1. Radiology Advisory Panel Meeting Radiology Advisory Panel Meeting Computer-Assisted Detection (CADe) Devices Joyce M. Whang Deputy Division Director Radiological Devices Branch Division of Reproductive, Abdominal and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health November 18, 2009

2. 2 Draft Guidance Documents Computer-Assisted Detection Devices Applied to Radiology Images and Radiology Device Data - Premarket Notification [510(k)] Submissions Clinical Performance Assessment: Considerations for Computer-Assisted Detection Devices Applied to Radiology Images and Radiology Device Data - Premarket Approval (PMA) and Premarket Notification [510(k)] Submissions

3. 3 Introductory Presentation Regulatory background CADe devices 510(k) guidance Clinical guidance

4. 4 510(k) Usually Class II devices Demonstrate substantial equivalence to predicate device PMA Paths to Market

5. 5 Determining Substantial Equivalence Option 1 has the same intended use as the predicate; and has the same technological characteristics as the predicate; or

6. 6 Determining Substantial Equivalence Option 2 has the same intended use as the predicate; and has different technological characteristics and the information submitted to FDA, including appropriate clinical or scientific data where necessary, demonstrates that the device: does not raise different questions of safety and effectiveness than the predicate; and appropriate clinical or scientific data demonstrates that the device is at least as safe and effective as the predicate.

7. 7 Class III Devices support or sustain human life are of substantial importance in preventing impairment of human health present a potential, unreasonable risk of illness or injury

8. 8 510(k) Usually Class II devices Demonstrate substantial equivalence to predicate device PMA Most Class III devices Demonstrate reasonable assurance of safety and effectiveness 510(k) Usually Class II devices Demonstrate substantial equivalence to predicate device PMA Most Class III devices Demonstrate reasonable assurance of safety and effectiveness Paths to Market

9. 9 Demonstrating Safety & Effectiveness Required levels of safety and effectiveness 510(k): substantial equivalence PMA: reasonable assurance Options for control arms no control arm comparison to similar device (e.g. predicate) comparison to standard of care (e.g. unassisted reading)

10. 10 Safety 21 CFR §860.7(d)(1) “There is reasonable assurance that a device is safe when it can be determined, based upon valid scientific evidence, that the probable benefits to health from use of the device for its intended uses and conditions of use, when accompanied by adequate directions and warnings against unsafe use, outweigh any probable risks.”

11. 11 Effectiveness 21 CFR §860.7(e)(1) “There is reasonable assurance that a device is effective when it can be determined, based upon valid scientific evidence, that in a significant portion of the target population, the use of the device for its intended uses and conditions of use, when accompanied by adequate directions for use and warnings against unsafe use, will provide clinically significant results.”

12. 12 Valid Scientific Evidence “Valid scientific evidence is evidence from well-controlled investigations, partially controlled studies, studies and objective trials without matched controls, well-documented case histories conducted by qualified experts, and reports of significant human experience with a marketed device, …” 21 CFR §860.7(c)(2)

13. 13 Valid Scientific Evidence “from which it can fairly and responsibly be concluded by qualified experts that there is reasonable assurance of the safety and effectiveness of a device under its conditions of use. “Isolated case reports, random experience, reports lacking sufficient details to permit scientific evaluation, and unsubstantiated opinions are not regarded as valid scientific evidence to show safety or effectiveness.” 21 CFR §860.7(c)(2)

14. 14 Least Burdensome Any clinical data, including one or more well- controlled investigations, specified in writing by the Secretary for demonstrating a reasonable assurance of device effectiveness shall be specified as a result of a determination by the Secretary that such data are necessary to establish device effectiveness. The Secretary shall consider, in consultation with the applicant, the least burdensome appropriate means of evaluating device effectiveness that would have a reasonable likelihood of resulting in approval” Section 513(a)(3)(D)(ii)

15. 15 Least Burdensome Whenever the Secretary requests information to demonstrate that devices with differing technological characteristics are substantially equivalent, the Secretary shall only request information that is necessary to making substantial equivalence determinations. In making such requests, the Secretary shall consider the least burdensome means of demonstrating substantial equivalence and request information accordingly” Section 513(i)(1)(D)

16. 16 CADe devices CADe Devices Applied to Radiology Images and Radiology Device Data identify, mark, highlight portions of an image, or aspects of radiology device data that may reveal abnormalities during interpretation

17. 17 Examples of Devices Covered CADe devices designed to identify and prompt microcalcification clusters and masses on digital mammograms colonic polyps on CT colonography studies filling defects on thoracic CT examinations brain lesions on head MRI studies

18. 18 Devices not Covered Devices intended for use during intraoperative procedures Computer-assisted diagnostic devices (CADx) Computer-triage devices

19. 19 Draft CADe 510k Guidance Device description Standalone performance assessment Clinical performance assessment User training Labeling

20. 20 Describing the Device and Data Device utilization Target population, type of imaging data, workflow… Algorithm Design and function Training process Evaluation Training and test databases Reference standard (ground truth) Scoring process

21. 21 Standalone Performance Detection/location accuracy Reproducibility testing with respect to imaging systems/acquisition Algorithm stability testing with respect to dataset/algorithmic changes

22. 22 Clinical Performance in 510(k) Guidance Clinical performance (reader study) is usually needed Potential control arms in clinical assessment studies for 510(k) device submissions

23. 23 User Training Description of process for training intended users of device when on market

24. 24 Labeling Recommendations on device labeling

25. 25 Draft CADe Clinical Guidance Clinical Study Design Study Population Reference Standard Reporting Postmarket Planning for PMAs

26. 26 Clinical Study Design Study endpoints Control arms Reading scenarios & randomization Rating scale Scoring Training of study readers

27. 27 Study Population Patient data (i.e., cases) may be collected prospectively or retrospectively enrichment with diseased/abnormal cases enrichment with challenging cases Data poolability, non-U.S. data

28. 28 Reference Standard (Ground Truth) Process for determining whether disease/condition present

29. 29 Reporting Recommendations on how to report and summarize study results

30. 30 Postmarket Planning Recommendations on postmarket planning for CADe Specific to Class III Premarket Approvals

31. 31 Today’s Agenda FDA Presentations Imaging Issues, Nicholas A. Petrick, Ph.D. Statistical Issues, Thomas E. Gwise, Ph.D. Clinical Issues, Robert C. Smith, M.D. Post-Approval Considerations, Cara J. Krulewitch, CNM Ph.D. FACNM Panel Discussion LUNCH Open Public Hearing Panel Discussion