[AJ2.4 Podcast ep28] This discussion delves into a commentary by Dr. Rob Califf on the nuanced question of when placebo-controlled trials are appropriate for vaccines, moving beyond simple yes or no answers. The core idea is that while Randomized Control Trials (RCTs) are the gold standard for proving cause and effect, several factors determine their ethical and practical application for vaccines. These considerations include the existing evidence for the vaccine's safety and efficacy, the inherent risk of the disease being vaccinated against, who bears the risk (individual vs. community), and whether it's a novel vaccine or an update. Ultimately, Dr. Califf argues that decisions on vaccine trial design require careful consideration of these complex dimensions rather than blanket statements, emphasizing that ethical and scientific factors must guide the process.