risk classification for medical device clinical investigations.; A classification for medical device studies.; A risk determination for a clinical study.
Statistical parameter requiring strong control when testing multiple endpoints
Approach to handling multiplicity
failing to conclude that a device was effective when it was
Pathologists must remain blinded to treatment arm
Bias making it difficult to characterize the true effect of the device
Related CFR Sections (5)
- 21CFR812.30§ 812.30 FDA action on applications.
(a) Approval or disapproval. FDA will notify the sponsor in writing of the date it receives an application. FDA may approve an investigation as proposed, approve it with modifications, or disapprove it. An investigation may not begin until:Read full regulation →
- 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 →
- 21CFR812.35§ 812.35 Supplemental applications.
(a) Changes in investigational plan —Read full regulation →
- 21CFR812.20§ 812.20 Application.
(a) Submission.Read 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 →
Related Warning Letters (10)
- 2024-11-05
Institutional Review Board (IRB)
Armstrong County Memorial Hospital
- 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
- 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
- 2023-01-24
Bioresearch Monitoring Program/Institutional Review Board (IRB)
Larkin Community Hospital Institutional Review Board
- 2022-03-15
Clinical Investigator (CI)
Sabine S. Hazan, M.D.
- 2022-02-15
Clinical Investigator
Richard J. Obiso, PhD dba Avila Herbals, LLC
See Also (8)
- The Content of Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications for Artificial Pancreas Device Systems: Guidance for Industry and Food and Drug Administration Staff (Status: Final)
- FDA Decisions for Investigational Device Exemption Clinical Investigations: Guidance for Sponsors, Clinical Investigators, Institutional Review Boards, and Food and Drug Administration Staff (Status: Final)
- Factors to Consider When Making Benefit-Risk Determinations for Medical Device Investigational Device Exemptions: Guidance for Investigational Device Exemption Sponsors, Sponsor-Investigators and Food and Drug Administration Staff (Status: Final)
- Investigational IVDs Used in Clinical Investigations of Therapeutic Products: Draft Guidance for Industry, Food and Drug Administration Staff, Sponsors, and Institutional Review Boards (Status: Draft)
- Research Involving Children as Subjects and Not Otherwise Approvable by an Institutional Review Board: Process for Referrals to Food and Drug Administration and Office for Human Research Protections: Draft Guidance for Institutional Review Boards, Investigators, and Sponsors (Status: Draft)
- Unique Device Identification System: Small Entity Compliance Guide: Guidance for Industry and Food and Drug Administration Staff (Status: Final)
- Certificates of Confidentiality: Guidance for Sponsors, Sponsor-Investigators, Researchers, Industry, and Food and Drug Administration Staff (Status: Final)
- Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics Guidance for Industry: Guidance for Industry (Status: Final)