True and false interindividual differences in the physiological response to an intervention

Shows that within-subject random variation — inevitable even with gold-standard measurement — is sometimes large enough to explain ALL apparent individual differences in response to an intervention.

True individual response differences are quantified only by comparing the SD of changes in the intervention arm with the SD of changes in a comparator arm (or from a prior repeatability study in the same population over the same duration). The difference between these SDs is what later literature calls the SD of individual responses (SDIR).

Most "individual response" papers conflate true biological variance with measurement error and regression to the mean. Popular plots of individual change scores are contaminated by random within-subject variation.

Using a simulated blood-pressure data set, the authors show that large individual differences in response can be suggested by such plots and analyses even when the true response is exactly the same in every individual.

If the SDs of change are similar in the intervention and comparator arms, true individual differences are clinically unimportant and any further "responder" analysis is unwarranted.