Interpreting the meaningfulness of treatment effects estimated in parallel groups designs: comment on Trigg et al

Draft guidance from the U.S. Food and Drug Administration states that one can interpret a treatment effect on a clinical outcome assessment-based endpoint when expressed as some difference between group means. Recently, Trigg et al. examined different approaches for deriving thresholds for interpreting such between-group differences. In this commentary, I make several observations to advance further discussion around this issue. Some key points are (1) rather than "between-group difference," specify the level at which you wish to infer a treatment effect: population or individual; (2) points of reference may be different for interpreting individual- and population-level treatment effect estimates; (3) who provides input and what types of anchor variables are used to generate points of reference might differ for interpreting individual- versus population-level estimates of treatment effect; and (4) in a parallel groups design, meaningful within-patient change is not especially relevant for understanding the meaningfulness of a treatment effect.