Variation of topical application to skin under good clinical practice (GCP): A "best performance" scenario

INTRODUCTION: Application of topical products by individuals is inherently variable and accurate dosing can be difficult to control. Variation of the dose used under optimal conditions in drug trials is unknown.

METHODS: This trial was part of a double-blind, randomized, placebo-controlled good clinical practice (GCP) study designed to investigate the local tolerability and safety on healthy skin of captopril 1% ointment versus a placebo ointment. Volunteers were instructed to apply an even layer of test ointment on a 51 cm(2) test area on the arm twice daily over a 3-week period. At weekly follow-up visits, tubes were weighed and adherence to treatment checked.

RESULTS: Of the 37 recruited volunteers, 36 (17 women, 19 men) completed the study. Their mean age was 24 (18-35) years. A 13.6-fold difference in the applied amount was found ranging from 1.26 mg/cm(2) to 17.19 mg/cm(2) per application at week 4, with median 5.60 mg/cm(2) applied versus 2 mg/cm(2) (standard for good application) resulting in a 2.8-fold over-dosage.

CONCLUSION: There was a major variation of test ointment application studied under GCP conditions with adherent participants. In dermatological practice, the variation is assumed to be even higher. This should be taken into account in clinical trials, especially dose-finding studies typically operating with 3-5-fold increments.