04P-0059
PDN 2
Volume 17-19

Volume 17

Petition Denial

References

Reference List

Tabs 1-61

Volume 18, 19

Footnotes

Tab 1, Footnote 1 - http://www.cfsan.fda.gov/~dms/nuttf-e.html

Tab 2, Footnote 2 - A meta-analysis is the process of systematically combining and evaluating the results of clinical trials that have been completed or terminated (Spilker, 1991, p. 793)

Tab 3, Footnote 3 - http://www.niams.nih.gov/ne/oi/

Tab 4, Footnote 4 - http://www.fda.gov/ohrms/dockets/ac/cfsan04.html, part 2
June 7, 8, 2004 Transcript, part 2, part 3, part 4, part 5

Tab 5, Footnote 6 - http://www.cfsan.fda.gov/~dms/ssaguide.html

Tab 6, Footnote 7 - Eburnation is a change in exposed subchondral bone in degenerative joint disease in which subchondral bone is converted into a dense substance with a smooth surface like ivory (Stedman’s Medical Dictionary)

Tab 7, Footnote 8 - An osteophyte is a bony outgrowth or protuberance (Stedman’s Medical Dictionary)

Tab 8, Footnote 9 - http://www.rheumatology.org/public/factsheets/oa.asp?aud=pat

Tab 9, Footnote 10 - http://www.niams.nih.gov/ne/oi/

Tab 10, Footnote 13 - http://www.clinicaltrials.gov/show/NCT00032890

Tab 11, Footnote 14 - http://clinicaltrials.gov/show/NCT00086229

Tab 12, Footnote 15 - http://ntp-server.niehs.nih.gov/NomPage/2003Noms.html

Tab 13, Footnote 26 - Chondropathia patellae is a disease of the cartilage and patella (Stedman’s Medical Dictionary and Dorland’s Illustrated Medical Dictionary). The patella is a bone in the knee commonly referred to as the kneecap.

Tab 14, Footnote 33 - A chondrocyte is a non-dividing cartilage cell occupying a lacuna (i.e., small space or cavity) within the cartilage matrix (Stedman’s Medical Dictionary).

Tab 15, Footnote 37 - A icytokine is a generic term for nonantibody proteins released by one cell population on contact with specific antigen, which act as intercellular mediators, as in the generation of an immune response (Dorland’s Illustrated Medical Dictionary).

Tab 16, Footnote 56 - A meta-analysis is the process of systematically combining and evaluating the results of clinical trials that have been completed or terminated (i.e., primary reports) (Spilker, 1991, p. 793). FDA uses meta-analysis to identify relevant primary reports, which the Agency then evaluates.

Tab 17, Footnote 58 - The background section of the FAC questions document (http://www.fda.gov/ohrms/dockets/ac/04/briefing/4045b1_06_a_Questions%20Revised.pdf) stated that FDA also refers to modifiable risk factors/surrogate endpoints for disease as “biomarkers” and further explained, in part, that a biomarker is “a measurement of al variable related to a disease that may serve as an indicator or
predictor of that disease. Biomarkers are parameters from which the presence or risk of a disease can be inferred, rather than being a measure of the disease itself. In conducting a health claim review, FDA does not rely on a change in a biomarker as a measurement of the effect of a dietary factor on a disease unless there is evidence that altering the parameter can affect the risk of developing that disease or health-related
condition.” See also the discussion of modifiable risk factors in the introduction to section I.B.1.

Tab 18, Footnote 61 - http://www.cfsan.fda.gov/~dms/ds-ltr11.html