Findings from the main 4-T trial showed that endpoint glycated haemoglobin were similar for patients randomised to biphasic (median: 7.1%), prandial (median: 6.8%) and basal (median: 6.9%) insulin-based therapies (P = 0.28) . Consistent with these findings, analysis of the qualitative interviews did not reveal widespread or systematic differences in reported adherence amongst patients in the three trial arms. Staff accounts, similarly, did not reveal obvious differences in the treatment, advice and care given to patients in different arms of the trial (hence data reported below cut across the three trial arms). However, whereas patients tended to present relatively unproblematic accounts of participating in, and taking their insulin during, the trial, staff highlighted various difficulties and dilemmas which arose during trial delivery. In particular, staff described experiencing a conflict between their roles and responsibilities as researchers and clinicians. This conflict became most apparent when they were required to treat to the trial's tight glycaemic target.
Below, we begin with patients' experiences of taking part in 4-T before considering staff perspectives and views. We will show that staff accounts need to be considered alongside those of patients to fully understand why there was limited attainment of the trial's glycaemic target.
Patients' experiences and views
Taking insulin during 4-T
As detailed elsewhere , virtually all patients described being motivated and committed to taking their insulin during the trial, as they perceived insulin as essential for their diabetes control and long-term health: "if you don't take your medication, then that's it" (P31); "it's a matter of life and death" (P16). Hence, only a minority reported extensive and intentional insulin non-adherence, the most extreme case being P29 who stopped taking insulin for three months after experiencing a severe hypoglycaemic episode requiring emergency services to be called out:
"I'd never had a hypo before, but I'd been feeling funny and I've maybe had a biscuit or something, I've had something to eat and it went away but this Sunday, for some reason, just after lunch, I just went berserk, I nearly wrecked everything in the house. And, of course, the wife panicked and she phoned for the doctor and this emergency doctor came out, because I was ranting and raving on and the wife was panicking." (P29)
While virtually all patients described sometimes forgetting to inject insulin, particularly when daily routines were disrupted, nearly half also talked about occasionally adjusting and/or deliberately skipping doses. In almost all cases, doses were altered or missed as a strategy to curb or avoid hypoglycaemia; for instance, when a meal was skipped or, in P10's case, before undertaking planned physical activity:
"If I'm going walking up the hills, I don't take any, I don't take any Rapid insulin. Either that or I'd be keeling over on the hills because my sugar levels, with doing the extra exercise, my sugar levels would be far too low... So I basically don't take any. And at the end of the day when I come back home, I check my sugar level and it's probably 6.5 or something like that and that's being out on the hills all day, eating as and when I needed." (P10)
Some also described titrating insulin doses according to foods consumed or in response to SMBG readings, to avoid hypoglycaemia or optimise control:
"I now adjust my insulin with the blessing of, eh, my blood sugar level. If they're below six, I use eight units in the morning. If they're above six I use ten. The only one I usually adjust is the morning one, because if I don't, I hypo." (P21)
In almost all cases, patients described discussing these strategies with 4-T staff and receiving their encouragement and support.
Titration and intensification of treatment
Patients tended to defer to 4-T staff when decisions were made about titrating and intensifying their insulin. Some also recalled instances when they had been aware of staff not following the TMS' recommendations. Patients described preferring to trust staff's judgement rather than the TMS, because of their holistic knowledge of the patient, their ability to "use common sense" (P11), and patients' experiences of staff taking their personal circumstances into careful consideration:
"Computers are great for maths or something like that but, for making decisions about people's lives, I'd rather have a human view point, that can weigh it up, look at all angles." (P20)
"I'd trust the nurse every time, cos everything was fed into the computer and sent down to Oxford, where as she was seeing me all of the time, what I'm looking like healthwise etc." (P22)
A minority, however, did describe becoming more involved in negotiating their insulin doses with staff as the trial progressed, prompted by experiences of hypoglycaemia which had led them to question or resist TMS recommended doses:
"The information would be put in and generally it would come back and say to me that I needed to increase the dose by quite a substantial amount. But actually the nurse knew I didn't want to do that, that I was wary to do it, and that also I am actually, I believe, very sensitive to insulin, to having hypos... And they were happy to reach a compromise; to discuss how I felt and then agree a path forwards." (P11)
Most patients were unaware of the 4-T target for glycaemic control and determined their own success or failure according to staff's encouragement and responses to their HbA1c results. In practice, this meant a patient could think they had 'done well' even though they had not reached the trial target, such as P2 who described how, "once it was seven point something, they were all delighted about it." The reverse could also happen, such as when P23 described how she had "felt a failure" despite getting her HbA1c down to 6.4%, "because they were always trying for 5.4, 5.6."
Staff experiences and views
Treating to target
All staff expressed ambivalence about the trial target (HbA1c ≤6.5) because it was tighter than normally aimed for in routine clinical practice and recommended in clinical guidelines. Some described feeling that "sometimes they were asking almost for people to be at too high a risk of hypoglycaemia" (RN17). Others highlighted the lack of evidence of long-term benefits of treating to a tight target: "over a 5 or 6 year period it doesn't seem to improve outcome to any great degree" (Phy3), or commented that "there is some evidence that if you do go too low, it can actually be dangerous" (Phy7). The emphasis placed upon tight blood glucose control rather than other risk factors was also questioned by some staff:
"We probably need to be much tougher on cholesterol, much tougher on blood pressure em, and just do the same as what we're doing for glycaemic control. We've allowed our thinking about this, about how glycaemic control can influence macrovascular events, and they don't really. It doesn't really shape, shape em, it's not going to, it doesn't stop people dying." (Phy5)
Staff also expressed reservations about applying a 'one size fits all' target to all patients commenting that, in clinical practice, treatments would "be individualised to each person" (Phy17). While tight targets were generally seen as appropriate and realistic when patients were relatively young, motivated/adherent and/or at risk of complications, staff described being less keen to pursue tight targets amongst the elderly, especially those who lived alone, and those who did a lot of driving or physical activity:
"A tight target is realistic for anyone who is, its difficult to have a age cut off, but um sort of under the age of 65, who is worried that high glucose levels will damage their blood vessels, and who is up for engaging in better control ... Contrast that with a very old person with lots of other problems in whom you're not going to do them any favours by tightening up their glucose levels. Because you've got to say to yourself, 'well, what are we actually going to achieve here if we make then tight and them falling, and then them being admitted with a fractured hip?'" (RN17)
"Some of them, because of their working lives, you know, they travelled a lot, or they were builders doing really physical work one day, maybe indoors and outdoors and that seemed to vary it. And if they were suddenly having lots of hypos sometimes you were better erring on the side of caution and being higher because at least that way they could still work, still function." (RN19)
As the above quotes suggest, worries "about patient safety" (Phy17) were widely discussed by such staff members. Some staff also raised concerns that increasing patients' risk of hypoglycaemia could potentially undermine trust and the long-term therapeutic relationship: "one hypo and they lose confidence in the system and it's very difficult to do anything with them." (Phy9)
Staff also highlighted the potential dangers of instilling a sense of failure in patients who had not reached the trial target but had achieved better control during 4-T. This informed the decision that some had made to not inform patients of the trial target.
Using the TMS
While generally considered a useful guide or starting point for determining patients' insulin doses, all staff, especially those who came to the trial with extensive diabetes clinical experience (see below), described regular deviations from the TMS' recommendations because, "it's for sort of for ideal patients, and not every patient is ideal" (Phy17). In most instances, deviations occurred when, based on their clinical experience, which included that of having previously used the insulins investigated during 4-T, staff considered TMS recommended doses to be too high and as putting a particular patient at risk of hypoglycaemia:
"I think it's difficult really because I've been doing it for x number of years and obviously was very comfortable with those particular insulins. And whether it be a fault of the protocol or the system or just my thinking, I don't know, but it did make you stop and think, 'well that just seems too much.'" (RN13)
In a few cases, deviations were also a direct response to patients' resistance or refusal to have their insulin doses increased after experiencing severe hypoglycaemia. Staff described how this could result in a balancing act "between keeping the patient in the study and trying to fulfil the protocol as best as you could." (RN13)
Some also conveyed concerns about the potentially flawed and 'untrustworthy' data upon which the TMS' recommendations were based. Nursing staff pointed out that the three days of SMBG data fed into the TMS could be a potentially inaccurate representation of a patient's blood glucose control over the previous months:
"But I'm looking back over quite a lot of readings, I would make my decision on that rather than just maybe the week the patient's coming in. Because you have other things, like maybe they've got a stressful week on or, you, you know, you've got the patient in front of you and you've got the diary in front of you, you would sum up and then make your decision." (RN15)
Some also speculated that SMBG data might occasionally have been fabricated by patients; typically when diaries were presented in pristine condition. It was also pointed out that the TMS did not factor in for symptomatic hypoglycaemia above the trial's SMBG 3.1 mmol/l threshold, or for experiences of 'near hypos'. Staff described how they would exercise their own judgement on such occasions, drawing upon their clinical experience:
"Because the thing is, we'd only write hypos in the system, but sometimes patients would be talking about near hypos and obviously there was no way of recording that. So with that in mind, if they said, 'oh, I always feel a touch lower before lunch' blah blah and they told you that quite a bit, there was no way to record that... And then so you'd think 'well I'm going to lower that then, that one, and then put it up a bit more later'. But the TMS didn't know that, so it would tell you different information and then you'd go "oh I'm not happy about that because I think that would drop them down too low." (RN19)
While staff perceived the TMS as a potentially useful tool for less experienced colleagues, such as those based in general practice, some nursing staff said they had disliked using it because they felt it had belittled and undermined their expertise:
"I think for any insulin start trial, you know, you can train a monkey to start insulin, but it takes somebody with more in-depth knowledge to identify where things are going wrong sometimes." (RN2)
Other staff members, however, were more positive about using this technology. They described their previous approach to managing insulin treated patients as having been overly conservative and commented that positive experiences of using the TMS had helped them overcome their resistance to intensifying insulin treatments in both the trial and in their clinical practice:
"We've always been used to rather more tentative doses to start people on. So you know, we would ordinarily have started people on 20 units a day and the slide rule said you start on 40 in the morning and 16 at night or something. Then you're going to step back a little from that and think 'hang on a minute, that seems rather a lot to me'. But once you got used to it, and learnt to trust it, then it seemed to work most of the time." (Phy14)
Negotiating the boundary between research and clinical practice
"Working as a DSN and a research nurse, that is a bit of an issue for me... I sometimes found myself in a bit of a dilemma where I think, well off trial, I wouldn't be doing this." (RN2)
As the above quote highlights, cross-cutting the staff interviews is the tension, and difficulties, encountered when the trial protocol required them to deliver patient care which differed from their routine clinical practice. While staff talked about experiencing a conflict between their roles as practitioners and researchers on such occasions, the greatest dilemmas were conveyed by RNs. While this was partly because they were responsible for delivering most direct patient care during 4-T, many RNs also came to the trial with extensive diabetes clinical experience as they had worked and/or were continuing to work part-time in a Diabetes Specialist Nurse capacity alongside 4-T (see table 1). As various staff members commented, the greater the RN's diabetes clinical experience the more likely they were to have deviated from TMS recommended insulin doses during the trial. RN6, for instance, who worked for a research company and did not have a therapeutic speciality, noted that, whilst she had "tended to just go for what was suggested on the computer", her more clinically experienced colleagues:
"were just putting in what THEY thought were the right doses and not going with the algorithm, the protocol." (RN6)
As well as deviating from the TMS' recommendations, clinically experienced RNs also offered patients extra visits and/or input (e.g. dietary advice, training in carbohydrate counting) to those outlined in the protocol, to reflect the care they would provide in their diabetes clinical practice. Some also indicated that they had given patients extra services and enhanced clinical care (such as a quick referral to a chiropody service) to foster treatment adherence and trial retention.