1. 1 A continued FDA Concern about Imaging Based Drug Trials Society of Nuclear Medicine Albuquerque, Feb 1-2, 2009 Orhan H Suleiman MS PhD, FAAPM Senior Science Policy Adviser Office of Oncology Drug Products Office of New Drugs

2. 2 Good science! Good scientific principles are essential for good imaging based trials: 1. Standardize imaging equipment; 2. standardize imaging acquisition, processing, and display protocol; 3.standardize readers. 4.Know the uncertainties- 1%, 5%, 20%, 50%, 100%, ?

3. 3 In order to detect change clinically, you need to assure the standard image remains constant.

4. 4 Conduct Quality Control Testing In order to assure that the images are being produced consistently over time you should… Quality control test, with a phantom, before, during, and at the end of the trial, which should assure consistency in equipment performance! This includes the use of the same software and imaging technique.

5. 5 History of Imaging Criteria World Health Organization (1970’s) Response Evaluation Criteria in Solid Tumors – RECIST (2000, 2008) 3-dimensional volumetric analysis (current)

6. 6 RECISTVolume - 3.5 % - 32 % baseline 30 days Diameter = 17.7 mm Diameter = 17.1 mm Volume = 886 mm 3 Volume = 525 mm 3 RECIST vs. Volumetrics Bensheng Zhao, MSKCC

7. 7 “Calibrate” Human Readers Train the qualified readers, prospectively! Use standard images to “calibrate” readers, either physically together, or with a detailed protocol. This should minimize adjudication. Protocol should specify data collection, viewing conditions, image scoring and other criteria.

8. 8 In closing… Quality control testing with appropriate test phantoms must be used on all imaging equipment used to generate clinical images during the trial. Ultimately successful clinical trials depend on using good science for the entire trial (drug, equipment, image, analysis).

9. 9 FDA 10903 New Hampshire Ave Silver Spring, Maryland 20993