Parallel–group design is a simple design in which each participant is randomly assigned to receive a particular treatment or not. Multiple drugs or treatments may be tested versus each other, and there is often a control or placebo group. Different doses of the same drug can also be simultaneously evaluated. This design is simple and eliminates the potential for drug interaction.

In a crossover design, in general, two treatments are evaluated. Each group receives two treatments but the order is randomly assigned. Prior to the crossover, the design appears to be similar to a parallel-group design. However, the crossover allows one to determine the benefit of adding one drug/treatment to another in a sequential fashion and which order is most beneficial. This design is appropriate for chronic conditions that are stable over time and for interventions that last a short time. It is important that the treatment drugs do not react with each other to avoid making inaccurate conclusions about the results. It should be noted that crossover designs have also been used to evaluate timing of surgical treatments; for example, in the NSABP B-18 trial, patients were randomized to receive either (neoadjuvant) chemotherapy followed by surgery or surgery followed by chemotherapy in order whether one sequence was superior to the other.

In a factorial design, two drugs or interventions can be simultaneously evaluated. With two drugs, four combinations of treatments and placebo are possible. Patients are randomly assigned to each group. For example, one group might receive drug A and drug B. Another group would receive drug A and placebo. Another would receive drug B and placebo, and another would receive two placebos. The factorial design can be very efficient, as data is gathered on two drugs at the same time. A drawback of the factorial design is the concern over potential drug interactions; however, this design also allows for the determination of synergies between two treatments.