The primary aim of dose-escalation trials (Phase 1 trials) is often to find the largest dose of a treatment that can be administered safely, often called the maximum tolerated dose (MTD). Rule-based designs such as the 3+3 design continue to be popular even though they can perform extremely poorly. The alternative to these rule-based designs are (Bayesian) model based approaches which use a statistical model to describe the dose-response relationship. The author lists several arguments why rule-based designs should not be used for Phase 1 dose escalation studies. (openaccessgovernment.org)