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Issues in the determination of “responders” and “non-responders” in physiological research

Atkinson, Greg; Williamson, Philip; Batterham, Alan M


Greg Atkinson

Philip Williamson

Alan M Batterham


As a follow-up to our 2015 review, we cover more issues on the topic of “response heterogeneity”, which we define as clinically-important individual differences in the physiological responses to the same treatment or intervention that cannot be attributed to random within-subjects variability. We highlight various pitfalls with the common practice of counting the number of “responders”, “non-responders” and “adverse responders” in samples that have been given certain treatments/interventions for research purposes. We focus on the classical parallel-group randomised controlled trial (RCT) design and assume typical good practice in trial design.
We show that sample responder counts are biased because individuals differ in terms of pre-to-post within-subjects random variability in the study outcome(s) and not necessarily treatment response. Ironically, sample differences in responder counts may be explained wholly by sample differences in mean response, even if there is no response heterogeneity at all. Sample comparisons of responder counts also have relatively low statistical precision. These problems do not depend on how the response threshold has been selected, e.g. on the basis of a measurement error statistic, and are not rectified fully by the use of confidence intervals for individual responses in the sample.

Journal Article Type Article
Publication Date Aug 1, 2019
Print ISSN 1469-445X
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 104
Issue 8
Pages 1215-1225
APA6 Citation Atkinson, G., Williamson, P., & Batterham, A. M. (2019). Issues in the determination of “responders” and “non-responders” in physiological research. Experimental Physiology, 104(8), 1215-1225.
Keywords Response heterogeneity; Inter-individual differences; Standard deviation; Responders; Within-subject random variability
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