IMPORTANCE

The US Food and Drug Administration (FDA) may consider historical controls, objective performance criteria, or performance goals as alternatives to concurrent control groups in clinical studies evaluating safety and/or effectiveness of high-risk medical devices. However, nonconcurrent control use has limitations.

OBJECTIVE

To examine frequency, justification, and clinically relevant details for use of nonconcurrent controls in pivotal studies supporting FDA approval of high-risk medical devices.

DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study from 2019 through 2023 of original high-risk therapeutic medical device approvals in the US.

MAIN OUTCOMES AND MEASURES

Frequency, justification, and clinically relevant details for use of historical controls, objective performance criteria, and performance goals and whether they had been established by the FDA.

RESULTS

From 2019 to 2023, the FDA approved 101 original high-risk therapeutic medical devices, of which 13 (12.9%) were not approved on the basis of any pivotal study. Among the remaining 88 approvals, 33 (37.5%) were based on pivotal studies that used concurrent controls for all analyses, 3 (3.4%) on single-group studies without the use of nonconcurrent controls, and 52 (59.1%) were based on at least 1 analysis using historical controls, objective performance criteria, or performance goals for primary safety and/or effectiveness end points. These 52 premarket approvals included 79 primary safety or effectiveness analyses using nonconcurrent controls: 9 historical controls (11.4%), 7 objective performance criteria (8.9%), and 63 performance goals (79.7%). Overall, 3 analyses (3.8%) provided justification for use of nonconcurrent controls. Clinically relevant details were provided for 19 analyses (24.1%) with respect to historical data publication dates and for 10 (12.7%) with respect to comparison of patient characteristics between pivotal studies and nonconcurrent controls. Four of 7 objective performance criteria (57.1%) and 0 of 63 performance goals had been established by the FDA.

CONCLUSIONS AND RELEVANCE

This cross-sectional study of high-risk therapeutic medical device approvals by the FDA over the past 5 years found that most approvals were based on analyses using nonconcurrent controls with limited justification and clinically relevant details, potentially creating uncertainty for patients, clinicians, and payers regarding the evidence establishing device safety and effectiveness.