Gastrostomy versus nasogastric tube feeding for chemoradiation patients with head and neck cancer: the TUBE pilot RCT

Initial screening visit

At this appointment patients were provided with information about the trial and an eligibility screening form was completed.

Consent and baseline visit(s), and randomisation

The consent and baseline visit took place at least 24 hours after the patient had been provided with the trial information. The patient’s eligibility was reconfirmed and their informed consent was taken, after which the baseline assessments and baseline questionnaires were completed.

The baseline data included site of disease, patient demographic information, tumour, node and metastasis classification, a record of whether or not induction chemotherapy was planned, a record of whether or not IMRT was planned, and whether or not the patient had been given any pre-treatment swallowing exercises and, if so, if the patient had complied with these (recorded as yes or no). Questionnaires included the MDADI, EORTC QLQ-C30 (version 3.0), EORTC QLQ-H&N35 and the SF-36.

Clinical assessments included body mass index and usual weight, measurement on the Performance Status Scale, normalcy of diet and data from oral health assessment performed as standard NHS care (includes information from a panoramic radiograph, a dental chart, periodontal and oral hygiene assessment plaque scores, oral opening measurement and oral dryness).

After the baseline data and consent visit took place, randomisation was performed. Patients were informed of their randomisation allocation and given the opportunity to ask further questions.

Intervention visit

Interventions were performed as follows (timing was dependent on the treatment arm):

• pre-CRT gastrostomy arm – gastrostomy tubes were inserted after the consent and baseline visit, and randomisation, but before any treatment (CRT/IMRT) took place

• no pre-CRT gastrostomy arm – nasogastric tube was inserted after the consent and baseline visit, and randomisation, at a point when the patient and/or clinician assessed that this was most appropriate.

Weekly data collection

Information recorded included:

• dates of induction chemotherapy plus number of cycles received

• regime of concomitant chemotherapy and number of cycles received

• details of RT technique, dose and field size, including mean dose to the pharyngeal constrictors

• weekly weight

• Performance Status Scale measurement, normalcy of diet

• gastrostomy tube site infections

• radiographs associated with tube placements

• pH problems requiring nasogastric tube placement

• tube changes (e.g. nasogastric tube to nasojejunal tube or nasogastric tube to another nasogastric tube)

• degree of reliance on feeding tube use (nasogastric tube, nasojejunal tube or gastrostomy tube)

• feed-related hospital admissions

• number of dietetic consultations

• quantity of enteral feed prescribed and quantity consumed

• district nurse visits and dates

• tumour status – clinically disease free, alive with disease or died of disease or other causes

• AEs.

Follow-up visit at chemoradiation therapy completion

All outcome measures were recorded at the end of treatment in addition to the migration of patients from nasogastric tube to gastrostomy tube, replacement episodes and removal of nasogastric tube/gastrostomy tube, if applicable.

Follow-up visit at 3 months post chemoradiation therapy completion

All outcome measures were collected as per the end of treatment. In addition to the use of health and PSS and costs to patients and their families/friends (excluding the use of weekly/biweekly services in a cancer clinic), data on the number of pharyngeal/oesophageal dilatations were collected per patient. Information on access to rehabilitation services was recorded, including frequency of dietetic and speech and language therapy follow-up.

Follow-up visit at 6 months post chemoradiation therapy completion

The same measures as per 3 months post CRT were recorded. Oral health assessment data were included.

Pre-implementation of the TUBE pilot trial

To understand the context of the trial, professionals’ views and expectations and patient pathway mapping, formal interviews were conducted with key individuals involved in treatment planning for HNSCC (e.g. nurses, speech therapists and ear, nose and throat surgeons).

Patient recruitment phase

Patients’ and professionals’ experiences of recruitment were the focus of this phase. Patients were recruited from multidisciplinary clinics, with research nurses providing trial information. Qualitative interviews were conducted with patients who consented to take part in the trial. The focus of these interviews was the patients’ experiences and understandings of trial processes (e.g. the information they were given, the recruitment encounter, their ideas and/or concerns about randomisation and consent) and the intervention (their willingness to undergo either feeding option; their ideas and/or concerns about the impact on health and acceptability).

Patients were interviewed within 2 weeks of the recruitment discussions and offered a choice of location and method of interview (telephone or face to face). As people often discuss clinical decisions with others,39 those patients who wanted to involve a family member in their interview were able to do so. Further interviews were conducted with professionals involved in some aspect of patient recruitment. Research nurses were given a digital voice recorder and asked to record their recruitment discussions with patients (with the appropriate permission).

Patient follow-up phase

Patients took part in qualitative interviews approximately 8 months after recruitment to explore the acceptability of the assessment tools and investigate their experiences of the intervention.

Qualitative study consent details: interviews

During the recruitment discussion, as part of which written consent was taken for participation in the TUBE trial, patients, and any friends or family present, were asked if they were willing to be contacted about an interview for the qualitative substudy. If so, their written consent was taken and their contact details were made available to the qualitative researcher, who accessed the data on the study database. In addition, patients were given a separate information sheet. Written consent was obtained before the start of the face-to-face interviews; the qualitative researcher kept a record of verbal consent for those interviews conducted over the telephone.

Patient and family/friend interviews

The qualitative researcher telephoned patients who expressed interest in the qualitative interview element of the study (including those who consented to and those who declined randomisation) to further discuss their participation. Patients and family/friends from sites in the North of England were offered a choice of location and method of interview (telephone or face to face). Patients and family/friends elsewhere were offered telephone interviews only. Patients who wanted to involve a family member in their interview were able to do so.

Interviews with patients took place at two time points: 1 or 2 weeks after the initial recruitment discussions (to understand the barriers to, and facilitators of, recruitment) and during patient follow-up (to understand patients’ experiences of trial participation).

Summary of interview data collection

• Took place 1–2 weeks after the recruitment discussion.

• Trial participants’ experiences of recruitment, views on supplementary feeding, reasons for participation and feelings about randomised allocation.

• Family and friends’ (of participants) experiences of recruitment, views on supplementary feeding, reasons for participation and feelings about randomised allocation.

• Trial decliners’ experiences of recruitment, views on supplementary feeding and reasons for declining.

• Family and friends’ (of decliners) experiences of recruitment and views on supplementary feeding.

• Eight months’ follow-up.

• Trial participants’ experiences and views of the TUBE trial (outcome measurement, etc.) and experiences of supplementary feeding.

Patient consent for observation/audio-recording of recruitment discussions

The observation and audio-recording of recruitment discussions have been key to improving recruitment processes in other randomised trials. We designed a three-stage consent process for this part of the study, balancing the need for informed consent with the need to not disrupt the process of consent for the TUBE trial. The main study information sheet, given to patients before the recruitment discussion, included a brief outline of the purpose and design of the observation or audio-recording of recruitment discussions.

1. At the start of the recruitment discussion, verbal consent to record the conversation was obtained. It was explained that more information about this would be given during the discussion and that there would be an opportunity to rescind consent at the end. Everyone present had to give verbal consent; if anyone declined, then the audio-recording did not take place.

2. Written consent for audio-recording was taken as part of the consent process for the TUBE trial. There were separate consent forms for those declining participation in the TUBE trial and for family/friends present. Everyone present had to give written consent for audio-recording; if anyone declined, then the recording had to be deleted immediately (while the person declining was present).

3. Those patients and family/friends who gave written consent for the audio-recording to be kept were given a follow-up information sheet. Prominently on the front page of this information sheet was the information that patients and family/friends had a further opportunity to change their minds about audio-recording by getting in touch with either the recruitment nurse or the qualitative study team.

Clinician interviews and observations

A qualitative researcher conducted the interviews with clinicians. Written informed consent was obtained to audio-record the face-to-face interviews and recruitment discussions. When telephone interviews were conducted, verbal consent was obtained at the start.

The aim of these interviews was to:

• understand and map processes of care in relation to supplementary tube feeding in patients undergoing CRT for head and neck cancer

• understand perspectives on supplementary feeding in patients undergoing treatment for head and neck cancer

• understand experiences of the TUBE trial, including those of patient recruitment.

The selection of clinicians for interview was purposive and informed by factors such as emerging variation in recruitment rates between sites and changes in key personnel.

Recruitment

The trial is closed to recruitment. The first patient was randomised on 10 July 2014 and the trial closed to recruitment with a total of 17 patients randomised. The last patient was randomised on 30 June 2015. The database was frozen on 5 May 2016.

Randomisation

Participants were randomised in a 1 : 1 ratio to either the pre-CRT gastrostomy arm or the no pre-CRT gastrostomy arm using a block-stratified block method (based on permuted random blocks of variable length), implemented using the Newcastle Clinical Trials Unit internet-accessed secure web-based system. Randomisation was stratified by site (Table 1).

Baseline patient characteristics

Demographic, clinical and surgical baseline characteristics and trial stratification factors at randomisation were compared across treatment groups descriptively. Descriptive statistics were tabulated by treatment group and overall. No significance testing was carried out owing to the randomised nature of the study.

Demographic characteristics included age, sex, weight and height. Clinical characteristics included the tumour, node and metastasis classification, dental characteristics and Performance Status Scale score (eating in public, understandability of speech, normalcy of diet). Trial factors included stratification factors (site), whether or not induction chemotherapy was planned and whether or not IMRT was planned (Tables 2 and 3).

Limited data are available on the characteristics of all eligible patients, including those not approached and/or recruited (n = 84). Age at screening was available for 83 out of 84 patients; the median age of these 83 individuals was 62 years [interquartile range (IQR) 58–67 years; range 38–85 years].

Table 2 shows that the majority of patients were recruited from site 3 (59%) and were male (94%), with a median age of 64 years (range 49–76 years) and a median weight of 84.8 kg (range 54.6–113 kg), balanced between the randomised groups. No patients had restrictions with eating in public and all had full normalcy of diet.

Table 3 shows that 65% of patients had human papillomavirus (HPV)-positive oropharyngeal tumours, and three patients in the nasogastric arm had nasopharynx tumours. Two out of nine patients (22%) randomised to the gastrostomy group and six out of eight patients (75%) randomised to the nasogastric group had a T3/T4 tumour stage. One out of nine patients randomised to the gastrostomy group and three out of eight patients randomised to the nasogastric group were node negative. All nine patients randomised to the gastrostomy group and six out of eight patients randomised to the nasogastric group were free of distant metastases.

Table 4 shows that dental information was not complete for all patients at baseline; the highest number of patients providing information for any particular component was 13 (76%). Initial decay, missing and filled teeth scores appeared balanced between the randomised groups, as did oral opening and oral dryness. Ten patients (59%) had oral hygiene aggregate scores recorded. Higher scores were reported in the gastrostomy arm, with a non-overlapping range of scores.

Defining populations for analysis

All patients who were approached about the trial are referred to as the screening set. All patients randomised to treatment are included, retaining patients in their randomised treatment groups and including protocol violators and ineligible patients. This group of patients is referred to as the intention-to-treat (ITT) set. All patients who started treatment are referred to as the treatment set.

Treatment received

The analysis set was the ITT set. Treatment was defined as CRT plus randomised intervention. CRT treatment was delivered as per usual centre practice and was usually completed within 2 months.

Adverse events

The analysis set is the treatment set. AEs were graded on a three-point scale of intensity (mild, moderate and severe):

• mild – discomfort is noticed, but there is no disruption of normal daily activities

• moderate – discomfort is sufficient to reduce or affect normal daily activities

• severe – discomfort is incapacitating, leading to an inability to work or perform normal daily activities.

A total of 230 AEs were reported in a total of 15 patients (Table 9).

Nine (3.9%) AEs reported were possibly, probably or definitely related to the randomised intervention. These were reported in six patients. Table 10 provides a line listing of all reported AEs; shading is used in the table to show those nine events that were possibly, probably or definitely related to the randomised intervention.

The number of patients experiencing at least one ‘moderate’- or ‘severe’-grade episode of each type is reported as a percentage of those receiving treatment in each treatment group. Six out of eight patients (75%) receiving a gastrostomy tube reported a moderate or severe event, and five out of eight patients (63%) receiving a nasogastric tube reported a moderate or severe event.

The number of treatment-related AEs is reported divided by the level of association, that is, if these were ‘definitely’, ‘probably’ or ‘possibly’ related to treatment. A total of nine AEs related to the intervention (defined as possibly, probably or definitely related) were reported in six patients: seven AEs in four patients (44%) receiving a gastrostomy tube, and two AEs in two patients (22%) receiving a nasogastric tube.

With such small numbers of patients randomised, it is difficult to be conclusive, but it appears that a higher proportion of patients treated with gastrostomy experienced AEs possibly related to the gastrostomy tube (see Tables 9 and 10).

Serious adverse events

The number of patients reporting a SAE was compared descriptively across treatments. A total of 16 SAEs were reported in 11 patients. None of the SAEs were related to the randomised intervention (Table 11).

Clinician-reported measures

Table 12 shows that the retention rate at the 3-month and 6-month clinician follow-up points was high, at 0.88 (95% CI 0.73 to 1.04), and balanced between the randomised treatment groups.

At 3 months, 79% of responders reported no restrictions on eating in public, maintained at 80% at 6 months. At 3 months, 100% of responders reported that they are always understandable in speech, which reduced to 80% at 6 months. At 3 months, 20% of responders had a full diet, which increased to 47% at 6 months.

Table 13 shows that retention at the weekly clinician follow-up was highest at 1 month post intervention, and balanced across the randomised treatment groups.

Tables 12 and 13 summarise the Performance Status Scale normalcy of diet measurements on a weekly basis, during treatment and over the course of the trial.

Patient-reported measures

Questionnaire scores were calculated and transformed as recommended by the specific research groups (MDADI, EORTC, SF-36). Scores are reported longitudinally over time, as raw scores were conditional on patient survival. Owing to small numbers, change from baseline was not calculated (see Tables 14–17). Some of the data are shown graphically in Figures 2–4.

Table 14 shows that the response rates to the three patient-reported questionnaires were high at 3 months (overall > 80% of all 17 patients) and maintained at 6 months, with good response rates in both randomised groups.

Given the small number of respondents, summary statistics are demonstrated as medians (ranges) between the randomised treatment groups. The data displayed in Table 15 are better represented graphically, as seen in Figure 2.

FIGURE 2.

Short Form questionnaire-36 items physical (a) and mental (b) component scores over time. NGT, nasogastric tube.

Figure 2 demonstrates graphically that both the physical and mental component scores from the SF-36 questionnaire dropped from a baseline score of ≈50 following CRT, and returned to baseline level by 3 months, maintained to 6 months. This trend was observed in both randomised groups. There was a trend for patients randomised to receive gastrostomy tubes to have slightly inflated scores (a ≈5-point increase in the physical component score, and a ≈10-point increase in the mental component score) across the time points, compared with patients randomised to receive nasogastric tubes.

Given the small number of respondents, summary statistics are demonstrated as medians (ranges) across the randomised treatment groups. The data displayed in Table 16 are better represented graphically, as seen in Figure 3.

FIGURE 3.

European Organisation for Research and Treatment of Cancer QLQ-C30 global health scores over time. NGT, nasogastric tube.

Figure 3 demonstrates graphically that the global health scores from the EORTC QLQ-C30 questionnaire dropped from a baseline score of ≈70 before CRT to a post-CRT score of ≈35. Scores improved at 3 months, but did not return to baseline level until 6 months. This trend was observed in both randomised groups. Scores appeared to be similar across the randomised groups, with a wide range of scores for both arms.

Given the small number of respondents, summary statistics are demonstrated as medians (ranges) across the randomised treatment groups. The data displayed in Table 17 are better represented graphically, as seen in Figure 4.

FIGURE 4.

MD Anderson Dysphagia Inventory global scores over time. NGT, nasogastric tube.

Figure 4 demonstrates graphically that the global scores from the MDADI questionnaire dropped from a baseline score of ≈80 to a score of ≈40 following CRT, and returned to baseline level by 3 months for patients randomised to receive gastrostomy tubes and by 6 months for patients randomised to receive nasogastric tubes. There was a wide range of scores in both groups.

Analyses were planned as descriptive analyses providing a comprehensive symptom profile of the patients. The mean [standard deviation (SD)] of baseline QoL scores was calculated and presented by treatment group for each domain. The mean (SD) changes in QoL from baseline to 6 months (end of the treatment period) and 12 months (end of the follow-up period) were calculated and presented by treatment group for each domain, conditional on the patients surviving.

Owing to small numbers, scores were calculated as the median (range) within a 6-month period only and are reported for global QoL scales.

Planned subgroup analyses

Subgroup analyses were planned according to subgroups defined by (1) induction chemotherapy plans at randomisation (planned, not planned), (2) age at randomisation (≤ 60 years or > 60 years) and (3) patients with severely reduced levels of swallowing (yes or no). Subgroup analyses were not carried out because the trial closed early.

Decision criteria

The decision to move to a Phase III trial was based on the following:

• Adequate timely recruitment with a 50% recruitment rate. The recruitment rate achieved was 23%, with the upper bound of the 95% CI being 33%. The justification to move forward with this design to a Phase III trial was based on an upper limit of the 95% CI exceeding 50%, which was not achieved, and, hence, the trial was not deemed feasible in terms of recruitment.

• Completeness of outcome measurement (MDADI at 6 months). Excluding those individuals who died during the study period, the successfully collected outcome data should have been ≥ 80%, as this was to be the primary outcome for the definitive Phase III trial. The MDADI response rate at 6 months was high at an observed rate of 88%. In addition, retention to clinical assessment at 6 months was also observed at 88%, and compliance with the randomised intervention was high at 94%, and, hence, the trial was deemed feasible in terms of completeness, retention and compliance.

• Economic criteria of the economic value-of-information analysis.

Clinical and organisational contexts

In this opening section, we focus on the range of contexts that had an impact on the implementation of the TUBE trial. We show how sites had different histories of preferences for feeding options. We show that there was an ongoing debate between professional groups regarding the use of nasogastric tubes and gastrostomy. Some sites offered only one option to the majority of the patients. Some sites were reflecting on current practice and thinking about changing options. Some, with the arrival of new team members, or the loss of old ones, were shifting emphasis. In addition to variation between sites, we show that there was considerable variation within sites in terms of preference of feeding approach. Often this related not only to perceptions of the benefits and disadvantages of each approach, but also to perceptions of the relative importance of these benefits. These tensions between the objectives and the priorities of groups of professionals underpinned some of the issues affecting the TUBE trial.

Given this context of variation in practice and preferences for supplementary feeding between and within sites, the rationale underpinning the TUBE feasibility study was clearly understood. The TUBE trial was consistently viewed as a worthwhile research endeavour, which would provide useful evidence to guide decision-making. Although HCPs identified the value of the TUBE trial in assessing the feasibility of a definitive trial, some respondents raised concerns about the perceived specificity of the research question. We also observed that the TUBE trial challenged some established patterns of work and the job specification of particular individuals or groups. There was an existing division of labour and expertise, whereby some HCP roles and responsibilities were intimately tied to specific feeding options and the organisation of care was tied to a specific modality. In this context, the TUBE trial was not a socially ‘neutral’ exercise, but rather a collaboration that was moulded – to varying degrees of success – to a local, historically encumbered, clinical environment of pre-existing tensions.

Clinicians’ preferences for particular feeding approaches

In general, nasogastric tubes were seen as less pleasant for the patient; they involved irritation to an area of the body already made sensitive by the cancer treatment and were more likely to become blocked or come out, or suffer other problems that could necessitate repeated trips to and from hospital, feeding was slower and hence more disruptive to everyday life and they were a visible sign of cancer treatment:

I think possibly because these patients having so much going on in your head and neck region an NG, it can be an extra burden because it’s irritating and it’s not nice as an extra thing that they need to come back and forth to hospital for. Whereas having a gastrostomy it’s away from the head and neck.

Avani (dietitian), Woodville

Gastrostomy was seen to be less problematic, although it was acknowledged that when problems occurred these could be serious. Some HCPs pointed out that complications of nasogastric tubes could also be serious; Patrick highlighted a death he knew about that had occurred when a nasogastric tube was accidentally placed in the patient’s lungs. SALTs and dietitians speculated that nasogastric tubes ‘might’ result in better long-term swallowing, but at the cost of a more difficult experience of tube feeding than with gastrostomy:

There tends to be a lot less . . . complications for the patients [with gastrostomy], . . . I feel that if someone has [gastrostomy], it’s there, and they’re almost ready to go for treatment. If they can’t swallow, they can get their pain relief through that. If they cannot drink, we can keep them hydrated. So it keeps them out of hospital. Whereas with the NGs . . . I spend a lot of my time sorting them out. People in the community, it’s blocked, they need to come in. Or . . . it’s come out, they have vomited [up the tube, or] they do not want to be attached to the pump. They are missing out on a feed because the ambulance picked them up too early, and they had to cut the feed down because of the pump. You know, there seems to be a lot more complications through the treatment with the NG. . . . that’s just what I see . . . through the treatment, you know. At the end of it, . . . with this long-term swallow.

Charlotte (dietitian), Woodville

Gastrostomy was sometimes described as being the ‘easy’ or ‘lazy’ option:

What most people postulate is that patients get lazy [with gastrostomy] and there is a degree of that. That they have got a tube in their tummy, they can stick stuff through it, so they don’t try. So therefore the gastrostomy gets labelled as a tube that is an easy route and that we shouldn’t put them in because patients don’t try, because it is there, but we don’t really have an awful lot of evidence to support that.

Rebecca (dietitian), Hamilton

Some HCPs suggested that patients who had gastrostomy used their tube earlier, and for longer, once swallowing became difficult than those patients who had a nasogastric tube.

Health-care professionals who worked regularly with patients requiring feeding tubes explained that both methods had advantages and disadvantages, and each was appropriate to specific cases. The factors that shaped the appropriateness of each type of tube were described as ‘complex’. Jenny, a SALT at Woodville, explained:

I guess it’s just the complexity . . . thinking about all the factors that affect . . . your decision [. . .] because neither [tube] are risk free . . . swallowing outcomes is just one thing, you know, if patients all hate having an NG – even though their swallowing outcomes might be better – then that might colour you to go for a gastrostomy, and I think that’s why a lot of centres do, do a gastrostomy because it’s based on some degree on patient’s experience. Also ease of managing them and it’s not necessarily . . . based on functional outcomes. It’s about getting them through the treatment, then what happens after that?

Jenny (SALT), Woodville

Jenny identified that the different types of tube shaped the work of HCPs in managing patients: gastrostomies were easier to manage in the patient population than nasogastric tubes. The reason for this difference was that nasogastric tubes could be coughed or vomited up, pulled out or otherwise dislodged relatively easily. Gastrostomy tubes were more permanent. Moreover, nasogastric tubes required more management, essential tasks being a pH check and regular cleaning of the tube. As Charlotte highlighted, feeding could also take longer with a nasogastric tube than with a gastrostomy tube because the nasogastric tube is of smaller diameter. Jenny made a distinction between the work of managing patients’ nutrition through treatment (via tube feeding) and management of patients’ long-term functional outcomes. Her account echoes our observation that different professional groups tended to express preferences for tubes that were complementary to the priorities and esteem markers of their role specifications. Nasogastric tubes were reported across sites as having less risk in comparison to gastrostomy on outcomes including patient mortality and infection, and a suspected better long-term swallowing outcome owing to patients’ lower resistance to having a tube inserted. These advantages may have provided a better match than gastrostomy with the priorities of senior clinicians under pressure to improve measurable outcomes:

Patients who are otherwise fairly fit and they’re able to understand how to manage a tube, those are the ones that I will be recommending the nasal gastric tube because they may stand to benefit in terms of the functional outcome. [. . .] These are, again, the questions that are in TUBE. For example, functional improvement outcome versus the convenience and the improvement in the quality of life. A gastrostomy, probably the quality of life is going to be easier with a gastrostomy in the short term. However, long term, the swallowing outcome, there is some thinking that a nasal gastric tube, people who undergo that approach will have a better functional long-term outcome.

Sally (oncologist), Hamilton

Sally’s account is helpful because the TUBE trial did not assess the two tubes on convenience or QoL measures. Her description of the nasogastric tube and gastrostomy, thus, reveals her opinion of the benefits and drawbacks of both methods, with nasogastric tubes identified as potentially leading to superior ‘functional outcome’.

In comparison, arranging the placement of tubes, managing patients’ nutrition and tube care and maximising QoL during the treatment period (and beyond) was the domain of dietitians and clinical nurse specialists. Gastrostomy tube feeding represented advantages to these professional groups in terms of the execution of their daily work tasks, interactions with patients, job satisfaction, and formal and informal markers of success:

We discuss about what’s going to happen to them, . . . which methods of feeding we would use, . . . and what would happen during their journey, making sure that they’re sort of nutritionally at the place that they should be for that point. Like psychological things with eating and stuff as well. So quite a wide variety of discussions . . . it would be sort of everything to do with that social aspect [. . .] how they’re going to manage during treatment but also their lives afterwards as well.

Avani (dietitian), Woodville

These tensions between the objectives and priorities of different groups of professionals underpinned some of the issues affecting the TUBE trial.

The TUBE trial in the context of clinical variation in practice and preference for supplementary feeding

Given this context of variation in practice and preferences for supplementary feeding between, and within, sites, the rationale underpinning the TUBE feasibility study was clearly understood. The TUBE trial was consistently viewed as a worthwhile research endeavour that would provide useful evidence to guide decision-making. For example, Jenny, a SALT, explained:

I think it’s a really valuable and important study and if we can get people to randomise and agree to do it, it will be really valuable to us because that will then . . . guide us a bit better in our decision-making for feeding tube options.

Jenny (SALT), Woodville

Although HCPs identified the value of the TUBE trial in assessing the feasibility of a definitive trial, some respondents raised concerns about the perceived specificity of the research question, reflecting the differences in perceptions of the importance of different advantages and disadvantages of the different feeding approaches discussed in the previous section. A frequent remark was that long-term swallow was an important outcome, but only one consideration in a much larger matrix of factors that might guide HCPs in their advice and decision-making with patients. Although a wide range of outcome measures might be anticipated by the research team for a future definitive trial, these plans were either not evident to HCPs or too far removed from their contemporary concern of recruiting to the TUBE trial.

For some, a trial focusing on long-term swallow did not sufficiently target concerns at the forefront of patients’ minds when first considering feeding tubes. For example, Sian, a SALT at a second site, explained that:

I think people may have a preference and that might be based on lots of different things . . . I ran [a] patient engagement group . . . and the wealth of reasons . . . [for using] feeding tubes was diverse . . . this particular trial is about swallowing outcomes but . . . those other reasons will always exist.

Sian (SALT), Otago

Health-care professionals described the potential results of a future definitive RCT and its impact on clinical practice. One concern expressed by surgical and oncological professionals was that a definitive trial might be redundant, of reduced impact, or impossible to adequately recruit to given new primary treatments for head and neck cancer. Simon, an oncologist, explained that:

. . . my own personal view is that we may not find an answer, black or white. It is always going to be shades of grey I’m afraid because treatment modalities have advanced. They are going to more personalised, molecular-based treatment, and the current outcome with the modern treatment modality, the long-term tube dependency rates are much lower, less than 5% [. . .] so the percentage difference in order to find one or other [as superior] is significantly [more], means the power of the study, the number of patients is going to be much higher to find even a meaningful difference . . . We can collect the data, we may never answer the question.

Simon (oncologist), Queenstown

Health-care professionals whose work remit was closely associated with tube feeding specifically (e.g. SALTs, dietitians and specialist nurses) emphasised the potential value of a definitive trial to inform their current practice. However, these accounts also indicated an evolving clinical landscape in which current evidence needs might be eclipsed by other concerns. For example, Rebecca, a dietitian, explained:

I think as a starting point . . . TUBE is perhaps a good start. But . . . there is a big move in the head and neck fraternity that it is a very bad thing to have a feeding tube. From a dietetic perspective they the tools of our trade, a bit like saying it is very bad, a physio [physiotherapist], for a patient . . . to have a crutch to walk, you wouldn’t take the crutch away. But it seems to be, my perception nationally is that it is such a bad thing for someone to have a feeding tube, and that is the bit I don’t understand . . . I think . . . that [a definitive trial] would have some impact, but I do think some of the questions would need to be altered or you would need to be looking at perhaps slightly different outcomes.

Rebecca (dietitian), Hamilton

As indicated by Rebecca, the concept of the TUBE trial and the potential results of a definitive trial were interpreted in the context of existing job specifications and skill sets, professional identities and remits of work (e.g. ‘tools of our trade’) or, even more broadly, the potential impact on debates within the professional head and neck cancer community.

Professional roles and identities

We observed that the TUBE trial challenged some established patterns of work and the job specification of particular individuals or groups. Implementation of the trial sometimes led HCPs to adapt or change their work to fit the needs of the RCT. At Otago, some work roles were in the process of being adapted to meet the needs of new treatment modalities. TUBE trial work was integrated into the pre-trial context of change.

Avani, a dietitian at Woodville, described three domains of professional expertise mobilised in the deployment of the TUBE trial. Initially, she described the differences and similarities between the practice of SALTs and dietitians, emphasising that both groups contributed to the TUBE recruitment process. She later compared these professional groups with a third group, research nurses:

Right, so it’s not as if the speech and language therapist would give the same talk that you give?

No but . . . they might do parts of it . . . I would say possibly in the past, it’s been a bit of a bone of contention before all this, not recently, that they would give some overlapping advice about an NG or [gastrostomy]. But I would say more recently that that doesn’t happen as much, it’s more . . . joint.

So thinking about the future . . . would you perhaps think that it would be a dietitian that would be involved in the recruitment rather than a . . . language therapist?

Yeah, I would have reservations if it was just the speech and language therapist, I would prefer if it was both of us together because . . . there would be questions about ‘well what difference would that be for my swallow?’ And I can give a very brief [overview], but it’d be, you know it’s their [area of expertise], that’s them . . . But definitely not without [a dietitian] yeah, yes! Because the nutritional implications of it would be . . .

[talks over] And what if it was just the research nurse? . . .

You see I would worry about that because, [nothing] against [Jackie or Samantha the research nurses], but they’re the nurse, they’re not a dietitian they don’t know all the ins and outs of why one method would be different and how we would feed. They can give . . . the PIS, yeah but that’s different from . . . practical [experience] . . .

At the start of the quoted interview, Avani described a past tension – a ‘bone of contention’ – between SALTs and dietitians at Woodville regarding overlapping skill sets. However, she emphasised that this disagreement occurred before the trial and ‘not recently’, and that current working relationships emphasised collaboration rather than competition. She compartmentalised clinical skills and information into distinct domains that could be claimed and ‘owned’ by each professional group in turn: nutritional topics for dietitians, physical swallowing issues for SALTs and research-specific work for research nurses. Avani’s account suggested a negotiation about clinical domains that pre-dated the TUBE trial. Figuratively, she sketched a virtual map of professional boundaries as she described them to the interviewer. In this context, the TUBE trial was not a socially ‘neutral’ exercise, but rather a collaboration that was moulded – to varying degrees of success – to a local, historically encumbered clinical environment.

At Hamilton, the TUBE RCT highlighted pre-existing tensions between three professional groups of HCPs, each of whom claimed areas of expertise that converged on nutrition support tubes. HCPs at two sites described the reaction of colleagues who perceived the TUBE trial as potentially threatening their role specification and job security. A consultant surgeon, Patrick, reported that:

If you look at staff it’s their personal held beliefs, you know some don’t think it’s a good [idea]. There is a couple of people in [Woodville] who felt very strongly that patients should be given gastrostomy and not anything else. And they respond to this partly because their job is based on looking at gastrostomy, so clearly there is a bias there, so these have been barriers from a staff perspective.

Patrick (surgeon), Woodville

At Otago, HCPs reflected on how the TUBE trial had been discussed before its implementation. A central concern was how to reconcile the research question with the job specification of a specialist nurse on site. Emma explained that:

I think it’s difficult to say actually, I think that we had to have quite a stiff talk locally about equipoise, because we have a feeding tube nurse [Katie] used to be called a [gastrostomy] nurse. We had to tread quite carefully to start with and actually just sort of make [her] realise that [her] job wasn’t sort of on the line, which I think is what [she] worried about if we switched to nasogastric feeding. I think it’s just there’s been a morph of her job plan and her role . . . [which has] morphed extraordinarily over the last 5 years and [Katie is] essentially a feeding nurse now, and [her] job role actually has shrunk, but rather than that mean redundancy or something, it’s like well there’s new avenues, new things . . . She looks after the NGs and she’s going to become our new part-time swallowing nurse.

Emma (surgeon), Otago

Nasogastric feeding is a technique that facilitates the reactive (rather than prophylactic) placement of a gastric tube. Emma described several vectors of change at Otago that potentially shaped the job specification of Katie the ‘feeding nurse’. The TUBE trial assessed gastrostomy, Katie’s specialist area, in comparison with nasogastric tubes, and, therefore, may have been perceived by Katie as a ‘threat’ to her employment or status (formal assessment of gastrostomy vs. nasogastric tubes might have worked in favour of HCPs whose work role was aligned with the technology shown to be superior. However, some HCPs reported that they did not welcome what they perceived to be a gamble that might result in the erosion of their job specification and/or skill set); changes in feeding support practices at the site had already begun to shape Katie’s ‘morphed’ and atrophied role. Her future within the clinical team would be driven by adaptation (‘new avenues, new things’) as treatment modalities changed. Sian, a SALT at Otago, reflected on the implications of a definitive RCT comparing nasogastric tube with gastrostomy on swallowing outcomes. Specifically, she felt that the evidence supporting one form of feeding tube over another might undermine the infrastructure invested by some clinical sites in the less effective method, and this might in turn affect jobs. Although job specifications could be adapted to take account of changing technologies (as in Emma’s case), concern about ‘shrinking’ roles or redundancy could be intrinsically harmful. Patrick, quoted earlier, reported that some HCPs were reluctant to participate in a trial that could ultimately reduce the utility of their specialist skill sets.

The intersection of a range of contextual clinical and organisational factors led HCPs to take additional steps to ensure the smooth integration of trial work at the site. As we outline in Integrating research, for the TUBE trial to be successfully embedded, all members of the team had to ‘buy in’ to the trial, work to enrol a range of people beyond the team and mould the timing of clinical services to fit the needs of the trial. However, before we discuss the work within clinical teams, we need to focus on the wider organisational and operational contexts, unrelated to feeding tubes, which had an impact on the implementation of the TUBE trial.

Site approval process

Despite attempts to streamline processes, delays in the process of obtaining site-level approvals for research in the NHS remain common. 52–56 The TUBE trial was no exception; during the study, only one site, Woodville, was open to patient recruitment for the intended 9 months, and Queenstown and Wellington were open for just 4 and 3 months, respectively. Rather than the intended 45 months of recruitment, this meant that the study was open for 32 months across sites (Table 20).

Although many of the delays related to issues such as workload in trust research and development (R&D) offices that were not unique to the TUBE trial, the context of head and neck cancer care, with clinical pathways that crossed different sites and trusts, proved to be particularly challenging.

At the Wellington site, Lara, an oncologist, described some of the barriers to implementing the research. She explained that R&D approval for her site had been held up, and after some investigation she discovered that this barrier could have been averted. Lara explained some of the challenges of integrating the TUBE trial in Wellington:

One of the requirements . . . to get R&D approval was to have some formalised arrangement, in writing, between ‘Wellington’ recruiting hospital and the centre where patients are treated, is that right, a service agreement?

Yes. So this is something that’s definitely held up opening this study, locally. So we’re in a situation . . . where the cancer centre, which delivers chemotherapy and radiotherapy [and where NGs are fitted] is on a different site to the surgical centres . . . where the new patient clinic is . . . It’s also where the gastrostomy tubes are put in.

[. . .]

So . . . the TUBE study kind of crosses [sites] really for us . . . half of the interventions happen in one site and half of the interventions happen in another . . . we didn’t predict this when we initially talked about the study.

A clinical pathway divided across two clinical sites was standard practice at three research sites. However, R&D issues concerning the allocation of funds for recruited patients had not been identified as barriers in previous deployments of the trial at these other sites. Lara explained why R&D permission had been delayed:

The problem is funding . . . for that patient recruited . . . So that would go to where the study is opened [the surgical centre] but then obviously if they’re kind of contracting out some of the work to the cancer centre . . . then the cancer centre tries to kind of bill them for that . . . It’s a kind of contract between R&D departments, and what they deem something that should be charged for or not charged for. . . . it’s a changing scene . . . It’s a little bit unpredictable. [Our R&D department] suddenly request funding for something . . . seem to appear out of nowhere, to be honest. That’s a block of many, many months in a pathway. You know I feel I should have unblocked it sooner, but really . . . I wasn’t . . . aware of what the problem was.

Lara (oncologist), Wellington

Lara outlined that her site would have only ‘a couple of months’ to actively approach patients before the recruitment window closed. Moreover, she explained that the flow of eligible patients into the clinic was ‘incredibly unpredictable’. Lara reported that she felt ’incredibly frustrated’ by her experience with the R&D department and doubted that her site would meet its recruitment target.

Changes to the cancer treatment pathways

Patients were eligible for the TUBE trial if they had stage III or IV HNSCC suitable for primary CRT with curative intent. Patients who had surgery before CRT were ineligible. Between study design and implementation, there was a shift towards greater use of surgery in this patient group, reflecting changes in the types of head and neck cancer presenting and changes to the head and neck cancer teams at some sites (with new consultants favouring surgical approaches). This meant that fewer patients were eligible for consideration for the TUBE trial. At Otago, Emma described a mismatch between the form of primary treatment typically recommended at the site and the TUBE criteria for chemoradiotherapy patients:

I think the other thing is there’s quite [a] limitation on . . . who [can be recruited] . . . they have to have primary chemoradiotherapy, and a lot of our patients don’t, we’re a very surgical unit, . . . so we’ve got a much smaller . . . cohort of people to use.

Emma (surgeon), Otago

When the TMG was made aware of the impact of these changes, a request was made to the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme to widen the inclusion criteria, with the support of the Trial Steering Committee. However, this was declined:

Many patients are treated with chemoradiation therapy following surgery for head and neck cancers. We have recognised recently that with the increase in Human Papilloma Virus related cancers, the presentation is often with small, sometimes clinically undetectable primary cancers with larger neck metastases. One management option for such tumours is to perform neck surgery followed by chemoradiation therapy to the neck and the primary site. Another scenario is where small oral cavity cancers may receive surgery followed by postoperative CRT owing to the presence of adverse histological features, where swallow function is unimpaired . . . in terms of the clinical decision making regarding gastrostomy vs NG tube, this post-surgical group is the same as the group currently included in the TUBE trial. The proportion of patients needing supplementary feeding in this group is the same as for the patients receiving primary CRT, and the previous surgery does not alter the decision making in favour of either gastrostomy or NG tube. Adding these patients to the trial cohort would therefore make the trial relevant to a wider group of NHS patients, and in the definitive trial should enable us to recruit more quickly, enabling us to more rapidly provide an answer to this important clinical question.

Letter to the NIHR HTA programme requesting permission to change the inclusion criteria

Operationalising swallowing eligibility criteria

During the initial phases of recruiting a new research site into the TUBE trial, the trial manager (Karl) and sometimes other members of the research team visited the site for a SIV. This meeting offered an opportunity for HCPs at the site to speak directly to the trial manager and raise any concerns that they might have about how the trial would fit into their existing clinical pathways. An issue raised at two observed SIVs was how the eligibility criteria for the TUBE trial might be applied to the patient population. Specifically, a few HCPs expressed concern that the criteria specifying the maximum grade of dysphagia for inclusion were too stringent. Field notes, written during the course of discussion in Wellington, present a record of opinion:

The Oncologist Lara asked her team to clarify how Grade 1 dysphagia was defined. Aadhira [SALT] said that she’d tried to look up the definition before the meeting and couldn’t find one. This prompted Karl to look up the definition provided in the protocol/supporting trial documentation. A discussion ensued around the definition of Grade 1 dysphagia. The consensus was that ‘starting to avoid some foods due to discomfort’ would be ‘beyond’ stage 1. Lara and Aadhira agreed that limiting recruitment to asymptomatic patients (or at least those without any discomfort) would probably limit recruitment to the study. Lara suggested that the protocol could/should be amended to include patients with Grade 2 dysphagia. There was a brief discussion about whether this would affect the trial outcomes, with no clear resolution.

Field notes, Wellington SIV, p. 3

During a subsequent interview, Lara explained that her only concern with the study protocol was the eligibility criteria, which might limit the number of patients she would expect to recruit:

I don’t think I have any concerns with [the design of the TUBE trial] . . . There are some small things about the inclusion criteria which may limit, or which may exclude some patients, but you know . . . in general terms I don’t have a problem with the study, no.

Lara (oncologist), Wellington

The definition of grade 1 dysphagia was also discussed in the Otago SIV:

Mary [SALT] then asked about inclusion of patients with grade 2 dysphagia. Karl explained the rationale for including people at grade 1 (or below) only . . . This led to a general discussion around the definition of grade 1 dysphagia and the concept of ‘normal eating’. Whilst Karl took the position that swallowing without pain should be classed as ‘grade 1’ or below, Simon’s view [Oncologist] was that a patient who could swallow but with pain, should be classed as Grade 1 (able to eat) . . . Simon’s argument stemmed from his concern that few patients presented who did not have some discomfort/pain and that therefore the trial would struggle to recruit . . . At this point Mary joined in the conversation and Karl agreed with her point that if patients had difficulty eating then this would be classed as an ‘altered’ eating pattern and therefore ‘grade 2’ dysphagia. Simon’s response was that the dysphagia grading system was based on a general toxicity grading, not a specialist system based on symptoms of dysphagia per se, and that therefore the various categories were open to interpretation. He concluded that eating with discomfort should be considered ‘symptomatic’ grade 1, whilst not being able to eat solids would be grade 2 . . . The discussion continued with Simon emphasising the potential lack of participants due to the dysphagia grading criteria.

Field notes, Otago SIV

Karl discussed this feedback with the chief investigator and TMG. Steps were taken to clarify the swallow exclusion criteria with all sites, including via a section in the third TUBE newsletter. The extent to which patients may have been inappropriately excluded from participation in the TUBE trial because of confusion about swallow criteria is unknown, but swallowing function remained one of a variety of reasons that patients were being screened as ineligible for the TUBE trial:

[Team member] updated the team with Otago screening issues – Otago have had a number of laser patients, palliative patients and one patient that did not have good enough swallowing capabilities therefore making them ineligible for the trial.

TMG minutes, 22 April 2015

Integrating research and clinical work

At some sites, the clinical and research pathway spanned several hospitals (Figure 5). This created a challenge for research nurses at Otago and Queenstown, as they required assistance from colleagues in primary treatment sites to keep track of patients and provide trial-specific information:

. . . this study is probably causing me a lot of headaches because the patients don’t have their treatment here . . . they go to [other site]. I have access to the [other site’s] database but not all aspects of it, so I don’t see the dietitian’s annotations because I haven’t got access to that. I’m trying to get access but it takes a long time.

Kate (research nurse), Queenstown

FIGURE 5.

Clinical and research pathway. (a) Hamilton; (b) Otago; (c) Queenstown; (d) Wellington; and (e) Woodville. AHC, allied health care; AHP, allied health-care practitioner; chemo/rads, chemoradiation therapy; ENT, ear, nose and throat; G, gastronomy; GFR, glomerular filtration rate; MD, multidisciplinary; NGT, nasogastric tube; PEG, percutaneous endoscopic gastronomy; PIS, patient information sheet; RN, research nurse.

Site initiation visits organised between PIs at each site and the TUBE trial manager were designed to address practical issues of implementation. While these were observed to work well in ‘priming’ clinical teams for the research, and generating and answering initial queries, the finer, but no less important, issues of implementation were left to clinical teams to organise for themselves. Emma, a surgeon at Otago, explained how HCPs prepared to implement the TUBE trial at their site:

. . . so we have educational meetings once a month, before our MDT and before we buy into any study we lay down what the study is and we look at the pathway of the study and how it can be integrated into our normal working pathway, because [we can’t agree to do research] without that because none of us have got the time. So looking at [another study running on-site] for example, which we’re really keen to recruit to, we’ve got issues because of some of the data that needs to be collected in Woodville during the treatment. Now it’s not the data collection that’s the issue, it’s if something goes wrong and they’ve got a SAE or something like that, then who’s going to collect that data? Yeah, and that’s got to be someone with research interest. So it’s hanging on trying to get the research team in [centre] to support our patients and that is always an issue.

Emma (surgeon), Otago

Emma’s account provides a good description of the organisation of key contributors to assess if they can collectively contribute to the work involved in implementing a new set of practices. Emma identified two streams of work: the ‘pathway of the study’ and the ‘normal working pathway’. A central concern for staff in Otago was whether or not the two pathways could be combined in a way that required minimal time resources to organise. This criterion was key to whether or not they ‘buy into’ the study. Towards the end of the quotation, Emma identified that an important component of collaboration across sites was networking with colleagues who had a ‘research interest’.

Across all the sites, we observed that the success or failure of the TUBE trial hinged on whether or not potential contributors and collaborators could ‘buy in’ to the study. Notably, HCPs reported that efforts to integrate the trial with routine work were no more challenging than those required for other trials. A challenge for all sites was arranging gastrostomies. The need for a gastrostomy appointment could not be ascertained before consent and randomisation. This foreshortened the ‘window’ for gastrostomy, which, in a ‘normal working pathway’, spanned from diagnosis to just before the onset of treatment. Therefore, this issue applied regardless of whether or not sites routinely offered gastrostomy.

Health-care professionals at Otago identified a critical ‘moment’ in the clinical pathway that may have prevented them from implementing the TUBE trial. The glomerular filtration rate (GFR) assessment identified if patients were suitable for chemotherapy. If patients were found not to be suitable, then they were also ineligible for the TUBE trial. However, the appointment ‘slots’ were not at a specific time and were dictated by the medical physics department. For the TUBE trial to work at Otago, it was necessary to arrange ‘expedited’ GFR slots:

. . . so in that first MDT where we decide about the treatment options . . . the patient information sheet, because that’s the point at which we discuss feeding with them anyway. Then after that they would be contacted by the feeding nurse and also by the research nurse and if they agree to participate, then they’d have an expedited GFR slot [. . .] Glomerular filtration rate slot, so if you’re having chemo[therapy] or radiotherapy you have to have a GFR before it to see if your kidneys are good enough for your chemo[therapy], yeah, so that has to be incorporated into the pathway, and that’s done at Otago Hospital. So they come back to have that done and at that point the research nurse would meet with them and the feeding nurse would meet with them . . . at the GFR visit, and then they would discuss the options and enrol them into the trial at that point. Then when they were enrolled . . . if they were then in the [gastrostomy] arm, then the feeding nurse could facilitate getting the [gastrostomy] pre-treatment . . . cos [sic] you’ve really only got a 2-week window with everything else that’s going on . . . so they’ve got to slot it in . . . to be honest this pathway just had to work properly, so we got the pathway to work properly.

Emma (surgeon), Otago

The expedited GFR slot was crucial for the implementation of the TUBE trial at Otago. Alexandra, the research nurse at the site, explained how this was arranged:

We spoke with medical physics to see if we could get a definite time and date to get a GFR done so that . . . we could bring [patients] back [to Otago] and actually approach them in person rather than just telephoning to see if they were interested. That way, if they say, ‘Yes’, we can get consent there and then and then we can get them randomised quite quickly so we know which arm of the study they’re going into.

Alexandra (research nurse), Otago

Identifying to which arm patients had been randomised was important to HCPs at Otago, because patients receiving gastrostomy would have their tube fitted on site, whereas patients receiving a nasogastric tube could have their tube fitted at a later date at a different site. As explained above, patients receiving gastrostomy needed to have the tube fitted before treatment. Therefore, the expedited GFR was a prerequisite for the successful integration of clinical and research pathways at Otago. Centrally, integrating the trial pathway into the clinical pathway meant enrolling a large number of people and activities within and across departments and, in some cases, across organisations.

At Woodville, HCPs reported a relatively smooth integration of the TUBE trial with routine clinical practices. However, Jackie, a research nurse, identified a potential issue in the early phases of recruitment. Specifically, it was unclear if patients who decided not to take part in the TUBE trial would have the option to choose between the forms of feeding assistance. If not, patients who preferred gastrostomy might have perceived the trial as their only means of accessing that treatment:

So . . . what was the initial look of [the TUBE trial] that made you think, ‘Oh, this’ll work quite well’?

. . . the actual treatment plan wasn’t being altered it was . . . almost, something peripheral to the main treatment. But, I think the question that was in my mind, . . . – and it’s really one of the questions that you’re very likely to be asked by patients – . . . was what would happen if people didn’t go on the study. . . . and the answers to that were very vague [laughter] . . . patients weigh up how much of . . . a difference taking part in the study is compared to not taking part in the study. And . . . at this site, people would almost certainly get an NG tube. And possibly a gastrostomy but only if there was a clinical indication And . . . I think up until yesterday, that’s not exactly what I was telling the patients . . . based on the information I’d had, kind of indicating that they had a choice between a gastrostomy or an NG off the study. Which, in theory, sort of but in practice they don’t. And that’s only came to light because a patient . . . said they didn’t want to do the study . . . because they wanted a gastrostomy, and not knowing what they’d been . . . told in the first place, I left it at that. But, since then . . . they’re not going to get a gastrostomy so . . . I’ll phone that patient back.

A potential strength of the TUBE trial was the ‘low impact’ of the research design: as Jackie explained, its impact on the treatment plan was non-existent for patients randomised to receive the ‘standard’ treatment at the site (nasogastric tube) or minimal if patients received gastrostomy. However, a trial design peripheral to the standard clinical pathway also contributed to the confusion for some patients, who perceived participation as curtailing their freedom to choose between the treatment options. Later in the interview, Jackie explained how she had adapted her recruitment approach:

What I say to patients is still, kind of, evolving . . . as of today, I’ll say to patients that off the study they’ll almost certainly get a NG tube but there is a possibility – not completely rule out the gastrostomy – but make it clear that there is, there would need to be a clinical indication for that.

Jackie (research nurse), Woodville

Jackie’s account is important because it demonstrates how HCPs adapted their practice over time as they formed an understanding of the way in which trial protocols could fit within existing patterns of work.

At the start of the trial, Jackie met with Jenny, a SALT. Between them they worked out a way of integrating research information with the standard guidance that SALTs and dietitians provided to patients in routine practice. Jackie explained:

The SALT and I met and decided that two lots of information that had to be [given]. And it wasn’t going to compromise the trial information if it was given at the same time, . . . [as] the standard information people would get anyway. . . . and also, from a trial point of view, it showed the trial was not peripheral to everything, that it was very much a part of what was going on. And that other [professionals] were on board as well . . . we ran that past the dieticians, they were perfectly in agreement as well.

Jackie (research nurse), Woodville

Earlier in the interview, Jackie had used the term ‘peripheral’ to describe a positive attribute: the trial would have little impact on the clinical pathway and would, therefore, not interrupt care. However, in the excerpt above, Jackie emphasised that the trial was ‘not’ peripheral in the sense of being removed from the core business of cancer care. Jackie worked to promote confidence in the trial among both colleagues and eligible patients by emphasising that the trial was integrated into core activities and priorities: ‘a part of what was going on’. It was important that Jackie demonstrated to eligible patients that the research was regarded with esteem by the HCPs central to their care. Integrating research information with key stages in the clinical pathway facilitated this aim.

The enrolment of other HCPs was also a key task of research nurses at each research site. Jackie explained that an important step in this process was the sharing of plans and ideas concerning integration of information with the professionals key to each step in the existing clinical pathway:

. . . so [a patient] would be identified at the MDT as having the right stage of disease and . . . going for radiotherapy. Then, I would check with the SALTs or the dietitians how that person’s swallowing was, because in the MDT, they will have done a swallowing assessment and that might exclude people [. . . if] their swallowing is really compromised . . . after the patient had the treatment plan explained to them, I would join . . . the dietitian and . . . explain the trial to the patient but do that alongside . . . the dietitian explaining about the different tubes. . . . we’ve combined what I say with what the dieticians say. And that makes sense because the information is, sort of, interchangeable. It makes more sense than, for example, the dieticians going in and given a whole lot of information about the different kinds of tubes . . . and then saying, ‘Oh, but, there’s also this trial.’ . . . So they combine well and it’s much, much more fluid way of explaining the trial and the tubes at the same time to the patients.

Jackie (research nurse), Woodville

Through a series of preparatory meetings, Jackie was initially able to fit research work neatly within appointments that would typically be run by SALTs or dieticians. Centrally, when they worked as a team to introduce the trial in the least disruptive way, the recruitment process was effective:

We had, between me and then the dieticians and the speech language therapists and the surgeons and the oncologists, we had kind of formulated a plan of how patients would be approached in that they would see the surgeon first who would give them a diagnosis and decide the treatment option and if they were going for radiotherapy, plant a little seed about the study, like ‘you’ll go and see the oncologist next, they’ll mention a study by the way’, and em . . . no more than that, just planting the seed. The oncologist would do the same, but maybe in a bit more detail, once they’d described the potential side effects of the radiotherapy they would introduce the study and say ‘Well, our research nurse and our dietitians will explain that further’. So it was like a kind of seed being placed, being planted, reinforced, but with this basic minimal information, and then when the patient saw the dietitian – it was either the dietitian or the speech and language therapist, usually it would have been the dietitian – I would go in with the dietitian, we’d see the patient together so that combined getting basic nutritional support information with the study information cos it was about the same thing, and it also made the research seem like part of the whole bigger treatment plan picture.

Jackie (research nurse), Woodville

Priming patients – ‘planting the seed’ – at each stage of the clinical pathway was an effective way to introduce the trial in the least disruptive way. Providing the right amount of information at each stage slowly built an idea about the trial in patients’ minds. As Jackie notes, it enabled the trial to ‘seem like part of the whole bigger treatment plan’. However, this priming work seemed to fail in the later stages of the trial, as some HCPs earlier in the clinical pathway worked harder to actively promote the trial:

The surgeons and the oncologists would, rather than plant a seed, would go into more detail about the study, which didn’t seem like the optimal time for the patients to take that information in and consider it. . . . If surgeons mentioned too much about the study before the oncologists, before the patient could see the oncologist, patients were being asked about the study, to consider a study about something they hadn’t had the information for yet, so that was all just very kind of confusing.

Jackie (research nurse), Woodville

Rather than having a positive effect on recruitment, recruitment was reduced. Priming made patients less receptive. Some had formed an initial opinion, some were confused and some were less willing to engage in yet another discussion about the trial. The reason for this increase in information-giving at all points across the care pathway was twofold: clinician enthusiasm for the study as well as, in much later stages, attempts to manage a shortfall in recruitment at this site.

Research nurses at two research sites described how they engaged in informal, interpersonal work to smooth the path of the trial at their site. A barrier to implementing the trial in Woodville was the possibility of increased demand for gastrostomies when the site usually provided nasogastric tubes to the majority of head and neck cancer patients. The successful integration of research work within local cultures of practice is key to the successful implementation of clinical trials. ‘Global’ issues that affect all research sites within a trial can be perceived by research teams as major barriers to research. In comparison, ‘local things’ within a research site can be construed as minor barriers. However, the informal, hidden work undertaken by RCT contributors in the implementation of trial protocols 57,58 is essential. Jackie explained how the issue of increased gastrostomies at Woodville was addressed:

. . . you know with the research . . . essentially, you’re asking people to do, you’re being a pest and you’re asking people to . . . do extra things or do things differently for no real benefit to them . . . [so] the job and the role is very much building up relationships with your colleagues that you work with.

So you’re being a pest to your colleagues then?

Yes. But it’s how you go about it because you could be demanding this, demanding that or you could, . . . do it in a different way where you’re, . . . collaborating and building up a relationship with different people you work with. Which, ultimately, from a . . . very practical point of view, gets the results that you want.

For example, on TUBE, the people . . . who are randomised to gastrostomy, I know who the secretary who’ll make that appointment . . . So I take the . . . request along in person . . . Because sometimes it might be tight [for gastrostomy] but it’s more likely that they’ll accommodate the schedule if that relationship is there.

Jackie (research nurse), Woodville

To successfully implement and embed the TUBE trial, teams had to work hard to integrate the trial pathway into the existing local organisational ‘normal working pathway’. They had to be willing to enrol a range of people and activities within and across departments and organisations. They also had to be willing to adapt their practices over time as they formed an understanding of how trial protocols could fit within existing patterns of work. New practices, such as joint consultations with the research nurse and dietitian, were introduced to offer a consistent, timely and balanced account of feeding options to patients. However, too much enthusiasm across the team could also cause problems. They had to build rapport with colleagues whose work underpinned key phases in the research pathway. In this way, they proactively sought to allay any patient concerns that getting onto the trial pathway would disrupt the clinical pathway. In Accepting randomisation to the TUBE trial, we report the example of Barry in Queenstown, where, despite considerable efforts to synchronise the research and clinical pathway, mismatches did occur, with detrimental effects on patient recruitment.

Managing patients’ burden

At the time of their diagnosis, patients were given a large volume of information. This concerned their diagnosis; the details of primary treatment and likely side effects; the clinical pathway, including appointments with a range of HCPs; the possibility of feeding assistance; the known risks and side effects of feeding methods; and any research studies (including the TUBE trial) for which the patient was eligible. HCPs were aware that patients were challenged by the health and practical implications of their new situation, the volume of information that they were asked to consider and the need to make decisions during this time. Sally, an oncologist, described the content of a typical ‘new patient’ consultation:

The problem . . . is that frequently the patient has only, just that week or even that morning, been informed that they have cancer, . . . it’s already a very extended consultation. It often takes up to an hour. It’s difficult for a patient, having just had that kind of news, to really focus for a whole hour. [As the] clinician, you have to . . . explain about their cancer, explain about what sort of treatments we can offer, and then the process of chemoradiation is rather involved because often it involves induction chemotherapy by itself first . . . Then . . . chemotherapy with radiotherapy, . . . the actual procedures involved within all that and all the professionals involved in preparing them for treatment. Then when you go onto the side effects, of course they’re starting to get quite overwhelmed. At this point you’ve probably already been speaking non-stop for about 30 or 40 min[utes] to get them to this point. Unfortunately, again, there’s probably constant interruptions, people coming into the room . . . maybe even coming to see the patient as well . . . so then you talk to them about the tube. . . . Lots of patients, you do have the concern that they’re just shutting down during the consultation and they’re not really listening. As I said, to have anyone talking at you for 45 min[utes] is very difficult, and when you’ve just been told you have cancer it’s very difficult to focus.

Sally (oncologist), Hamilton

Health-care professionals were mindful of the emotional impact of diagnosis, ‘. . . that kind of news’, and the practical and decision-making work they required of patients. In addition to being asked to consider ‘factual’ information about cancer and methods of treatment, patients were required to help organise their treatment pathway. This required the patient to take on some responsibility at a time when they might have wanted to devolve control to others. Patients reported co-ordinating appointments, travelling under time constraints to unfamiliar locations (sometimes across several hospital sites) and keeping specialist HCPs abreast of delays in other parts of the clinical pathway. Sally acknowledged that there was preparatory work to orientate patients to this new role, describing ‘. . . the actual procedures involved . . . and all the professionals involved in preparing them’. Throughout interviews with both HCPs and patients, the concept that patients were often ‘overwhelmed’ during this phase of their diagnosis and treatment was common. Discussion of feeding tubes and eligibility for research studies usually occurred towards the end of the new patient consultation, at a time when some patients were struggling to absorb any more information (‘shutting down’).

As noted above, the TUBE trial research activities were designed to fit into pre-existing clinical pathways to avoid patient burden. However, at some sites, routine care required patients to attend one site for diagnosis and pre-treatment clinics and another site for their actual treatment. These pathways were complicated when patients were randomised to a treatment that was not a standard recommendation at the site. Table 19 summarises standard recommendations outside the TUBE trial by site. Figure 5 includes the clinical pathway figures for each site. A few of the HCPs using terms indicating discomfort to describe approaching patients to participate in the TUBE trial soon after diagnosis. Charlotte, a dietitian at Woodville, explained that she had not previously recruited to a trial. She reported that transitioning from the role of a therapeutic clinician to a ‘researcher-recruiter’ was ‘difficult’:

Sometimes found it a bit difficult, you know when you do feel that you’re putting upon a patient . . . cos you do have to bother them with TUBE I suppose, and it’s an extra bit of information, . . . they’ve had enough and you know that you have to kind of put it to them, I find that a bit difficult. [. . .] Some patients . . . were getting diagnosis . . . treatment plan, . . . everything, it was way too much and that was when it became, you felt a bit embarrassed and you felt, you know, that it’s not the right time.

Charlotte (dietitian), Woodville

The language used by Charlotte conveyed her sense of self-consciousness in approaching patients and asking something from them, rather than delivering a service. 59 Those HCPs who discussed discomfort in approaching patients for research often commented that the trial involved asking patients to process ‘an extra bit of information’ at a time when they were both vulnerable and in receipt of a large volume of material concerning their clinical pathway.

Not all HCPs were concerned about approaching patients about research soon after diagnosis. Jenny, a SALT, explained her perspective on recruitment:

How do you feel about that day where they’re getting . . . a lot of really unpleasant stuff that they’re hearing. How do you feel about them being offered the research at that point?

I don’t really feel strongly that it shouldn’t be done at that point because, partly because I don’t know how else it would be done, but also at that point we only said; ‘we’re doing a research study’ and they’re given information that we would be giving them anyway and then they’re given the information sheets to take away . . . and then it’s followed up so I don’t think that’s really particularly adding a lot on top of what they’re already [getting]. . . . going to be very variable because you’ll have people who . . . they’ve got all their questions. They want to know as much as they can at that point and then you’ve got people that just can’t wait to get out of the doctor’s room and they don’t want to hear anything else . . . So . . . you’re never going to get it right for everybody I don’t think. . . . I think . . . it’s important . . . to how we practice and how we treat people and that outweighs for me that . . . extra overload.

Jenny identified that, for the TUBE trial to function, it was necessary to approach patients soon after diagnosis (so that there was enough time to organise a gastrostomy if required). At the end of the excerpt she explained that the evidence produced from research ‘outweighs’ the ‘extra overload’ of the provision of research-specific information alongside clinical material. Jenny also stressed that the TUBE trial information was very similar to that which would have been provided to patients ‘anyway’ in routine clinical work. She also identified the varying clinical needs and receptiveness of patients to research.

Health-care professionals recognised the difficulty of the role of recruiters in settings such as cancer care. One HCP, Sian, identified that recruiting patients to clinical trials required a shift in the patient–clinician relationship. This switching of roles required a new set of skills and, importantly, placed HCPs in a social dynamic that was unfamiliar to them: a position whereby the ‘power’ of the interaction lay with the patient rather than the professional. 60 In the early stages of the trial, we became aware of some HCPs’ fears and concerns about overburdening patients with trial information at a time of distress, uncertainty and vulnerability. However, following qualitative work with patients, we formally reported back to them that patients felt that the timing of the approach was appropriate, given the sensitive way in which they felt the teams handled the discussions and valued the opportunity to discuss research. All except two patients either welcomed an introduction to the TUBE trial at the start of their clinical pathway or, in some cases, felt that it was relatively inconsequential or ‘no bother’ in the grander scheme of their diagnosis. The two who felt that it was an unwelcome interruption at a sensitive time nevertheless understood the rationale and the potential value of the research. Patients who accepted and declined randomisation reported positive responses to the timing of the TUBE recruitment discussion and content of the PIS:

One of the things that certainly the speech therapists, dietitians, everybody worries about is that you are overloaded with information.

Yeah, no, I didn’t feel that . . . I’d say I’d had time to process . . . and I think actually it’s, you know, it’s an appropriate time to mention it at that stage, ‘cos it does seem sensible to raise it at the earliest time really, to me anyway [laughter].

[. . .]

I mean for example I’m one of those people that always wants to know as much as possible [laughter], yeah, and that, you know, keeps me, that, that makes me feel more empowered, the more information that I’ve got, but I also recognise many people aren’t.

Patients also indicated that the information about the TUBE trial was presented and discussed in a way that avoided any pressure on them to participate, and were positive about their interactions with the research nurses:

There wasn’t any, there was definitely not any pressure. And even when you come back [research nurse] was very good, how would you put it, to step back and let you decide you don’t feel that they’re pushing you, they’re sort of letting you at your pace.

Paul, Woodville (declined randomisation)

They also reported that the presence of the study ensured that they made the right decision and so avoided decisional regret. In this way, the formal feed-forward work aimed to ameliorate the fears of HCPs who were initially concerned about the potential of overburdening patients.

Distributed equipoise

There were preferences for specific feeding options both across and within sites. However, for the TUBE trial, the key elements were whether or not and how these preferences were communicated to patients. At three of the research sites, HCPs identified a lack of individual clinical and professional equipoise as a potential barrier to recruiting patients to the TUBE trial. At Otago, HCPs described a concerted team effort to present equipoise to eligible patients in support of the study. This extra attention to equipoise was underpinned, in part, by historical practices at the site that had favoured gastrostomy:

. . . the way that we tended to manage some of our patients historically, there had to be a sort of, we had to present the evidence, i.e. that there wasn’t any, and try and make everybody within the team approach the study with equipoise, and I think that was, for us, one of the factors that we really wanted to make sure that we got right. And then from there actually, in terms of recruitment and everything I think it went reasonably well.

Emma (surgeon), Otago

To make sure that equipoise was distributed across all members of the team, this site undertook a series of ‘role play’ and practice sessions explaining the different feeding approaches. Such proactive and reflexive approaches were reported as having an impact and were reflected in the recruitment rate at Otago, which was one of the highest in the study:

I don’t really have any views with regard to the treatment arms for the outcomes for the study. And I have to admit everyone’s being pretty good who’s involved in the study, no one’s giving any opinions which has been quite interesting [. . .] they’re all, they’re very aware that they’ve got to maintain equipoise and they’re just, they are trying to do that.

Alexandra (research nurse), Otago

In this way, some sites explicitly worked to address the historical ‘preference’ of the site.

Health-care professionals at Woodville and Otago described informal and collaborative processes of evaluation regarding their activities within the TUBE RCT. Jackie, the research nurse at Woodville, reported how recruitment practices at the site had ‘evolved’ over the lifespan of the trial. Jackie described how the recruitment techniques had been adapted through communal appraisal with dietitians at the site:

Compared to when [the trial] started to now, [the recruitment approach has] kind of, evolved. So I think it will just keep evolving like that. What, certainly, has changed is the first couple of patients who said ‘no’, said no because they didn’t want a gastrostomy and the dietitians and I had a bit of a debrief about the information that we were giving. And we, kind of, concluded that what we were probably not doing was promoting gastrostomy. We were being equal but we were being so equal that it meant almost, meant that the patients would say, ‘Well, there’s no advantages, but there’s a lot of inconvenience with the gastrostomy,’ compared to the NG tube. So we did, kind of, alter and, so now explain, quite clearly, in a quite structured way, ‘This is the advantage, that’s the disadvantage . . . and this is the advantage of that, that’s the disadvantage.’

For example, I . . . think we were mentioning the gastrostomy, ‘You would be in hospital for 3 days’ and not mentioning that with the NG tube that you’d be in hospital for 3 days. So, we’ve, kind of, fine-tuned that to say that, ‘Well, you’ll be in hospital for 3 days at some point . . . it might be at the start, it might be half-way through’.

Jackie (research nurse), Woodville

Through discussion and peer feedback, HCPs at these sites actively sought to both evaluate and then change their practice in order to demonstrate a balanced and information-rich account of each feeding option. Avani, a dietitian, describes the aspects of the process she went through:

So you feel that in thinking about the experience of the recruitment, you feel that recruitment is a bit more hopeful than you first thought?

Yeah . . . we’ve had some discussions, ‘cos I’ve done two and Charlotte [another dietitian]’s done two. We’ve discussed with Jackie [the research nurse] as well how we’re discussing things and I ask Charlotte to listen to what I’d said, I haven’t listened to what she, but she’s told me what she’s said and so we’re going to try and do it so it’s exactly the same for everybody. So for example, I’d said: ‘and for the nasogastric tube you’d be hooked up to the feeding pump for a long, long time’ and she said that wasn’t quite right [laughter]! . . . So now I’ve reflected on that I’ve thought ‘right’ . . . So we’re learning from it.

Some teams worked collectively to present equipoise at all contacts with patients at which feeding options were discussed – even when, in private, they may retain a preference. They worked hard to demonstrate a consistent approach to the presentation of options.

However, some teams reported that different members of the team expressed preferences for specific feeding options at different points across the clinical pathway.

The historical preference of sites was an issue identified by HCPs when discussing how the TUBE trial was received in the workplace. This was most pronounced at Hamilton, where preparation for and care of gastrostomy patients had been overseen by one professional group. A raft of factors contributed to a long-standing difference of opinion between senior medics and allied health professionals at the site regarding the ‘optimum’ approach to tube feeding for the majority of patients receiving chemoradiotherapy for head and neck cancer. A professional whose department had built expertise in gastrostomy (and who later developed a supportive infrastructure for nasogastric tubes) reported that the expertise of her department had been overlooked by the consultant oncologists responsible for recruitment. The TUBE trial, therefore, became a focus for pre-existing debates and workplace politics. There was evidence that eligible patients were given a direct ‘recommendation’ for a nasogastric tube by their consultant:

I will say to patients, ‘. . . you’re going to have . . . a 78% chance of requiring a feeding course, and I will recommend that you have that through an NG.’ That’s it. . . . a lot of patients do go on to have [gastrostomy], because our dietitians favour that, and then when they see the patients they will often tell the patients to have a [gastrostomy].

Janet (oncologist), Hamilton

Janet reported routinely advising patients to have a nasogastric tube, but indicated that dietitians at the site advocated gastrostomy. Janet downplayed the influence of her direct recommendation to the patient on recruitment; however, it is notable that recruitment to the trial was poor at this site. Janet suggested a strong bias by the dietitians and indicated that it was the dietitian’s recommendation, rather than hers, that influenced patients’ decision-making. Another dietitian at Hamilton offered a similar narrative regarding the influence of consultant oncologists:

Lots of the patients came to us and said that they had been told their swallow would be better if they had a nasal gastric tube, even though there is no evidence to support that, so then they wouldn’t go into the trial [. . .] Some patients unfortunately have picked up on the fact that there is a bit of a difference of opinion between the dietetic team, the speech therapy team and the medical team, but they will always go with what their consultant [oncologist] says for the vast majority.

Rebecca (dietitian), Hamilton

In this way, patients at this site are primed about which option may be appropriate for them before any detailed recruitment discussion. Some patients are caught in a dilemma. In consultations with different members of the team, they are offered different opinions. Then, in the context of a recruitment consultation, clinical uncertainty is outlined as they key issue that is driving the trial. As Rebecca highlights, their consultant’s preference strongly influences a patient’s treatment decision.

A second oncologist at Hamilton explained why, in her view, a direct recommendation to the patient was appropriate:

Since we’ve been offering them the TUBE study, what I’ve been saying to the patient is that there is a study that’s trying to evaluate which tube may have more benefit over the other and that we don’t really know the answer to the question as to which tube is the best tube. I then go on to explain to them what I recommend for them [. . .]. Ultimately, we will make clear what our recommendation is because they need guidance. Patients do not necessarily, you know, they are not clinicians. They don’t have the full knowledge as to all the different potential benefits and disadvantages.

Sally (oncologist), Hamilton

Sally is very clear that, even in the context of speaking to a potential recruit to the TUBE trial, she feels duty-bound to offer patients her recommendation. For her, patients do not have access to ‘full knowledge’ and so they need her ‘guidance’. One of her patients, James, described how he felt that his consultant, Sally, held a strong preference for nasogastric tubes:

Dr [Sally] was saying about the throat muscles, in quite simple terms, ‘use it or lose it’. That’s, I think, what she was trying to say. I think she’s an advocate of . . . ‘you’ve got to keep swallowing as long as you can’ . . . and this nose one seems to be showing that, whereas the stomach one, people give up a lot quicker. Because of the pain [they tend to use the gastrostomy tube] . . . so therefore, they’re losing the use of the muscles, so therefore, the recovery time is taking a lot longer.

James, Hamilton (randomised to receive a nasogastric tube)

James recalled an explanation given by Sally for the superiority of a nasogastric tube over gastrostomy in relation to long-term swallow outcomes. Throughout his interview, James highlighted how his consultant’s guidance was a priority for him. However, it is notable that James did decide to be randomised. In his account, he understood that the reason for the trial, in part, was to add evidence to Sally’s judgement that nasogastric tubes were superior. Participation was, therefore, a logical step for James in his support for Sally.

Enacting equipoise

Four of the sites have specific local organisational preferences for either nasogastric tubes or gastrostomy. However, in the context of the TUBE trial, HCPs needed to mark that these local preferences were, in part, uncertain, open to change and potentially not inclined towards the best option, hence the reason for asking people to think about taking part in the trial. They needed to create and sustain a position of organisational equipoise without undermining or overly selling their current practice, so as to enable a patient to have the option of being in individual equipoise themselves.

In the audio-recorded consultations, we can see how HCPs worked hard to explain two key points to patients. The first was that both types of tube were regarded as effective treatments, and were in use at different sites. However, one type of tube had been chosen over its alternative at the site the patient attended. The reasons underpinning this choice by the site were not made explicit. The second point explained to patients was that, despite the site having ‘chosen’ a standard treatment, a trial to assess which tube was ‘best’ was required. The following excerpt is taken from a follow-up recruitment consultation. This patient, Lesley, and his partner, Laura, had already taken part in an initial recruitment consultation with the research nurse. They were visiting the consultant to further discuss the options and make a final decision:

And we said, ‘Well we’d prefer to have it in the stomach because he’s already, you know, [Right] sore round that area [Right], the nose and that’ [Right. Mmm]. But we’ve, we’ve heard that it’s the, the procedure anyway to have it –

That’s right.

Down the throat, yes.

The natural process in the hospital at the minute is to have the NG tube put in as you need it when you’re going through the treatment.

Right, yes. Right.

And this is why they’re doing the research study in the first place because they don’t know whether, if, if they put a tube into your stomach, whether that improves people’s treatment and after care or whether, or whether it makes, whether it makes a difference or not.

Following Laura’s question, note here how the consultant clearly marked that routine care – ‘the natural process at the minute’ – at the hospital was the nasogastric tube. In this way, they work to confirm their understanding. Note how the consultant stated that it was current practice – ‘at the minute’ – and then went on to introduce the reason for the trial (that there is uncertainty – ‘because they don’t know’). In three of the consultations, we have a similar pattern in which the local focus on nasogastric tubes is briefly discussed, at relevant moments, in order to contextualise some aspect of the discussion about the trial processes. Notably, this works to produce routine care as a product of custom and practice at this site. As the research nurse noted to a patient and carer, ‘but that’s just local preference and the policy here. In different parts of the country, the policy’s different’.

However, with the consultation that involved both a research nurse and a dietitian, we see a slightly different approach. Centrally, the issue of nasogastric tubes as routine care at this site was repeatedly returned to as a topic throughout the whole consultation. The discussion took place approximately half-way through the consultation as the HCPs responded to the patient’s question regarding which type of tube was the more popular:

Well at this –

Well, it’s kind of at this centre –

At this centre we would use this [nasogastric tube], but everyone’s different depending on the different cases and what way you present. For you we would be using the tube in your nose to start with, but then other centres would put in the tummy tubes beforehand for everyone and that’s where we’re a bit stuck, isn’t it?

Yes, so that’s just another illustration of, there’s no agreement even between doctors or agreement between different hospitals about which is the best one to use.

Recruitment consultation, Woodville

The dietitian and the research nurse collaborated closely in positioning the local preference at Woodville for nasogastric tubes as a product of custom and practice, whereas gastrostomy tubes are given to everyone at ‘other centres’. Both HCPs worked to use clinical uncertainty as a way to reflexively demonstrate the need for the trial. Just after the sequence above, the research nurse marked nasogastric tubes as ‘the standard’ treatment at the site. The patient then raised a question about the timing of tube insertion. This was discussed in relation to the timing of gastrostomy surgery and contrasted with a nasogastric tube:

Do I get this tube irrespective, or is it in? If I go for the trial is it in early?

No, it wouldn’t be in any earlier. We would treat you exactly the same. The only difference would be that if you were allocated to the tummy tube arm, that you would have that in before you started your treatment. We’d have to get you in and it’d be there ready for you.

Right.

Whereas, if you were allocated the one in your nose, you probably wouldn’t even notice you were in the trial, because it would be exactly the same practice that we would do.

Right, yes.

Recruitment consultation, Woodville

In the excerpt above, inserting a nasogastric tube was marked as ‘exactly the same practice that we would do’. Again, inserting a nasogastric tube was formulated as the standard treatment, to the extent that to take part and receive a nasogastric tube would mean that, potentially, the patient would not ‘even notice’ that they were taking part in a trial. Taken individually, the work of marking insertion of a nasogastric tube as standard and usual practice at Woodville seems unremarkable. However, if a particular type of tube was repeatedly marked as ‘standard care’ over the course of a consultation, it is understandable that some patients may respond by being reluctant to ‘deviate’ from the established clinical pathway. We should note that this patient, later in the consultation, does outline their preference for gastrostomy, the non-standard care at this site. Patients interpreted the purpose of the trial from multiple stimuli such as information sheets and discussion with relatives, but also, importantly, their interactions with a range of HCPs at the site.

The challenge for HCPs recruiting to the TUBE trial was to present the trial as a rational exercise while also defending the local site’s standard practice of offering only one treatment to the majority of patients. Some patients responded by declining randomisation, remaining within the reassuring boundaries of standard care. Others reported that the clinical ‘uncertainty’ underpinning the TUBE trial was an opportunity to express their treatment preferences. If that preference was not the ‘standard’ treatment, then patients reported randomisation as offering them the possibility of accessing their preferred treatment. If patient’s preferred treatment was also the standard treatment, then the TUBE trial was reported by patients as having little to offer them. A third group of participants were ambivalent about the type of feeding tube they received. If the TUBE trial was perceived as having a small impact on their clinical pathway, then this group tended to report a favourable view of participation. Patients’ accounts of the decision-making process are explored in the next section.

The local context of the TUBE trial recruitment discussions

The series of meetings concerning diagnosis, treatment, side effects and research presented patients with a range of unfamiliar and challenging possibilities. Patients described previous health and research experience to explain how they made sense of their current circumstances. Most reported that they enjoyed good physical health prior to diagnosis (n = 9), had no first-hand involvement with feeding tubes (n = 11) and that they had not previously taken part in research (n = 12). Although symptoms leading up to diagnosis varied, all emphasised how shocked they were to receive a diagnosis of cancer and how quickly treatment and associated procedures (such as crafting a protective mask for radiotherapy) were organised once a diagnosis had been made. Jenny, the spouse of a patient, explained that:

[The consultant] had told him . . . that he suspected that he may have . . . cancer of the throat and the back of his tongue . . . to say we were astounded, shocked and bowled over is a bit of an understatement . . . [After he] was diagnosed . . . it was amazing the way that the whole thing just kicked in, you know, the whole machine started to move [. . .]. He was diagnosed I think on the Tuesday . . . We went to Otago on the Friday [of the following week] and we met an awful lot of people that [. . .] It was just a whirlwind [. . .] We were introduced to everybody and their grandmother, and tests were arranged, and all of that stuff. And it was at that point that we met the lady from the hospital who told us about, obviously the trial, the study that yous [sic] were doing, and explained everything, and asked us to think about would John be prepared to be a part of it.

Jenny (relative of John, randomised to receive a nasogastric tube), Otago

Jenny’s analogy to a ‘whole machine’ which ‘started to move’ provides a good example of how patients explained the rapid implementation of a complex care pathway, including multiple interactions with HCPs across a MDT. Patients praised HCPs for the assistance they received throughout this process, and welcomed the swiftness with which care was enacted.

Patients placed their trust in the assessment of HCPs, who informed them that, despite current feelings of vitality, in the near future they would likely experience the unpleasant side effects of treatment. Bill reflected on his current health and what he had been told about the effects of chemoradiotherapy:

I’ve been told that the treatment I’m going to get with the chemo[therapy] and the radio[therapy] thing, that it is actually going to take it out of me a bit, you know, and I am going to feel tired and physically drained more than anything, . . . I’ve been told, – not knowing myself – but I’ve been told that it will actually, physically drain me [. . .] because at the moment, I’m physically fit, I’m mentally fit, and I’m alert. So, you know, it’s . . . so at the moment, everything has been as per normal.

Bill (randomised to receive gastrostomy), Queenstown

Bill made a distinction between an expert forecast of his health – ‘I’ve been told, not knowing myself’ – and his experiential state: ‘at the moment, I’m physically fit’. Patients emphasised the importance of the HCPs who helped them to understand their options, the likely effects of treatment and strategies to adapt to new dietetic needs. A perception that the clinical team were being ‘honest’ about likely outcomes was particularly valued. Jenny, the wife of the patient, John, described their experience:

They’ve been on the money with everything. So I mean [John] went in New Year’s Day to have the tube inserted, and New Year’s Eve he was eating a sausage roll . . . By the Wednesday he couldn’t take anything orally. And they told us that . . . [it] actually just makes you feel more confident in them. Because they tell you how it is, so when they’re saying to him that they’re delighted with the way things are going, with the treatment progression, you believe them. Because you’ve got no need not to believe them. Do you know what I mean?

Jenny (spouse of John, randomised to receive a nasogastric tube), Otago

Health-care professionals were mindful of the importance of honesty and the building of trust in their interactions with patients. Both HCPs and patients valued trust in their clinical relationships, and honesty was reported as nourishing trust.

A key component of participants’ accounts was how the trial fitted within the broader narrative of their care. The amount of information that patients were required to process, and the many appointments that they were asked to attend, was often overwhelming. Patients described meeting a range of HCPs in close succession, or as Jenny phrased it, ‘a whirlwind . . . everybody and their grandmother’, and reported struggling to process the emotional and practical implications of their diagnosis. In this context, information about the TUBE trial was sometimes seen as an unwelcome addition to an abundance of clinical material. Ralf, who declined to be randomised, explained that:

I don’t know who it was [that told me about the study]. I don’t remember who it was with. I don’t know whether it was with the dietitian or what. I can’t remember now.

It’s all a bit of a blur?

Yes. I’ve seen so many different people, in different hospitals, it’s unbelievable.

Right. You’re getting a bit confused by it all?

No, not confused. I’m all right at the moment, because I’ve got all my dates through for my chemo[therapy] and my radiotherapy, and everything else. At the moment, it’s levelled itself out.

So it was more that you just had so many things being given to you all at the same time?

Yes, so many different booklets on what to eat, what not to eat, this, that and the other, and everything else, you know? . . . When they start giving you a load of pamphlets . . . I think to myself, ‘I cannot go all through that.’ The whole time, you’re either at the hospital, or you’re reading about the hospital, or whatever.

Patients reported feeling a sense of control, or that their situation had ‘levelled itself out’, when the clinical pathway had been arranged: dates were set, and practical considerations such as travel arrangements were in place. Ralf made a distinction between his state of mind at the time of the interview – ‘I’m all right’ – with how he felt during diagnosis, when he was first introduced to the TUBE trial, agreeing with the interviewer’s suggestion that it had ‘all [been] a bit of a blur’. A recurring theme in patients’ interviews was a distinction between the diagnosis and treatment discussions, and a later point on the clinical pathway at which patients like Ralf reported a calmer, more determined state of mind.

Making sense of the TUBE trial

Recruitment discussions for the TUBE trial were described by patients as being embedded in deliberations concerning diagnosis and form of primary treatment for cancer and secondary treatment (e.g. feeding tubes). Patients emphasised that treating cancer was their first priority. When asked how they first heard about the TUBE trial, most patients described a conversation that flowed as a logical extension to discussions about treatment modalities, treatment effects, and the likelihood of requiring a feeding tube. Jonathan recalled his experience:

When you were approached about the study, what were your initial thoughts about it?

I didn’t know if I’d have to have a tube, but when they explained that it will get bad with the swallowing and that, I said I accept what is going to be done with the tube. They said, ‘Would you like to go in with the study?’ and I said, ‘What does that involve?’ and she told me then that there were two lots [of tubes]. She said but you can’t pick, it’s random with a computer. We’ll do a random test. I said that’s not a problem. Then she put me through the procedures and to sign and read everything about it, and I accepted that and then it’s gone from there to now [. . .]

Jonathan described a logical connection between the news that his swallowing would deteriorate, that he would probably require a feeding tube and that he was eligible to participate in a study comparing two different types of tube. Jonathan’s recollection of what the trial would involve for him as a patient was the process of randomisation: he would not be able to choose the method of feeding assistance. His account is important because one of the most significant aspects of the TUBE trial for all patients was the decision of whether or not to agree to randomise their treatment.

Comprehension of the rationale underpinning research and the design features that shape participants’ involvement is a key component of informed consent. Much has been written in the literature on participants’ recall and understanding of information about trials,62 strategies to improve informed consent procedures63 and the success of different informed consent procedures. 64 Evidence from this body of work indicates that participants’ recall of key research concepts, such as randomisation, equipoise and research aims, is usually incomplete when measured against the PIS or protocol. However, participant accounts of research design may prioritise features that are most relevant within the context of their own illness experience. Throughout the interviews with patients, we observed a range of responses concerning the rationale underpinning the TUBE trial. All patients were able to describe the trial as a comparison of two methods of tube feeding. However, responses regarding the rationale for the research varied. Bill provided a concise and coherent description of his understanding of the TUBE trial:

. . . what [the research nurse] said was that, at the moment, just say for arguments sake, France will put [nutrients] through your NG. And Germany will put [nutrients] through a [gastrostomy], through your stomach. Spain, they, you may use either/or. Nobody knows which the best is: for the patient, or for the future. So what you are actually doing, is actually studying the pros and cons of having it through the nose, and the pros and cons of having it through the gastrostomy, and then you will use this information then, to make it a standard procedure, that is my understanding of it. For the benefit of the patient in the future.

Bill (randomised to receive gastrostomy), Queenstown

Bill’s account identified that the study aimed to compare nasogastric tubes and gastrostomy and that there was a lack of agreement across clinical sites regarding which method was ‘best’ for the patient. He also described a longer-term goal: that the research might support a single method, which would become ‘standard procedure’. Noticeably lacking within Bill’s account was a description of what specific outcomes were being compared, that is, a definition of ‘best’. Rather than discuss long-term swallow, Bill referred more generally to ‘the pros and cons’ of each type of tube. Most patients explained that there was a difference of opinion across clinical sites regarding which method was superior, but few described long-term swallow specifically as a key outcome of a future trial. Craig, like Bill, also emphasised differences across clinical sites in his description of the TUBE trial:

. . . both [types of tube] have been used in different areas. I know here tend to use NG more than gastrostomy feeds, or have done in the past. But I think . . . different centres use different things. And then they all swear by what they use, [their method] is going to be the correct thing, obviously! But I think anything that can actually clarify the outcome of that is going to be good for this [condition] in general.

Craig (randomised to nasogastric tube), Woodville

Craig identified that robust preferences for the different types of feeding tube were held by different clinical sites. Differences of opinion regarding the superiority of one method over another were held at the level of a collective (e.g. a clinical research site) in both Bill and Craig’s accounts. Issues around individual clinical equipoise did not feature in patients’ accounts of the TUBE trial, likely because all but one research centre reported ‘typically’ recommending one form of tube.

The TUBE trial was reported by most patients as focusing on an important area of their care by comparing feeding tubes. However, a few patients did question whether the trial was driven from a position of clinical uncertainty or as a vehicle for proponents of one method to prove that their preferred approach was superior to colleagues. A few patients were also uncertain of what the TUBE trial aimed to achieve by comparing methods of feeding assistance. Sarah suggested that the trial might compare levels of satisfaction between patients randomised to receive a nasogastric tube and those randomised to receive gastrostomy:

In your own words, what’s your understanding of what the study is about?

I don’t know that I’m entirely clear. I think they’re looking at these two options that people are faced with, and trying to assess, relatively, levels of satisfaction with the different options. It seems to be more an experiential thing; about the patients’ experience, not necessarily the medical outcome, because I suspect that’s not really in contention.

Sarah doubted that the TUBE trial would compare nasogastric tubes and gastrostomy on nutritional or functional medical outcomes. She contrasted medical research with what she perceived to be a ‘softer’, more experiential assessment of ‘levels of satisfaction’. Sarah’s account is useful because she demonstrated two important points common to most patients’ accounts. Some patients – like Sarah – assumed that clinical questions about feeding tubes would have been established a long time ago: ‘that’s not really in contention’. Therefore, the TUBE trial was not, to use Sarah’s term, a ‘medical’ or a ‘priority’ study in the larger context of medical research and cancer treatment. Second, understanding the rationale for the TUBE trial was not as important as understanding contemporaneous concerns, such as what treatment entailed and how to proceed along a clinical pathway. This perspective was also underpinned by the perception that the TUBE trial was not a ‘medical’ study. In this regard, Sarah’s account of what she perceived to be the rationale for the TUBE trial also supported her decision not to take part.

The timely and efficient progression of treatment was a central concern for all patients. The TUBE trial was generally reported in positive terms when it was perceived to fit seamlessly within a clinical pathway. Liam offered his interpretation of the TUBE trial:

. . . I mean, it’s a minor thing, a choice between a [gastrostomy] and the nasal one, as far as I’m concerned, because it’s just a feeding tube. I mean, I could understand somebody doing clinical tests for things that are lot, lot more, [pause], I wouldn’t say ‘important’, but a lot more life-threatening. If I can put something back in a small way, I would do it . . . I mean, I consider a feeding tube, in my situation, to be a minor operation, and it’s going to help me when I finally have radiotherapy and chemo[therapy]. I could imagine that some clinical trials which probably might be drug trials or something like that, or procedures that might be more [experimental], you’d have to find out which way to go, which is more safe than other ways, you know, more or less.

Liam (randomised to receive gastrostomy), Woodville

An observation reported by most patients (and HCPs) was that the TUBE trial compared existing, routine technologies; as Liam explained, ‘. . . it’s just a feeding tube’. Neither arm of the trial involved an experimental treatment. Moreover, regardless of whether or not patients took part in the research, it was likely that they would require either type of tube to support their nutrition. In Liam’s estimation, therefore, the TUBE trial did not present a risk to his health or care, compared with clinical trials of more experimental treatments, and required almost no deviation from a standard clinical pathway. These features of the trial worked either to support or diminish its perceived attractiveness to individual patients. Patients like Liam, who perceived the trial to be unobtrusive (‘it’s a minor thing’), identified an opportunity for an altruistic act – to ‘put something back’ – via the TUBE trial, while pursuing the central activity of recovering from cancer. Some HCPs, mainly at one site, reported that when multiple research opportunities were available for patients, some opted for studies that were perceived to be more ‘important’, by virtue of their focus on novel or adapted forms of primary treatment, than a study comparing established forms of secondary treatment.

Accepting randomisation to the TUBE trial

Patients who agreed to randomisation offered three different types of reasons:

1. They had no strong preference and saw the trial as having little impact on their care pathway.

2. They had a treatment preference but viewed their contribution to this research as more important than pursuing their preference.

3. They had a preference for the treatment that was not usually available at their site, and so they agreed to randomisation as it may have given them access to that treatment.

Altruism was the most frequent motivation articulated within patients’ accounts of why they agreed to be randomised. However, the research question also contributed to a comparatively unobtrusive study design, and this was cited as attractive by patients who were all primarily concerned with the primary cancer treatment over issues of feeding. Most patients reported a desire to contribute to medicine, and to help other patients and the process of cancer treatment, for example:

What informed your decision to say, ‘Yes I’ll, I’ll be randomised’?

It is about time I put stuff back to medicine [laughter] [. . .] this is something that needs to be sorted . . . you know, both, both have been used in different areas. I know Woodville tend to use NG more than [gastrostomy] . . . But I think at different, different centres [they] use different things. And then they all swear by what they use is going to be the correct thing, obviously. But I think anything that can actually clarify the outcome of that is going to be good . . . for what you’re getting out of [medicine] you’ve got to give back sometimes as well.

[. . .]

And I don’t think I was pushed to make a decision there and then with [the consultant] . . . [there’s] nothing to lose really, . . . And it’s, it’s answering a few questions rather than actually changing particularly what goes on.

Craig explained in his interview that his treatment preference had changed since his diagnosis, from initially preferring the concept of gastrostomy to seeing benefits to receiving a nasogastric tube. Ultimately, Craig had no strong treatment preference. However, for Craig, there was ‘nothing to lose’, as the TUBE trial remained relatively ‘unobtrusive’ in his clinical pathway. He positions the study as only ‘answering a few questions’ and not ‘actually changing particularly what goes on’. In this way, the relative impact of having a choice about feeding options was seen as minor in contrast to what he saw as the primary element of his care pathway.

Another patient who accepted randomisation indicated that he was relatively uninterested in the study design or purpose, stating that ‘it’s irrelevant to me’ [Mike (randomised to receive gastrostomy), Woodville], as a research study such as the TUBE trial was largely incidental to his primary treatment. He was happy to contribute to research as a by-product of, and in recompense for (‘I owe you’), receiving treatment. Interestingly, a few patients explained that volunteering for the TUBE trial was more important to them than getting their desired treatment:

OK. So how, how did you feel about it being framed like that, that you would have no choice over [your treatment]?

. . . well it didn’t worry me, or unduly concern me, because as I say, I’m a grandfather, and I have children, and if anybody could benefit from this study, I would be more than happy for it to be either an NG, or [gastrostomy] so it didn’t make no difference to me. Personally, I would have liked to have had a choice because of social activities as well, because even though I know I won’t be as active, . . . or fit enough to go out socialising, it’s still a bit of a . . . disfiguration I suppose [to have an NG] . . . because you’ve got . . . the pipe, coming out your nose, and being stuck across your face. Whereas the other way, it would be on your stomach, nobody will actually see it as such, so it was a bit of a personal thing . . . I would prefer to have it on the stomach, rather than through the nose.

Clearly, the description of nasogastric tubes provided by Bill, in particular his concern about the associated visual impact (‘disfiguration’) in social situations, suggested that he had a reasonably strong personal preference for gastrostomy. However, Bill stated that:

I am a donor, I got a donor’s card. [. . .] So if anything did happen to me . . . they would be able to use any part of me they want to, . . . I’m quite happy to do that, . . . I’m not one of those selfish people, . . . I was brought up to help other people, . . . as I think the song says, if I can help somebody on my way, then my living won’t be in vain.

Bill (randomised to gastrostomy), Queenstown

For Bill and for others, the social good of taking part in research outweighed their personal preferences. In this way, altruism was positioned as a central motivation in such accounts.

As noted above, four of the sites had a specific local organisational preference for either nasogastric tubes or gastrostomy. If a patient’s preference was different from the standard treatment, then their only opportunity to access it was through accepting randomisation. At one of the sites where only one feeding method was offered in routine practice, recruiting HCPs indicated that patients may have participated in the TUBE trial in order to access the otherwise unavailable treatment. In a recorded recruitment consultation, Carys and her relative indicated a preference for gastrostomy, which was not normally available at the site. During the consultation, it became clear that participation in the TUBE trial would present a possibility of being given the preferred treatment:

The only concern I have is that I’ve got chronic asthma and the tube down the nose to me sounds a bit restrictive, for me. So therefore I would prefer the other one. But then there’s the worry of infection.

[explains the two different tube methods] . . . If you were not going to join the trial . . . the tube of choice would be the one that’s going down your nose. That’s the standard treatment and the standard way of supporting patients in this trust. If you did choose to go on the trial it would be randomly decided between the two. So there’s a 50% chance if you go on the trial that you’d still have the same kind of treatment you would have –

[interrupting] So you can’t elect to have the stomach tube if you weren’t going on the trial?

No. The policy here is –

The nasal tube.

The standard use, the standard tube is the nasal one.

OK, right. Well that makes it easy doesn’t it?

Yes, I’d go with that.

In this context, the local organisational preference framed the patient’s decision-making to accept randomisation. So, if someone was not in equipoise, but rather had a strong preference for the non-local option, their only choice was to enter the trial to potentially realize that preference. As one patient notes, with a preference for gastrostomy:

Yeah, we’ve got to, we’ll do the research treatment.

Right. And you understand that you might get the tube, you might get the feeding tube but you might get the –

Yeah. I’ll just get the hang of it.

Recruitment consultation, Woodville

As this was the only way to potentially access the gastrostomy treatment path, the patient felt that they had no option. Their preference (which they framed as ‘the research treatment’), which was established through the trial process itself, was not sustainable without taking part and even then, not guaranteed. Patients who had a treatment preference but could access that only through the trial explained that they would have accepted the treatment they were randomised to. Only one patient in our sample reported that they would have withdrawn from the study if they did not receive their preferred treatment.

As is common in the research on participation in trials, the majority of patients who agreed to take part situated their motives as tied to altruism. 65–67 However, as Canvin and Jacoby68 and McCann et al. 69 note, this is a ‘weak altruism’ or a ‘conditional altruism’. By this they mean that:

. . . although people may initially have a tendency to participate in a trial based on a willingness to help others or contribute to a general good, this is unlikely to lead to trial participation in practice unless people can also recognise that trial participation can benefit (or at least not harm) themselves in ways that they regard as salient.

McCann et al. ,69 2010

© McCann et al. ; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Thus, some patients can be altruistic and are able to demonstrate to the clinical team that they are willing to help others, as they felt that there was little or no downside for them in taking part in the research. However, in the case of some patients, taking part meant that they might also actually get access to their preferred treatment. Interestingly, the option of taking part in the qualitative substudy gave those who declined randomisation an opportunity to also be altruistic in that they could say ‘yes’ to part of the research study.

Living with nasogastric tubes

Craig was randomised to receive a nasogastric tube and, although he did not have a tube at the time of his interview, his account, in part, vindicated proponents of the nasogastric tube. At the time of his interview, he was managing to continue eating and using nutrient supplements. At his initial interview, he reflected on his pre-treatment preference for gastrostomy. He outlined that, initially, he wanted a gastrostomy:

Because once it was in it was in . . . My feeling is possibly, looking back on it, that probably your motivation to keep eating and striving when you’ve got something that’s already there waiting to be used might not be as good . . . I’m on week 5 now, I’ve just finished my fifth chemo[therapy session] out of the six and I’m still eating.

Craig (randomised to receive a nasogastric tube; initial interview), Woodville

When the time came for insertion, the experience could be unpleasant. Jonathan’s tube was dislodged on two occasions when he was sick: he described how, while the tube was in place, he had a ‘sickly’ feeling which was relieved when the tube was removed. Each time this necessitated another unpleasant insertion experience:

Yes, when it came out it after I was sick, the last time came out . . . A nurse put [the nasogastric tube] in there and she kept on pushing and pushing and the pain was horrendous. I was shaking and there were tears in my eyes. I said, ‘Stop, I can’t take any more pain,’ and she pulled it out and she went to the other nostril and she said, ‘I’ll try in there,’ and she put it down there and that hurt as well, but she got it down in that one. I do not know if she did any damage down inside, because my throat is swollen now and I can’t manage, it’s a job to swallow . . . Oh, it was, terrible. It was only for 5 minutes at the time, I forgot about it after then. The tube was down so I was back to normal, but at the time it was terrible.

Jonathan (randomised to receive a nasogastric tube), Queenstown

Jonathan’s account of the unpleasantness of nasogastric tube insertion was supported by that of Joseph, who had a strong preference for gastrostomy after a previous experience of having a nasogastric tube, and entered the TUBE trial as it was his best chance of receiving a gastrostomy in a site that otherwise had a preference for nasogastric tubes:

I says ‘I do martial arts’, I says ‘I’ve trained to endure things like that’ and when they started putting that tube up my nose, Jesus I wish I’d have been put to sleep . . . it is the only thing I can think of is like an alien creature crawling through your body, you know when you . . . see these films where there’s somebody dying and they see the little, the spiders and that crawling up their nose and in their mouth [. . .] it’s like a scary feeling really, it feels as if your body has been taken over by something.

Joseph (randomised to receive a gastrostomy), Woodville

In his second interview, Jonathan explained that he had a fear of tube dislodgement, stemming primarily from the process of tube insertion, an event that dominated his experience of treatment:

The only thing is I [was] self-conscious because I’d be twisting and turning at night. I had to pull on the side of the window and I had to watch that I didn’t – I’d only lie on one side, you know, because otherwise I would pull the tube out. I was subconsciously concerned about that.

Jonathan (randomised to receive a nasogastric tube), Queenstown

A concern raised frequently by patients regarding the nasogastric tube was the social stigma associated with a tube visible on the face. Jonathan explained how his nasogastric tube made him feel self-conscious in public:

Yes, I wouldn’t walk around the town because all the people were looking at you . . . I don’t give a damn, myself, but [it does] make you feel a little bit [conspicuous] . . . people ask you ‘Is that oxygen’ and I said, ‘No, no,’ and explained you know. People staring when they see you, and that sticking through your nose . . . I used to do it myself anyway it’s no wonder people look at me, I used to do it myself, ‘Oh look at that poor bugger tube in his nose’ you know. Anyway it’s happened to me now so I knew what to expect. It still makes you a bit dubious going out though.

Jonathan (randomised to receive a nasogastric tube), Queenstown

Contrary to the expectation that patients with a nasogastric tube would have a tube for only short periods of time and maintain oral feeding, Jonathan described how his tube was in place for ‘months and months’, and that during that time he relied totally on the tube for nutrition:

While you had the tube in, did you manage to eat as well while the tube was in?

I couldn’t eat anything round the outside. When the tube was in, everything went down the tube.

Everything went down the tube?

Everything; injections, morphine, paracetamol, everything went down the tube.

So you weren’t swallowing anything at all?

Water. I could sip some water, but that was about my limit then.

Jonathan summarised his experience with the nasogastric tube:

If I were to have it again I would be asking for the stomach one . . . If ever I’ve got to do it again, I will be demanding the stomach one. I don’t want to go through the nose one again.

Jonathan (randomised to receive a nasogastric tube), Queenstown

Clearly, we have very limited data on this topic. However, what we have supports health professionals’ perceptions that a nasogastric tube is more problematic for patients than a gastrostomy: insertion is more unpleasant, feeding takes longer and is more socially isolating and dealing with problems that occur is more demanding. There was some evidence that patients with gastrostomy did retain their tubes for longer. However, they described how they did consume food and fluids orally for taste, social and other reasons, using the gastrostomy to ‘top up’ otherwise inadequate oral feeding. Other factors, notably issues with tooth loss, may limit a return to full oral feeding in both patients with a nasogastric tube and those with a gastrostomy.

Model description

An economic model developed as a Markov model was built in TreeAge Pro^® (TreeAge Software, Inc., Williamstown, MA, USA) to estimate the cost-effectiveness of gastrostomy tube feeding compared with nasogastric tube feeding. The population considered was patients with head and neck cancer undergoing CRT, assuming a cohort with an average age of 60 years, to represent the average characteristics of the population with this condition and requiring this type of nutritional support. The time horizon of the model was 6 months. A time cycle of 1 month was chosen, as it was felt that a short time period would be sufficient to capture all important costs and effects, and would also be necessary because of the rapidly changing nature of the health states of head and neck cancer patients receiving nutritional support. A lifetime time horizon was not possible because of insufficient long-term data. The model structure is shown in Figure 6.

FIGURE 6.

Markov model used to assess the cost-effectiveness of ‘pre-treatment gastrostomy tube feeding’ vs. ‘nasogastric tube feeding, as necessary’. G, gastrostomy, NGT, nasogastric tube.

The entire cohort began in the ‘nutritional support’ state, which is the point at which insertion took place. From this health state, patients moved along a pathway in which they could experience an insertion-related AE (gastrostomy tube only) and subsequently remain in this health state, die from other causes, experience a fatal or non-fatal major AE or end nutritional support. Determined by the events experienced during this initial pathway, patients moved to one of three subsequent health states, comprising ‘off nutritional support’ after removal of nutritional support as the result of a sufficient increase in independent nutritional intake, ‘nasogastric tube/gastrostomy tube’ because of non-adherence at the insertion stage requiring a switch to the alternative type of nutritional support and ‘dead’ following death from other causes or from a major insertion- or tube-related event, or they remained in the original health state. Once in the ‘off nutritional support’ health state, the patients either remained in this health state or died from other causes. When patients experienced non-adherence requiring a switch to the alternative type of nutritional support, the clinical pathways described were the same as in the main alternative intervention arm. Transition probabilities (probabilities of progressing from one stage of the model to the next or probabilities of transitioning to subsequent health states) were used to link the starting point of the Markov process to the end point.

The model was designed to estimate costs from the perspective of the NHS and PSS and outcomes in terms of QALYs gained in each arm of the model,71 with costs and QALYs accumulated dependent on the transitions between health states. QALYs were generated using health utilities, which are preference weights measured on a cardinal scale of 0–1 (whereby preference can be equated with desirability) combined with quantity of life-years. 71 The difference between the costs, incidence of health outcomes and impact on QoL and mortality between treatment options was used to estimate the incremental costs and effects of gastrostomy tube feeding. The model also attempted to incorporate second-order uncertainty by assigning distributions to a selection of input parameters. All costs were for a price year of 2014–15. A 6-month time horizon was adopted; therefore, discounting of costs and effects was not required.

Mortality

In the age category as identified in the demographics of the study population, life tables were used to determine the probability of death for individuals in this age category. As the model time horizon was only 6 months, an assumption was made that the probability of death in each month would remain constant over the 6-month period. The monthly probability of death was estimated based on data on the annual mortality rate for patients in this age group, provided by the Office for National Statistics. 78 It was assumed that the risk of death from other causes was constant, irrespective of health state.

Resource use and costs

Information on the precise description of the resources required for each intervention was partially based on data derived from the feasibility study, augmented when necessary by members of the study group and published economic literature. From all participants recruited into the trial, resource use data were collected and costs were estimated for each method of nutritional support. Paucity of data led to other sources, as outlined above, being utilised. Unit costs were taken from appropriate routine sources, such as NHS Reference Costs 2014 to 2015,73 PSSRU80 and the British National Formulary81 for medication.

For the cost of a gastrostomy tube insertion, the non-elective short stay costs of endoscopic and radiologic insertion of a gastrostomy tube were used. The Healthcare Resource Group (HRG) code for PEG for adults is Z93A, with activity of 5497 procedures in total, whereas, for RIG, the HRG code was YF01A with a corresponding total activity of 2635. Based on the total activity of these two HRG codes reported by the NHS Reference Costs 2014 to 201573 for the specific year, 68% of the gastrostomy tube insertions were done using the percutaneous endoscopic technique. A weighted average cost was, thus, estimated. In addition to the actual insertion, patients receive information about the tube the day after the procedure, by a dietitian or a nurse specialist, for approximately 30 minutes. Insertion and education costs were combined to derive a total gastrostomy tube insertion cost of £777.

The nasogastric tube insertion procedure is less complex. The cost of intermediate upper gastrointestinal tract procedures for adults in an outpatient setting was used to inform the value of a nasogastric tube insertion cost (£167). 73 The same cost was used for nasogastric tube-related AEs (e.g. tube reinsertion). AEs associated with the gastrostomy tube are related to insertion complications and major events such as infection, and are more severe than those associated with the nasogastric tube. Clinical experts advised that AEs (both insertion-related and major events) associated with the gastrostomy tube would require an average of 4 additional days in hospital for monitoring of the patient and/or treatment of the adverse effect, and costs were estimated accordingly.

Patients who have enteral feeding tubes inserted need to be monitored to ensure that there is no tube misplacement and that the tube is functioning properly. It was assumed that monthly monitoring costs would be the same in both arms of the model, and the costs were based on a weekly 30-minute hospital dietitian-led appointment. The monthly cost of nutritional intake was also estimated based on information from the literature,82 and was assumed to be the same in both arms of the model. The cost of a tube removal was estimated based on expert clinical input. It was advised that the process takes 10 minutes, on average, for nasogastric tube removal and 20 minutes, on average, for gastrostomy tube removal, and that this procedure would be conducted by a nurse. It was assumed that patients dying as a result of an AE would receive 4 days of specialist inpatient palliative care. The cost of medical specialist palliative care for adults over 4 days (£482) was included in the model. 73 The perspective adopted for the model was that of the NHS/PSS, and a price-year of 2014–15 was applied. The unit costs included in the model can be found in Table 26.

Estimation of quality-adjusted life-years

For the cost–utility analysis, estimates of clinical effectiveness and cost-effectiveness were expressed in QALYs. 71 For each health state, a health state utility was defined. A focused search to identify utility data, including a search on the Cost-Effectiveness Analysis Registry, was conducted; however, no useable data were identified, with the exception of baseline utility values. 83 Baseline utility values for patients with head and neck cancer undergoing CRT, and experiencing low-severity CRT AEs, such as dysphagia, mucositis and xerostomia, were sourced from the literature83 and utilised in the model.

The other utility estimates used within the model were based on strong assumptions and best-guess estimates from clinical experts. These assumptions are discussed in a later section. All utility values included in the model were transformed to reflect the time cycle of the model and to ensure that the relevant output parameters were presented in terms of QALYs. Baseline utility values and utility decrements can be seen in Table 27. The lack of utility data, along with other data limitations, means that the economic evaluation should be considered an exploratory analysis, rather than a definitive assessment of cost-effectiveness.

Model assumptions

Owing to the limited research in this clinical area, and the difficulties experienced in patient recruitment for the associated feasibility trial, a number of assumptions were made regarding the model structure and input parameters.

Input parameters

Deterministic sensitivity analysis

A sensitivity analysis was performed to determine the impact of changing key parameters on the model results. Therefore, many of the model parameters were subject to one- and two-way sensitivity analyses, using hypothetical increases or decreases, to determine the key drivers of the model results. In addition, threshold values were explored when data were missing by varying estimates through a range thought possible (based on the advice of the stakeholders involved in the study). Deterministic sensitivity analyses were also carried out to test for the effect of assumptions and variability. The majority of the clinical parameter values were varied extensively in the sensitivity analysis.

Assessment of cost-effectiveness

The analysis was designed to generate the cost per additional QALY15 gained from gastrostomy tube feeding. When available, data were entered into the model as distributions in order to fully incorporate the uncertainty around parameter values, so that a PSA could be undertaken. In decision modelling, many of the parameter values are often estimated with a degree of uncertainty. There is a need to propagate the joint parameter uncertainty in terms of decision uncertainty, and, thus, distributions are assigned to parameter values. Relevant distributions were informed by the systematic reviews and meta-analyses, additional literature and expert opinion. The PSA was run with 1000 simulations and cost-effectiveness planes and acceptability curves were produced in order to identify the probability of gastrostomy tube feeding being cost-effective across a range of willingness-to-pay (WTP) thresholds. Estimation of costs and QALYs were calculated as the expectation over the joint distribution of the parameters. This quantification of decision uncertainty also provided the starting point for assessing the value of additional research.

Results of the cost-effectiveness analysis

This section presents the results of the cost-effectiveness analysis. The base-case cost-effectiveness analysis results should be interpreted with caution, given the assumptions made in estimating many of the parameter values.

The base-case results shown in Table 28 indicate that the intervention of gastrostomy tube feeding is absolutely dominated, that is, it is costlier and less effective than nasogastric tube feeding. A number of assumptions were made in the estimation of the input parameters, largely around utility values, which led to this result. The results from the PSA (Figure 7) show that the largest number of points are in the north-west quadrant, indicating that the intervention of gastrostomy tube feeding is likely to be costlier, and less effective, than the comparator. A very small number of these points are below the WTP threshold value of £20,000 per additional unit of effectiveness gained, indicating that the intervention is unlikely to be cost-effective. The cost-effectiveness acceptability curve shown in Figure 8 indicates that the intervention has a low probability (maximum 37%) of being cost-effective at all of the WTP values presented, whereas Table 29 presents the output from the cost-effectiveness acceptability curve and the likelihood of the intervention being cost-effective at WTP threshold values of £10,000–40,000.

FIGURE 7.

Cost-effectiveness plane of ‘pre-treatment gastrostomy tube’ vs. ‘nasogastric tube feeding as necessary’: base-case analysis.

FIGURE 8.

Cost-effectiveness acceptability curve of ‘pre-treatment gastrostomy tube’ vs. ‘nasogastric tube, as necessary’: base-case analysis. NGT, nasogastric tube.