Use of imaging biomarkers for regulatory studies.

Imaging often plays an important role in pivotal clinical trials of drugs or devices that have been submitted for approval to regulatory agencies that grant approval for the marketing and sale of these products on the basis of documentation of their safety and efficacy. Imaging biomarkers can help substantiate either or both of these characteristics. This article focuses on how to successfully incorporate imaging biomarkers into clinical trials through a process of careful planning and diligent execution. Planning starts with posing and then answering a number of questions that pertain to the product under study. What will the claimed benefit of the product be? Is there a current standard of care that involves imaging, and will that standard of care help in the documentation of safety and efficacy? Are there relevant novel imaging biomarkers? Are there any relevant guidance documents issued by the regulatory agencies? After imaging biomarkers are identified, their role and benefit must be understood. Will they help diagnose subjects? Will they stratify subjects for enrollment? Will they identify those who are more likely to benefit? Will they help document progression of disease and effectiveness of intervention? Execution must occur in close collaboration with regulatory agencies and with the involvement of imaging experts and imaging core laboratories to ensure attention to key components: imaging charter, investigator training and certification, 21 CFR Part 11 (Part 11 of Title 21 of the U.S. Code of Federal Regulations)-compliant data management, real-time incoming image quality control for eligibility reads and investigator feedback, and centralized image analysis for safety and efficacy by certified readers.