Preference, adherence and acceptability of three non-medicated intravaginal rings of differing external diameters: a randomized, crossover trial.

Abstract

Background: No empirical data support the 54-58mm external diameter of intravaginal rings (rings) currently available and in development for contraception and other indications. Understanding how external diameter affects preference, adherence, and acceptability is critical for optimizing future product development.

Objectives: Our primary objectives were to determine which of three non-medicated rings of differing external diameters was preferred and yielded the highest adherence. Secondary objectives were comparing acceptability, patterns of adherence, and safety of the three rings.

Study design: In an open-label, three-way crossover trial, healthy, HIV-uninfected, monogamous, sexually active, non-pregnant,18-40-year-old cisgender women and their male partners in Atlanta, GA and the Bronx, NY were randomly assigned to the sequence of using three non-medicated silicone rings (46mm, 56mm, 66mm external diameters)continuously for approximately 30 days each (90 days total; November 2021-December 2022). We tested whether end of study preference for any of the three rings was greater than 0.33 (binomial proportion, exact test). We used mixed-effect regression models with random intercepts by participant to compare adherence (ring never out for longer than 30 minutes in 24 hours); and probability of removals (including reasons for removal), expulsions, and the ring being out of the vagina all day, per ring, per day of use with the 56mm ring as the reference group; and to compare scores on a novel 19-item acceptability scale with items related to ease and experience of use, and impact on sex.

Results: 23/24 women completed the study (median age 26.7 years [SD 3.78]). Most were college graduates (92%), White (63%), non-Hispanic (79%), single (79%), and nulliparous (92%). At study end, 59% preferred the smallest (46mm) ring versus 18% each for the 56mm and 66mm rings (p=0.0045). The proportion of participants who were adherent did not differ significantly by ring (46mm, 78%; 56mm, 75%; 66mm, 59%; p=0.30), however, odds of expulsion were higher for the 46mm (OR 5.72, 95% CI: 1.25-26.1) and 66mm (OR 25.9, 95% CI: 6.11-109) rings than the 56mm ring. The 66mm ring also had greater odds of being out (removal or expulsion, any length of time) than the 56mm ring (OR 6.50, 95% CI 3.46-12.2). Mean acceptability scale scores were identical (4.54/5) for the 46mm and 56mm (smallest and medium) rings and significantly higher than the largest, 66mm ring (3.94/5; p<0.001).

Conclusions and relevance: Although the 46mm ring was preferred by more women and had higher rates of adherence compared to the other two rings, the 56mm ring was rated as equally acceptable with significantly fewer reports of expulsions/removals compared to the other two rings. These data confirm that the current 54-58mm diameter of vaginal rings on the market and in development is acceptable and performs well. Future studies should explore the effect of other mechanical attributes, such as compressibility, on preference, adherence, and acceptability, as well as investigating ring characteristics in other populations.