“Unique, but Similar”: The Paradox of Evidence-Based Medicine

Emily Wheater // During UK lockdown, I watched a debate on the subject of the existence (or not) of ‘the female brain’. In her concluding remarks Gina Rippon (author of The Gendered Brain), after arguing for the motion that ‘there is no such thing as the female brain’, said ‘I think every brain is different from every other brain’.

This comment struck me as significant, both in being evidently true, but also a little frustrating. It is true that our brains, and living beings more widely, are unique, and yet it is also true that there exists much similarity between individuals (something also stressed by all speakers during the debate). The need to balance the two truisms that we are all different from one another and, simultaneously, that we have much in common is one that is present within most efforts, scientific, artistic, or philosophical, to understand the human condition. 

My frustration stemmed from the conclusion that if it were really the case that we are all really so different and unique, then one might conclude that most of the medical science community is currently engaged in a fruitless endeavour. Much of the enterprise is, after all, predicated on the assumption that by experimenting and observing our research or reference group, Group X, we will learn something that we can apply to Group Y, due to some important commonality between the two groups. Group Y in this case might be a patient population with a particular diagnosis. Group X might be a group of people with the same diagnosis enrolled in a randomised clinical control trial (RCT); group X might even be a group of experimental animals, zebrafish or mice, modeling an aspect of human disease. We hope that findings in our research on Group X, be it made up of human, rodent, or ichthyic individuals, will be generalisable to other groups.

The evidence-based medicine paradigm has been extraordinarily successful, and it is predicated on this notion of similarity. The patient sitting in front of a doctor is unlikely to have been involved in the exact RCT that demonstrated the efficacy of a specific treatment. Yet the doctor may still recommend that treatment because, extrapolating from available evidence and applying it to the case before them, the doctor supposes it will help their patient.

There are, of course, flaws and difficulties. The validity of findings from the RCT to this patient may limited, and the treatment not well suited to the patient. This problem arises in particular when there is systematic exclusion of people with certain characteristics from the research, such that the patients eligible for clinical trials are consistently not representative of the patient group that health workers encounter in their clinical practice. The male sex bias in medical research and its consequences have been extensively demonstrated by writers such as Caroline Criado Perez in Invisible Women and Dr. Alyson Macgregor in Sex Matters. Women, often absent from the reference group that is explicitly studied but present in the wider patient population that is generalised to, are served less well by research that excludes them. This is because as a group they are less similar to the reference group than other men are likely to be. This issue of representation in research applies to other characteristics: ‘difficult to reach’ populations, or patients with complex co-morbidities [1,2].

Personalised or precision medicine (PM) has arisen from the advent of genomics and offers a response to this critique of evidence-based medicine. The aim of personalised medicine is to provide care and treatment to a patient that is tailored according to that individual’s specific profile of characteristics (such as genetic, biomarker, or psychosocial factors) to maximise therapeutic effect and minimise adverse effects [3]. It is sometimes framed as a competing paradigm to evidence-based medicine [4]. However, personalised medicine can be viewed more as an extension of the existing paradigm. In taking into account genetics and molecular profiling its promise lies in refining the ‘reference groups’ that are so crucial to evidence-based medicine, which in turn enables better prediction for the individual patient [5].

There is a moment from a BBC documentary, Big Cats About the House, that illustrates this tension brilliantly. It involves Maya, a baby black jaguar, who was rejected by her mother and subsequently adopted by Giles Clark, who runs a big cat sanctuary in Kent. Several weeks into her fostering Maya is not quite meeting the developmental milestones that Clark expects, based on observations of her contemporaries in the wild. Worried, Clark rises one morning, still in darkness, and drives many miles and many hours to a specialist veterinary practice. There, little Maya has a structural MRI scan. The narrator tells us that they are looking for ‘abnormalities in the soft tissue of Maya’s brain and nervous system’. Much is made of the fact that this is the first time, that anyone is aware of, that a jaguar has ever been in an MRI scanner.

As it turns out, in the absence of profound injury, or defect, the scan is inconclusive. With the anatomical structures present and correct the only finding of note are some bright spots in the brain. The veterinarian comments that if observed in a human infant at an analogous developmental stage these might be a cause for concern. If observed in a puppy they would be quite normal. But Maya is neither a human baby nor a puppy and, this again, being the first jaguar to have had an MRI scan means that there is no frame of reference within which to interpret this image. Shrug.

It’s an artful moment of anti-climax following the buzz of ‘first ever’, and a neat demonstration of the unique-but-similar paradox. However much we were to measure and to probe and to scan her, our understanding of Maya the individual jaguar would still be limited by what we don’t know about jaguars—the collective. With no reference for what constitutes ‘normal’, we cannot say what is unique about Maya.

We, and our brains, are all unique and different, and it is certainly important to remember this. But it also only gets us so far, and a balance must be struck with seeking commonalities. After all, little Maya the jaguar cub only makes so much sense on her own.

Caroline Criado Perez, 2019. Invisible Women. Random House.

Dr. Alyson J. McGregor, 2020. ‘Sex Matters: How male-centric medicine endangers women’s health and what we can do about it.’ Quercus.

[1] Shaghaghi, A., Bhopal, R. S. & Sheikh, A. Approaches to Recruiting ‘Hard-To-Reach’ Populations into Re-search: A Review of the Literature. Heal. Promot. Perspect. 1, 86–94 (2011).

[2] Fortin, M. et al. Randomized controlled trials: do they have external validity for patients with multiple comorbidities? Ann. Fam. Med. 4, 104–8 (2006).

[3] Chow, N., Gallo, L. & Busse, J. W. Evidence-based medicine and precision medicine: Complementary approaches to clinical decision-making. Precis. Clin. Med. 1, 60–64 (2018).

[4] Hays, P. Personalized medicine: paradigm shift or revolution. Genet. Med. 21, 1662 (2019).

[5] Kent, D. M., Steyerberg, E. & Van Klaveren, D. Personalized evidence based medicine: Predictive approaches to heterogeneous treatment effects. BMJ 363, (2018).

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