In a symposium titled “Beyond Placebo: Designing and Implementing Next Generation HIV prevention HIV prevention Trials”, presentations provided regulatory, statistical, ethical, and community perspectives on the current dilemma in designing new randomised clinical trials (RCTs) in the era of highly effective FTC/TDF as standard of care. From the regulatory perspective, Jeffrey Murray from the US FDA noted that non-inferiority trials may not be possible in women due to absence of a consistent historical comparison. New non-inferiority trials may be possible in MSM, but because the interpretation of non-inferiority trials depends on infection rates, as adherence increases the rate of new infections decrease (meaning it will require trials with potentially unfeasible large sample sizes or very long follow up.) From the statistical perspective, Deborah Donnell noted that potential solutions for future designs may include: refining the statistical approaches by changing the measurement scale (e.g. use of relative difference, restricted mean survival time, or averted infection ratio); increasing the operational efficiency of RCTs (for example using multi-arm trials or multi-arm multi-stage designs); or modifying the population enrolled in the trial based on participant unmet needs or willingness to use current standard (FTC/TDF).