An arm of a clinical trial is a group of patients receiving a specific treatment (or no treatment). Trials involving several arms, or randomized trials, treat randomly-selected groups of patients with different therapies in order to compare their medical outcomes. In trials for novel therapies, patient in the experimental arm, receive an experimental drug and are compared with patients in control arms. Patients in control arms can receive an active comparator (i.e., another therapy used to treat the same condition as the experimental therapy), a placebo comparator (i.e., an inactive therapy), or a sham comparator (i.e., an inactive therapy made to look identical to the active therapy). Importantly, patients in the control arm, even if receiving a placebo, still receive standard of care appropriate for their condition. Clinical trials are designed with ethical standards to ensure that all participants have access to effective treatment and their rights are protected. Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously.

Single-arm or non-randomized trials, in which everyone enrolled in a trial receives the experimental therapy, are common in Phase 1 and 2 testing. While Phase 3 trials are frequently randomized in order to provide more precise data on safety and efficacy outcomes, a Phase 3 trial might use a single arm if a small target population makes conducting a randomized trial impractical. In these cases, researchers must use endpoints like response rate that can demonstrate clinical impact in the absence of direct comparison data.