Designing a Clinical Study With Dietary Supplements: It's All in the Details

Abstract

A successful randomized clinical trial of the effect of dietary supplements on a chosen endpoint begins with developing supporting data in preclinical studies while paying attention to easily overlooked details when planning the related clinical trial. In this perspective, we draw on our experience studying the effect of an ethanolic extract from Artemisia dracunculus L. (termed PMI-5011) on glucose homeostasis as a potential therapeutic option in providing resilience to metabolic syndrome (MetS). Decisions on experimental design related to issues ranging from choice of mouse model to dosing levels and route of administration in the preclinical studies will be discussed in terms of translation to the eventual human studies. The more complex considerations in planning the clinical studies present different challenges as these studies progress from testing the safety of the dietary supplement to assessing the effect of the dietary supplement on a predetermined clinical outcome. From the vantage point of hindsight, we will outline potential pitfalls when translating preclinical studies to clinical studies and point out details to address when designing clinical studies of dietary supplements.

The potential link between dietary factors and patient recovery in orthopedic surgery research

“…An extension ( 1 ) of the STROBE statement provides recommendations for reporting observational studies on human nutrition, and an extension ( 2 ) of the CONSORT statement assists with the necessary information to be included when reporting randomized controlled trials on herbal remedies. Though, there is a need for more tools ( 3 – 6 ) to guide the design of robust studies. In this opinion article, we discuss the fundamental understanding of the dietary exposure concept, not debated by other means, which shall facilitate the formulation of a hypothesis for human nutrition studies in orthopedic surgery.…”

eNODAL: an experimentally guided nutriomics data clustering method to unravel complex drug-diet interactions

“…Pre-clinical nutrition science is now equipped with conceptual frameworks and multi-factorial experimental designs (Floyd et al ., 2022), such as the geometric framework for nutrition (GFN) (Simpson et al ., 2017), that can separate nutrient-nutrient and nutrient-non nutrient interactions and map response surfaces for different traits (from molecular to life-history responses) in n -dimensional nutrient space. Adding to this explanatory power is our ability to readily measure a myriad of ‘intermediary’ phenotypes as produced from large-scale ‘omics’ experiments.…”

“…These outcomes generate insights into how experimental factors interact to determine health. The challenge now is how best to analyze the datasets produced from these multi-factorial experiments, where the number of omics features tends to be much larger than the sample size (Floyd et al, 2022;Thangadurai et al, 2022).…”