Optimal Design of Clinical Trials of Dietary Interventions in Disorders of Gut-Brain Interaction.

There is accumulating evidence for the fundamental role of diet in the integrated care of disorders of gut-brain interaction. Food is a complex mixture of components with individual, synergistic, and antagonistic effects, compared with the relative purity of a pharmaceutical. Food is also an inherent part of individuals' daily lives, and food choice is strongly tied to food preferences, personal beliefs, cultural and religious practices, and economic status, which can influence its ability to function as a therapeutic intervention. Hence, randomized controlled trials of dietary interventions carry unique methodological complexities that are not applicable to pharmaceutical trials that if disregarded can pose significant risk to trial quality. The challenges of designing and delivering the dietary intervention depend on the type of intervention (i.e., nutrient vs food supplementation or whole-diet intervention). Furthermore, there are multiple modes of delivery of dietary interventions, each with their own advantages (e.g., the high precision of feeding trials and the strong clinical applicability of dietary counseling trials). Randomized placebo-controlled trials of dietary interventions are possible with sufficient attention to their design and methodological nuances. Collaboration with experts in nutrition and dietetics is essential for the planning phase; however, even with expert input, not all challenges can be overcome. Researchers undertaking future dietary trials must be transparent in reporting these challenges and approaches for overcoming them. This review aims to provide guiding principles and recommendations for addressing these challenges to facilitate the conduct and reporting of high-quality trials that inform and improve clinical practice.