Eight sites were represented in the interviews; four sites recruited one patient each (B, D, F, J). Seventeen health professionals were interviewed between November 2019 and July 2020, including 10 surgeons and seven research nurses; four were male and 13 were female (Table 1). Seven patient interviews were conducted from July to September 2020; four with the women recruited to the MIAMI trial and three with women who declined to take part in the trial. Overall, five patients underwent TM and two had mastectomy as their definitive surgical procedures.
Table 1
Health professional interviews for sites that recruited and did not recruit to MIAMI.
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Recruiting sites (n = 4)
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Non-recruiting sites (n = 4)
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Total interviews (n = 17
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Surgeons
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4
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6
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10
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Research nurses
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3
|
4
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7
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Males
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1
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3
|
4
|
Females
|
6
|
7
|
13
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The overarching themes generated were grouped into 1) Factors influencing equipoise and recruitment and 2) Effects of a lack of equipoise. Within these themes health professional sub-themes described the barriers to recruitment in ‘the treatment landscape has changed’; and the effects of this as ‘staff preferences and beliefs influencing equipoise’, and how different the treatments were for patients. Patient themes influencing recruitment included ‘altruism and timing’ of trial approach; and the effects of a lack of equipoise as ‘influences from consultants and others’; and ‘diagnostic journey doubts’ which determined whether women agreed to take part in the trial. Themes are shown in Table 2 and are presented below with illustrative quotes: staff quotes are identified by role and site; patient interviews identified by site and whether recruited to the trial or not.
Table 2
Themes described by health professional and patients that influenced equipoise and recruitment to the trial.
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Health professional themes
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Patient themes
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Influences on equipoise and recruitment
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The treatment landscape has changed
- St Gallen consensus and usual care treatment has changed.
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Altruism (to help others) – recruited patients;
Timing -too many trials offered
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Effects of a lack of equipoise
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Health professional preferences and beliefs:
- Impact on patients
- Treatment arms of the trial are so different
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Patient preferences reinforced by health professionals
– ‘we can save your breast’
Diagnostic journey doubts
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Health professional themes.
1) Influences on equipoise and recruitment - The treatment landscape has changed.
The acceptability of TM as standard practice for MIBC changed during our study and especially following the international St Gallen consensus meeting in March 2017 [4, 5]. Despite guidelines recommending that patients should be encouraged to take part in well-designed RCTs, this consensus statement has inevitably influenced surgical opinion and increased confidence in breast conservation for MIBC.
“Most of us take the view that although there’s no really hard evidence that conservation surgery for multifocal, multicentric [cancer] has been trialled properly, we know that the St. Gallen consensus is that it might be suitable, provided you can achieve clear margins. Because St. Gallen has pronounced on this then I think people are moving that way in terms of their threshold for doing conservation surgery.” (Surgeon #3, Site C, non-recruiting site).
“Well there is no evidence from randomised control trials, but there is plenty of evidence that multiple cancer with clear margins has equal or similar survival and local recurrence rate, …. if you are going to believe large cohort evidence, then that’s an option for us” (Surgeon #7, Site E, non-recruiting)
“Many in the MDT seem convinced by the data that is emerging so far, even though that’s not trial data, there is no research data, especially when … they are truly multifocal, as opposed to multicentric I guess... So yeah, broadly multiple issues before we are actually at that stage that we randomise, but mostly I am sure it must be a shared issue with other centres”. (Surgeon #16, Site B, recruiting site)
Consequentially treatment patterns at breast care centres changed with more BCS being offered as usual care. This, combined with the pool of eligible patients being smaller than expected, made it difficult to recruit patients to the trial.
“When the evidence is coming out suggesting that breast conserving surgery and radiotherapy has a survival advantage over mastectomy, it’s quite hard to not offer that as an option for a patient, when you’re looking at somebody who has got a double E breast and you know perfectly well you could take 300 or 400 grams away, get both the tumours out and still leave them really nice breasts, very hard to say to them you need to have a mastectomy.” (Surgeon #9, Site A, non-recruiting).
“So I think probably the biggest problem was lack of patients suitable, so patients who had either got too extensive disease, and therefore wouldn’t have had conservation anyway, and that reduced the pool of patients down quite substantially…” “the problem that we then had was lack of equipoise by the patient.” (Surgeon #3, Site C, non-recruiting).
2) The effects of lack of equipoise – Health professional preferences and beliefs
Conveying equipoise and running a trial within the context of shared decision-making consultations was challenging. Health professionals often felt uncomfortable conveying the current lack of evidence for treatment and did not present trial options in a balanced way because they were not in equipoise, believing that certain eligible patients might be more suitable for a breast conserving procedure.
“It’s very difficult to sit there and say to the lady well the standard treatment would be this, but ….. we’ve now got to think of perhaps some different options, and at the moment we don’t know scientifically which is the better, to take all the breast tissue away or perhaps to be able to take just two areas away, and we’ve got a trial going on. I would say virtually everybody said well you said “you could preserve the breast beforehand, can you not do it now?”” (Surgeon #9, Site A, non-recruiting).
“The problem was with the surgeons … at the MDT, would say look this patient would be suitable for some kind of breast conserving procedure technically therefore they were not happy to randomise them to mastectomy”. (Surgeon #6, Site J, recruiting)
“I think it’s still the equipoise issue though particularly with this study. I know our clinicians are used to introducing studies with equipoise, but it’s cobbled with the fact that they’re only allowed to give limited information at a time when a patient normally asks questions about what the next treatment is going to be involving.” (Nurse #11, Site D, recruiting)
“And when you are selecting patients, a lot of patients … about a third of patients will say to me, “You tell me what the best operation for me is,” which is an almost impossible question to answer.” (Surgeon #15, Site F, recruiting)
Impact on patients. Staff found discussing the RCT particularly challenging to talk to patients who expressed strong preferences and opinions for either treatment. These patients often had multiple contacts and received advice from a range of individuals during their pre-operative journey.
“.. either they wanted to save their breast, or they didn’t. Equipoise wasn’t coming into discussion, almost before you told them ‘you had breast cancer’ they knew what they wanted.” (Surgeon #7, Site E, non-recruiting).
“Women said “Well if you’re prepared to randomise me to breast conservation then that’s the thing I want, because you are not saying to me you have to have a mastectomy, you are saying I can go into this trial, therefore I am not having a mastectomy.” (Surgeon #6, Site J, recruiting)
“I think when they come to us they pretty much have made up their mind what is the treatment they want, and at that point we say well we don’t know what you’re going to get, you might get mastectomy even though they want the mammoplasty, then it’s something that puts them off, and that’s why the randomisation is the biggest barrier.” (Nurse #13, Site B, recruiting)
“I would sit in the MDT and I would sometimes highlight [MIAMI]… and then the patient was often discussed the same day that they are seen, so it was a difficult situation to then get in to see the surgeon… because they had often already been talked to by somebody else.” (Nurse #14, Site K non-recruiting)
Treatment arms of the trial are so different. Staff also commented that an additional recruitment barrier was the notable difference in the surgical treatments and consequently it was a big decision for women to make.
“I think that when it comes down to two treatments that are so different, it’s not like you’re choosing between one chemotherapy drug and another that may or may not have very slightly different side effects, we’re talking about two fundamentally different procedures with fundamentally different outcomes and I really do feel that a randomised trial was not the way forward to answer this question. As I say I am open to studies and things like that, but we needed to do the trial in a different way. So, I was expecting that it would be very difficult to recruit to.” (Surgeon #15, Site F recruiting)
Patient themes.
1) Influences on recruitment - Altruism and timing.
Recruited patients: Altruism: Patients recruited into the trial appreciated the detailed nature of trial information given to them and were generally satisfied with the questionnaires they completed. There was a common desire to help advance medical science for members of their family and the wider female population.
“If there’s anything that can help women, I will do it”. (P146, recruited, site F)
“I have two grown up daughters and a daughter-in-law myself, and you want to do it for other people, you want to do it for the next generation. So that was the attitude I had when I accepted.” (P569, recruited, site B)
Others agreed because they believed that taking part in the trial was the only way to receive BCS.
“So, because there wouldn’t have been any other option, it would have been straight to mastectomy you see apart from the study.” (P118, recruited, site D)
Timing of study approach was crucial for all patients: One patient felt that being introduced to the trial during the initial consultation was too overwhelming, as she was still coming to terms with her diagnosis and had a fear of the cancer spreading.
“You’re trying to process the fact that you’ve got what you’ve got, then you’re trying to process the fact that you’ve got to have a major operation at some point, and then all this stuff just gets thrown at you, and then the study as well.” (P233, declined, site F)
Two participants were invited to take part in more than four research studies and questioned the burden of research.
“There was a point where I began to think this is ridiculous’.. ‘perhaps they don’t know how many trials they are asking people to take part in”. (P494, declined, site B)
2) Effects of lack of equipoise - Patient treatment preferences influenced by ‘We can save your breast’. Treatments available at breast care centres depended not only on a finding of multifocal cancer, but also upon which surgeon was present at the initial consultation when diagnostic biopsy results were given. Patients were frequently offered information about MIAMI after this consultation, which may have been too late for some patients. Several women had a priori treatment preferences (ahead of randomisation) relating to their age, fear of cancer spreading, and the fact that cancer had been identified relatively early. Even so, two of them still agreed to take part and were randomised to their preferred treatment.
“So they asked me if I would like to join the study and I said oh yeah I’ll try it, no problem…I wanted to have a full mastectomy, … it came back mastectomy and I went thank God…” (P623, recruited, site J)
Proffered treatment options inadvertently discussed by surgeons during early consultations potentially risked undermining later discussions when RCT options were introduced with equipoise. Two (declining) women appeared to have been heavily influenced by the views and recommendations of their treating consultant. One was told, ‘we can save your breast’ and that a mammoplasty was ‘appropriate’.
“He said, “We can save your breast if you would like to,” and I said, “Well if you can.” He would remove the cancerous lump and do a bit of reconstruction at the same time. So that was all agreed. …Then I was offered the MIAMI trial, [after the initial consultation] and the lady rang up and said to me, “[Doctor] has put you forward for the MIAMI trial.” Well now, I’d had this half an hour consultation … it had been planned with my consultant to have a lumpectomy… So that was the reason that I refused.”(P494, declined, site B)
“This [mammoplasty] obviously suited me, so at that time having to have a computer decide for me wasn’t an option. They told me what was best for myself, so that’s what I went with”. (P542, declined, site B)
Diagnostic journey doubts.
Patients reported that their opinions changed over time due to the influence of different advice from various individuals and improved understanding about treatments. Some women initially felt positive about joining MIAMI but found that ‘doubt began to set in’ as they progressed through their appointments. One woman acquired a preference for mammoplasty and was randomised to this treatment arm, another opted to have a mammoplasty after being randomised to the mastectomy arm.
“So when they introduced MIAMI to me I was quite happy to have a look at it and go ahead with it… once I got into it doubt started to set in.” (P569, recruited, site B)
“..then a week or so after I thought I don’t know, and I will say from the day that they told me that’s what was going to happen right up until the morning that I went in to see the breast surgeon to confirm what was happening, I swayed between one or the other.… because it wasn’t so much the surgery it’s the reconstruction after it.” (P146, recruited, site F).