In a behavioural testing room of a clinical research facility, a well-dressed, white-haired woman is undergoing a battery of cognitive, neurological, and physiological tests. The facility, flanked by huge beech trees and set back from the road, was once a place for the severely mentally ill; known in the 19th century as a lunatic asylum, and later, a secure psychiatric unit. Now, it is used for research only. Many of its visitors are what you’d call ‘healthy volunteers,’ although their recruitment is often based on early markers of being ‘at risk’ of psychiatric or neurological conditions. This ambiguous status of being ‘healthy’ but ‘at risk’ of becoming unhealthy is an increasingly familiar one in an age of precision and preventative medicine; the latest re-drawing of the threshold between the “normal” and the “pathological” in defining health (Canguilhem 1945/1991).
Elizabeth is one such healthy volunteer in what is known as a ‘readiness cohort’: part of a longitudinal study to track Alzheimer’s disease and identify eligible participants for prevention trials. The tests will determine how far, if at all, she is along the so-called ‘disease pathway’ – a biomedical trajectory spanning from biological markers, to early signs of cognitive decline, to diagnosable dementia (Swallow 2019). The linearity of this disease pathway is translated into the logics of clinical trial design, as a (seemingly) simple measure of when participants should be invited to become part of an intervention trial. To be eligible for an upcoming trial (to be ‘trial-ready’) Elizabeth must be on this pathway, but not too far along – she must be ‘at risk’ but not have crossed the threshold to a diagnosis of dementia. At the end of the visit, the study doctor simply explains that she no longer needs to come in for such regular biomarker testing. To the doctor’s surprise, Elizabeth is disappointed that she won’t have a chance to go into the MRI machine, with its dark tunnel and mysterious whirring tones; not only does she find it enjoyable, she likes to know she is “doing her bit” for science and medicine while she is “still useful.”
In this piece, we draw on ongoing ethnographic research to explore the concept of ‘readiness’: the right time to participate in or launch a pharmaceutical drug trial (Brenman and Milne n.d.). Here we engage with work in medical anthropology and science & technology studies (STS) that follows practices of (re)defining and navigating biomedical thresholds across particular sites (Dumit 2012, Moran-Thomas 2019). We also seek contact with those who have observed the salience and harsh politics of the threshold more broadly (Jusionyte 2018). Within the readiness cohort we have been observing, the threshold marking the right time to participate is generally defined in terms of an individual’s biological and cognitive trajectories, and that individual’s psychological state of willingness to enter into a drug trial. It is the lack of alignment between these states that results in the change to Elizabeth’s study regime: whilst she is more than willing to become a trial participant, her cognitive function scores suggest she is ‘not ready.’ Elizabeth’s becoming ‘not ready’ reflects a wider shift taking place in the study, whereby most of the study population who were not likely to be eligible for an upcoming trial were moved to a less intensive, less expensive study protocol. And so, strangely, if a drug trial were to be launched tomorrow, Elizabeth would no longer be eligible. Her routine data remain valuable for tracking her aging brain, but the intensive biomarker testing excludes her in favour of ‘trial-ready’ subjects.
This bio-psychological construction of trial ‘readiness’ is bound up with what can be considered a kind of ‘cognitive bias’ (Wolf-Meyer and Yates-Doerr, this series); one that sets aside the practical work of aligning biologies and psychologies with the technoscientific promise, interests, and market processes of pharmaceutical innovation. But this work is precisely what helps us understand empirically how thresholds for intervention are drawn and redrawn in experimental drug trials. In fact, how thresholds for ‘trial readiness’ are just one moving part of this scientific project, and are therefore contingent on more than simply what goes on in the brain.
We consider what happens when we look beyond the brains and minds of individual research participants as one way in which we might re-work such a bias in biomedicine. Specifically, we explore how the economic, academic, and corporate determinants of ‘readiness’ intertwine with biological and psychological ones. This, we argue, tells a story that de-centres the brain and incorporates a different, distinctly non-neutral set of actors and interests, while resisting generic tropes about the role of the pharmaceutical industry in psychiatry.
What has made Elizabeth ‘not ready’ for a drug trial? Who or what decides where the threshold for ‘readiness’ lies? And what might this threshold tell us about other trajectories and timelines that run parallel to disease pathways firmly located within the brain? Changing scale somewhat, from small behavioural testing rooms to a vast conference centre in Geneva, we learnt more about how ‘readiness’ was being operationalised and why the threshold between ‘ready’ and ‘not ready’ seemed to be shifting. Throughout the annual meeting for the readiness cohort study, leaning against tall coffee tables on faux marble floors, we asked those who designed and coordinated the study what ‘readiness’ is and how it was being put into practice within this particular public-private partnership.
Despite the linear ‘disease pathway’ models of cognitive and biological change that mark the most recent (re)conceptualisations of Alzheimer’s disease (Milne and Latimer 2019), thresholds for readiness emerged as highly flexible, pragmatic, and workable in the context of this study. In the words of one industry partner: “readiness will look different in a year from now, in two years from now, because new interventions might come on board… you see, it kind of fluctuates.” What the industry partner was describing to us was a system wherein the eligibility thresholds were being shifted in response to particular drugs. We learnt that the reason so many participants had recently become ‘not ready’ was less about changes in psychological willingness or even disease progression, and more about the kind of drugs in the ‘pipeline’ for new trials.
While the scientists maintained their excitement about early pharmaceutical intervention (“the earlier, the better”, as Annette Leibing (2014) has put it), the pharmaceutical industry partners were less ‘ready.’ The Alzheimer’s disease pharmaceutical market operates in a specific historical context of ongoing failures and setbacks (PhRMA 2018). Whilst some companies have made the pursuit of an Alzheimer’s disease cure central to their brand, others have shied away from such time-consuming endeavours with costly setbacks. In this public-private partnership, there was a lot resting on developing drugs that showed an effect on cognitive decline. The promise of such partnerships is to enable companies to collaborate with each other and with public sector partners in a way that ‘de-risks’ pharma research (Laverty and Meulien 2019). However, the process of establishing readiness brings to the fore the balancing act involved in such efforts, between a clinico-scientific logic of ‘the earlier the better’ and commercial imperative not to test drugs ‘so early’ that effects would not be captured on regulator-approved measures. The self-described “neutrality” of this collaborative platform (ibid.) was not about being intrinsically disinterested (financially or scientifically), but rather, referred to the goal of this ongoing balancing act. This is how ‘readiness,’ as an analytic as well as the condition we have been describing empirically, became characterised by its workability – its contingency on moving parts and changing thresholds in a scientific project being put into practice.
All of this feels a long way from Elizabeth and the opportunities or expectations she may have for participating in a clinical trial. But perhaps that is the point: the location of readiness (where this temporal threshold is achieved) has important implications for how we understand disease trajectories – when bodily and cognitive change becomes pathological and, crucially, treatable. We have sought to relocate, or at least disperse, this concept of trial readiness by shining a light on the changing needs and promises of disease modelling and drug development. The ‘right time’ for intervention is about the nature and pace of neurocognitive change, but it is also about the evolving willingness, capacities, and politics of the pharmaceutical industry, as new public-private partnerships are formed. We hope that by denaturalising the story of readiness – by reworking this particular cognitive bias – we open up ways to think more broadly about the politics of timing and temporal thresholds, and of brains and biology in preventative biomedicine. In doing so, we hope that anthropology and science studies can engage with threshold shifts (from ‘ready’ to ’not ready’, or even, ‘pathological’ to ‘normal’), extending the story beyond the brains of research participants, and throughout the drug development pipeline.
Natassia Brenman is a Postdoctoral Researcher at the University of Cambridge, doing ethnographic work on the early detection and prevention of Alzheimer’s disease, primarily in the UK. She is currently developing her work on temporality, technology and vitality in the field of dementia for her forthcoming ESRC fellowship based at Goldsmiths University. This project speaks to a broader set of interests in the changing face of psychiatric diagnosis, including different or emergent ways of making sense of ‘the normal’ and the ‘pathological’ in mental health. Natassia received her PhD from the London School of Hygiene and Tropical Medicine in Medical Anthropology. Email: firstname.lastname@example.org. Twitter: @NFBrenman
Dr Richard Milne is Senior Social Scientist in the Society and Ethics Research Group at the Wellcome Genome Campus and Senior Visiting Research Fellow in the Department of Public Health and Primary Care at the University of Cambridge. His research focuses on social and ethical questions associated with the development of new medical technologies, particularly related to Alzheimer’s disease dementia and genomic medicine. He is currently working on a Wellcome Trust-funded study of how experts and members of the public address novel and recurring ethical questions associated with the development of data-driven tools for the detection of cognitive decline. Twitter: @rjmilne
Brenman, Natassia and Richard Milne. n.d. “’Ready for what?’ Timing and potentiality in Alzheimer’s disease research.” Manuscript submitted for publication.
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Leibing, Annette. 2014. “The Earlier the Better: Alzheimer’s Prevention, Early Detection, and the Quest for Pharmacological Interventions.” Culture, Medicine, and Psychiatry 38 (2): 217–36.
Milne, Richard and Joanna Latimer. 2019. “Alzheimer’s Disease and the Development of a Post-Genomic Science.” New Genetics and Society 1-13.
Moran-Thomas, Amy. 2019. “Thresholds.” In Traveling with Sugar, Chronicles of a Global Epidemic, 89–138. Berkely: University of California Press.
PhARMA. 2018. “Alzheimer’s Medicines: Setbacks and Stepping Stones” https://phrma.org/en/Alzheimer-s-Medicines-Setbacks-and-Stepping-Stones accessed 1 July 2020.
Swallow, Julia. 2019. “Markers of Biology and ‘Being’: Imaginaries of Deterioration and the Biological Redefinition of Alzheimer’s Disease.” New Genetics and Society.
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