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

Abstract

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.

Fibre intake and supplementation during treatment for haematological malignancies: A scoping review

“…Participants with different habitual fibre intake may have different microbiome responses to a fibre supplement 34 . One observational study used both diet histories and food records 21 to assess fibre intake, both of which may have limitations 35 . However, accurately measuring dietary intake is complex and using more than one method may be beneficial.…”

FODMAPs—Do they really affect IBS symptoms?

“…Given such factors together with the high placebo response in IBS (25, 26), the importance of a randomized, double-blind, controlled study design has long since been raised (25, 26). In addition, dietary confounding is a major challenge when supplementing foods (6). Therefore, as a basic requirement a double-blind design should substitute the same food(s) in each intervention, effectively ensuring that outcome differences should be purely related to the interventions.…”

“…However, removing foods from the diet poses a risk to confound the effect of the intervention with that of placebo, since the blinding is lost. The low FODMAP diet is well known among IBS patients, hence there is a high risk that prior knowledge will shape the clinical responses to a sizable extent, potentially even greater than the actual intervention (6). Another well-known situation is the Hawthorne effect, i.e., change of behavior in response to being observed, which may affect the outcome of the study (6).…”

“…The low FODMAP diet is well known among IBS patients, hence there is a high risk that prior knowledge will shape the clinical responses to a sizable extent, potentially even greater than the actual intervention (6). Another well-known situation is the Hawthorne effect, i.e., change of behavior in response to being observed, which may affect the outcome of the study (6). provoking with one FODMAP component only.…”

Application of The FODMAP Diet in a Paediatric Setting

“…There is no current gold standard for measuring dietary adherence to a FODMAP diet. However, expert opinion recommends measuring actual intake of the dietary component in question [ 40 ]. This can be done utilising the Monash University database of FODMAP content of foods.…”