Mind the gap: widening the demographic to establish new norms in human physiology

Abstract

The Journal of Physiology has a long and proud tradition of publishing studies of human physiology at the forefront of the field, cultivating and curating significant advances in our understanding of the functions of the body. The Journal of Physiology is further enriched by exploration of the science of life across many species and model systems. It is a standard bearer for the field, standing on the shoulders of many fine physiologists in our community who contribute to the reputation of the discipline in the wider scientific community. Importantly, as it should, The Journal of Physiology has moved with the times and has not shirked responsibility in upholding standards for the field, striving to be a leader amongst leaders. Diversity is at the heart of many of our institutions, including The Physiological Society and her academic journals. The gender gap is narrowing. A different, but related, narrative is played out, in its own way, on the pages of The Journal of Physiology when one considers the balance achieved in mixed-sex studies involving human participants (Table 1). Sex is now firmly embedded as a core consideration in the design of research studies. Analysis of original research articles published in The Journal of Physiology between January 2017 and December 2019 reveals that 27% of the total original research articles involve human participants or human tissue samples, with the total number of human studies and relative proportion increasing year-on-year (Table 1). Encouragingly, two-thirds of studies involving human participants are mixed-sex studies, and whereas there remains a broad imbalance within many studies, suggesting the need for further change, when all human studies in all fields are combined the average ratio is 57%:43% (male:female), with about one-half of all studies in human participants achieving an outcome that sits within the 1.5:1 range. Mixed-sex studies of exercise, cardiovascular and muscle physiology are male dominant, with notable exceptions. Mixed-sex studies of motor control and movement, proprioception, and CNS plasticity are often female dominant. Encouragingly, for publications in 2019, the proportion of mixed-sex studies had increased and the balance achieved therein improved, compared with the preceding two years. There remains a considerable portion of single-sex studies, with a male bias. Studies exclusively in male participants represented 20–31% of publications involving human participants, with the lowest proportion published in 2019 (Table 1). Again, it is evident that studies of exercise, muscle and cardiovascular physiology emerge as areas that commonly study male participants only. Studies exclusively in female participants account for 8% of published studies involving human participants and tend to relate to aspects particular to the female sex (pregnancy, menopause, reproductive disease), with some exceptions. There are ∼3 times as many single-sex studies in males compared with females within the 3-year period of review (Table 1). Noting that sex differences in physiology are increasingly recognized, it appears that there is further scope for improvement across all fields of study in physiology, wherein findings can adequately apply to both sexes and/or allow for robust comparison between sexes. Whereas authors are commended for the design of mixed-sex studies, there are many examples of studies published in the period of review with >4:1 sex bias. In small population studies, this often plays out as the inclusion of just one or two female participants (or less commonly one or two male participants). Clearly, this precludes analysis of potential sex differences, which proves problematic at times even in well-balanced studies that have a small sample size (e.g. n = 5 vs. n = 5). Moreover, if sex differences exist, then the pooling of data increases variability and may be such that there is less statistical power to detect a meaningful physiological difference than the original sample size might have suggested, unless accounted for in the design phase. Indeed, this potential for added variability is often cited as the basis for the exclusion of female participants in studies. Understandably, there are often logistical challenges affecting study design. It is also important to acknowledge that mixed-sex studies may not be concerned overtly with sex as an independent variable and may faithfully explore the relevant hypothesis in a mixed-sex study, which if balanced and robust reveals outcomes relevant to males and females. These points are familiar to authors and readers of The Journal of Physiology. However, recognition of sex differences in physiology in health and disease draws sharp focus on the need for studies that explore the extent of those differences and the underlying mechanisms at play that explain the bases of the differences, or robust confirmation that there is no difference at all. Importantly, this approach is evident in papers published in The Journal of Physiology during the period of analysis, with exemplar publications illustrating similarities and differences between sexes across different domains of physiological function. Collectively, the community should strive for such study design to be the norm. Diversity is multi-faceted. The diversity of physiological function in health reasonably extends to ageing. Discussion of diversity is incomplete without consideration of race and ethnicity. There are many excellent studies published in The Journal of Physiology that have focused on age-related differences, comparing young and older participants in health or disease (or both and sometimes in both sexes). However, the study of young participants (especially healthy males) dominates the recent literature (Table 2). There are few studies of older participants, especially healthy middle-aged participants. The latter demographic is better represented in studies of disease, wherein, when included, age-matched healthy participants provide added insight through inclusion as control participants (Table 2). There is a relative paucity of studies in older (>65 years) participants, and fewer studies in older women compared with older men. On the face of it, the age bias is perhaps not unexpected. The Journal of Physiology publishes more studies of physiology in health than in disease (Table 2). Young participants provide the gold standard for physiology. As with sex, the known or presumed age-related differences in physiological processes can encourage exclusion of older participants, unless age is a factor of interest in the study design. Again, it is worth noting and celebrating that the latter approach is not universal. Clearly, more studies focusing on the physiology of ageing per se are required. But, one can also reasonably suggest that more studies that widen the demographic of healthy participants to include older participants are warranted. Y (31); Y+MA+O (4); Y+MA (2) Y+O (1); MA (2); MA+O (1); ? (2) Early life (3); Y (3); Y+MA (6); MA+O (2); Y+O (1); Y+MA+O (1); ? (2) Children (1); Y (26); Y+MA (2); Y+O (2); MA+O (1); O (1) Early-life (1); Y+MA (6); MA (4); Y+MA+O (3); MA+O (2) Early-life (1); children (1); Y (21); Y+MA (3); Y+MA+O (1) Y+O (3); MA+O (1); O (1); ? (2) Y (2); Y+MA (2); Y+MA+O (4); MA+O (1); O (1); ? (2) One can readily appreciate the interest and focus on nutrition, training, and peak muscle and cardiorespiratory performance in studies of young athletic participants. Indeed, the more important gap in this area of investigation relates to sex, more than age. Older, recreationally active and sedentary people matter too! And they are studied, but to a much lesser extent. Of course many factors contribute to selection bias within a field of study, including the logistics of complex study designs and the not-insignificant commitment required of participants. These factors and others such as recruitment across university campuses heavily shape the demographic of many studies. In field studies, such as at high altitude, the available pool of lowlander participants is often limited. Interestingly, for these reasons, there is often a widening of the demographic in participant recruitment to ensure adequate sample size, with potentially greater heterogeneity. Whereas this is often regarded as a limitation (sometimes motivating exclusion criteria related to age when young participants are available), one could argue that it is a potential strength of such a study in that it captures the ‘normal’ physiology of a healthy population across a broad age profile. Moreover, the outcomes of a study in a mixed group of participants may have greater bearing on the wider population to whom the study is especially relevant. Race and ethnicity are terms sometimes understood as interchangeable and yet also recognized as distinctly different in the context of genetics and custom or culture. Genetic differences can be considered the least- and most-relevant factor in studies of biological differences between populations. Genetic variability can be greater within a racial category than between races (much like diversity of opinion and personality) and as such not a principal factor to the core study, and yet may be emphasized as a defining and deterministic driver of major physiological differences between populations (e.g. lowlander versus Sherpa). Biogeographical ancestry emerges as the key influential factor amongst a complex contemporary landscape that includes socioeconomic factors. Interestingly, very few studies published in The Journal of Physiology include information on participant race or ethnicity, beyond studies of indigenous peoples such as the Sherpa, where this identity is the centrepiece of that unique class of studies. Some funding agencies mandate collection of participant-determined ethnicity and race, including multi-racial categorizations and explicit inclusion of minority groups, with noble interests in widening diversity in participant recruitment. This often better relates to socio-political than anthropological constructs, but is important for various reasons. The fundamental findings published in The Journal of Physiology reflect the physiology of a multi-racial, multi-ethnic global population. The studies are informed by the participation of such populations and the findings are wholly relevant to them. Reporting of race and ethnicity may better reflect this position and may serve to further encourage recruitment of a wider demographic with diversity in mind. A key quality measure for editors of The Journal of Physiology is the standard of study design and execution. The Journal of Physiology strongly encourages our community of contributors to continue to raise the bar in the design, delivery, reporting and critical appraisal of studies in human physiology (as it does in parallel for all studies). Whether related to sex, age, race or ethnicity, selective recruitment strategies may be ironing out the creases that are characteristic of our collective form. There are clear gaps in the knowledge base and perhaps a risk of a skewed understanding of ‘normal’ physiology in a healthy population. A broader understanding of the diversity of physiology in our population, where it exists, lends itself to a better appreciation of the natural variability in physiological responses to stressors in health and disease. A broader representation of our diverse population lends itself to a better appreciation of the relevance of the findings published in The Journal of Physiology to a wide demographic. Contributors’ views on these matters of debate are sought and will help to shape The Journal’s policies into the future. None. Sole author. None.

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