Each of these four types of clinical trial structure has some relevance for the ME/CFS research field, addressing different objectives. The parallel structure is a simple design that’s ideal for a “does it work?” kind of treatment comparison. The factorial structure, as the description above indicates, is best suited for studying multiple treatments, both individually and in combination. For a disease as complex and multi-systemic as ME/CFS, evaluating multiple treatments is needed. As ME/CFS afflicts a heterogeneous population, a crossover structure may be helpful. Having each participant serve as their own control can remove some of the confounding factors that influence results. Finally, an adaptive structure is attractive for use in ME/CFS because participants are more likely to receive an effective treatment. While this structure makes interpreting the results of the trial significantly more complicated, it may be worthwhile in some cases.

As a practical example, since Open Medicine Foundation’s Life Improvement Trial (LIFT) is testing pyridostigmine, low-dose naltrexone, and the combination of the two drugs, it uses a factorial clinical trial structure. For more information about the LIFT, you can read the protocol paper here. 

Why is clinical trial design so important?

The design of a clinical trial can impact the success or failure of the trial, regardless of whether the treatment itself is effective or not. Therefore, it’s critical to select a clinical trial structure that is best suited for the objective of that particular study.

On top of needing to choose the structure that fits the trial objective, other components of clinical trial design are critically important for the participant experience. There are aspects of this that will be covered at other times (e.g., digital health and participant optionality), but the clinical trial structure will also impact the participant experience. Ultimately, it’s important to balance the scientific objectives and what’s best for the patients.