This book explores the new applications of established theories or adapts theoretical approaches in order to illuminate behaviour in the field of food. It focuses on social processes at the downstream end of the food chain, processes of distribution and consumption. The book reviews the existing disciplinary approaches to understanding judgements about food taste. It suggests that the quality 'halal' is the result of a social and economic consensus between the different generations and cultures of migrant Muslims as distinct from the non-Muslim majority. Food quality is to be viewed in terms of emergent cognitive paradigms sustained within food product networks that encompass a wide range of social actors with a wide variety of intermediaries, professional and governmental. The creation of the Food Standards Agency (FSA) and the European Food Safety Authority (EFSA) occurred at a juncture when perceptions of policy failure were acknowledged at United Kingdom and European Union governmental levels. The book presents a case study of retailer-led food governance in the UK to examine how different 'quality logics' actually collide in the competitive world of food consumption and production. It argues that concerns around food safety were provoked by the emergence of a new food aesthetic based on 'relationalism' and 'embeddedness'. The book also argues that the study of the arguments and discourses deployed to criticise or otherwise qualify consumption is important to the political morality of consumption.
Commercially produced genomic tests for cancer diagnosis, prediction and treatment are being incorporated into NHS care, albeit unevenly and with much contingency in practice. A range of genomic tests are under research and development as part of the widening diagnostics market: a recent report estimated that the tumour-profiling market would be worth $12.4 billion by 2024, with genetic biomarkers accounting for the largest share. 1 Companies are producing suites of tests for different cancers and/or tests which work on multiple cancers. For example, Oncotype DX, discussed in detail in the preceding chapter, is now part of a wider set of tests called Oncotype IQ manufactured by the parent company Genomic Health, including tests for other kinds of breast cancer, prostate and colon cancer. 2
This chapter investigates the development of one such molecular profiling test that has the potential to guide future management of locally advanced or metastatic cancer, but is not yet fully embedded in standard NHS care. Exploring how smaller-scale clinical research creates and prepares the way for further public/private partnerships to deliver personalised medicine, we focus on a feasibility study in an NHS hospital for a commercial molecular profiling test developed by a US company that we are calling Virtue. The multi-platform profiling test can guide treatment decisions for locally advanced or metastatic, gynaecological cancers. 3 First, we look at how the feasibility study was part of building an evidence base for molecular tumour profiling in gynaecological cancers and cancers more widely, and the kinds of value making this involved. This traversed efforts to attain precision and actionability and negotiate the place of commerce with a view to the health service of the future. Secondly, we explore the experiences of patients involved in the study and how they and their family members navigated this experimental space, making sense of the benefits and limitations of the study and associated test as part of their wider cancer experience. We explore the promise of this study, routinely called a trial by the practitioners and patients involved, and the kinds of uncertainties and ambiguity this could bring for patients and their families even as they ‘add more evidence into clinical practice’ (Metzler 2010). Focusing on patients with advanced or metastatic gynaecological cancer also gives us insights into a different set of experiences from those of ER+/HER2–/LN– early-stage breast cancer patients discussed in the previous chapter. These patients are often older and have experienced cancer for longer, affording different kinds of investments in the future and engagements with new technologies and the certainties they promise. In short, they have a poor prognosis, have already experienced recurrence and are running out of treatment options.
We draw on multiple sources of data to build this case study, including news reports, commercial websites, online patient forum discussions, policy documents, interviews with 16 gynaecological cancer patients who participated in the study, and seven of their family members, conducted in 2017, and three practitioners who ran the feasibility study, interviewed in 2018 and in 2019, when we followed up with them about the results. Before we explore patient and family member accounts, we first look at the ways in which the test can be seen as part of ‘a new era for cancer survival’ for metastatic and advanced patients (Nawrocki 2018), focusing on the kinds of companies involved in this bioeconomy and the ways they work with clinicians. We go on to consider how Virtue's test, currently only available privately outside of research studies, is being configured for entry into the NHS via this feasibility study (which we are calling VGT), setting out the negotiations around evidence performed in this experimental space.
Precision oncology for advanced gynaecological cancers
A swell of activism has recently grown around gynaecological cancers, historically regarded as a ‘Cinderella cancer’ (Jasen 2009). Gynaecological cancers, including womb (uterine and endometrial), ovarian, cervical, vulval and vaginal cancer, are more common in post-menopausal women in the UK, with the exception of cervical cancer, which tends to affect younger women more. Although womb cancer is the most common of these cancers, it is ovarian cancer that is the most visible in gynaecological cancer activism, with an increasing number of ovarian cancer charities involved in ‘knowledge activism’ (Rabeharisoa et al. 2014) 4 as public awareness of symptoms is still relatively poor globally and in the UK in particular. Survival rates have not improved greatly and diagnosis often comes late. We interviewed several ovarian cancer patient advocates during our research. These people were endeavouring to raise the profile of ovarian cancer, to ensure that ovarian cancer patients were not ‘left behind’ while resources went to more common or more high-profile cancers, such as breast cancer. They also saw themselves as playing a role in educating women about its symptoms and to make sure these were taken seriously.
The challenges faced by ovarian cancer patients were compared to those of other cancers, where improvements had already occurred. As a young patient advocate and statistician, Rebecca, who was diagnosed with a rare type of ovarian cancer in her thirties, commented:
it really annoys me, like, on Facebook … your ten friends, ‘I'm hosting this for breast cancer’ … I'm thinking ‘oh god, why don't you just tell the woman the symptoms rather than, you know, have some of these chain emails that people just do?’ … there's always something for breast, what about ovarian or … not all the cancers are in, are pink, there's other colours …
These concerns about a lack of support for and awareness about ovarian cancer meant that Rebecca was particularly invested in social media campaigns such as Everything Teal. She was also optimistic about the prospects of a breakthrough in precision medicine research:
I reckon in about the next ten years … hopefully we'll have a breakthrough or … perhaps if we could just … get more funding and get more like what breast has done because breast has had such a significant increase in survival rate … I know no cancer's nice, but that's more like the gold standard of thing where I've got more the Cinderella type of cancer …
Many tests offering personalised genetic information are marketed directly to consumers – 23andMe being the best-known of these platforms. Direct-to-consumer genetic testing covers everything from ancestry, traits and characteristics to polygenic risk screening for susceptibility to disease (Hogarth and Saukko 2017). This is part of a process of what Metzler has called ‘biomarketization’ where biomarkers take increasing salience in the prediction and diagnosis of disease (Metzler 2010; see also Hogarth and Saukko 2017; Prainsack 2017). Companies specialising in molecular tumour diagnostics are particularly focused on developing links with private and public healthcare providers to deliver their tests, given the need for expert analysis of results in a clinical context. This means they must find ways to work alongside or in line with clinical practice and in-house hospital pathology services which have a long history of testing genetic and other biomarkers as part of diagnosis and prognosis, and of meeting stringent research governance processes within public institutions.
There are a number of larger companies in this market, including Illumina (see Chapter 5), but many companies in this sector are smaller and relatively young. Ranging in size and configuration, the companies typically offer a range of services and/or tests framed in terms such as cancer diagnostics, personalised healthcare, functional precision medicine and/or precision oncology. Their websites feature a range of patient and practitioner testimonials in the form of case studies and short films, similar to direct-to-consumer genetic testing services (Arribas-Ayllon et al. 2011). An example of this is Guardant Health's film about Guillermo, a man in his forties from Chicago with metastatic stomach cancer. 5 The film tells us how Guillermo's doctor ordered a range of molecular tests when he came to him for his (third) opinion, at a point where he was very unwell and only had a short time to live. The Guardant 360 proved to be crucial as the cancer showed the EGFR marker (EGFR amplification) and enabled the clinical team to target treatments which dramatically improved Guillermo's health and well-being. Even though this is not a cure, the film offers hope that the team will be able to offer new therapies when his disease progresses and ‘get back on top of it’. Tests like these are part of controlling the disease by trying to anticipate drug responses in order to find further, more targeted options to stifle the disease's progression, hopefully extending life and quality of life.
UK patients do not access molecular tests in the same way as US patients such as Guillermo, as most treatments are provided as part of NHS care. In England many of these tests are performed by a network of regional laboratories as part of the Genomic Medicine Service, which specifies which genomic tests are commissioned by the NHS in England, the technology by which they are available, and the patients who will be eligible to access the tests in a National Genomics Test Directory. 6 A national whole genome sequencing service has also been developed in partnership with Genomics England, following on from the 100,000 Genomes Project discussed later in Chapter 5. At the time of writing there are only two commercial tests listed in the directory – Oncotype DX (Chapter 2) and Prosigna, another test that detects the risk of certain types of breast cancer recurring.
UK patients paying for private healthcare can obtain tests not available as part of NHS care, or access them via private health insurance; others can only access tests via research studies (Moore et al. 2019). Diagnostic companies have therefore formed a range of partnership arrangements with private healthcare providers in the UK to facilitate uptake of the tests and to build the evidence of benefit required for licensed practice. For example, Cambridge-based Oncologica® UK Ltd (established in 2014) recently announced a partnership with ‘a leading UK private medical insurer’ that allows funding of the Oncofocus® cancer test. The company's press release notes that customers who meet agreed clinical criteria will be able to access the test, which will inform the selection of targeted therapies. 7 This includes patients with advanced common cancers not responding to standard treatment, cancers for which there is no standard therapy and carcinoma of unknown origin. Analysing the DNA and RNA extracted from routine biopsy samples, Oncofocus® profiles 505 actionable mutations linked to 700 targeted therapies and immunotherapies that are approved or under trial. 8
Research partnerships with NHS clinicians are also crucial to this developing market, not just because there are many more patients being treated in these settings than in private healthcare in the UK, but because partnerships of this sort build connections with clinicians who can be important advocates for the test in evaluation and appraisal processes for its wider uptake in the NHS, based on their expertise and experience in using it in practice. This is especially important in the case of molecular diagnostics, as although improved overall survival with lower weekly healthcare costs resulting from molecular profiling for advanced/metastatic cancer patients have been reported in the US (Haslem et al. 2018), the evidence base for benefit is limited in health systems such as that of the UK (Nawrocki 2018). The longer-term benefits of targeted treatments are also difficult to establish in this group, as many patients relapse after a couple of years on the drugs (Marquart et al. 2018).
Virtue's VGT: case study
Virtue is a US-based company with a European branch and international ‘partners’ in countries such as Australia. It provides multi-platform molecular profiling for several cancer types. The test, which we are calling VGT, has been developed to identify molecular biomarkers that can help to target treatments for metastatic cancer, using a range of tumour-profiling techniques to analyse protein, RNA and DNA in a sample of the tumour tissue.
As the clinical oncologist who coordinated the VGT test told us in an interview, Virtue is ‘a company relatively small in the grand scheme of pharma but it's one of many start-ups that have offered similar things’. Virtue's online promotional materials include patient testimonials and links to films, information about the expertise and technologies involved in its platform, and the steps involved in developing personalised recommendations for each patient. Emphasis is placed on the breadth and power of molecular evidence and analysis to give precise results. Patient testimonials include a film featuring an older woman who has been living with cancer for over a decade, thanks in part to molecular profiling provided by Virtue which helped tailor her treatments. The patient praises the company for its support through the process and emphasises how thankful she is for the extra time that the tests have given her. She speaks of her sense of duty to advocate for other patients and how rewarding this has been. This film is part of a set of other patient films, all of which involve patients with metastatic or recurrent cancer who have benefited from this test after standard care options had been exhausted. The section with information for patients on the company website invites patients and family members to share their stories too, alongside details of physicians who have previously ordered the test and guidance on payment arrangements.
VGT is currently only available privately in the UK and is not yet approved as part of standard care in the NHS, although it is accessible to some patients enrolled in research studies and trials taking place in NHS hospitals. Some private health insurance companies also cover VGT on a case-by-case basis. NICE has synthesised the limited evidence of benefit in a briefing document to support NHS commissioners and staff, including contributions from specialist clinical commentators with experience of using the test and of the study we researched. As is common with many such tests, some evidence suggests that the test does contribute towards improved outcomes for patients, but there are no randomised controlled trials or studies of particular cancers to confirm this and no evidence of cost-effectiveness. Most of the studies cited were prospective and non-randomised, comparing VGT-guided therapy with what clinicians said they would probably have done if it had not been available.
We first learned about the feasibility study of Virtue's VGT test when we interviewed the principal investigator (PI) for the study, at the end of a wide-ranging interview in which he discussed his clinical experience with patients and his wider university and NHS roles. The study was part of a number of activities in which the PI was involved, focused on digital technologies in healthcare or what he called ‘next generation informatics’ in the NHS, evoking the power of ‘big’ data linkage across the region and institutions via the innovation of large, complex healthcare platforms incorporating a range of biological and social data.
The PI mentioned Virtue after we spoke about our plans for further interviews with patients and offered to help us organise access in the hope that we would be able to conduct ‘exit interviews’ with patients on the VGT study and feed our results into the overall evaluation of the test. Here we became recruited into the mission of improving personalised medicine for patients, albeit in a loose and unstructured way. We were also told that the VGT study came about through serendipity, when the PI met a Virtue representative at an international meeting and a discussion about how to generate evidence of the ‘cancer outcomes’ following the test ensued. The PI and Virtue subsequently went on to work together to design a single-centre study and source funding for the work. Initially, they planned to do a prospective study for cancers of unknown primary origin, but this presented logistical problems and would have required them to work at scale, with a budget beyond the scope of funding available. The company was also unable to provide its test for free during the study, given that it was a small company without significant resources. As the PI explained: ‘that meant that we did the study as part of routine care and it was very much can the clinicians in the clinic just enter the data and do the testing and see how it influences the management decisions that were taken’; but it still ‘felt like we were at the real cutting edge of molecular testing’. As a result, the study was designed to assess the feasibility of NHS adoption of VGT in the treatment of women with gynaecological cancers. 9 Virtue's solid tumour biomarker testing uses a range of tumour-profiling techniques to analyse protein, RNA and DNA in the tumour. A formalin-fixed paraffin-embedded biopsy was sent to Virtue's laboratory in the USA for analysis. Virtue's proprietary algorithm generates a patient report recommending a course of action, which is sent electronically to the clinician within 14 days to inform clinical decision making. NHS England funded this evaluation through a Regional Innovation Fund, which aims to ‘support and promote the adoption of innovation and the spread of best practice across the NHS’.
According to the protocol, the study was categorised as a safety/efficacy study with modest purpose, as the clinician who coordinated this study explained: ‘It was a pilot study to look at whether this is feasible within an NHS environment … whether it could theoretically lead to any benefits to the NHS in terms of costs and to see what the costs where of offering a commercial molecular profile.’ ‘Ironing out’ adequate logistics included collaborating with the pathology department and handling specimens from packaging, labelling and sending off, to record keeping. Crucially,
a patient would firstly need to be relatively asymptomatic … we would have to send their tumour off to America … it would be profiled and we'd get the tumour sample back with a molecular profile. So, to do that, the patient needed to be able to wait twenty-eight days to get their next lot of chemotherapy.
The team were interested in what this would mean for patients, if it would be detrimental and if it was acceptable.
In trying to test and improve logistics the team were researching and innovating technical, bureaucratic and cultural as well as molecular processes of personalisation. Clinical participation also had to be facilitated through the study design, as the coordinator explained:
one of the difficulties in, is that the … profile still requires a certain amount of interpretation because you, you get an answer in the sense that you get a green box that says ‘Recommend this drug’, or a red box that says ‘Don't recommend this’, and a grey one that's neutral. But actually, you have to be fairly confident … in trusting that profile and the evidence on which it's based. And, of course, I guess one of the things that's difficult is … empowering the clinicians to be confident about that.
So if you've got a consultant who knows the area well, as all of the consultants will, then they will know that they're recommending three drugs based on trial A, B and C, and they'll be able to tell you about A, B and C. They'll be able to sit a patient down and tell them about A, B and C and how many patients responded and for how long, on average. With this profile, they get a green box, a, a grey box and a red box and a list of preferences, some of which apply to that cancer and some of which apply to other cancers. And so their ability to have an oversight of all of that, I think, is very low. And so that's … a different way of working for the consultants and meant that there was a lot of discussion between them about what was the right thing to do.
Now, actually, we took a lot of the risk from that away in terms of they weren't prescribing drugs that they wouldn't be prescribing anyway … All of the drugs were already available to that patient. I'd imagine it'd be a lot more difficult if that wasn't the case [pause], if that makes sense.
So it's an entirely different level of evidence to a gold standard randomised controlled trial … which makes it very difficult. And so that's where I talk about sort of there was lesser risk in ours because we're only using things that have come out of a gold standard randomised controlled trial.
Trusting the ‘black box’ of the algorithm for clinicians reliant on seeing and interpreting evidence from clinical trials was thought likely to be difficult, so the study team limited the treatments the profile recommended to drugs and associated trials that the clinicians were already familiar with in order to inculcate trust in the study and to derive value from it. Making evidence-based medicine more explicit, ensuring clinician buy-in and reducing risk by prescribing drugs that have already gone through an approvals process to establish evidence of benefit allowed the study to focus on how to work in and with a limited range of grey areas.
The feasibility study generated uncertainty and interpretation work for clinicians. But coordination also involved negotiating uncertainties about the quality of evidence going into and being produced by the feasibility study itself. For the coordinator, who worked with the PI, this involved managing their own lack of understanding of the link between algorithm and evidence, as in the extract below:
Could you, could you explain the … nature of that literature being cross-checked?
I can and I can't … So (laughs) … from my understanding of the algorithm, it would, if you like, just go through PubMed and say, well, let's say someone's got over-expression of HER2, which is a particular marker on the cells that's commonly known from breast cancer … and it would then look through the literature and look for manuscripts that … abstracts … it would look at drugs that are most likely to cause a response or toxicity or any relevant outcome in cells with HER2 expression, or tumours with too much HER2. It would do that, from my understanding, in patient series trials but also in [laboratory studies] as well.
It also involved accepting limits in the quality of evidence being collected. As the coordinator also noted, the study team could not do a full study of cost-effectiveness, but could instead ‘provide a signal for benefit’ by collecting a range of data on health economics, outcomes (progression-free survival), quality of life, toxicity and technical data (time to send and retrieve sample), which has not been published at the time of writing. He continued: ‘it's difficult to empower patients with this, I think, because we haven't yet reached a level where we have the evidence base to empower the clinicans’. The study was nevertheless considered to be valuable because generating signals of benefit was a small contribution towards the development of a better evidence base, creating the conditions for better-powered research in the future.
As well as managing uncertainties among clinical colleagues about the value of the test and the study to generate incremental and modest value for the field of personalised medicine, the coordinator also had to manage patient expectations where the perceived value of the study could be much higher. The coordinator told us they had to field requests to participate from patients being treated elsewhere. These patients had learned about the research from sites such as clinicaltrials.gov or the CRUK website and included some patients who were planning to pay for the test privately and were willing to travel to be part of the study. The study only had ethical approval to include ‘local patients’, so these requests were declined. The coordinator drew on these experiences to express concern that the proliferation of studies and trials which only some patients could access, either because they were fortunate to be treated in centres where more trials were running or because they were wealthy enough to be able to travel, would lead to inequities for patients. This was linked to a set of worries about the complexities of cancer and over-promises to patients, ‘matching’ the ‘promise and hope with this new approach to cancer … that patients hear a lot about in the media’ with ‘the reality of medicine’. In a similar vein to the oncologists interviewed for Chapter 2, the coordinator expressed scepticism about ‘hype’: ‘part of me wonders … whether the proliferation in things like molecular profiles and so on [have] … moved so far ahead of where the evidence is to catch up that, that has its own risks’:
we don't understand key bits of the study of biology to shape it yet … for [Virtue] we may, for instance, have sent off an ovarian tumour sample from straight after their chemotherapy … but that tumour sample may have different markers to one two months later. We don't yet understand how that changes … there's so much complexity now…
In these reflective excerpts the coordinator manages uncertainties to get buy-in for the study while at the same time dealing with excessive expectations and what they framed as patients’ need for certainty.
This gives us an insight into the ongoing work of negotiating expectations of personalised medicine for clinicians involved in these kinds of local small-scale studies or trials, including reflecting back on the worth of studies in which they have played a part. The nurse involved in recruitment to the study also looked back on how patients responded to requests for participation, emphasising their positivity and hope, and praising the staff involved:
I think we maybe had one patient who declined it. They were all quite excited by it. They all thought, you know, this is going to benefit me. I need – I want to be involved with this. … so it was … usually a positive … discussion with the patient … and they were very interested. Some of the patients asked to take a copy of their report away … presumably they – they couldn't understand it fully but – but they want – you know, they were very interested in it.
What made them … expect to … benefit … from [the profile]?
I think the gynae consultants are very good at … explaining … I've sat in with quite a lot of consultants over the years, and registrars as well. And some are better than others. But I think the gynae team are very good at explaining. And I think probably from – that they understood what … they were being told and what they were being asked to do. And that … potentially by identifying biomarkers … in their blood we could see which treatments would … help and which ones probably wouldn't help … there's a range of treatments you can have for ovarian cancer. And some of them, the … response to treatment rate is quite low; you know, less than 25%. … they felt that they'd have more control perhaps over their [pause] over their treatment and decision making, And their … clinician would have more information how best to treat them, of course.
In this account the nurse underlined the value of participation in the study for patients as a key outcome, focusing on their willingness to participate and apparent sense of control as valuable in their own right and linking this to the skills of the clinicians involved in the study. The lack of opportunity to otherwise access more targeted treatments was also mobilised as a key reason why this test was experienced as valuable by patients.
In the next section, we focus more closely on how patients accounted for their participation and experiences of VGT and the benefits it brought. As we shall discuss, this included accounts of optimism, control and enthusiasm for the test offering more specific information and opportunities for tailored treatments. These positive accounts and expectations were, however, tempered by experiences of unmet expectations in some cases. For other patients, their accounts of expectations and/or experiences of the test and the study were much less positive. To make sense of these themes and this diversity, we explore how genomic approaches such as the VGT study were incorporated into patients’ different approaches to uncertainties provoked and at times resolved by the test as part of crafting foreshortened futures. We explore how these tests offered some kinds of certainties but also generated uncertainty and ambivalence; we also consider when the test did not have resonance or meaning for patients, particularly patients who were not invested in future-crafting beyond the day-to-day. However, we also show how engaging with the test enabled these advanced cancer patients to hope for ‘other things’ even when their personalised results did not significantly impact on their treatment and prospects. This included being part of a bigger future via their research participation.
Patient accounts of participation in the VGT study
Practitioners in our study were keen to underline the benefits of the test and the study for patients facing foreshortened futures and limited treatment options. But in other respects, as in the discussions with the coordinator above, they were concerned about unrealistic expectations among patients because of a lack of evidence of benefit. Clinicians and patients were routinely operating in conditions of uncertainty in the clinic, and in this particular study, but the test offered hope of finding treatments to which the patient would respond well. It was, however, far from universally valued, and patients were elsewhere being cautioned by professionals and patient advocates about uptake of these tests because of a lack of evidence of benefit, albeit within an overarching regime of anticipation of benefit in the future. For example, in a cancer charity forum thread discussing two different commercial tumour-profiling tests, including Virtue's, one of the moderators noted a lack of randomised control trial evidence of benefit, or evidence of benefit in particular cancers rather than cancer in general. Although welcoming the tests as a positive development, the moderator noted their cost and difficulties with interpreting the results to guide treatment decisions.
As we mentioned earlier in the chapter, we were enrolled into this accretion of evidence when we were invited to interview patients who participated in the VGT study by the PI. We were also steered away from observing consultations with patients where the results were discussed, given the potential sensitivities of these consultations and the logistics of being in the right place at the right time. The research nurse who was in charge of the VGT study informed us of the dates of outpatient appointments for patients who were participating in the feasibility study (72 patients in total); we waited to be introduced to the patients by the oncologists, typically after the consultation. Oncologists only mentioned our study to their patients when they felt it was appropriate to do so. We approached 21 patients and, as noted above, interviewed 16. Five patients either declined to participate or were unable to be interviewed due to ill health. Ten interviews were conducted on NHS premises, arranged to coincide with their hospital visit if possible, and six interviews were conducted in patients’ homes because it was more convenient for them. During these interviews we carried out an in-depth exploration of participants’ experiences of cancer and care in general and the feasibility study in particular, including at which point in their treatment they were approached by research nurses, what they expected from the test and their actual experience of it, how the molecular results were discussed, and how treatment decisions were eventually made. We explored what participation in this study meant to interviewees, and how they managed and made sense of the research and clinical encounters in relation to their previous experiences of care and participating in research, and their hopes for the future.
This particular cohort of late-stage cancer patients were ‘living in prognosis’ (Jain 2007) at the time of our study. Many of them had experienced difficult cancer journeys and were in the later stages of incurable cancer or faced a high risk of metastatic recurrence (Roberts and Clarke 2009; Brown and de Graaf 2013). This makes their experiences particularly valuable for investigating aspirations for personalised care and treatments, bringing fresh insights to a literature that is dominated by the experiences of younger, often more active patients or patients with well-researched cancers with a better prognosis, such as breast cancer (see Miller et al. 2014). For the VGT study participants, the priority was keeping cancer at bay with the hope that, in the future, their cancer might become a managed, chronic illness, rather than seeking a cure. Preparing themselves for future treatments was important for patients who had seen their cancer recur. Most of these patients had experienced long-term treatment or multiple cycles of chemotherapy alongside other treatments, so it was also important to secure decent intervals between treatments to recover from treatment side-effects and more importantly to prepare for the next cycle of treatment.
Although a test such as VGT was, for us, an ideal example of implementing molecular personalisation in a research setting, it turned out that it was by no means central to patients’ long and complex cancer journeys. Some patients even struggled to recall the test as it faded into a blur of clinical/research encounters. Against this background, we were struck by how participants still managed to generate diverse accounts of the Virtue test. Our research participants expressed different degrees of interest, understanding and knowledge about the science and technique behind molecular personalisation. But instead of focusing on ‘mis/understandings’ (Dixon-Woods et al. 2007), we try to situate these accounts within their wider accounts of cancer and care.
As cancer becomes more treatable, if not curable, many people are living with advanced or metastatic cancer. In England it has been estimated that there are thousands of people who have survived for several years with the most advanced stage of cancer, according to recent research from Macmillan Cancer Support and Public Health England's National Cancer Registration and Analysis Service (2017). 10 Patients with late-stage cancers have often experienced long and difficult cancer journeys, including delays in diagnosis and other complications such as multiple co-morbidities. Feeling like a ‘time-bomb’ (Davies and Sque 2002), some of these patients are living with ‘contracted time’ (Lewis et al. 2016). For many, recurrence is a matter of ‘not if but when’, as one interviewee in our study put it. For some patients this awareness involves thinking ahead and preparing for the ‘multiple future-times’ (Brown and de Graaf 2013), trying to be ‘one step ahead’ of their cancer. But for others extended futures are set aside for living in the near future. For many of these patients, their priority was to make incurable cancer treatable and manageable for as long as possible, protecting and improving their quality of life. In so doing they are navigating a different kind of future than early-stage patients who might hope for cure or lengthy remission.
In what follows, we focus on three major themes that occur across our set of interviews: first, a wide range of promises and expectations as described by patients and family members; secondly, the multiple reasons for disappointment and frustration they had to deal with; and finally, how for some patients, the VGT study was not as salient as it was for other more active, relatively younger patients.
Promises of Virtue
Virtue held considerable value for many of these patients and their family members with whom we spoke. Dennis described his understanding of the VGT offered to his wife Helen, both in their seventies, as a ‘magic formula they were using in America’. Together with his wife, he hoped that ‘re-testing the biopsy’ would suggest a ‘better treatment or more appropriate treatment’.
Such hopes were particularly marked among younger patients in our study, for whom Virtue was part of a more concerted effort to access tailored treatments and engage with the possibilities of personalised cancer medicine. These patients told us they were actively searching for trials of tailored treatments and seeking second opinions at teaching hospitals running trials. Researching alternatives to current or proposed treatment was an important strategy for maintaining a future, which included seeking private cancer care or overseas treatment. These patients were not, however, naïve about the promise of cutting-edge tests and treatments, carefully weighing benefits to quality of life against cost or side-effects (for themselves and for their family). This was a relatively solo set of pursuits for some of these patients. Although they supported their fellow patients by making the occasional donations to fundraising efforts, they did not all participate in collective action or support online. One patient, Donna, who was in her fifties, was an exception. A particularly proactive and well-informed patient, Donna was involved with a national ovarian cancer charity and other patient forums, where she told us the VGT study (which she called a trial) came up in discussion:
I'm also on … a Facebook site which is just for ovarian cancer … sufferers and we share information and links to different sites … it's a comforting site; people really talk to each other … and they … might say, ‘Oh, … I'm going on the VGT trial. Has anybody heard of it?’ And then we'll all add our comments and – if we've had it and that kind of thing, so that's quite useful … So when I do the research or when I'm talking to people, people will talk about the VGT trial but they may have been on a different chemotherapy to me … So I think there were one or two people but we tend to talk more about the side effects of the chemo rather than the trial itself. So there was something about some of your samples are sent away but then because of what that forum is about it was more about how you feel rather than the trial itself.
This excerpt gives us an insight into hopes about being on a trial, but focuses more on the comfort offered by comparing experiences even when these were different, with the emphasis on managing side-effects and emotions evoked by participation. Donna also told us that doing research, weighing information and archiving information of clinical trials was a source of reassurance:
I do a lot of research and I save quite a lot of links to different trials and I just think well, okay, well, if I start to feel ill again and it comes back I'll click on this one. So I've got a list of different things I can read.
For Donna, and others, participating in research like the VGT study was one small part of a menu of research opportunities for securing her own future, with the added benefit of helping future patients; as Donna said, ‘Hopefully it helps me and it should help others as well. So I will try anything really.’
VGT was also experienced by other patients and their relatives as valuable because it offered bespoke care as well as hope. June and her husband Bob told us about their particularly difficult experience with June's previous care team who said there was no treatment they could offer her. For this couple, VGT study participation offered hope where it had previously been dashed. It also meant an extension of personalising care she had already been receiving from her current care team. Bob associated June's participation in the VGT study with the insurance of personalised care:
I say, the only thing that I gleaned from that [meeting with clinician] was that they were going to take more interest in June's case other than put her into the normal – what we used to call cattle market … where the whole process was like a cattle market.
For Bob, the VGT study was a gateway to more experimental and special options as opposed to standard ‘written in stone’ treatments, and this was a risk they were prepared to take even though he was aware that this meant June would be a ‘guinea pig’.
just going for a regular treatment that they were offering … there were nothing outside that they could offer you. But my understanding with this is there's a possibility that would be something that would benefit to treat June's condition but it's not necessarily what's already available, it might be a, a trial that you would volunteer to do … I thought, well, if the outcome isn't so rosy [on] the path we're treading now, and there was any possibility that there was something that could improve the situation, either not guaranteed but possibly it'd be worth taking a chance, you know what I mean, for whatever reason. Whether or not it would be to prove a point that it wasn't going to be successful if … they did that treatment, but June would [have] been like a guinea pig say, in order to trial this treatment.
This promise of molecular personalisation was also associated with being privileged to be part of a study where only a small number of people's samples were ‘sent off to America’, in the words of Mary, a patient in her sixties. Mary's cancer was picked up by a routine smear test when she was 57. When we asked her about motivation for taking part in this study, Mary explained:
They were doing this trial of sending off to America, the tumours that … I had and they were going to look at it in a molecular genetic level with a view to being able to personalise my treatment … Of course, if somebody says [that] to you, you're not going to say no are you? And I was told that … there was only … about seventy or eighty people in the country that had been … allowed to have this done.
For other patients, VGT was an improvement on ‘standard’ forms of cancer care that they experienced. For instance, another associated Virtue with ‘individuality’ which is opposed to current ‘conveyor belt’-like care. Sally, who was diagnosed in her forties and had since experienced multiple recurrences, said,
treating everybody individual[ly] is a good idea … it's difficult for doctors, nurses seeing so many people every day, and I suppose it can tend to be, like a conveyor belt, people coming in and you're saying the same thing. Maybe a bit of individuality might be quite a good thing.
Throughout these accounts of promise, the comfort and reassurance of what was perceived to be more personalised care emerge as important values of the test and the study, for patients and their relatives. Futures were being crafted through the experience of care being more advanced and tailored to the individual in the present. For other patients, and in other respects, the experiences of the study were less positive, and involved recognising and managing disappointment, as we now go on to discuss.
Across patients’ and family members’ accounts, it was common that the VGT study was described as not being particularly burdensome. Their participation was framed as requiring minimum effort, such as no extra visits to the hospital as might be the case with other clinical trials, and it was regarded as non-invasive. Participation did, however, bring additional emotional work in other respects, as participants and their families made sense of risks, disappointment with their results, and conflicting expectations and experiences of the study.
Before deciding to enrol on the study, patients had to weigh up the benefits and risks of participation; patients needed to decide, with consultants’ guidance, if they were okay about waiting for the results to come back (as it meant a delay in treatment for 4–6 weeks), as the quote from Marjory below illustrates:
Because you have to delay your treatment so to go on the trial you have to accept that your treatment is going to be delayed by two months – six weeks [to] two months – something like that. So obviously there is a risk but I talked to Doctor [name of oncologist] about the risk and he didn't think that it was a fast growing – so I decided that, and even if it was I still thought, I've got more scientific basis of it working out by going through the trial than I have if we just guess or take an educated guess.
Marjory told us about her scientific background as evidence of her competency in engaging with the scientific aspects of this and other research on ovarian cancer, as she described why she was prepared to wait for the VGT results. However, not all patients were happy about waiting. Another patient, Kate, told us quite a different story. For Kate, waiting for one month was ‘a bit tough because I wasn't having any treatment at all and I was aware of the fact that my tumour marker was going up and my cancer was getting worse’. Kate described her disappointment when the results came back,
I think that's why I was disappointed that it was just the bog standard treatment [that was recommended]. I felt like saying, ‘I could've had this a month ago’, you know, cracked on and it would've, you know, perhaps caught it a bit earlier I know it's only a month…
Here the value of the test declines when experiences do not match expectations of tailored treatments and the gamble of waiting does not pay off.
Participants also had to find ways of managing disappointments which arose when their sample was not of sufficient quality to generate meaningful results. As with other research we followed, there was a risk of sample failure with the VGT study. For instance, another patient, Sally was told that her sample ‘wasn't brilliant’. When we asked how she felt about this she said,
Well I was a bit gutted really, ’cause I was expecting this miracle thing that was going to happen to me and, you know, but they did get quite a lot of information from it they said, so yeah.
Right, could you … elaborate, what do you mean by miracle? In what sense?
… because it's a personal diagnostic test, I just thought, maybe they were going to find something that they'd not seen before, or something that maybe would work that I've not tried. Maybe I didn't really understand it all properly, but, I don't know, you just, it's just hope I think, just hope, there's always hope.
Sally described how she got some consolation from the fact that they did find ‘some good things’ which might help future patients.
Participants also told us of their disappointment at options for treatment being discounted by VGT because the patient did not have the ‘right mutations’. This could be experienced as part of a series of routes closing off. For instance, we spoke to Donna's husband Ewan when he accompanied Donna for her last radiotherapy session. For Ewan, participating in research meant reversing Donna's bleak prognosis,
I just know that trials give me a lot of hope because if we're just going along the path of the chemo and the gap is getting less between the chemo, then you're on the downward slope really. By being on a trial, who's to know that, you can make that shoot up, that slope.
Despite Ewan's hope, Donna's test results were disappointing, as Ewan explained:
[W]hen we sent the biopsy away it came back … they're saying, ‘Well, that's not a route that you can take because you don't have the right mutation.’ So you just sort of ignore it then because you're not going to pursue that route … Like I say … she didn't have the BRCA; she didn't have the mutation for [VGT] and … she can't have immunotherapy so I don't know whether that's the stage of it or the … condition … that she's got…
This extract captures another common strategy of patients and family members handling disappointment when the VGT results did not turn out to be a gateway to further treatments, focusing instead on the next steps and ‘moving on’ to source value from other research, tests and treatments. Ewan also talked about his efforts to support and maintain positivity for Donna as part of this process, although he acknowledged that it was challenging. Ewan said,
I think [pause] for her to deal with it positively, she has to in her mind I think, still think that it's going to be cured. I don't necessarily think that, which is difficult in a relationship. So obviously I don't voice that … at all if I'm honest. I may discuss it with myself.
Ewan's story captures the challenges for many carers as well as patients, navigating family members’ hopes alongside their own, calibrating how positive and sceptical they can be against each other's feelings so as not to cause further upset and to maintain some equanimity.
The appeal of ‘precision’ promised by the Virtue test also sat at odds with patients’ desires to have a variety of options, as Jean, a teacher whose cancer had returned and spread to her lung, described:
So it [the test results] did say that paclitaxel was probably not a good one for me, and that was the chemotherapy that I'd absolutely hated. That was the one that made me feel really poorly, so … at that point I was really glad to see that it said paclitaxel wasn't good, because I thought that meant I'd never have paclitaxel again, but actually I've realised that's a silly thing to have been grateful for because it might be one of my only options at some point, so … you want your options as wide as you can really, though I would prefer not to need it again.
Balancing expectations, individually and collectively, to craft value from participation in this or future research involved managing disappointment in the present and retrospectively, as emotions were reviewed and revised in the face of diminishing options.
Other patients described their disappointment about the lack of novelty from the VGT test result, that is, when the test just confirmed that the same treatment as before was the best option, as in the extract below from Tracy, a civil servant who had just turned fifty when we interviewed her:
I think when, when I first went onto the … trial and then waited for the results coming back, I imagined that'd be this whole big thing of information, that there'd be lots of information there and things that I could be given that I could look through and, and read up. I was a bit disappointed, to be honest with you (laughs), at the end of it when they just confirmed that they were going to give me … the same treatment, I think, that I'd had for the … cancer before. So it's like, well ‘hello (laughs), where's the rest of, where's, where's, where's this, where's this encyclopaedia that's coming back then with all these results as to what works, what doesn't work and everything?’
We see the clash of expectations around what was the reality of the study, echoing the promissory discourses around trials more generally, and the realities of a smaller-scale study which was already operating with limited treatment options as part of the incremental approach to ironing out logistics and gathering evidence to find a pathway for adoption into NHS care in the future. However, for Belinda, like others in our study, having ‘other options and things … when the disease progressing and gets any worse’ that ‘would help … further along the line’ was a way of keeping their futures open and remaining optimistic.
Participating in the VGT study was a means by which these patients preserved the possibility of future treatment even when it did not directly affect their current treatment. Regarding the test results as reserve for future treatment or a springboard for more cutting-edge treatment (for example off-label drugs or combinations of drugs) gave patients and their spouses hope and offset immediate disappointment about not being given ‘more cutting-edge’ and novel treatments in the present.
The complexities of accessing drugs recommended by VGT on the NHS could nevertheless generate frustration and disappointment when promises of precision were unfulfilled. For instance, Tracy could not get a particular targeted drug, recommended by the test, until her cancer recurred. She compared her situation to gambling on ‘Bully's Prize’, referencing a popular darts gameshow from the 1980s, where competitors who gambled their winnings on a star prize and lost were invited by the host to ‘have a look at what you could have won’. Tracy elaborated her frustration as follows:
So it seems a bit ridiculous that I'd have to go through waiting for it to come back again and then go through all my treatment before I could be offered that drug. […] And from a cost point of view, it just doesn't make any sense to me either.
I was told that you could pay for it privately … but you'd be looking at about £70,000 a year, and that once you start paying for it yourself, you'd have to continue because the NHS would never pick up the cost. Whereas if you go third line and they start you on it, after twelve months, drug companies give it for free.
So yeah, I did get the information about the additional drug, yeah. It's a bit like Bully's Prize, ‘come and have a look at what you could've won,’ isn't it, really? (laughs)
Tracy criticised the organisation of care in the NHS and its rules of eligibility for treatments, which was not only frustrating for herself but she also felt was not cost-effective in the long term.
This echoes a more general sense expressed by some patients and captured in the excerpt from the ovarian cancer advocate quoted at the start of the chapter, about VGT being able to deliver tangible benefits given the limited options for gynaecological cancer treatments. One patient, Jean, told us she had learned from her own research that VGT was ‘related to breast cancer rather than ovarian cancer’, but expressed disappointment that there was much less of an evidence base in the case of ovarian cancer. She was told by her oncologist that ‘if you'd [got] breast cancer we would say straight away … a hormone blocker, but we don't have that set in evidence’. This meant that the interpretation of the VGT results was not as ‘black and white’ as she expected. This made her realise that ‘I don't think it's helped me quite as much as I hoped it would do.’ Like many other patients, Jean nevertheless expressed her gratitude and hope for future patients as follows: ‘I'm still grateful that somebody's trying it. And presumably they'll build up a bank of research from doing that that will help others as well, which has got to be a good thing.’ Jean's framing of her participation being of value to future patients was linked to a strong sense of the value of the NHS and a concern that, left unchecked, pharma could be ‘bleeding the NHS to death’. Jean told us she had a solution to the problem of the high costs of genomic medicine for the NHS:
You cap what drug companies can charge. At the moment I do believe the drug companies are bleeding the NHS to death. That's my belief … I understand they're a business. I understand that and that their raison d’être is about making money for their shareholders, but I wish somewhere in their – in their ethics was something that was about helping people as well rather than their reason for existence to be to make profit. I believe that if there was a cap, if the government put a cap on what they were allowed to charge, the amount of profit they were allowed to make, that that would mean there'd be more money for this kind of thing.
When I was on the trial, one of the things that concerned me was I'm on a trial where they're finding information that might be useful. Will they then charge so much for it that people – that it won't actually be useful? … I think the pharmaceutical companies will bring the death of the NHS at some point, which is very sad … for people in the future and I think it's really, really sad because I think the NHS is one of the most magnificent things that's been set up.
Jean was unusual in the sense that she advanced an overtly political analysis of molecularisation and the need to limit profit and protect the NHS so that future patients could benefit. For other participants who had experienced or were contemplating the prospect of disappointing results, the possibility of helping future patients was also important, although this was expressed in much more general terms, as a kind of consolation, for example: ‘if it doesn't help me, it will help others but hopefully it will help me too’.
Through these various rhetorical strategies, personal ‘future disorientation’ (Roberts and Clark 2009) was managed through appeals to ‘future patients’ by ‘hoping for other things’ (Ehlers and Krupar 2014) such as helping future generations, as in the quote from Tracy below:
But I do understand that it will help them in the future, you know, when they know that they've tried that and that hasn't worked. Then they've got other options that are, that are there. I just thought it'd be a lot of information that they'd come back with. And I'm told that it is a lot of information but … they don't obviously give me all that because that's not going to help me.
Similarly, June and her husband Bob described their understanding of how research works by combining results and how they were part of it – many individual research projects will not work, but each ‘failure’ helps research as a whole, including themselves.
[Bob] Yeah, the only downside to that is that if it didn't work they'd know that that's a dead end but they've used you [June] to find that. But having said that, it's worked for people coming behind that they know it's – that route's not going to be available
[June] … while you're trying all these things, all that information is being pulled … So that it's going to help other people … As well as you … Well, [if it doesn't work] I would go onto the column where it didn't work, into a percentage thing.
The value of participation for June became a matter of helping future patients.
Lack of salience
VGT results had to be processed by patients in relation to an array of treatment experiences and decisions, which sometimes resulted in this particular study blurring into other studies and trials they had previously experienced or anticipated as part of their future. We did, however, encounter a small group of patients for whom the VGT study held very little salience. These were among the oldest patients we spoke to and all faced a bleak prognosis: one patient told us she had reluctantly agreed to receive palliative care to address co-morbidities and other complications, another patient was on third-line chemotherapy, and two other patients were anticipating another recurrence of their cancer. While two of these patients told us that they had a lot of support from their husbands, the other two patients had less support from family members. One of these patients had lost her husband to cancer while she was undergoing her own cancer treatment and the other patient's husband had early-onset dementia.
For this group, putting trust in their care team was particularly important, much more so than embracing the idea that VGT would transform their prospects. Their participation in the VGT study was a matter of trust, and continuity of care was key, with the test slotting into rather than determining these arrangements. These patients were also not as well connected, digitally or otherwise, with other patients due to their limited mobility and/or their stoic inclination to ‘desire a private disease experience’ (Kaiser 2008: 79). This did not mean that these patients were completely disengaged from gleaning information and doing research. They spoke of the need to ‘keep fighting’ cancer, and they were doing what they could manage to support that effort, such as regularly collecting newspaper cuttings about new cancer treatments which they might be able to mention to their oncologist. However, the VGT test did not figure in accounts of their current and future care in any detail, and there was minimal engagement with what genomics involved or meant. Instead, a strong emphasis on stoicism or getting through each day was evoked in their accounts, rather than a strongly articulated sense of future, as the following encounter with one of our participants, Maureen, illustrates.
We interviewed Maureen in the chemotherapy unit while she was receiving her infusion. When we first met her at the clinic she was with her husband, but on this occasion she was alone. She apologetically explained that her husband would not have been a great interviewee for us as he has dementia. She added that both her and her husband found the waiting and boredom of a long chemotherapy session difficult, and she struggled to ‘entertain him for eight hours’ let alone encouraging him to engage in a research interview. In the interview, Maureen focused on her ongoing pain in her lower body and how hard it had been for her to address this, with the VGT test getting only a passing mention. Referencing reduced resources in the NHS, Maureen linked her depleting options with ageist media coverage, as she satirically commented: ‘Oh, all these old people are taking up all the beds, they're living too long and they're costing us too much.’ Having had a discussion about palliative chemotherapy, Maureen shared her worry about being regarded as an undeserving ‘bed-blocker’. For patients such as Maureen, VGT was a secondary part of their efforts to secure the kinds of personalised care they valued and hoped to maintain, a care she was concerned was under threat from rationing and discriminatory interpretations of deservingness.
These accounts sat within a wider narrative of cancer and care where the importance of stoicism was highlighted, which at times made these interviews particularly challenging when the perception was that there was no special story to tell. It was not surprising that two out of the four interviews in this group were the shortest among all sixteen interviews. Both patients’ dominant account was of getting on with things:
It happened. I've got to put up with it. it could've been somebody else. I didn't say ‘why me?’… I've always been a very quiet type, a person that just takes it. It's me, that's the way it is.
[I] just take everything in my stride.
VGT in this context was not imbued with particular meanings or emotional work, as patients concentrated their efforts on managing day to day.
In this chapter we have considered how the feasibility of introducing a novel, commercial, molecular profiling test into the NHS was examined in a research study designed to develop an evidence base for wider implementation, as part of efforts to transform the way the NHS offers profiling and to understand how to make this valuable to patients and clinicians. A range of professionals (including social scientists) were being enrolled in these efforts, alongside patient participants. There were numerous uncertainties around the development of the test and its future in the NHS, just as there were uncertainties for patients and practitioners making sense of test results from which evidence of benefit has to be drawn. The predictive potential of the tests was therefore highly contingent, as was the extent to which the results being produced could prolong or maintain a future for patients with advanced cancers. The promise of precision was therefore vague and underspecified.
Chapter 2 explored the uptake of a genomic intervention in cancer care and its place in practice. This revealed that the technology was far from fully embedded and that its promise was much more contingent than some of the press coverage might have suggested. This chapter has presented further evidence of the conditionality and incrementalism in genomic medicine in the cancer clinic. Although there was a clear impetus to enhance precision and actionability in the case of VGT, its value could be fleeting or unrealised because of the complexities of cancer, health and family commitments. For some patients and their families engagement with the study offered a sense that options were being created or sought out by their care team and, even if no new options arose for them personally, they would arise for patients in the future, extending or transposing the promise of prediction and actionability into the future. For another group of patients, however, the test was not invested with particular promise and the personalised kinds of care they sought were more immediate as they focused on managing their cancer symptoms day to day.
This contingency and flexibility in the use of the test, its results and implications for patients was, of course, a product of professional efforts to find new pathways and protocols for embedding the test into practice, ‘smoothing out’ processes as well as delivering precision to individual patients. It also extended to the way the study was loosely framed as a trial by both practitioners and patients, and the various different ways the algorithm and the evidence base being developed were described to us as we proceeded with our research.
Through these processes we see the value of the test as something always in the making: value was dynamic in the sense that it was negotiated across place and time and interpreted differently by the actors involved. Practitioners, patients and family members appreciated the value of the test in various ways – ranging from its totemic value of precision and personalisation to its value as a source of reassurance or comfort in the face of uncertainty. But in other respects, the value of the test fell away, as its promise was not realised through the study design or processes (e.g. sample failure) for professionals and for patients who had hoped for something more from their participation. Other kinds of value could sometimes be salvaged from these disappointments and setbacks, including the possibility of benefit for future patients, but value nevertheless retained a precarious and contingent quality and value making required considerable emotional and articulation work from patients, family and practitioners.
In the next chapter we turn to consider how these contingencies and complexities played out in another kind of personalised cancer medicine, focusing on a much larger-scale UK-wide trial with similar aims of developing infrastructure, tackling stubborn cancers, building evidence to make more treatments available for the future, and supporting drug development more widely.