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.
We have explored molecular profiling for some breast cancer patients for whom targeted treatments have a longer history than for most cancers, but where the introduction of commercial tests is relatively recent in UK contexts. We have also considered gynaecological cancer patients accessing another commercial test as part of a feasibility study. For other cancer patients, personalised medicine is experienced via a new generation of larger-scale, multi-sited adaptive clinical trials. It is to this platform that we now turn.
As we discussed in Chapter 1, randomised control trials (RCTs), the ‘gold standard’ of evidence-based medicine, have been superseded by what Keating and Cambrosio (2011) describe as a ‘new style of practice’ in medical oncology, based on large trials across multiple sites to develop targeted therapies for subtypes of cancers based on genomic profiling. Multi-arm trials test several different treatments at once. If a particular drug is not proving efficacious the trial arm can be closed and new treatment arms brought in (Medical Research Council 2014; West 2017), depending on response and recruitment rates. Trials adapt as results come in, a different methodological approach to traditional RCTs.
Such trials hold out particular promise for patients for whom prognosis is poor and treatment options are few. Lung cancer is an example of one such intractable cancer with very poor outcomes. Patients with lung cancers are typically diagnosed in the late stages of the disease, making it more difficult to treat. Later diagnosis is partly a feature of the difficulties with identifying cancer symptoms, but also a result of the stigma and shame associated with lung cancer in particular, as it is associated with smoking, which may further delay the seeking of help (Chapple et al. 2004). Lung cancer is also associated with deprivation, where smoking rates are taking longer to decline, exacerbating inequalities (Powell 2019). Lung cancer is also difficult to treat due to the late stage of diagnosis, the challenges of surgery (and biopsy) and other difficulties with the health and social circumstances of patients. Genomic research has identified a range of molecular subtypes of lung cancer (EGFR, ALK) suitable for targeted treatments, and both mutations may be tested for during treatment pathways, but prognosis is still poor. The more successful developments of targeted treatments in breast and blood cancers have yet to be replicated in lung cancer, and current national efforts are underway to promote research and develop new targeted treatments.
Multi-site, multi-arm trials are important to building personalised medicine in health services such as the NHS, developing partnerships across centres, regions and with industry, embedding infrastructures of delivery, and investigating how to maximise participation and acceptability among clinicians and patients. Such trials are part of a programme of transformation of healthcare provision to embed personalisation, alongside other larger projects and initiatives such as the 100,000 Genomes Project, discussed in the next chapter.
In this chapter we investigate one such adaptive, multi-arm, multi-site trial for lung cancer, examining how the optimising logic of the trial was enacted and the kinds of value that emerged in the process (Montgomery 2017a; 2017b ). We show the ways in which trial leaders, practitioners, patients and family members gave meaning to the promise of the trial and sought to realise value for patients now and in the future. This was clearly difficult to accomplish in practice, and we capture how patients’ and indeed clinicians’ disappointments and anxieties manifested and were managed, in part, through efforts to calibrate expectations. This included lowering (personal) expectations (Gardner et al. 2015) and cultivating expectations that other patients would benefit in the future instead. In doing so, we draw on an analysis of professional literature, press and website coverage on the trial, as well as observations and interviews conducted between 2016 and 2018. We interviewed 14 practitioners (12 clinicians – including four nurses, three pathologists and two scientists), observed 21 encounters in clinics (two MDTs, two biopsy procedures for the trial, 17 consent meetings for participation in the pre-screening), interviewed five patients who participated in the trial (and two of their family members) and five patients who participated in pre-screening for the trial. We also gathered data from two online forums and platforms where the trial was discussed by patients and their relatives between 2015 and 2017.
Stratified medicine and an adaptive trial
The National Lung Matrix Trial (Matrix) is a multi-site, multi-arm, adaptive trial of treatments for people with lung cancer, based on the molecular profile of their cancer, linked to a pre-screening Stratified Medicine Programme 2 (SMP2). It is funded by Cancer Research UK (CRUK) and run by the University of Birmingham CRUK Clinical Trials Unit in collaboration with the Experimental Care Research Network, NHS and industry partners (initially Illumina, Pfizer and Astra Zeneca). We became interested in researching this trial following discussions with one of the investigators, who was very engaged with precision oncology and saw the trial as a major exemplar of this new approach. With their assistance we were able to develop a case study of the pre-screening component and the trial at one site, which included interviews and observations with staff and patients. We subsequently expanded our case study to include another hospital, partly because it was difficult to recruit patients to our study (there were small numbers being recruited to the trial and patients were unwell, so approaching them to request interviews and observations was not always appropriate). As we will discuss, the trial turned out to be an exemplar of the difficulties with making personalised genomic medicine for cancer work for current patients in treatment.
SMP2 is an observational, pre-screening study, designed to screen up to 2,000 non-small-cell lung cancer (NSCLC) patients in order to identify genetic changes in their tumours. This determines their eligibility for entry into the Matrix trial, where they will be matched to treatments based on the genomic profile of their cancer, and the benefits of these treatments will then be assessed. SMP2 has an additional aim of ‘continu[ing] to pioneer the use of next-generation sequencing (NGS) technology in the NHS to prove large scale genetic testing works within the NHS’. 1 The trial, while offering promise to patients, is also preparing the infrastructures and processes to make personalised genomic medicine feasible. This includes the following developments, described on the CRUK website:
Our Technology Hubs are centralised, quality assured molecular diagnostic NHS laboratories in Birmingham (West Midlands Regional Genetics Service), Cardiff (All Wales Medical Genetics Service) and London (The Royal Marsden). They use innovative NGS technology to detect a variety of changes in a patient's tumour DNA sequence. The NGS panel, consisting of 28 genes, was developed in close collaboration with Illumina, and can be updated regularly to reflect the needs of the programme.
The study design notes:
The management of patients with non-small-cell lung cancer (NSCLC) has been transformed in the past 10 years. The identification of EGFR-activating mutations as a predictive biomarker for the use of EGFR tyrosine kinase inhibitors ushered in the era of stratified medicine in NSCLC . Only 4 years elapsed between the description of EML4-ALK fusions  and the registration of crizotinib for treatment of ALK fusion-positive disease. Alongside these therapeutic advances have been a change in the regulatory landscape; the provisional registration of crizotinib was based on high signals of activity in non-randomized, single-arm studies . A series of publications culminating in the data from The Cancer Genome Atlas (TCGA) for both adenocarcinoma and squamous cell lung cancer have considerably widened the number of potentially treatable targets, albeit in small molecularly defined patient cohorts [4, 5]. Efficient testing of drug–biomarker combinations is necessary in order to unlock the true potential for stratified medicine for NSCLC. The National Lung Matrix Trial (NLMT), funded by Cancer Research UK in partnership with AstraZeneca/MedImmune and Pfizer, includes many of the potentially actionable molecular aberrations identified in NSCLC. (Middleton et al. 2015: 2464)
SMP2 and Matrix followed on from SMP1, a ‘proof of concept’ study, which involved molecular pre-screening of cancer patients with melanoma, breast, ovarian, lung, colorectal and prostate cancer at eight hospitals to establish feasibility for the NHS and acceptability to patients. They are run via the Experimental Cancer Medicines Centres Network (ECMCN) formed in 2007, with funding from CRUK, NIHR and UK Departments of Health. The network involves 18 adult and 17 paediatric cancer centres to ‘assist in the delivery of early phase cancer studies between research partners to enable faster and more personalised patient benefit’. 2
Presented by the trial website as ‘the largest precision medicine trial in non-small cell lung cancer globally’, 3 Matrix involves a rolling programme of recruitment to treatment arms which can close and open as knowledge about the effectiveness of drugs develops through the research. In press releases about the trial, the principal investigator (PI), Dr Gary Middleton, based at the University of Birmingham CRUK Clinical Trials Unit, noted:
This is one of the largest ever personalised medicine trials in any cancer, one which attempts to match the right treatment to the right patient based on an in-depth understanding of what makes their own cancer cells grow and survive.
For our patients, it's a tremendous opportunity to access a wide-range of therapies tailored specifically to their particular type of lung cancer. For people caring for lung cancer patients in the UK, it's exciting to be able to offer these treatments to patients when they're still at a very early stage of clinical development.
With this Matrix trial, cancer medicine in the UK now becomes a key global player in the search for more effective targeted therapies for people suffering from this devastating disease.
As is common in narratives of this sort, the PI emphasises the excitement and promise of the trial and the opportunities it affords patients by giving them access to experimental treatments. The trial is also contributing to the scaling up of UK capacity in the promissory bioeconomy of genomic medicine.
By mid-2016, after it had been running for around a year, the ECMCN reported that the trial had recruited 50 patients, rising to 100 by November that year, with patients receiving one of ‘8 Investigational Medicinal Products provided within this trial by either AstraZeneca or Pfizer, within 17 of the 21 distinct cohorts’. 4 At this point the trial also received an extension and continues to recruit at the time of writing. Seven of the treatments being trialled during our research were targeted agents (provided by AstraZeneca or Pfizer) with the eighth arm for patients with non-actionable mutations. As the Birmingham University description of the trial notes:
A secondary objective of the trial is to provide the opportunity for industrial partners to test novel agents in the cohort of patients who are not positive for any of the actionable targets in the trial, referred to as the no actionable genetic change arm. In particular, if interim analysis shows significant activity for one of the targeted drugs in a targeted group then it may be relevant to assess the putative biomarker specificity of this drug by including it as a treatment option for the no actionable genetic change arm. Such an assessment could be important to inform the design of future trials for that drug. During the course of the trial, any drugs that are selected for allocation to the no actionable genetic change arm will be included in a pipeline of options that become available sequentially. The first drug to be tested in this arm is durvalumab (Cohort NA1). 5
This multiplied the experimental value of the trial, facilitating opportunities for drug companies and patients to experiment with novel drugs.
By December 2016, 87 out of 107 patients were receiving targeted treatments, and plans were underway to develop two new cohorts with treatments provided by another pharmaceutical partner for other patients. The trial was designed to expand in this way to increase the numbers of patients involved. 6 The trial was also supported by expert review groups to improve the process of obtaining and analysing samples, including via training of appropriate staff: ‘Through working collaboratively across disciplines we are committed to improving existing NHS clinical and laboratory pathways to increase the number of molecularly eligible patients identified and subsequently treated with novel targeted therapies.’ 7 The importance of developing better processes and technologies was a major theme in news about the trial featured in the ECMCN webpages that give an account of its progress. Although there was considerable optimism about recruitment continuing to improve, with new recruiting centres and treatment arms being opened up, more patients and more ‘meaningful results’ were still needed for the trial to be a success. This all involves considerable work and engagement from healthcare staff, as well as patients, as the following extract shows:
SMP2 has recently completed the fifth comprehensive sample and data audit. The team will shortly be distributing audit reports to enable sites to identify areas for improvement. Performance across the network is steadily improving, and their focus now is to challenge sites to test as many patients as possible through SMP2 and carefully track eligible patients through to NLMT. We need commitment and support from the entire ECMC network to increase recruitment and maximise translation between SMP2 and NLMT, to ensure that this study continues to deliver.
The SMP2 team has been working closely with Illumina, our genetic technology provider and the three Technology Hubs/genetic testing laboratories, to develop a new and improved version of the 28-gene NGS panel. The new version, launched on 20 March 2017, features increased probe coverage, particularly in poorly performing regions, to reduce the gene fail rate and the addition of gene regions to the panel to allow new drug treatments to be delivered via NLMT. These improvements should mean that a higher proportion of patients receive a more meaningful result from their first sample, increasing the number of patients molecularly eligible for NLMT without the need for a repeat biopsy or repeat sample being tested. 8
Counting the numbers of patients screened in SMP2 (800 patients screened in 2017 ‘alone’) and recruited to Matrix (197 by the end of 2017) was an important means by which the trial leaders sought to establish markers of success in the earlier years of the project (an approach we will also find in the next chapter in relation to the development of WGS for cancer patients as part of the 100,000 Genomes Project). 9 However, after 2017 there is little information on recruitment in the public domain, with the main project website information for patients noting that the aim is to recruit upwards of 600 patients, around 30 per cohort, 10 with the target ‘amended throughout the course of the trial with the addition of more treatment arms and cohorts and removal of arms and cohorts showing insufficient signal of activity’. 11 CRUK reports that by November 2018 the trial had recruited 250 patients. There is also a report of high attrition rates between screening and entry to the trial arm (circa 90 per cent), including on social media where we found a slide from the trial entitled ‘The inevitability of attrition’. At the time of writing there are eight trial arms, and the non-actionable arm and two other arms have closed. 12 It is also noted that recruitment is expected to end in 2021.
The trial is a prominent example of precision medicine, with the difficulties around recruitment and treatment benefit acting as a spur for further investment and organisational/professional change, rather than as a sign of failure (Hiley et al. 2016). The trial has been framed as a success for the state, cancer charities, professionals and the market. When the Secretary of State for Health, Matt Hancock, visited a strategic University/NHS alliance in Birmingham in 2018 he learned about this ‘ground-breaking’ trial. 13 When a deal was signed with the pharmaceutical company Mirati Therapeutics to include its experimental drug sitravatinib in another arm of the trial, its CEO noted that the programme presented an ‘exceptional opportunity for clinical research’. 14 In a 2018 Telegraph article entitled ‘Personalised Medicine “Transforms” Survival Chances in Incurable Cancer’ which focused on results from a US study presented at the American Society for Clinical Oncology (ASCO), a CRUK representative explicitly mentioned Matrix when interviewed about the topic:
Drugs that target changes in a patient's cancer cells have transformed the way cancer is treated, as this study illustrates.
Cancer Research UK scientists are currently advancing this tailored approach via several studies aimed at personalising treatments, such as our National Lung Matrix Trial which is matching lung cancer patients to targeted drugs that will work for them with the ultimate goal of saving more lives by finding the right treatment for each person. (Bodkin 2018)
Through these processes it is not just the trial that is ‘rolling’ or evolving in terms of recruitment targets and arrangements, treatment arms and funding arrangements; its values also evolve as it is variously presented as, on the one hand, transformative, groundbreaking and part of a new era, and on the other, as part of a more modest process of incremental change and development of services, professional capability and infrastructures. Overcoming the difficulties and challenges of recruitment and attrition becomes part of the process of transformation as the value of the trial is reasserted rather than undermined. The development of new insights into knowledge, actionability, validation processes and valuation measures were also considered successes of the trial, rather than health gains for patients per se. The trial and the programme were, thus, optimised in practice, through efforts to improve treatments for patients, as we now go on to explore in more detail.
Making the trial work
The Matrix trial was often one of the last treatment options for patients following the completion of standard options (usually chemotherapy and/or radiotherapy). Recruitment into and remaining on the trial was challenging, not just because the patient's molecular profile had to match a trial arm that was open for recruitment, but because the sample also had to be of the right quality and the patient had to be well enough to participate and meet a range of other eligibility criteria. The SMP2 pre-screening study was the first step to being part of the trial. At this stage, patients gave their consent for surplus tissue from routine biopsies to be analysed using next-generation sequencing technology. Entry into the trial also required patients to consent to a further separate biopsy procedure to collect tissue to be analysed using next-generation sequencing at a separate institution to direct entry into one of the trial arms. Ensuring that these samples were of sufficient quality and quantity involved considerable articulation work, or ‘artful integrations’ including configuration and customisation, ‘incorporating technologies into everyday working practices and keeping them working’ (Suchman 1996: 407).
Enthusiasm and support for SMP2 and Matrix from one of the main investigators and one of the research nurses on the trial enabled us to develop our initial plans to follow patients and practitioners working on the trial at one site. For these actors, Matrix held considerable promise as a new paradigm of personalisation, but it brought with it the challenge of implementation, as one consultant oncologist noted:
It's taken many years … to bring it into clinical focus … that genomic medicine is important. And I think the things that have really been the tipping points in doing that have always been … market authorisation of … a drug for an actionable mutation, and subsequent cancer drugs fund or NICE guidance supporting its use in, in practice … once they come into place … there's been a headlong rush to try and institute it that wouldn't have been possible if a lot of backroom work hadn't been done for many months or even years …
… a lot of that work of building teams who are flexible and adaptive at the interface between clinical and laboratory medicine … is necessary to get a good … in-house solution to genomic testing. And that can't be turned … on a sixpence when NICE give their guidance.
We also encountered considerable scepticism and concerns about the trial when we engaged with lung cancer practitioners involved in recruitment. This was linked to a general sense of the difficulties of working with very unwell patients, difficulties with implementation and a vague sense of beleaguerment with the bioeconomy of which the NHS is a part. As another consultant noted:
I think the genomics has changed … threshold for some patients … by virtue of our own data on what the chance of these mutants is, it's allowed us to have more … personalised discussion with the patient about whether or not they go for a biopsy, but … if they don't want it, then they don't get it.
[But] … our patient cohort … is quite deprived, low education achievement, low familiarity with medical advances … I'm sure in a breast cancer clinic that's different, in the lung cancer clinic no one turns up with a Google search or anything like that, or hardly anyone … we have occasional middle-class patients, but they're few and far between, so no … the population as a whole is very … has a very low level of understanding of [genomics]
My concern is the very cosy relationship between pharma and the other … groups, and the professional groups as well, and I think pharma will often be … behind the scenes cheering these people on … when they are in the newspaper … these are all tragic stories, of course they are, I mean I see these patients every week and it's very sad that you have young … patients with young families and it's devastating … but sometimes when you're deciding how to invest limited funds there will always be losers and … there needs to be a degree of equity across the list in terms of … who loses out, because there are the people who lose out when expensive things get funded, you just never see them, they're just never there in the papers.
Working in this context was challenging for clinicians trying to give patients the best possible care, and included managing some difficult dilemmas around supporting patients to pay for targeted treatments privately, despite the general view in the team that private medicine was problematic. As one consultant put it, ‘I don't want to deal with money.’
Practitioners were engaged in an intricate balancing act to recruit patients on to the SMP2 pre-screening study and access targeted treatments on the Matrix trial, and ensure they were receiving the best possible care at the right time, protecting patients who were too unwell to participate (e.g. having another biopsy), or keeping the trial ‘in reserve’ for when the initial round of treatments was no longer working, and not raising hopes unnecessarily. Some were sceptical about the value of the study given its complexity and the difficulties with getting a result which would direct entry into one of the treatment arms. Even those practitioners who were more positive, such as the nurses directly involved in recruiting patients to the pre-screening study and caring for patients on the trial, had to navigate numerous difficulties with recruitment, sampling and obtaining results from tumour tissue and managing patient expectations and disappointments. This involved working with a complex mix of organisational arrangements, materials and emotions, while trying to optimise the care of unwell patients with often rapidly deteriorating health.
Several described feeling ‘hopeless’ about the trial, with others describing it as a ‘soul-destroying’ process, because of the high attrition in recruitment from the pre-screening study to the trial. This included a series of ‘failed’ samples which either did not pass quality control to be suitable for analysis or did not produce evidence of genetic changes that would mean that the patient could be recruited to one of the treatment arms of the trial. This led some practitioners to change how they ‘sold’ the pre-study to eligible patients who could be well enough to participate in Matrix, including managing and, at times, lowering patients’ expectations of results being returned that would direct entry into the trial. Not explicitly mentioning Matrix or treatments available on the trial arms was one strategy that was sometimes adopted, illustrated in extracts from fieldnotes below, where two patients were separately being interviewed about consent for SMP2. The first extract follows on from a discussion about where the tissue will go for analysis and what form it will take (a section from a block, to another hospital) involving one of the clinical trials assistants (CTA) responsible for recruitment:
The CTA goes on to explain that by testing the tissue they're looking for 28 genes, which might help ‘further down the line’ but also stresses that the patient ‘shouldn't worry about this’. The patient nods and agrees, ‘yeah, alright, why not,’ and doesn't ask any further questions. CTA: ‘you're great’ (laughs). The patient thoroughly reads through the consent but doesn't ask any further questions – seems more concerned about the CTA having to take blood ‘there won't be any left’! Whilst the CTA labels the vial, she asks whether the patient has ever been a smoker, ‘yes (looks at me) but I've cut down now’. He describes how his daughter visits him and complains about him smoking – ‘we can smell it’! [Sense of shame here.] The CTA ended the consultation by thanking the patient ‘for helping us’ and wished him luck with his treatment.
Here we see the CTA downplaying the possibility of SMP2 coming up with results quickly, lowering expectations (Gardner et al. 2015), taking on the burden of worrying about results on behalf of the patient and keeping the encounter focused around the patient's positive outlook and willingness to help.
The process with the second patient is similar:
The CTA introduced herself and asked, ‘did the consultant give you a leaflet about stratified medicine?’ The patient explained that he hadn't but she couldn't be sure as her granddaughter deals with most of the information, ‘she takes everything in’. The CTA went on to explain what the study entails ‘it's looking at the genetics to look at different types of cancer, we send a sample of your tissue to look at the DNA (little bits and pieces) and send to the Royal Marsden for analysis.’ The CTA explained that they're looking for 28 genes, which may mean the patient's eligible for research ‘further down the line’ (the patient nods and agrees). Again, the CTA stressed that the patient shouldn't worry and that if they're eligible the consultant will ‘talk this through with them’. The patient is given the opportunity to ask questions but doesn't and just asks about whether they need to do anything ‘nasty’ to get the tissue sample. The CTA explained that they didn't and that it would just involve sending old tissue along with a blood sample ‘one off sample’. At this the patient threw her hands in the air and said ‘get on with it, do what you've got to do’ and laughs. Throughout the appointment the patient seemed quite passive ‘yes, yeah, nodding’ and I was unsure exactly how much information they were retaining. The CTA took the patient's blood and I waited by the ECG machine (no chairs). Ending the appointment, the CTA said that she hoped the patient would get some results back but that ‘I won't bother you again’! She also thanked the patient who said again how much of an important role her granddaughter plays when accompanying her to appointments etc, ‘she's fantastic, does everything’. The patient also told us … her granddaughter is expecting a baby and had just been to do some shopping. Once the patient had left the room and the CTA was finishing the paperwork she said ‘that lady's got a great-grandchild on the way, it's so depressing because she'll probably die.’ ‘People just drop and die and there's no way of knowing. I really think it's all down to DNA; it's a DNA lottery.’ ‘Along with melanoma it's my least favourite cancer.’
This extract gives us an insight into some of the frontstage and backstage work (Lewin and Reeves 2011) involved in the pre-screening study and its potential as a gateway to recruitment to the trial. Frontstage the work could involve decentring some of the details and purpose of the trial and focusing on the pre-screening study in clinical appointments. This was a means of putting patients and family members at ease, being positive about their future, trying to reduce the burden of involvement (information to be processed, time spent in the appointment) and offering an opportunity for care and expressions of gratitude. Backstage, in team meetings and corridor talk, there were other kinds of emotions – frustration, sadness and disappointment to be managed, given the poor prospects of many of these patients. Staff also had to carefully negotiate approaching patients about the study, resolving conflicts among themselves in the process. For example, we were told patients with brain metastasis (mets) could be entered into SMP2 but they were not eligible for Matrix. This could result in tense conversations between the senior CTA and the consultants. Consultants were reluctant to approach patients with brain mets for recruitment into SMP2 because of how unwell they were and because they would not be eligible for Matrix. SMP2/Matrix were conflated as one study here (SMP2 leading to Matrix), but at times, when eligibility criteria conflicted, the senior CTA had to do a lot of work to convince consultants of the value of recruiting patients to SMP2 despite not being able to enter them in to Matrix, including the possibility of other treatments being recommended or contributing to future patient benefit.
Oncologists also sought to downplay the importance of the trial to treatment, as this clinician explained:
So one is when you see a patient initially … we don't really go into much detail of what SMP involves ’cos when they come to see … the complexity of the treatment … is vast and we perhaps don't have … all the results to make their initial treatment decision. So we'll go through about four, five scenarios and by that stage, you know, they're absolutely … saturated. So, you'll mention the Matrix, saying, ‘Oh, and by the way, we're doing this study which doesn't involve anything else apart from blood tests. It's looking for a potential treatment in the future … you may or may not be eligible for it.’ So, it's a sort of loose conversation and then they obviously meet with [the research nurse] who has a more detailed conversation about it.
But the way … at the initial diagnosis we mention it as … almost like an afterthought so it's not … a focus ’cos it's not a first line treatment so it's not the focus of that. And then most patients actually don't really remember it … it's only when … they unfortunately relapse or … we then go back to them and … someone will say, ‘Oh, oh, did the results come back from SMP2?’ And then the majority of time we say, ‘Actually, they have and you're not eligible’ or they've failed, and then we have that dilemma about do you then re-biopsy them?
Making the pre-screen study and trial valuable to patients was therefore an ongoing process, a question of timing when to give information, as well as adjusting the amount and type of information being provided to the patient's circumstances. By offering more established kinds of personalised care as part of the recruitment process, the personalising impetus of genomic medicine in the process is reworked within caring practices. This also involved having to manage disappointment and make further decisions about trying again to see if the patients could be recruited. We observed discussions and were given examples of patients whose samples had been reanalysed several times in a concerted effort to get them on to the trial at a point at which ‘time is running out’.
On other occasions where results from SMP2 were not expected to lead to involvement in the trial by clinicians but patients were nevertheless hopeful, practitioners sought to manage this, including via ‘avoidance tactics’ without ‘dampen[ing] hope’. For example, nurses spoke with us about avoiding walking through a waiting area so as not to encounter a patient who had been calling every day for results.
Cultivating a sense among patients that the benefits of participation were greater than their own individual benefit was another strategy for managing potential disappointment, in the words of the senior CTA:
Most of the patients will enter strat med [Stratified Medicine Programme 2] with the understanding that it's going to help somebody else … a lot of the patients don't care if it helps them. They just care that it helps somebody else. I've had patients say, ‘As long as I don't have to go through the same thing that I'm go – you know, somebody else doesn't have to go through what I'm going through, then I'll sign up to anything.’
And why do you – why do you think that – that is?
I think they feel like they can give back, I think like they're giving some value. Their life is like some kind of a value, their experiences have given value to … research and to patients in the future. I think they want to see … especially lung cancer cured, yeah.
Invoking benefits for future patients, rather than the patient in the pre-screening study who was not able to make it on to the trial, was a way of offering a sense of purpose and contribution for patients with few treatment options and foreshortened futures. Consultants also prioritised other opportunities such as immunotherapy (approved by NICE in 2017) where they viewed these options as more likely to prolong survival time. The trial therefore slotted into an ongoing process of managing patients’ hopes and optimising their chances by prioritising treatments and keeping other options in reserve according to the patients’ state of health and cancer type/results – as well as their capacity to cope with this information and decisions.
‘Living in hope’ (CTA) about the potential of the pre-screening study and trial involved difficult and painstaking work to try to optimise the prospects of a successful result by caring for the tissue itself. This included the CTA stewarding and tracking tissue as it moved between local laboratories (for sample preparation and then DNA extraction) and onwards to the national laboratory, as well as chasing results. It was also evident during biopsy procedures and laboratory analysis as practitioners sought to extract value and optimise the patient's chances of participation in a treatment arm of the trial. This was difficult and painstaking work given that the tissue sample being used for analysis was often very small, which meant that procuring and extracting DNA was a complex process resulting in a number of test failures. In order to offset the potential for failure, pathologists as well as geneticists and clinical trials staff described ‘maximising the tissue’ as well as thinking ahead to what might be needed from the tissue in the future (Swallow et al. 2020).
Making the screening study and trial work as a package inevitably involved tensions between staff as they sought to balance the different priorities of treatment and research. This is further illustrated in the extract from a fieldnote below, where the CTA is trying to find patients to consent to SMP2:
Each week the CTA double checks with each consultant whether she can recruit the patients she's identified as being suitable for SMP2. She checks with the consultant who seems reluctant to discuss ‘I thought the Matrix had finished’ ‘it's not you again’ … It transpired that three of this consultant's patients wouldn't be suitable – the consultant describes these patients as ‘knackered’ and the CTA explains that she's not sure whether she believes him [this is the same consultant she feels doesn't understand the meaning or utility of SMP2/Matrix for lung cancer patients]. One of the patients had dementia and so couldn't be approached. The CTA checked with a different consultant whether she could consent the final 2 patients and following what was quite a lengthy discussion [I waited in the corridor] CTA explained to me that she would approach one of the patients …
As I was stood chatting with both the CTA and a research nurse, a patient and their family member/friend headed to the consultant's room [consultant who is reluctant to allow CTA to recruit his patients] and the CTA smiles and whispers ‘[The consultant] smiled when he went past, did you see – he must have been the knackered patient, I didn't believe him at first!’ Responding to this the research nurse asks ‘is he … being obstructive?’ The CTA agrees and tells us how slow it's been for recruitment lately although also she stresses her efficiency, ‘I've consented everyone!’
In an earlier observation the issue of numbers and progress with the trial also came up:
I asked whether she could show me the report that she sends each month to CRUK. The CTA explained that at the moment her ‘numbers are really bad’ and stresses that this will look like she's ‘not performing’ when actually ‘it's not my fault’ – ‘I have my numbers of the year but it doesn't look like that.’ I asked what happens if she doesn't get her quota of patients consented each month ‘I don't know, I probably get called in to an office somewhere’ – hesitant when I asked this question and kept reiterating that she'd consented enough patients for the year ‘just keep on going’ – showed January's numbers – ‘look I consented 16 patients in this month’.
We got chatting about the observations we're doing in the labs – ‘oh you can tell us why samples aren't being processed then – why they're just left … you can spy for us’ (laughs).
Here we can draw further insights into the work that key personnel such as CTAs do to try to make the pre-screening study and the trial work, persistently cajoling consultants, chivvying laboratories, recruiting allies such as our researcher, in an effort to meet recruitment targets. These excerpts also illustrate the concerns of staff who acquired an unwelcome sense of responsibility for the trial's slow progress, trying to recuperate its value by focusing on recruitment to the larger screening study instead – a study which also aims to transform the NHS's capabilities in genomic sequencing.
In this section we have explored how practitioners sought to make the pre-screening study and trial work for patients, and for the network and trial coordinators, via an array of calibration, articulation and uncertainty work. Deriving value from the trial for individual patients, the research programme and future patients was difficult and could be secondary to efforts to care for patients in the here and now. Nevertheless, practitioners expended considerable energy on trying to get a result of value that would offer patients access to the trial and further targeted treatments, including retesting, tracking samples and encouraging other practitioners to join these efforts. Calibrating patients’ expectations was also an ongoing process of optimisation to offer sufficient but not excessive hope.
Patients accessing and being on trial
The complexities and attrition rate of the pre-screening study and trial, together with the poor health of patients and the pressures on the clinical team, also meant that we found it difficult to observe and interview patients through their journey from the pre-screening study to the trial. We only managed to interview a small number of patients on the trial, as well as another group of patients on the screening study who did not manage to get on to the trial. We approached recruitment with caution, aware of the precarious position of patients, the likelihood of deterioration, and difficulties with biopsy procedures and attrition. We were concerned not to add to the burden of work and engagement that the trial required from patients as well as healthcare staff.
As discussed above, part of the way in which practitioners sought to manage patients’ expectations of the pre-screening study and trial was to provide specific details about their options at the optimum time so as not to ‘saturate’ patients with information or raise false hopes. They also sought to offer the opportunity of the trial at the right time when other options had been explored and exhausted. This meant that the patients we interviewed and observed when they were being recruited to SMP2 were often not told about Matrix explicitly. This was partly because of known problems with tissue analysis and the likelihood that no actionable mutations would be found, but it was also because some of these patients were very unwell and unlikely to survive to receive the results.
In observations and interviews with patients who consented to be part of SMP2, expectations of personalised treatments arising were nevertheless present, albeit in quite vague terms. An example was Richard, a man in his forties with advanced NSC lung cancer that was responsive to the ALK inhibitor, crizotinib. For Richard, surgery was not an option due to the spread of cancer to lymph areas and blood vessels. Personalised treatments were the very best the NHS had to offer and he wanted to play his part in their efforts to help him by being positive about his prospects:
But I believe that that's an informed decision … other people have done that for me … we have this amazing system in this country … if they've gone away and done these tests then I believe them. People make mistakes in all walks of life, I would, I would understand that if, if something went wrong … at least you gave it a go and … we're not … saying, well that's the end of that then … I'm a fighter and I'd like to think everybody's doing their very best … to help me …
… they've said, ‘right okay, this is targeted, this is what we think is the best plan of option for you, and if it doesn't work, we gave it go and we'll try something else. And if that doesn't work, we'll try something else.’ So … why would I close any of those doors?
I remember … [my oncologist] … telling me about these genetic mutations and that I was only a one in twenty case, and I actually had to say to him, ‘sorry, is this a good thing or is this a bad thing?’… I think I've been taking these tablets for about eleven weeks now … and they were talking about maybe a nine-month process … I have good days, some days I have bad days, some days … while I've got everyone, my family and professionals around me, while I've got everybody doing everything that they can, well, you stay positive don't you? …
As well as keeping his future open, Richard also framed being part of research and experimentation, and trusting in clinicians, as part of progress towards a cure for future patients:
people have said to me, ‘oh it's a good job you didn't have this twenty years ago’ … Well maybe in twenty years’ time, they'll be saying to people, well thank god we've got a cure for cancer now, because if this had happened to you twenty years ago, you'd be in this, all this experimental stage where no one really was a hundred per cent sure.
For Richard, helping himself with more personalised treatments was also about helping other patients to access this kind of medicine in the future, as he explained earlier in the interview: ‘if I can be involved in that for my particular problems … not just for me … then why would I, why would I rebuff that opportunity … I think that would be silly’.
This balancing act between personal and collective futures was also evident in an interview with another patient, Michael, who told us that he stopped smoking instantly after his diagnosis because ‘you [health service] help me and I'll help myself’ is his ‘motto’, and how he tried to get his mother to stop too. He went on to reflect on how being on the trial was helpful:
It helps … the tablet, it helps your own mind. That's it. But basically, you're helping other people behind you. ’Cause then … my trial might say right, it works with their DNA. And then another part of it, that one, put the two of them together … Bang. We've cured him … I might go in … a fortnight and she'll go, that tablet is working. It's no[t] growing. And it's no[t] breaking up. Take this other one. We've trialled it with other people … Put the two tablets together and it might shrink and disappear.
Through these kinds of accounts, patients established their sense of purpose and hope, bolstering their identity as a worthwhile, active and valuable person as a way of coping with what was often a shocking discovery of cancer which encroached on their future (Chattoo and Ahmad 2003; Hubbard et al. 2010; Brown and de Graaf 2013).
Although lung cancer patients are typically less active in self-advocacy than other kinds of cancer patients, active engagement and self-advocacy was at times a strong feature of patients’ and family members’ accounts of Matrix in online lung cancer patient forums. This included examples of patients encouraging each other to ask about Matrix, seek second opinions concerning eligibility and to chase results with the hospital. For example, in a discussion about the unpleasantness of the bronchoscopy to obtain a biopsy and the difficulties with waiting on results one patient commented:
we were told about a month ago that they were asking [the hospital] for my biopsy. only now told that they had mislaid it. we kept having to ring the [hospital] just to warn others that if they haven't heard for a bit make sure that they haven't lost you in the system. 15
Patients and relatives supported and advised each other about how to get on to the trial too, for example:
First thing ask to take part in the National lung matrix, ours is in the [hospital] ask to be tested for EGFR its the cancer gene that determines whether they can use a non chemo drug such as immunotherapy. If your hospital doesn't do trials like ours … get a consultant at one that does. It sounds like you can't opt for radiotherapy if it has spread but everyone is different and how well you are.
Don't take one person's expert opinion do your own research and both decide. If we had my wife would have been in a hospice by now and I have no doubt about that, now she has been in the garden all day and gone out shopping amazing difference in hospitals, and this isn't private our good old NHS.
You are at the worse stage as you don't have enough info, like Brexit really, it gets better. The [hospital] is outstanding and I hear the [other hospital] is as good. Our Professor … is so passionate and yet the first thing the oncologist in [another hospital] said at diagnosis do you want some morphine to take home. Keep strong and keep positive
As this excerpt illustrates, patients expressed both gratitude and frustration with the NHS as part of these accounts, simultaneously evoking personal responsibility while also signalling commitment to a public spirit of care. Their accounts demonstrate the unevenness of information provision about the trial and about the capacity to access it. This mixing of emotions and values was a feature of what patients described as having ‘nothing to lose’ and a sense of taking control over advanced cancer through this kind of activity:
you can only but ask (OR SHOUT) if you think you might be right for this. If you don't ask you don't get.
[name], just go for that link from [name] & see what happens.
COME ON SUNSHINE GO FOR IT !!!!!
Frustrations, typically focused on the NHS, ranged from difficulties with accessing the trial to waiting for results, as in the extracts below:
Had 10 week break should get results tomorrow of the matrix trial, hopefully I might get lucky and get on a trial this time
Having not qualified three times for new treatments so far. Don't get me wrong I am very happy for those who have the protein to be accepted, but from what I can see that is only a minority, even though I am told that they work just as well for the people who haven't got the protein but maybe not for so long, so to me in a word to me it is nothing short of rationing.
Through these kinds of exchanges forum contributors articulated their sense of individual and collective self-worth, resisting unwelcome kinds of stratification while advocating personalisation in other respects, framing the work of being a cancer patient or relative in this world of experimental medicine as one of persistence against the odds to try to get to the next level of access to treatment:
My brother was signed up for SMP2, leading on to the Lung Matrix Trial, but his original biopsy returned a technical failure on the gene testing. It was simply too poor quality. They can't get another biopsy from his lung as his lung tumours are too small (the biggest is about 1.3cm) and although he has extensive brain mets, including one at 2.5cm, a biopsy of a brain met isn't standard NHS practice. Anyway, the good news is he might be ALK+ too, as a review of his original ALK test (initiated by the request for his biopsy block for SMP2) has been interpreted as having granular positivity for ALK. They can't confirm that without another biopsy, and they don't consider this as definitely ALK positive, but it's a ray of light. That review would never have come about if it wasn't for SMP2/Matrix. So, go for it … like [another forum user] I would say you never know what might come out of it!
‘Rays of light’ provide a sliver of hope for the future for these more active patients pursuing treatments, even as scientists and clinicians might have been much less optimistic. Although patients and relatives did engage with the molecular details of diagnosis as part of discussing their options, online exchanges were not places where lung cancer patients and relatives necessarily grouped around the details of specific subtypes. Instead they supported and encouraged each other, alongside family members, to move through the levels of access to acquire personalised information that might hold the promise of future therapies.
Other patients were less proactive in researching or engaging with detailed information, as was the case with the metastatic gynaecology patients encountering the VGT study as discussed in Chapter 3. Derek, a man in his sixties, had lung cancer which was diagnosed late and had spread to his spine. In an interview, he told us he too hoped for treatments from his participation in SMP2, something he described as ‘selfish’, but he also wanted to help future patients, such as his descendants. He was bewildered and shocked by his diagnosis and told us he coped with this by putting his trust in the clinicians, and not trying to find out too much about the details of his cancer. So his route into the study had been more passive than the kinds of approaches discussed above, as was the case with other patients we observed and interviewed. For these patients participation was part of their effort to ‘carry on living as I did before’, on the basis that something might come out of their participation, given that targeting treatments is better than a ‘blanket’ approach which ‘bombard[s] everybody exactly the same’. The SMP2 study, and the possibilities of targeted treatments, were but one part of a wider approach to living with cancer rather than a unique source of particular promise.
For patients who were successful in getting on to the trial the benefits could be self-evident, just as they were for patients such as Richard, already on targeted treatments and engaging with research in SMP2. When asked directly about her reason for participating in the trial, another patient, Marion, who had recently had brain surgery because her cancer had spread, and had recently joined the trial, explained:
Well I don't see how it can hurt. Anything that's going to … that might have any kind of positive result has got to be good. It's better than doing nothing about it. And it might do something really positive. And stop the cancer altogether. Because they can't guarantee that the brain tumour won't return again. Apparently, that's a possibility.
The possibility of stopping the cancer growing, which her husband, Malcolm, later described as ‘arresting its development’, drove Marion's involvement in the trial. As another patient in her forties, Victoria, noted, it ‘buys you a bit more time’. Victoria was just finishing treatment as we interviewed her. She had previously recovered from ovarian cancer but had gone on to develop lung cancer. She explained,
Because obviously my cancer's not curable but it's treatable, but every time something stops working, we have to think, well what's the next thing, what is coming? I know there's lots and lots of research that's being done into lung cancer at the moment … how can you, how can you advance any sort of knowledge if you're not involved in, in trials really? And also, it does give you a good understanding of what the treatment landscape looks like, or might look like, and to me … it's helpful to know what things might be on horizon, or you know, what trials might be available …
Future-crafting of this sort involved the intensive and ongoing work of remaining hopeful. Janet recognised how treatments had improved since her sister had died from skin cancer several years previously. Janet was on the no-actionable genetic change (immunotherapy) arm of the trial (now in remission). She emphasised the importance of trust and fortitude:
You know, if it weren't for them, there'd be a hell of a lot of us not around still … so what do you do? You turn round and say, ‘No I don't think I'll bother today,’ so I could wake up and think, ‘oh do you know what, I'll have a bit of cancer today’. So it's either put your trust in them and know that they can give you something what kills it or keeps it bay, or sit in a corner and slap your head against the wall. Fear worries me. Well sorry, I'm not that sort of person.
You know, just got to do what you've got to do, don't you, at the end of the day and you don't want to stop here, so you do it.
We interviewed Jenny, with her husband Paul, at a cancer centre. Both were in their seventies and Jenny had recently started a targeted treatment on one arm of the Matrix trial. They described how the Matrix trial (which Jenny transferred hospitals to join) had given them hope after Jenny had been told she was no longer responding to treatment. For Jenny and Paul this involved resisting the idea that she had only five months to live:
[Paul] I've an issue with this because averages don't work. Anyway, so … your response was, ‘Give me anything.’
[Jenny] Yeah, anything and everything (laughs) … I'm really pleased to be on the trial and I think I'm very lucky because of what the consultant said right at the beginning, because the first thing I did was count the five months … I think I really appreciate the trials because I think if it wasn't for them, if I believed what that … consultant told me, I wouldn't be here. So I really think it is the trials that have helped.
Being on trial was often a last hope for patients, but it also offered reassurance and care, in part because it signalled that consultants were working hard to keep up with her cancer:
[Jenny] Oh, they were absolutely fine. I mean they did say, they told me that it was affecting my liver … and that there would be alternative treatment.
[Paul] They were very positive about…
[Jenny] They were, yeah.
[Paul] … that there's always something else. And they also … said, ‘There is another trial.’ They'd already spoken (laughs softly) to [this hospital] and there's a trial now called the, the Lung Matrix Trial, which tries to pinpoint people with similar DNA or whatever. And … she would go on that. So we were…
[Jenny] Really positive then.
[Paul] … told, given bad news and then good news. So that was … really good because it was ongoing. They also rang you later (laughs softly) didn't they…
[Paul] And said, ‘If anything goes wrong, ring us. We may have another treatment for you here.’
[Paul] Yeah. So I mean that side of it's been fabulous.
[Jenny] Yeah, yeah.
[Paul] The only issue is they don't communicate very well (laughs softly) with each other, do they? Well this is it with hospitals. I don't think they do, do they?
The work of the hospitals to keep options open was a source of reassurance and hope. Jenny and Paul continued,
[Paul] [They told us] ‘If that doesn't work, we'll … have something else here.’
[Jenny] ‘We'll, we'll always have something else for you.’
[Jenny] And that was a phone call to my house, you know, after I'd been, finished with [that hospital] … I thought that was amazing, you know. So I thought, well if this doesn't work, maybe I can give them a ring…
Although these accounts contain familiar logics of promise and hope from trials which can also be found in patients’ accounts of other sorts of trials and treatment, they also reference the promise of adaptability and responsiveness to cancer according to personal and specific genomic changes – key distinguishing features of this new generation of trials and the personalisation of treatment on offer.
For Janet, Jenny and Paul, personalisation via the trial also offered a more precise hope. Janet, even though she was on the non-actionable arm of the trial (i.e. her treatment was not based on genetic changes), nevertheless experienced the treatment as personalised:
when they did the second [biopsy] and they said they've actually got whatever it was they were looking for, I thought ‘yes … they've found something, they have found it’ … I think what must have gone through my head at the time was, well if they find whatever they're looking for in this DNA and they … made … some sort of drug or whatever the case may be … I'd expect them to sort of like say to me, ‘right we've done this, we've got this. This is what it is. It's from your DNA, it's from your body, so we know your body's going to accept this drug and it's going to help.’
I mean, it'll never go, I don't suppose. It'll never ever go, but the one on my lung has shrunk because … I've had radiotherapy … These in my neck … I can't even feel them now, but like I say, if it weren't for … all these drugs and putting stuff together and seeing what makes this … do this, then I probably wouldn't be here.
For Jenny and Paul,
[Paul] … being on a trial, there's always a risk of it not suiting you or it being cancelled because it suits you but it doesn't suit a lot of other people.
[Paul] I think the Matrix way is better because it's trying to aim at suiting you, or you and a small percentage of people, and say ‘for these people it's great, so we'll carry on; for these other people, it's not so good, so we'll do something else’. And I think that's the whole, that's –
[Jenny] It's a lot more choice in treatments.
As Paul explained, this was more positive than his mother's experiences of undergoing chemotherapy:
[Paul] [going on the trial] that was a big relief to both of us, actually, because … although you said … you'd spend a fortune on wigs, you didn't really want to, did you?
[Jenny] (laughs) And said, if I had to wear a wig, I would have a lot of them (laughs) and very expensive (laughs).
[Paul] Well, historically, I know … my mother died of cancer and had the most terrible chemotherapy, because it was just the same, they stuffed the same poisons into her as they did to everybody else … whichever cancer it was … And I think, nowadays, what they're doing is it's the same as going and getting a suit made to measure rather than buying one off the peg. It's … better for you and it might only be a tiny tweak.
As Jenny noted elsewhere, the totemic value of the trial brought an enhanced sense of personalisation: ‘I got in my head that if they actually found some sort of treatment [that] shrunk mine … I should be offered it ’cause at the end of the day, it's part of me. You know, it's part of my body, it's my DNA.’
Maintaining hope while on the trial was, however, a complex affair that involved numerous balancing acts. As Paul noted, more time had to mean quality time: ‘Well I think anything that holds out the possibility that she could have longer and better quality of life, I think these two things, longer, but we don't want longer if there's not quality … So it's longer and better quality.’ Patients on the trial also described hoping to keep the ‘cancer at bay’ in Janet's words, while also keeping open the possibility of a longer-term and more remarkable result, as described by Michael:
’Cause that's what the tablet's to do. Just … it's to stop it growing and stop it spreading, breaking up and spreading. And if that happens it just means then you get on with your life…
… it's just something that's there and it's not going anywhere. That's it. So then maybe such-and-such'll get something that'll make it disappear altogether. But at least it's no[t] growing.
Other participants experimented with the hope that practitioners are going to produce a ‘magic cure’, as Marion's husband Michael put it. For example, in Victoria's interview she joked:
What I told my consultant when I started it, I said, I want nothing less than a headline out of this, and she said, ‘we'd go Daily Mail,’ so it was a new and unexpected life goal (laughs). So yeah, no … peer review journals for it, cause we were going straight, straight for the top (laughs).
Here Victoria reflects on building rapport with clinicians and leaving a legacy, thereby maintaining hope. As Michael explained this could also involve avoiding certain trains of thought: ‘I don't ask them how long have I got … I'll know myself. So … but I just hope the trial maybe worked for me and I get … I don't know if I've got two weeks, two years or twenty years…’
However, in other respects, patients reflected on the need to lower expectations (Gardner et al. 2015), as Victoria explained:
I think also, as patients, there's got to be some sort of acceptance, so I suppose of the limits of what medicine can do … of course you want research to always be, pushing the boundaries … but in reality how does that translate into what can it actually do for you and does that mean that, you know, just because we can do something, well does that mean we should be keeping people alive at all costs … if I was going into my consultant every few weeks and saying … ‘what are you doing to make sure that … you keep me alive, or you can cure my cancer?’ we wouldn't be getting very far. We're having to work together to understand that we can't cure this, but we can … maintain my quality of life … and my health actually, you know, for as long as we possibly can.
Victoria's sense of partnership with the clinical team can, however, be contrasted with Janet's doubts about her care. Janet received treatment on the trial that was not funded by the NHS and she described her anxieties that in a year's time they might decide not to fund the treatment further. She raised these concerns with the consultant who said they would ‘cross that bridge when we come to it’, bracketing the future to protect patients from the possibility of failure and disappointment.
Being on the trial involved living with uncertain futures where much was at stake. It also involved managing side-effects and disappointments with care, as the extract below from one of the Cancer Patient Discussion forums illustrates:
It's been many months since I have posted an update for the simple reason is the phase 2 drug trial (matrix Arm C) has been doing what it says on the tin … keep the tumour growth at bay.
Side effects … feel very tired on the recovery week due to low red and white blood counts (3 weeks of drug and 1 week off for recovery) and cough gets worse near the end of each cycle however apart from that all has been all good.
Had 6 weekly CT scan just after xmas and they saw very slight growth of the tumour, plus a small secondary bone cancer (treated with radiotherapy) so ‘we’ started looking for a plan B which also included possibly moving my treatment [to another hospital].
The CT scan last week – the trial drugs have completely failed, or has the cancer mutated so the drugs are no longer effective? Noticeable tumour growth plus fluid on lung, second lymph node has growth to a possible infected size. Probable infection in liver.
All a bit of a shock as we had our rose-tinted glasses on and were hoping just small amount of small growth.
Well shit happens and we move on. We always knew that I would have to be off any treatment before moving onto another trial assuming something is available. We are just off the current trial a bit earlier than expected.
Bring on the next trial… 16
Here we see the work of reinterpreting failure and orienting to the future, as well as some of the problems associated with too much hope being attached to these trials by patients and family members. Patients nevertheless welcomed the care they had received while on the trial, particularly the time spent with research nurses discussing difficulties around treatment and uncertainties. For Marion and Michael the trial also provided them with the opportunity to feel more involved in their care, affording an extra level of care: ‘giving me an MOT’, in Michael's words, and, for Marion, feeling ‘very closely monitored … that makes me feel good … it's better than just leaving you not knowing what's happening’. Victoria also welcomed this:
so I'd rather, in a way that they were taking a bit of care of me rather than sending me away, see you in six months and see if your arm's dropped off or anything … I tell all of my friends it's like going up another level in a computer game … Do not go to level one, go straight up the lift to level three, where five nurses are waiting for you. So yes, it's lovely, I feel much more looked after.
The importance of developing relationships and spending time with healthcare staff was also important as Jenny and Paul described:
[Paul] And it is that sort of positive from some of the nurses. We had a lovely nurse, [name of nurse], in, in [hospital] who used to tell us all about what she was doing and where she'd been.
[Jenny] Yeah, everybody's got…
[Paul] And the girls up here in the—
[Jenny] … time, time to talk to you.
[Jenny] You know, it's not as though you're a – I don't know. ‘Sit there and we haven't time cos we're busy.’
[Jenny] You know, everybody has the time to sit down and have a chat with you.
[Paul] But … here … the nurses and the, the consultants always seem to have a decent time to spend with you.
[Jenny] Yeah, yeah, there's no rush. There really isn't.
[Paul] I've never felt rushed out of the consultancy…
[Paul] … without being asked if there was anything else we wanted to talk about.
I think that's it really. We just feel that there's caring people, with time.
As this exchange illustrates, being on the trial meant spending time and developing partnerships with clinicians which was experienced as comforting; an example of how trials create the space for additional carework from busy staff, which patients and relatives greatly value.
For patients facing an advanced lung cancer diagnosis, adaptive trials such as Matrix are an opportunity to extend severely diminished futures, keeping options open and being positive about living with cancer even though there is no cure. This was articulated in terms of being fortunate to be part of something advanced or cutting-edge in some cases, and via a detailed engagement with the particularities of research design or experimental treatments in other situations (particularly in the online forums), with the idea of tailored or targeted treatments resonating with commonsense understandings that precision is better than blanket or one-size-fits-all approaches. For some of these, often younger patients and their relatives, advocating for participation in trials and engaging in detail with the processes and its complexities as they tried to negotiate access to experimental treatments was a way of optimising their health despite the cancer diagnosis, somewhat mirroring the work of nurses chasing samples and results. For other patients their engagement with the trial and pre-screening study was more passive, a matter of trusting in the clinicians in an effort to gain more time, particularly for older patients, as was also the case among the gynaecological cancer patients discussed in the previous chapter. Persistence, fortitude and positivity were nevertheless key virtues for patients across these different groups.
Participation in the pre-screening study and trial was also, on occasion, an opportunity to demonstrate commitment to helping other patients in the future, although this was inevitably framed as a secondary benefit in favour of personal benefits. Accessing more personalised care was another valuable part of participation; spending time with nursing staff was particularly important for patients as they sought to carry on with their lives and maintain self-worth in the face of narrowing horizons. Participation could nevertheless generate uncertainties and anxieties about waiting, about treatments after the trial or side-effects and lack of effectiveness of treatments. As with the breast and gynaecological cancer patients discussed in the previous chapters, adaptive trials generate promise and hope for the future among lung cancer patients, but this can be fleeting, contingent and overshadowed by ongoing and growing uncertainties and worsening health.
Adaptive trials are a key feature of the personalised cancer medicine landscape, offering patients experimental, targeted treatments and reconfiguring institutional arrangements to mainstream next-generation sequencing as part of care. In the case of lung cancer patients, this offers a new set of options for patients with some of the worst outcomes, given that lung cancer tends to be diagnosed at an advanced stage. Patients affected with lung cancer also tend to have less financial and social capital with which to manage their condition, since it is associated with disadvantage. Practitioners are therefore keen to make these new opportunities work for these patients, but they are also operating in difficult circumstances, in services where resources are pressurised and outcomes are disappointing. The screening and trial arrangements of which they are a part are also complex and difficult to implement, not least because obtaining and analysing a sample of sufficient quality involves many intricate steps and numerous actors, taking time and asking patients to wait when their futures are already foreshortened and their health continues to deteriorate. Making this trial work – for institutions and for patients – therefore took considerable care, marked by calibration, articulation and navigation work for practitioners and, at times, patients and their relatives.
Such work always has to be weighed against the perceived needs of patients for whom care in the moment can trump the possibility of future treatments emerging from the trial. Practitioners and patients sought to maintain hope and salvage other kinds of value, such as care in the moment, when results were disappointing. Participation or engagement with the trial and its possibilities could generate additional uncertainties, anxieties and disappointments that also had to be managed by staff, patients and families. Patients did this work alongside their relatives, sometimes in public forums where they engaged in detail with the trial arrangements and processes. But for other patients there was less engagement with the technicalities of the trial and more of a focus on relations of trust and care with clinicians – two different ways of enacting hope with persistence, fortitude and positivity. Together, these activities and expectations formed part of an ongoing process of optimising the possibility of the trial that worked alongside efforts to optimise treatments and sequencing infrastructures to deliver the new era of personalised cancer medicine.
In her study of adaptive trial methodologies, Montgomery notes that
the temporal politics of adaptive design straddle a … diffuse set of scientific institutions, from profit-seeking big Pharma to publicly- and philanthropically-funded academia. What is at stake is not so much the creation of commercial value through the promise of a given vision, but the creation of value – moral, epistemic and commercial – through the ability to know the unknowns and to fix the future as it unfolds. (2017a: 237)
We can see these forms of value emerge, diverge and fade across the different levels at which the trial and pre-screen study on which it depended were orchestrated and experienced by practitioners and patients. Making a success of the trial for practitioners and for patients could mean different things, but in each case it involved ongoing processes of careful tinkering in an effort to chase and realise value, even when this could be fleeting or minimal. This work kept the trial going, enabling the extraction of other kinds of commercial value in the future through drug development and improved trial processes. Big pharma was remote from the clinic, but the hopes inspired by the possibility of ‘drugs that work’ for current and future patients were ever present. Yet practitioners, relatives and patients trying to make the pre-screening study and the trial deliver personalised care to patients also generated value for the consortia, institutions, funders and investors in this new form of personalised medicine. This spurred further faith and investment in the UK bioeconomy, enhancing scale, and innovating new kinds of pathways, research consortia, valuation practices, gene panels and, of course, the data required for the innovation of new drugs. As we go on to discuss in the next chapter on whole genome sequencing studies, these processes of generation and extraction of data are crucial to the promise of personalised cancer medicine, even if it is not yet being delivered at scale to current patients.