Flo Digital Contraceptive Study

Summary

The goal of this clinical trial is to learn if the Flo Digital Contraceptive (FDC) app can effectively prevent unintended pregnancy in women aged 18 years and older residing in the United States. The main questions it aims to answer are: What is the rate of unintended pregnancy in women aged 18-35 years using FDC as their sole method of contraception under typical-use conditions, measured using the Pearl Index? What is the cumulative probability of unintended pregnancy over 13 menstrual cycles for all participants, including those with regular and irregular cycles? Participants will: Use the Flo Digital Contraceptive app in 'prevent pregnancy' mode as their primary method of contraception for up to 13 menstrual cycles or 18 months, whichever comes first Wear an Apple Watch (Series 8 or later, or Ultra) while sleeping to collect nightly wrist temperature data, which the app uses to detect ovulation Log menstrual cycles, sexual activity, and any use of emergency contraception directly in the Flo app Complete monthly electronic surveys (ePROs) administered by the study team covering pregnancy status, adherence, safety, and experience Complete a baseline demographic survey at enrollment and an exit survey at the end of participation

Detailed Description

Study Overview The FOCUS trial (Flo Contraceptive US Study) is a prospective, single-arm, non-randomized, decentralized clinical study evaluating the contraceptive safety and effectiveness of the Flo Digital Contraceptive (FDC) - a fertility awareness-based Software as a Medical Device (SaMD) - in preventing unintended pregnancy. The study is sponsored by Flo Health Inc. and conducted by Lindus Health Ltd. as the Contract Research Organization (CRO), with participant recruitment across the United States. The FDC is a proprietary machine-learning algorithm integrated within the Flo Period \& Cycles Tracker app (iOS). It uses menstrual cycle history and physiological indicators of ovulation - primarily overnight wrist-skin temperature measured via Apple Watch (Series 8 or later, or Ultra), with optional urinary luteinizing hormone (LH) tests - to dynamically classify each day of the user's cycle as either 'Not fertile' (unprotected intercourse permitted) or 'Use protection' (abstinence or barrier contraception required). The FDC operates as an API-based SaMD integrated within the Flo app as the target user interface. The algorithm predicts daily fertility based on user-provided inputs, with predictions dynamically updated as new data is received. Wrist-skin temperature is continuously monitored throughout sleep, which accommodates variable sleep schedules and is a reliable method for detecting biphasic temperature patterns associated with ovulation. For participants with irregular cycles, the FDC algorithm adaptively expands the 'Use protection' window in proportion to detected cycle length variability. Following enrollment confirmation and FDC device activation, participants log menstrual period dates, sexual activity (including whether barrier methods were used), and any use of emergency contraception in the Flo app. Participants are followed for up to 13 menstrual cycles or 18 months from device activation, whichever occurs first. Study Objectives The primary objective is to evaluate the typical-use contraceptive effectiveness of FDC in preventing unintended pregnancy among women aged 18-35 years with regular menstrual cycles (21-35 days), using the Pearl Index assessed against a pre-specified clinically acceptable upper limit of 10 pregnancies per 100 woman-years. A supporting secondary analysis uses Kaplan-Meier life-table methodology to estimate cumulative pregnancy probability over 13 cycles for all participants, assessed against a pre-specified cumulative threshold of less than 10%. Participants will be censored from the life-table analysis for voluntary withdrawal, loss to follow-up, study completion, or ineligibility. Secondary objectives will evaluate perfect-use effectiveness of FDC in the highest-risk population (aged 18-35 years), and typical-use and perfect-use effectiveness of FDC in the full intended-use population (aged 18 years and older), using the same statistical approaches. Exploratory objectives will evaluate typical-use effectiveness across pre-specified subgroups: cycle regularity (regular vs. irregular), Flo user status at enrollment (existing vs. new), and recency of hormonal contraceptive discontinuation (within vs. beyond 3 months prior to enrollment). Sample size Target enrollment is 3,800 participants, determined by the more conservative of two sample size calculations. The Pearl Index analysis requires approximately 900 participants (568 woman-years of exposure), while the Kaplan-Meier analysis requires 3,800 participants to achieve 80% power. A per-cycle dropout rate of 8% is assumed, corresponding to approximately 66% cumulative attrition by cycle 13. Safety Monitoring Given that FDC is a SaMD with no direct physiological interaction, the primary safety concern in this study is unintended pregnancy. This risk is monitored continuously through multiple safeguards including monthly pregnancy surveillance via ePRO and Flo app logging, participant-initiated reporting, and regular independent review by a Data Safety and Monitoring Board (DSMB). Regulatory and Ethical Oversight FOCUS is classified as a significant risk device study under 21 CFR Part 812. Enrollment will not commence until Institutional Review Board (IRB) approval has been obtained and FDA has granted IDE authorization. Informed consent is obtained electronically via Florence Healthcare in a fully asynchronous, documented process compliant with 21 CFR Part 11. Results will be publicly disclosed regardless of outcome in accordance with regulatory requirements and Good Publication Practice guidelines.

Eligibility Criteria

Interventions