Single-arm clinical trials: design, ethics, principles

Abstract

Although randomised controlled trials are considered the gold standard in clinical research, they are not always feasible due to limitations in the study population, challenges in obtaining evidence, high costs and ethical considerations. As a result, single-arm trial designs have emerged as one of the methods to address these issues. Single-arm trials are commonly applied to study advanced-stage cancer, rare diseases, emerging infectious diseases, new treatment methods and medical devices. Single-arm trials have certain ethical advantages over randomised controlled trials, such as providing equitable treatment, respecting patient preferences, addressing rare diseases and timely management of adverse events. While single-arm trials do not adhere to the principles of randomisation and blinding in terms of scientific rigour, they still incorporate principles of control, balance and replication, making the design scientifically reasonable. Compared with randomised controlled trials, single-arm trials require fewer sample sizes and have shorter trial durations, which can help save costs. Compared with cohort studies, single-arm trials involve intervention measures and reduce external interference, resulting in higher levels of evidence. However, single-arm trials also have limitations. Without a parallel control group, there may be biases in interpreting the results. In addition, single-arm trials cannot meet the requirements of randomisation and blinding, thereby limiting their evidence capacity compared with randomised controlled trials. Therefore, researchers consider using single-arm trials as a trial design method only when randomised controlled trials are not feasible.