A Noninferiority Margin for Acne Lesion Counts
When comparing different active treatments, a noninferiority—also called one-sided equivalence—study design is used. This study design requires the definition of a noninferiority margin. the threshold value of clinical relevance. At present, a noninferiority margin of 10 percentage points is conventionally used for the change in acne lesion counts, but it lacks empirical validation.
We analyzed the data of 4,081 patients with moderate to severe facial acne. The treatment effect was recordedby the investigator as the relative change in lesion counts from baseline (objective assessment). At the end of the treatment period, patients rated themselves as having their acne condition improved, unchanged, or worsened (subjective assessment). We compared the changes in lesion counts with the patients’ self-assessment to derive an empirically validated noninferiority margin
We found that an empirically validated noninferiority margin of 10–15 percentage points for facial acne lesion counts is appropriate.
Key WordsNoninferiority margin Acne Choice of delta Active control
Unable to display preview. Download preview PDF.
- 2.US Department of Health and Human Services. Food and Drug Administration, Center for Drug Evaluation and Research. Clinical/medical guidance for industry acne vulgaris: developing drugs for treatment. September 2005. Available at: http://www.fda.gov/cder/guidance/6499dft.pdf. accessed January 16. 2007Google Scholar
- 3.ICH (2000). International Conference on Har-monisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH harmonised tripartite guideline. Choice of control group and related issues in clinical trials. Recommended for adoption at step 4 of the ICH process on July 20, 2000, by the ICH steering committee.Google Scholar
- 6.SAS Institute Inc. 2004. SAS/SIAT® 9.1 Users Guide. Cary, NC: SAS Institute Inc.Google Scholar
- 7.SAS Institute Inc. Available at: www.sas.com.
- 8.Schmitt GJ. Scale development for clinical as-sessment. In: Schwindt AD, Maibaich HI, eds. Cutaneous Biometrics. New York: Kluwer: 2000.Google Scholar
- 9.Loock W, Double-blind, randomized, multicenter study with SH T 470 FA in comparison with Di-anc®-35 in women with acne over 9 treatment cycles. Schering AG internal research report number AM80, June 18, 1998.Google Scholar
- 10.van Vioten WA, van Haselen CW, van Zuuren EJ, Gerlinger C. Heithecker R. The effect of 2 combined oral contraceptives containing either drospirenone or cyproterone acetate on acne and seborrhea. Cutis. 2002;69(4 Supp)):2–15.Google Scholar
- 14.Bongartz M. Multicenter, double-blind, random-ized parallel group study on efficacy of 0.03 mg ethinylestradiol and 2 mg dienogesl in comparison to triphasic ethinylestradiol and norgesti-mate over six cycles in patients with acne papulopustulosa. Schering AG internal clinical study report number A07062, June 21, 2002.Google Scholar
- 15.Wack C. Multicenter, double-blind, randomized parallel group study on efficacy of 0.03 mg ethinylestradiol and 5 mg drospirenone (DRSP) in comparison to triphasic ethinylestradiol and norgestimate (NGM) over six cycles in patients with mild to moderate acne papulopustulosa. Schering AG internal clinical study report number A07148, February 25, 2003, as amended.Google Scholar
- 16.Schneider A. Multicenter, double-blind, randomized parallel group study on efficacy of 0.035 mg ethinylestradiol/2 mg cyproterone acetate and of 0.035 mg ethinylestradiol/2 mg cyproterone acetate in combination with 10 mg cyproterone acetate in comparison to triphasic ethinylestradiol/norgestimate over 6 cycles in women with acne papulopustulosa. Schering AG internal clinical study report number A18566, July 2, 2004.Google Scholar
- 17.Zimmermann D. A 12-week, randomized, double-blind mullicenler study comparing the clinical efficacy and safety of azelaic acid 15% gel (SH H 655 BA) with its vehicle (SH H 655 PBA) in patients with mild to moderate acne. Berlex Inc. internal clinical study report number A09241, September 16, 2004.Google Scholar
- 18.A 12-week, randomized, double-blind mullicen-ter study comparing the clinical efficacy and safely of azelaic acid 15% gel (SH H 655 BA) with its vehicle (SH H 655 PBA) in patients with mild to moderate acne. Berlex Inc. internal clinical study report number A09242. September 16, 2004.Google Scholar
- 19.Gaupe K. An 8-week controlled, double-blind pilot study comparing the initial clinical effect of 15% azelaic acid hydrogel SH H 655 BA with 20% azelaic acid cream (Skinoren®) during twice-daily topical treatment of patients with papulopustular facial acne. Schering AG inter-nal clinical study report number AU36, January 15, 1999.Google Scholar