Perspective: Design and Conduct of Human Nutrition Randomized Controlled Trials

Abstract

In the field of human nutrition, randomized controlled trials (RCTs) are considered the gold standard for establishing causal relations between exposure to nutrients, foods, or dietary patterns and prespecified outcome measures, such as body composition, biomarkers, or event rates. Evidence-based dietary guidance is frequently derived from systematic reviews and meta-analyses of these RCTs. Each decision made during the design and conduct of human nutrition RCTs will affect the utility and generalizability of the study results. Within the context of limited resources, the goal is to maximize the generalizability of the findings while producing the highest quality data and maintaining the highest levels of ethics and scientific integrity. The aim of this document is to discuss critical aspects of conducting human nutrition RCTs, including considerations for study design (parallel, crossover, factorial, cluster), institutional ethics approval (institutional review boards), recruitment and screening, intervention implementation, adherence and retention assessment, and statistical analyses considerations. Additional topics include distinguishing between efficacy and effectiveness, defining the research question(s), monitoring biomarker and outcome measures, and collecting and archiving data. Addressed are specific aspects of planning and conducting human nutrition RCTs, including types of interventions, inclusion/exclusion criteria, participant burden, randomization and blinding, trial initiation and monitoring, and the analysis plan.

Errors in the implementation, analysis, and reporting of randomization within obesity and nutrition research: a guide to their avoidance

“…In an oft-paraphrased maxim of Lachin [108], "the best way to deal with the problem [of missing data] is to have as little missing data as possible." This goal may be furthered through diligent administrative follow-up and constant contact with subjects; further considerations on minimization of loss-to-follow-up and other missingness may be found elsewhere [115,116]. However, having no missing data whatsoever is often not achievable in practice, especially for large, randomized studies.…”

The Multifaceted Roles of Diet, Microbes, and Metabolites in Cancer

“…In contrast to cigarette smoking, for example, which can be expressed as pack-years, food contains thousands of molecules, is not easily quantified, varies geographically, and humans are notoriously inaccurate in reporting consumption [29]. Although it would probably be best to define dietary exposures using food patterns [30], most current research has focused on specific nutrients. A series of recent review articles highlighting the studies examining cancer in relation to specific dietary patterns labelled Mediterranean [31], Western, Ketogenic [32], or other such common dietary patterns [33], demonstrate that the nutrients or food groups that are specific to these diets appear to underscore potential mechanisms behind the positive or negative effects correlated with these diets.…”

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“…General participant considerations were discussed in Lichtenstein et al ( 2 ). The choice of study population influences the generalizability of the study results.…”

“…The randomized schedule for the sequence of interventions was provided by our statistician. More complex studies that assign participants to different groups may randomize by blocks or clusters to minimize bias, ensure that groups have similar baseline characteristics, or minimize contamination of the intervention as discussed in Lichtenstein et al ( 2 ).…”