Best (but oft forgotten) practices: Applying the target trial framework in nutrition research

When randomized trials in nutrition are not feasible, timely, or ethical, observational studies serve as important pillars of evidence-informed clinical decision-making and public health guidelines. Given that diet is dynamic, multidimensional, and multifactorial, causal questions of dietary exposures are often complex. Consequently, research questions are often poorly defined, making study findings difficult to interpret and implement in the real world. Conceptualizing the design and analysis of observational data like a hypothetical pragmatic randomized trial, a target trial, is one approach to improve the specificity and interpretation of causal questions. Protocol components, including eligibility criteria, treatment strategies, and assignment procedure, outcome and follow-up, causal contrast, and statistical analysis plan, are clearly specified and subsequently implemented using available observational data. In this paper, we explain the target trial framework approach, describe examples from nutrition research, demonstrate the practical steps of performing a target trial study, and discuss the methodological challenges and opportunities of applying the framework to nutrition research.