Evaluating clinical trial design: systematic review of randomized vehicle-controlled trials for determining efficacy of benzoyl peroxide topical therapy for acne

Abstract

Determined efficacies of benzoyl peroxide may be affected by study design, implementation, and vehicle effects. We sought to elucidate areas that may allow improvement in determining accurate treatment efficacies by determining rates of active treatment and vehicle responders in randomized controlled trials assessing the efficacy of topical benzoyl peroxide to treat acne. We conducted a systematic review of randomized vehicle-controlled trials evaluating the efficacy of topical benzoyl peroxide for the treatment of acne. We compared response rates of vehicle treatment arms versus those in benzoyl peroxide arms. Twelve trials met inclusion criteria with 2818 patients receiving benzoyl peroxide monotherapy treatment and 2004 receiving vehicle treatment. The average percent reduction in total number of acne lesions was 44.3 (SD = 9.2) and 27.8 (SD = 21.0) for the active and vehicle treatment groups, respectively. The average reduction in non-inflammatory lesions was 41.5 % (SD = 9.4) in the active treatment group and 27.0 % (SD = 20.9) in the vehicle group. The average percent decrease in inflammatory lesions was 52.1 (SD = 10.4) in the benzoyl peroxide group and 34.7 (SD = 22.7) in the vehicle group. The average percentage of participants achieving success per designated study outcomes was 28.6 (SD = 17.3) and 15.2 (SD = 9.5) in the active treatment and vehicle groups, respectively. Patient responses in randomized controlled trials evaluating topical acne therapies may be affected by clinical trial design, implementation, the biologic effects of vehicles, and natural disease progression. "No treatment" groups may facilitate determination of accurate treatment efficacies.

Topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis: Results from the ATMOS-1 and ATMOS-2 phase 3 randomized controlled trials

“…The effect of vehicle in these trials, though much smaller than the effect of GT, has been observed in other dermatology trials 17,18 and indicates the importance of using a matching vehicle comparator in hyperhidrosis trials and appropriate excipients for GT. Limitations to consider when interpreting data include the relatively short duration of the trial compared with the chronicity of hyperhidrosis; however, long-term safety data for the open-label extension of these trials have been reported, and the results are consistent with those observed in the current trials.…”

Topical Glycopyrronium Tosylate for the Treatment of Primary Axillary Hyperhidrosis: Patient-Reported Outcomes from the ATMOS-1 and ATMOS-2 Phase III Randomized Controlled Trials

“…Though further study in younger patients will be useful, it should be noted that a post hoc analysis of the pediatric patient population from these trials showed an advantage with GT across multiple efficacy measures [25]. Finally, the effect of vehicle in these trials has been observed in other dermatology trials (e.g., acne studies [26, 27]) and indicates the importance of using a matching vehicle comparator in hyperhidrosis trials as well as inclusion of appropriate excipients for GT. The GT towelette contains the following excipients: citric acid, dehydrated alcohol, purified water, and sodium citrate [19].…”

Topical Antiacne Drugs Delivery Systems

“…Cutaneous side effects from topical antiacne agents and potential drug delivery [22]. Another study by Lamel et al (2015) revealed that clinical trial design, implementation, the biologic effects of vehicles, and natural disease progression influenced the patient responses in randomized controlled trials evaluating topical acne therapies for determination of efficacies of BPO [25].…”