1 FDA Perspective on Global Evaluation of Facial Acne Brenda Carr, M.D. Medical Officer Division of Dermatologic and Dental Drug Products FDA

2 §Challenges to scale design §Benefits of a common scale §Attributes of a scale §Examples of scales Outline

3 Challenges to Scale Design §pleomorphic nature of acne §variability in lesions §variability in natural course §what to assess

4 Benefits of a Standard Scale §Objective basis for treatment assessment §Assessment of disease status in clinical trials §Interpretation of trial results

5 Attributes of a Scale §A limited number of levels §Levels which are sufficiently described §Levels which indicate the “clear” (no acne) and “almost clear” state §Static measures to reflect a point in time §A high degree of correlation with lesion counts

6 Examples of Scales

7 Example #1 (Leed’s) §Grade 0 (no acne) to Grade 10 (most severe acne) §Grades 0 to 2: subdivided by 0.25 increments; 9 grades §Grades 2 to 10: subdivided by 0.50 increments; 17 grades

8 Example #2 (Cook’s) Grade 0: Need not be perfect; 3 small comedones and/or small papules if they are scattered Grade 2: Very few pustules or perhaps 3 dozen papules and/or comedones; no big or prominent lesions; lesions are hardly visible form 2.5 m away Grade 4: Between 2 and 6; red lesions and inflammation to a significant degree; worthy of treatment Grade 6: Loaded with comedones; no inflammation; or inflammatory lesions; must have numerous pustules; lesions are easily recognized at 2.5 m; some pustules may be quite large, 1 to 2 cm Grade 8: Conglobata, sinus, or cystic type acne; or a highly inflammatory acne covering most of the face; yellow pustules extend to neck and chin

9 Example #3 0 = worse 1 = no change 2 = slight improvement 3 = moderate improvement 4 = excellent improvement

10 Example #4 0 (None)= occasional comedones, but no evidence of acne requiring treatment 1 (Minimal) = non-inflammatory lesions predominate, several comedones and small papules/pustules, no inflamed nodulo-cystic lesions 2 (Mild) = non-inflammatory lesions predominate, multiple inflammatory lesions several to many comedones and small papules/pustules, perhaps 1 small evolving or involuting nodulo- cystic lesion 3 (Moderate) = inflammatory lesions are more apparent, many small papules/pustules, perhaps a few inflamed nodulo-cystic lesions 4 (Severe) = highly inflammatory lesions predominate, variable number of comedones several to many papules/pustules, several to many inflamed nodulo-cystic lesions

11 Example #5 0 (Normal)= clear skin with no evidence of acne vulgaris 1 (Almost clear) = a few to several (up to 15) non-inflammatory lesions (comedones) are present; a few (up to 7) inflammatory (papules/pustules) may be present 2 (Minimal to Mild) = several to many (>15) non-inflammatory lesions (comedones) are present; a few to several (>7) papules/pustules are present; no nodulo-cystic lesions 3 (Moderate) = many (>20) non-inflammatory and inflammatory (>20) lesions are present, there may or may not be 1 small nodulo-cystic lesion 4 (Severe) = High degree of inflammatory disease; papules/pustules are a predominant feature, variable number of comedones may be present; there may or may not be a few nodulo-cystic lesions

12 Example #6 0 = Normal, clear skin with no evidence of acne vulgaris 1 = Skin is almost clear: rare non-inflammatory lesions present, with rare non-inflamed papules (papules must be resolving and may be hyperpigmented, though not pink-red) 2 = Some non-inflammatory lesions are present, with few inflammatory lesions (papules/pustules only; no nodulo-cystic lesions) 3 = Non-inflammatory lesions predominate, with multiple inflammatory lesions evident: several to many comedones and papules/pustules, and there may or may not be one small nodulo-cystic lesion 4 = Inflammatory lesions are more apparent: many comedones and papules/pustules, there may or may not be a few nodulo-cystic lesions 5 = Highly inflammatory lesions predominate: variable number of comedones, many papules/pustules nodulo-cystic lesions