Principles and design considerations of clinical trials

Clinical trials are gold standard for evaluating any interventions used to screen, diagnose, prevent or treat urologic cancer. There are generally four phases (I to IV) of clinical trials for the development of a new intervention. Each phase focuses on different scientific questions and is commonly treated as a separate clinical trial. Designing and conducting a clinical trial requires careful thoughts and considerations. A properly designed trial will minimize the amount of bias present in the study while greatly improving the success probability of the trial. We discuss the basic principles and the design and implementation considerations of clinical trials. Our discussion explains the definition of study objectives, selection of primary and secondary endpoints, inclusion and exclusion criteria for patient selection, and treatment and placebo choice. Other important aspects discussed include randomization and blinding. Randomization is the cornerstone methodology to minimize bias in clinical trials, which can balance both known and unknown confounders among different treatment arms, providing compelling and unbiased evidence for the comparison of the treatment arms. We discuss various randomization schemes. Sample size calculations for common types of outcomes in clinical trials are described and illustrated with examples.