The importance of proper placebo-control in sexual medicine medical device trials
Krychman, M1; Allan, B2; Wilkerson, D3; Bell, S3
1: Southern California Center for Sexual Health and Survivorship Medicine, United States; 2: Allan Centre, Canada; 3: Viveve Inc., United States
Objective(s): To evaluate the placebo effect for a medical device that uses monopolar radiofrequency (RF) with cooling when treating women experiencing symptoms of sexual dysfunction and to assess the importance of inclusion of an appropriate placebo control in clinical trials for women’s health.
Material and Method(s): A prospective, longitudinal, randomized, blinded, placebo-controlled, multi-center clinical study was conducted for the treatment of sexual dysfunction with vaginal introital laxity as a primary symptom. The treatment is an outpatient monopolar RF procedure that couples energy administration to heat underlying tissue while cooling and protecting the vaginal mucosa. Efficacy and safety have been published elsewhere. This international study is the first and only of its kind ever done for RF treatment for sexual dysfunction. Subjects were randomized in a 2:1 ratio to either the active (90 J/cm2) or sham (≤1 J/cm2) treatment groups. Nine sites were chosen in multiple countries (Italy, Spain, Canada and Japan). Subjects were followed up at 72 hrs., 10 days, and 1, 2, 3, and 6 months post-treatment. Patient reported outcomes included the Female Sexual Function Index (FSFI) and a 7-point Likert scale assessment for vaginal laxity.
Result(s): A total of 155 premenopausal female subjects that did not have any major protocol deviations were included in this analysis. The procedure was well tolerated, preformed in ~30 minutes in an outpatient setting without the need for topical anesthetic or pain medications. Recovery to activities of daily living was immediate. Results demonstrated a statistically significant, clinically meaningful difference at 6 months between active treatment and sham intervention. The active treatment group 3 times more likely to report “no laxity” (p≤0.006). However, the sham treatment group showed a substantial placebo effect at early timepoints, with a 31% and 33% increase in “no laxity” at months 1 and 3, respectively. By 6 months the treatment effect was more apparent.
Conclusion(s): In order to adequately power and design future research initiatives, investigators must take into account the possibility of a substantial “sham effect” for sexual dysfunction studies; underscoring the importance of placebo/sham-controlled trials to ensure that the effect being seen is actually due to the investigational product. In addition, the inclusion of a proper sham or placebo rather than no treatment, especially for medical device studies, is very important.
Work supported by industry: yes, by Viveve Inc. (industry initiated, executed and funded study). The presenter or any of the authors act as a consultant, employee (part time or full time) or shareholder of an industry.Go Back