Innovation and Biomedicine

Ethics, Evidence and Expectation in HIV

M. Michael, M. Rosengarten

• Publisher: Palgrave Macmillan
• Year: 2013
• Print ISBN: 9780230302679
• eBook ISBN: 9781137316677
• Topic: Social Sciences
• Subtopic: Ethics & Moral Philosophy
• Index: Social Sciences

With its focus on the offshore randomized control trials of a Pre-Exposure Prophylactic pill (PrEP) for preventing HIV infection, the volume develops a sustained analysis of the complex, virtual and topological dimensions of the expectations, ethics and evidence that surround the innovation of PrEP.

1

Introduction: Setting a Scene

It is a commonplace to worry about the pace of innovation in biomedicine. From the perspective of some actors, innovation moves too quickly, throwing up complex regulatory issues and ethical dilemmas that are sometimes barely tractable. For others, innovation cannot take place fast enough: in the here and now, there are lives to be saved and there is suffering to be eased. Often these two contrasting apprehensions toward biomedical innovation reside simultaneously in a single actor (whether that actor be individual or collective). This ambivalence reflects the contradictory character of much that passes for biomedical innovation. With the development and arrival of a new drug, technology, procedure or intervention, not only might lives be saved, but they can also be endangered at one and the same time.

However, portraying the concerns associated with biomedical innovation in terms of such ambivalence misses the point on several levels. Or rather, it frames the issue in a very particular way that reflects, mediates and enacts a series of ontological, epistemological, political, social and ethical perspectives. By way of initial illustration, let us focus on the possible negative impacts of a new therapy. Immediately, we might note that it is not only the health of bare lives that is potentially placed at risk. This intervention can also negatively affect, for example, local and national communities, civil rights, economic opportunity, wider health system provision or particular types of gendered relations. To make this observation is to begin to shift our understanding of that intervention. Ontologically, it is not simply constituted of its material composition and technical properties (for example, such and such a pharmaceutical compound, such and such an effect on a disease entity or such and such side-effects on a human body) but emerges out of a nexus of complex, multifarious and shifting relations that includes a range of material, individual, community, institutional, policy and political actors. Epistemologically, an intervention is not knowable simply through the assumptions that inform bioscientific and biomedical techniques (for example, the objectivity of randomized controlled trials) but through a model of knowing, or engagement, that aims to capture the situatedness, relationality, emergence and performativity of a representation of a biomedical intervention. Such interventions are not politically and socially neutral, or even complicated in the sense that there are very many political and social factors to be taken into account in order to develop, deploy and assess an intervention. Rather, these social and political elements are complex in that they relate to each other recursively: the borders between social categories or political actors come in and out of focus in sometimes unusual and unexpected ways. Ethically, the intervention is judged in relation to a set of impacts that extends far beyond the individual or the statistically aggregated body. But further, this process of ethical judgement that identifies and compares positive and negative effects has its own particular trajectory. It reflects, mediates and enacts a practice of ethics which folds into and contributes to the ontological, epistemological, social and political emergence of the intervention.

Hopefully, the foregoing should have provided a preliminary sense of a series of interconnected relations – ontological, epistemological, material, social, political and ethical – through which we can approach biomedical innovation. Or, to put this another way and introduce another term, we can address biomedical innovation with the aid of the notion of ‘assemblage’. We shall have quite a lot to say about this idea along with a number of other supplementary concepts such as ‘object’ and ‘thing’, ‘topology’, ‘enactment’, and especially ‘event’. However, what we can point out here is that this particular formulation, albeit all too vague at the moment, is not just derived from the theoretical literature. Crucially, it is also shaped by our engagement with specificities of biomedical innovation within the HIV field, and especially the randomized controlled trialling (from here on referred to as RCT or RCTs) of a pre-exposure prophylactic intervention, a pill taken every day that ostensibly decreases the risk of HIV infection (PrEP).

That is to say, our thinking on innovation and biomedicine is worked through a particular example of, in some ways, a rather unexciting innovation – a pill made up of existing drugs that can serve as a prophylactic against ‘the’ HIV virus. Needless to say, this does not have some of the key features of more ‘exotic’ innovations, most obviously those associated with cutting edge, ‘high technology’ biomedical research such as stem cell-based regenerative medicine (for example, the fraught regulatory quandaries and ethical dilemmas of using human embryo-derived materials, or the transformation of the clinical landscape implied in the promises associated with stem cell research). Nevertheless, the complexities entailed in, and the potential associated with, a seemingly ‘simple’ or ‘mundane’ intervention like PrEP are a match for those of any of the more ‘dramatic’ or ‘spectacular’ biomedical innovations. In other words, the divide between ‘exotic’ and ‘mundane’ biomedical innovation is highly porous.

Now, we would not wish to imply that PrEP is merely an example, an illustration, a medium – to be sure a highly consequential one – with which to work through an array of issues concerning biomedicine and innovation. Rather, we are also interested in PrEP in itself, not least because it may have a major impact on individuals, communities and nations in which the risks of HIV infection are particularly elevated. For instance, through our extended case study one of the things to which we aim to draw attention is how innovation maps onto global asymmetries in wealth and medical infrastructure. Ironically, as we shall detail at some length, an asymmetry such as the effects of impoverished medical provision are not only the targets of innovations such as PrEP but also, within the parameters of practices specific to the RCT testing of interventions, a pre-requisite for the realization of PrEP as an innovation. But first we must set the scene by presenting a preliminary historical backdrop to the emergence of PrEP.

HIV and PrEP: a testing backstory

In July 2012, the United States Food and Drug Administration (FDA) approved the use of daily oral PrEP consisting of two antiretroviral drugs Tenofovir (TDF) and Emtricitabine (FTC).¹ The two drugs were already approved for use in treating existing HIV infections but their officially approved use as a means of preventing infection confirmed that they could now become medically available for those of HIV negative status. That is, they could be legally prescribed for those not infected with HIV but for whom there is the possibility of sexual exposure to the virus. FDA approval followed a review of laboratory-based evidence and a series of RCTs, which we discuss throughout the book. United States approval is likely to pave the way for a number of other countries to consider the implementation of PrEP. However, the issues raised by PrEP implementation are complex and the response to these in many ways shows a field grappling with the use of costly and potentially toxic antiretroviral drugs for widespread prevention purposes. In this book, we review some of the history of PrEP, drawing on various articles and reports that reflect but also – as our analysis will consider – have participated in the emergence in PrEP. In many respects we believe that the understanding of PrEP by the HIV field – including its promise, challenges and, for some, its wrongheadedness (where it is considered as the wrong approach to prevention) – can be traced to the manner of its development.

Although the first round of PrEP RCTs in the countries of Cambodia and Cameroon failed due to controversy about their ethics (and heated debate continues over the validity of a RCT with injecting drug users (IDUs) in Thailand that was set up at the same time), such controversy did not generate what we regard as any sort of radical rethinking. Specifically, the field did not draw on these cases to interrogate seriously the research technology of the RCT, the ethics of conducting RCTs in low and middle income countries or, crucially, standard distinctions between ‘behavioural’ and ‘biomedical’ intervention. Instead, a ‘coming together’ was engineered by the International AIDS Society (IAS) funded by the philanthropic organization Bill & Melinda Gates Foundation (see IAS, 2005) and, separately but with many of the same participants, by UNAIDS (2006). This ‘coming together’ involved large scale consultations and some weighty reports that ultimately concluded with statements of commitment to greater community consultation and participation in the planning of trials. The reports, in particular, placed emphasis on the need to inform and provide follow-up care for trial participants (see Rosengarten and Michael, 2009b).

Of course, we do not wish to imply any insincerity on the part of scientific stakeholders, that is, the trialists and their sponsors, or that the community stakeholders were in any way ineffectual in putting forward their concerns, or that community consultation and participation have no place. Nevertheless, we can suggest from a reading of such documents (as well as numerous other published materials that ensued in the wake of the early controversy) that little, if any, challenge was made to the technology of the RCT and the bioethics associated with it. In the absence of an appropriately interrogative engagement with RCTs and bioethics, one upshot has been that the field generally enacts PrEP as a singular chemoprophylaxis dependent on user adherence – a framing that comes up in almost all recent literature on PrEP. This seems to miss out not only on much of the complexity of PrEP and its testing and implementation, but also on the potential traction that PrEP might have with its various users. It thus seems to us even more imperative to revisit the work of the RCT and bioethics.

To put this in slightly different terms, what we have here is a story of multiple actors (including international research funders, international regulatory agencies, scientific experts, and articulate, media-savvy protestors) whose efforts have generated an intervention but one that in many respects confounds those who must decide on its take up. We also have a story of the tragic need for more effective prevention. Yet the very question of what makes for effective prevention, is precisely what remains to be fully explored.

In 2006, a publication first-authored by Inge Derdelinckx (and including amongst its listed authors the prominent scientist Mark Wainberg and consultant for the IAS report on PrEP discussed above, Yasmin Halima), contained the statement:

In 2004, almost 5 million people became newly infected with HIV, emphasising the continuous need for effective prevention strategies ... behavioural interventions [condoms, abstinence] may not be able to curb the HIV epidemic as much as needed ... . (Derdelinckx et al., 2006:1999)

Here we refer to the statement as not only indicative of a continuing epidemic but also as illustrative of how the HIV field is enacted through the entrenched distinction between ‘behavioural’ and ‘biomedical’ interventions that, in itself, has significant implications for the development of PrEP. The distinction of ‘behavioural’ and ‘biomedical’ is readily assumed to map to the disciplinary divide of social sciences and biomedical sciences. Yet it is equally plausible that the disciplinary divide has generated the distinction. Although it is clear that the authors doubt that the use of condoms or abstinence from sex are sufficiently viable strategies for preventing HIV transmission, they do not consider that all forms of intervention involve social practices (even a vaccine requires scientists doing things collectively and users actively accessing it) and that a prevention pill, especially, will involve ‘behaviour’, as they put it (Kippax and Stephenson, 2012). In succinct terms, a prevention pill acquires its capacity to be so only through use, which inevitably entails social relations and practices (which are also, of course, sociomaterial). Yet, as we shall see, the RCT is not designed to investigate this. Indeed, it seems designed to avoid inquiry into what makes an intervention effective by distinguishing what is ‘effective’ from what can be statistically demonstrated as ‘efficacious’.²

So, with PrEP, we find RCTs are designed to establish the preventative capacity of the drugs while excluding much of what is involved in their use (and hence in the accomplishment of prevention); this follows, we have suggested, from the disciplinary distinction between the ‘behavioural’ or social and the ‘biomedical’. Accordingly, statistical estimates of the efficacy of PrEP have been calculated, to date, by collecting surveillance data from RCT participants about their dosing, and also in some cases about their sexual activity. Important here is the comparison between what people report about dosing and what drug levels in their blood show. If drug levels are low in an individual’s blood, this is used to explain lack of ‘efficacy’: the lack of drug impact is put down to insufficient levels of the drug in the blood. And yet, this excludes from consideration why an individual might not dose as required in the first place – our basic point is that surely users’ dosing (or not dosing) is an element key to whether PrEP can become a pre-exposure prophylaxis or not.

The bifurcated nature of prevention and PrEP RCTs that can be found across much of the HIV field and which reflects and mediates a relatively uninterrogated notion of what is effective, directs us to the question of ethics. How is it possible for millions of dollars to be expended on RCTs and yet so few to be spent on research addressed to the complexities of everyday negotiation of HIV risk (see, for example, Peters et al., 2010)?

For the HIV field, bioethics in the form of a set of principles is set out in various UNAIDS and WHO reports. The principles themselves are derived from moral philosophy and are specifically enshrined in the Helsinki Declaration ³ with adjustments to address concerns raised in response to HIV RCTs in low and middle-income countries. These sorts of RCTs are commonly referred to as ‘offshore RCTs’ to underscore the qualitatively different health and medical contexts in such countries compared to that of the trial sponsor. Indeed the disparity between the sponsor’s country and what was proposed for the early PrEP trials in Cambodia, Cameroon and Thailand can be said to have, at least in part, mobilized opposition to the trials by local groups who expressed concern that the trials were unethical. Some even queried whether the trialists would carry out such trials on their ‘own’ people, their own family members (WNU, 2004; Rosengarten and Michael, 2009a).

We will discuss this controversy in some detail in this chapter and again in Chapter 5 and 7 where it will be enacted in different ways. For immediate purposes, it will be useful to set out how the undertaking of ‘offshore HIV trials’ generates an ethical dilemma or paradox. Different accounts provide contradictory data on how a trial affects perceptions of HIV. On the one hand, some suggest that a trial may engender ‘risk compensation’ by creating a false sense of security about HIV risk due to the promise of a new technology. On the other, some claim that trials actually improve community awareness of the protective value of existing measures such as the use of condoms (Paxton, 2012:559). But even where trials are able to improve community awareness of HIV risk and to increase the capacity to implement health and medical measures, there remains the possibility that trials may affect health status in the long term by adding to the burden on local medical resources:

Epidemiologically, they are the people with the greatest need for effective prevention; statistically, they also present the most efficient opportunity to test interventions but the poverty and disempowerment that generate vulnerability to HIV infection also serve as barriers to medical care and services. Thus, the people most appropriate for enrollment in international HIV prevention trials are also the people least likely to have access to HIV treatment and care in their local communities. (MacQueen et al., 2007:554)

Our point is that HIV prevention, as articulated by Derdelinckx et al. (2006) cited above, can set in train a series of interconnected approaches that actively exclude from consideration the complex way in which transmission and its prevention by specific interventions play out in different settings. What we suggest in our review of PrEP is that new ways of problematizing HIV, prevention and treatment are required and that a reworking of the existing problematic requires conceptual tools appropriate to this task. Indeed, throughout this book we set ourselves the task of contesting many of the distinctions that have become commonplace in social scientific as well as in biomedical scientific thinking. Of course, thinking is itself not a practice that can be sequestered from material practice. We try to show that the framing in terms of distinct stable entities – including PrEP but also subjects, bodies, drugs and trials – fails to address the complexity of sociomaterial efforts to achieve ethically effective interventions. Put simply, if prevention is to take place – in this instance through the uptake of PrEP – it must perform an alignment of sorts with the sociomaterial relations and dynamics that characterize those for whom it is intended. PrEP’s controversial status cannot be disentangled from the technology of the ‘efficacy-testing’ RCT and the legitimation of this by a particular version of bioethics. In sum, the technical and social warrants that are mobilized for RCTs in their current form (where only a delimited set of effects are of concern) exclude precisely those elements that characterize the everyday use of the candidate medical intervention – elements that variously flow into, but also from, the candidate intervention’s use.

Studying and theorizing PrEP

Needless to say, the historical sketch above is by no means innocent. Indeed, to write ‘a history’ of the HIV/AIDS crisis and the biomedical response to it is a highly problematic undertaking for, as with any history, it is in principle always a site of contention and a text open to revision. Nevertheless, it can serve as a semi-stable backdrop against which we set out our detailed discussions of PrEP, even while our recounting of PrEP serves to, more or less subtly, re-write that history.

In thinking about PrEP in this way, we situate it in relation to a range of empirical settings, most obviously different offshore RCTs, and a series of discussions about the ethics of those trials. On one level, we might say that we are following PrEP as it moves from one setting to another – say, from particular ethical discussions about its testing through specific RCTs to the ways in which such testing of PrEP was seen by particular HIV activists to raise enormous political problems. In this historical narrative of contrasts, the meaning of PrEP is being con...

Table of contents

• Cover
• Title
• 1 Introduction: Setting a Scene
• 2 A Brief and Partial History of Randomized Controlled Trials (RCTs) in the Context of HIV Prevention and Treatment
• 3 Theory and Event: Approaching the Study of PrEP
• 4 The Gold Standard: The Complex Singularity of PrEP, RCT and Bioethics
• 5 PrEPs, Multiplicity and the Qualification of Knowledge and Ethics
• 6 On Some Topologies of PrEP
• 7 Conclusion: Eventuating the Methodology of Trials
• Notes
• Glossary
• Bibliography
• Index