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Review
. 2024 Jul;109(7):1099-1108.
doi: 10.1113/EP091557. Epub 2024 May 19.

Myths and Methodologies: Standardisation in human physiology research-should we control the controllables?

Lucy H Merrell  1 , Oliver J Perkin  1 , Louise Bradshaw  1 , Harrison D Collier-Bain  1 , Adam J Collins  1 , Sophie Davies  1 , Rachel Eddy  1 , James A Hickman  1 , Anna P Nicholas  1 , Daniel Rees  1 , Bruno Spellanzon  1 , Lewis J James  2 , Alannah K A McKay  3 , Harry A Smith  1 , James E Turner  4 , Francoise Koumanov  1 , Jennifer Maher  1 , Dylan Thompson  1 , Javier T Gonzalez  1 , James A Betts  1
Affiliations
Review

Myths and Methodologies: Standardisation in human physiology research-should we control the controllables?

Lucy H Merrell et al. Exp Physiol. 2024 Jul.

Abstract

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts.

Keywords: control; physiology; standardisation.

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Conflict of interest statement

A.K.A.M. has received research funding from the Australian Institute of Sport, Boston Children's Hospital's Female Athlete Program, Amazentis Life Sciences and the Swiss National Science Foundation; and has completed paid consultancy for PepsiCo. L.J.J. has current/previous funding from Entrinsic Beverage Company LLC, Entrinsic Bioscience LLC, Herbalife Europe Ltd, Bridge Farm Nurseries, Decathlon SA, PepsiCo Inc., Volac International; has performed consultancy for PepsiCo Inc. and Lucozade Ribena Suntory; and has received conference fees from PepsiCo Inc. and Danone Nutricia. In all cases, monies have been paid to L.J.J.’s institution and not directly to L.J.J. J.T.G. has received research funding from BBSRC, MRC, British Heart Foundation, Clasado Biosciences, Lucozade Ribena Suntory, ARLA Foods Ingredients and Cosun Nutrition Center; is a scientific advisory board member to ZOE and 6d Sports Nutrition; and has completed paid consultancy for The Dairy Council, PepsiCo, Violicom Medical, Tour Racing Ltd, and SVGC. J.A.B. is a named investigator on research grants funded by BBSRC, MRC, British Heart Foundation, Rare Disease Foundation, EU Hydration Institute, GlaxoSmithKline, Nestlé, Lucozade Ribena Suntory, ARLA foods, Cosun Nutrition Center, American Academy of Sleep Medicine Foundation and Salus Optima (L3M Technologies Ltd); has completed paid consultancy for PepsiCo, Kellogg's, SVGC and Salus Optima (L3M Technologies Ltd); is Company Director of Metabolic Solutions Ltd; receives an annual honorarium as a member of the academic advisory board for the International Olympic Committee Diploma in Sports Nutrition; and receives an annual stipend as Editor‐in Chief of International Journal of Sport Nutrition & Exercise Metabolism.

Figures

FIGURE 1
FIGURE 1
A summary of key variables to consider controlling when designing studies of human physiology, with examples to demonstrate continuums of practical strategies that may be employed from little control to tight control. The degree of control for each variable within a given study should be specific to the context of the research question and practical constraints. Meds, medications; PA, physical activity.
FIGURE 2
FIGURE 2
A graphical representation of the endogenous ovarian hormone fluctuation throughout a ‘typical’ menstrual cycle in eumenorrhoeic women. Potential phase outcome data derived from Baker and Driver (2007), Colenso‐Semple et al. (2023), Meendering et al. (2005), Oosthuyse and Bosch (2010).
See this image and copyright information in PMC

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