Nonconcurrent Control Use in FDA Approval of High-Risk Medical Devices

Area of Science:

• Medical Device Regulation
• Clinical Study Design
• Regulatory Science

Background:

• The US Food and Drug Administration (FDA) permits nonconcurrent controls (historical controls, objective performance criteria, performance goals) for high-risk medical device evaluations.
• However, the use of nonconcurrent controls presents inherent limitations in establishing device safety and effectiveness.

Purpose of the Study:

• To analyze the frequency, justification, and clinical details of nonconcurrent control use in pivotal studies for US FDA-approved high-risk therapeutic medical devices.
• To assess whether established performance criteria or goals were FDA-defined.

Main Methods:

• A cross-sectional study of original high-risk therapeutic medical device approvals by the FDA between 2019 and 2023.
• Examined pivotal study designs, focusing on the use of concurrent vs. nonconcurrent controls and the provision of justification and clinical details.

Main Results:

• Of 88 high-risk device approvals based on pivotal studies, 59.1% utilized nonconcurrent controls for primary safety/effectiveness analyses.
• Performance goals were the most common nonconcurrent control (79.7%), but justifications and clinical details were limited (3.8% and 24.1% respectively).
• Only 4 of 7 objective performance criteria and none of the performance goals were FDA-established.

Conclusions:

• The majority of high-risk medical device approvals rely on nonconcurrent controls with insufficient justification and clinical detail.
• This practice may lead to uncertainty for patients, clinicians, and payers regarding the robustness of evidence supporting device safety and effectiveness.