Clinical Trials

Non-randomised trial designs and other studies

Clinical trials are carried out in a number of stages. Early stage trials usually involve small numbers of patients. Particularly for drugs, early stage studies are needed to assess safety and unwanted side effects, after early laboratory testing has been completed. (See Resources and Information).

Phase 1 trials usually involve a small group of healthy people, or sometimes patients. They are mainly aimed at finding out how safe a drug is. This is often the first time that a drug will have been tried in human beings.

Anthea describes what a Phase 1 trial is. No-one knows what the side effects will be and whether...

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Age at interview: 58

Sex: Female

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Phase 1 trial is they don’t know what the results are going to be. They don’t know what side effects you’re going to have. They don’t know how well it’s going to work, whether it’s going to work. It’s got to be started somewhere, and [sighs] if, if the phase 1 trial does work on some, they might be able to adjust it to do a different, using the same drugs used in a different way. I actually found out this morning that the dacarbazine could actually be given in tablet form as well, which I didn’t know. But it’s very, very expensive in tablet form, so obviously money does, money obviously comes into it, so that’s why it’s done as a intravenous one. But [sighs] you know, we’ve got to start somewhere and you can only do so much on animals. You don’t ever know what’s, what the human body’s going to do. You know, I look back, when I knew it was a phase 1, and thought of the four chaps that almost died, which was a phase 1 trial*, and thought, “No, you know, it’s closely monitored, very closely.” Because the first two treatments they were taking blood tests every fifteen minutes. It was lots of blood tests so that’s why you were in all day, but very, very closely monitored. And you know, I have been closely monitored. Each time I come there’s ECGs, blood pressure, temperature, urine samples, blood tests.

*FOOTNOTE' Anthea is referring to a Phase 1 trial at a commercial research unit based at Northwick Park Hospital in 2006 when several healthy volunteers became extremely ill. Early phase studies are carried out precisely because we need to find out about possible risks and side effects before giving the treatment more widely.

By the time a drug reaches Phase 2, researchers will know more about it. In Phase 2 the aim is to test the new drug in a larger group of people to better measure safety and side effects, and see if it has a positive effect in patients. Sometimes Phase 2 trials may be randomised, but sometimes not. (See ‘Feelings about being allocated (randomised) to a treatment group’).

Julian joined a Phase 1 prostate cancer trial hoping it would benefit him, but also to help find...

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Age at interview: 61

Sex: Male

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I think it was the idea that I should go for the treatment that was most likely to benefit me, and so the - there was also an element of sort of scientific curiosity. I was quite keen to take part in an experiment, an interesting experiment, and of course pleased if there was benefit to other people. And as time goes by and as I am stable on this drug I’m more and more thinking about that aspect of benefit to other people, in terms of finding out what the long term consequences are of the drug. So if the consultant put it to me that maybe I’d be on the drug so long that all the cancer cells were eliminated and I need no longer continue with the drug, I’d be inclined to say, “Well, I think I should continue, because then we’ll find out when the drug is safe in the long term.”

Do you know how long they’re, I mean are they just going to give it to you indefinitely at the moment. Is that the plan?

That’s the plan at the moment, yeah.

Okay, yep.

Yeah.

And I think you said the trial is now finished in the sense that they’ve recruited everyone.

The phase 1 trial is complete and so they’re not recruiting for the phase one trial any more.

But there are phase 2 trials going ahead, that is trials which - so phase - I should explain it - a phase 1 trial aims really just to check toxicity of the drug. How big a dose can you tolerate and are there terrible side effects which would discourage you from using the drug? And then a secondary goal of a phase 1 trial is to begin to see whether the drug is effective. But the primary goal is a more basic thing, just toxicity and dosage adjustment.

So that phase 2 trials that are going on now are aimed more at finding out how effective it is in selected smallish groups of patients, and there are several of those trials going on, some in England, some in other countries. More than one drug company is involved, so there are alternative drugs that target this same enzyme. And some of them are restricted to patients with breast cancer, for example, others to patients with ovarian cancer. I am a rarity as a prostate cancer patient with an identified BRCA mutation, and I think at least one of the trials leaves open the possibility of recruiting people like me with BRCA2-dependant prostate cancer.

Tom was invited to join a non-randomised Phase 2 trial of chemotherapy for inoperable lung cancer...

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Age at interview: 63

Sex: Male

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So this young lady asked me if I would like to take part in a clinical drug trial, and she explained the situation. She says, “It might not help you. There’s no guarantee.” She says, “It might help other people further down the line.” And again she said, “You’re a perfect patient for a drug trial, for a clinical trial.” She says, “You’re young, you’re fit and you’re healthy” [laughs]. You know, even I had to laugh – I was young, fit and healthy, the only problem I’ve got is I’m dying from lung cancer, you know.

So anyway, that was okay, so she says, “Right, I’ll phone the trials unit and see what I can do.” So she phoned up, got an appointment there for the following week. Went along and, you know, a medical, a check-up to see that I was okay to take part in a trial, so I was accepted into the trial, which I believe was a phase 2 trial. It wasn’t randomised and as I said, I think I just quite followed, not quite followed the mice, but their tails were just disappearing round the corner.

It was six months of chemo. I was quite fortunate I wasn’t too bad with the side effects. It ended up there was a kind of group of us of four or five. There was about eight people I think getting the drug, but there was about four or five of us always seemed to be at the same point where we were, of getting the course of the drug but we’re at different stages of actual lung cancer. So during the course of that, you know, one was dying, a couple of weeks later another one would die, so it was a case of thinking, “Well, you know, who’s next? When’s it going to be your turn?” so to speak.

He knew he could stop if the side effects became too bad. He felt the staff explained it well,...

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Age at interview: 63

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We were all getting the drug, and there were, the explanations from what I can recall were very good. It was explained again about I can withdraw at any time, if they find I’m having bad effects with the drugs that they’re giving me or, then they would pull me out, because I think obviously they were looking at the quality of life, as well as trying to find out if this drug was effective, you know. I have no complaints about that side of it at all and the nurse, the research nurses who were involved also were very good at explaining, and they would take their time, either if myself, or Helen, or any of the other patients who were there had questions. Some patients didn’t have questions. As usual some people want to know everything and some people don’t want to know anything, some people want to know a wee bit, you know. But because my, I felt whatever was going to happen to me, whatever decisions I was going to take it was going to affect my whole family, so I wanted to know everything, which perhaps maybe made it a bit easier for the medical staff because they knew, “Well, Tom wants to know, so we can talk to him, we can tell him”, you know. But I have no - on recollection the medical staff at that time were very good with their explanations.

Tom, Anthea and Julian all understood that, especially with early phase trials, there are possible risks and side effects doctors may not yet know much about. (See also ‘Side effects and queries’). As with all trials, there was also no guarantee of benefit. But given that they all had advanced forms of cancer and other treatments were either not possible or had stopped working, they were keen to try anything that might help, as well as perhaps benefiting others. As Anthea says below, it was also a way for her to keep positive and feel she was doing something. (See also ‘Reasons for taking part in a clinical trial – personal benefit’ and ‘Reasons for taking part in a clinical trial – helping medical science and other people’).

The doctors explained very honestly their uncertainty about the treatment and the risks. Careful...

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Age at interview: 58

Sex: Female

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They were very specific saying that, “It is a trial. It’s early days. We haven’t got any results”, that a lot of the tests that went along through the process of the trial had been changed, and, and a lot of the blood tests were made more regularly, because it had been trialled in the States and they’d had one person die on the trial through kidney failure because they hadn’t been monitored, they hadn’t monitored the effect as much. So I knew that, and they had, they had made more blood tests available so so they could, they did monitor you very, very carefully, and have been, in all the trials, I’ve been monitored very, very carefully.

And that I think that they have been very, very honest. The doctors have been very honest. You know, that “This, this is a trial. We haven’t got any definite results. It has worked on some people but we’ve, we haven’t got a percentage of who it works on,” [sighs]. And I was told that the chances of the Taxol one working that it was a fourteen per cent chance that that would work. And my attitude was, “Well, somebody’s got to be in that fourteen per cent.” I wasn’t in that fourteen per cent. That one didn’t work. But I wasn’t given any percentages on this one, because it is a phase one trial and I was only number twenty-six. So I knew that it was a very, very sort of new trial, and I was prepared to take that risk.

Anthea was determined to give herself the best possible chance of beating cancer after other...

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Age at interview: 58

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If there was any chance of stopping the disease, or halting it for any length of time, I would give, I would want to give myself that chance. If I said, “No, I don’t want to. I don’t want to do this”, I think I could have had regrets, saying, “Well, if I’d have done that, perhaps I would have still been here.” You know, once you start getting ill, “Well, if I’d have done that, perhaps I’d have stood a better chance. Perhaps it would have slowed down the disease.” And there would have been lots of ‘what ifs’. I’m not into ‘what ifs’. I want to be positive, and I think anybody that knows me will say that I am a very positive person. I’ve had lots of knocks. I’ve had lots of things that I could have said, “Well, why me?” But you pick yourself up, and you’ve got to look to the future. You, you can’t, you can’t look and think, “Well, why did that happen?” These things, things happen in life. “Why me?” I’ve done that. “Why me?” But when I’m feeling, if I’m feeling down then yes I do, do think, “Why?” You know, “Why is it me? What have I done wrong to deserve this when there’s so much going on in this world that it could be somebody else?” But [sighs] when I think logically and positively, then I think, “Well, yes, it’s got to happen to somebody. It’s happened to me. I’ve got to get on with it.” I want to do lots more things in this life and if I’m to do those then I’ve got to take the chance of these trials.

So your main reason for taking part is about taking every chance for your own--

Yes.

--benefit.

Plus the fact it might help - if it doesn’t help me, it might be something that will help somebody else, and if it helps somebody else to save them going through the trauma that I’ve been through, then I’m, I’m happy to do it. If it, if it helps anybody, you know - it might be it might be a friend, it might be a relation, it might be somebody I don’t, don’t ever have contact with or know, or know that it’s helped them - but if I’ve done this and it does help somebody, then all well and good. There’s a purpose to it.

These participants all described their own side effects as relatively mild, though some had met other people in the trial who had to give up because of side effects. All were impressed by the amount of monitoring and tests carried out. (See also ‘Appointments, monitoring and questionnaires’).

Julian describes the high quality of care and monitoring in his Phase 1 trial.

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Age at interview: 61

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But, as I say, I think I’ve just been extremely lucky. And I should also say I’ve been treated extremely well by the hospital that I went to. So when you start the phase one trial you have to go into hospital for a week while they check on how the drug is behaving in your body. And I’ve always found the nurses and all the staff are extremely friendly and remarkably cheerful. That was the impressive thing about this specialist cancer hospital, what a cheerful atmosphere it had, in spite of the fact that people were often very ill there.

So I don’t know if I should say a bit more about the details--

Yeah, and what it was like.

--of the trial and what it was like.

Yes.

So once the decision was made, then there was an adjustment to be made to my previous hormone targeted drugs, so I stopped one of those. I had to wait a few weeks for that to clear out of the system and then went into the hospital for a week, or maybe it was less than a week, anyway, for a few days, in which time lots of blood samples were taken. I was given the drug. The rate of clearance of the drug from my body was monitored. The response of my cells to the drug was also checked with a clever method that involved plucking hair from your eyebrows and then doing some microscopic staining on it to see what how the cells were behaving and seeing if they were responding to the drug in the way that was anticipated.

And so the first day or two blood samples were taken at frequent intervals, every few hours, so you’d get woken in the night for blood samples to be taken. And then, again I forget all the ins and outs, but roughly speaking after that was over samples were taken at rarer intervals. Then there’s a period of a few months when I had to go once a week to be checked, and after that I dropped back to once a month. So every month I go. I have some blood samples taken. I have my heart function checked because I have some heart difficulties, unrelated to the trial I should say. And I talk to a doctor, not usually the consultant, but usually one of his registrars or assistants. I guess I’m an easy case, because I don’t really have any great problems. And the next day I get the results of my PSA measurements, and they’re quite good about telling me what the results of the tests have been each time.

I should say a bit about side effects. So that’s a big issue if you’re in a phase one trial, especially. So the experience, if you - I’ve seen the summaries, descriptions of how the trial has been going so far. There have been some public talks about it by the people running the trial. And the position is that, very roughly speaking, of the people who you would expect to benefit, that is the people who have mutations in either of these two relevant genes, about half show a good response. Most of the people in the trial have had advanced cancer, so they’ve been recruited to a phase 1 trial because other treatments have failed. And that usually means they’ve had quite severe other treatments and quite advanced disease.

So I was peculiar, because my disease had never been very advanced but the two standard treatments had failed in a technical sense, but I hadn’t had anything very severe. I’d just had these hormone suppression therapies.

Anyway, so it’s understandable that not everybody benefits, even if you might hope that they would, because they’d been very ill in various ways, and also some of the drug treatments that they’ve previously had are ones which, as we now know, are liable to lead to resistance to treatment with this particular drug.<

Tom wanted to emphasise the difference between early phase trials in healthy volunteers compared to people who are seriously ill.

Joining a trial when you have a serious illness is very different to 'healthy volunteer' trials....

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Joining a trial when you have a serious illness is very different to 'healthy volunteer' trials....

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Age at interview: 63

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I still speak to people who talk to me and they say, “What did you say? Clinical trial, what is that?” There is a lack of knowledge, a lack of education, perhaps, coming out about clinical trials. One of the things that did surprise me about the episode – what was it - a couple of years ago, at was it Northwhich?

Northwick Park*.

Northwick Park, there was bad publicity about clinical trials at that time, but I think what people have got to remember, and possibly what didn’t come out enough, was the fact that that was not a clinical trial that we are actually talking about today. That was a clinical trial where it was healthy people being paid to take part in a trial, in an experiment, say. That is a totally different thing from if you have an illness and you’ve got the best treatment, but you’ve got the option of taking part in what might be something new. It’s a whole different ball game, it’s a different kind of trial, I believe. I think one of the things that did come out of it I was told that all of a sudden there was many more volunteers to take part in clinical trials. That was a clinician said that, it’s not that long ago in fact that we were talking about it, and he said yeah, the enquiries they got about people taking part in clinical trials rose because of Northwick Park, so which surprised me. But that, like I said, that was a totally different kind of trial and I think there was bad publicity about that, but that’s not the kind of trial, I think, that we are seriously discussing here. But yeah, I don’t know how you, it’s a difficult one to get people - because it’s something that probably people don’t really want to know about anyway, until they’re in the situation. One of the things that clinicians have said to me, and I have briefly mentioned earlier, was the fact of patients asking them questions, and the sort of inclination was that, “Well, patients should know what to ask”, and I said, “Well, with all due respect”, I said, “Patients don’t sit, people don’t sit at home and say, ‘Well, maybe in the future I’ll get heart disease or a cancer, I’d better read up on it now and find out what I’ve got to ask’.” I said, “Come on, join the real world. People don’t do that. It’s when they’re diagnosed, that’s when they go, or if someone close to them gets diagnosed with a serious illness, that’s when they go and try and find out about different things, but they’ve got to be able to get the information.” And I said, “You can help give them that information.”

*FOOTNOTE' Tom is referring to a Phase 1 trial at a commercial research unit based at Northwick Park Hospital in 2006 when 6 healthy volunteers became extremely ill.

‘First-time-in-humans’ studies are carried out precisely because we need to find out about possible risks and side effects before giving the treatment more widely.

A copy of the Inquiry Report of this incident can be downloaded from the Department of Health website.

In Phase 2 trials we can start to get some idea of whether a treatment works for some people, and what kind of side effects they experience. But controls and larger numbers are needed in randomised Phase 3 trials, which compare new treatments with current standard treatments or placebos. Phase 3 trials can also find out more about how common and serious any side effects or risk are. Sometimes even when Phase 1 and 2 trials suggest a new drug is promising, when it is tested in Phase 3 trials the results do not show it makes a significant difference.

People in early phase trials can find it hard to accept this if they have personal experience that suggests the drug has worked for them, as Julian commented.

He can see that often a placebo might be safer than the trial drug. But in his case, he feels the...

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Age at interview: 61

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It’s hypothetical and it’s probably difficult to, to answer, but if you were further down the line--

Uh-huh.

--and this was a phase three trial--

Uh-huh

How would you have felt about randomisation and the possibility of being allocated to a group that might not be getting this particular drug?

Well, knowing what I know now [laughs], I would be very uneasy about being randomised to the placebo treatment, because I think there’s strong evidence the drug brings a benefit which you couldn’t achieve any other way.

But, so if I were to be in a… my sister always made the point that for most trials the ideal thing was to be in the placebo branch of a randomised trial, because then you got very close monitoring from good medical staff and you were likely to do well because of that. And most drugs, trial drugs, didn’t do you all that much good and might hurt you, so [laughs]. However, in this case it’s not like that, I think.

*FOOTNOTE' This raises difficult questions about the level of evidence needed before a drug can be said to work. Julian’s personal experience had convinced him the drug was effective in his case. However, although his clinical team felt the drug was promising they also felt there was not yet enough evidence, so they needed to test the drug further in a Phase 2 trial. Sometimes, even when Phase 1 and 2 trials suggest a new drug is promising, when it is compared in Phase 3 trials with the standard treatment in a much wider group of people the results do not show it makes a significant difference. (See ‘Non-randomised trial designs and other research’ and ‘What are clinical trials and why do we need them?’).

Some people we spoke to had been involved in other kinds of non-randomised study. Pam was given the cancer drug lapatinib which had not yet been licensed for use in the UK. (It was later licensed in July 2008). Women who were eligible could only be given the drug as part of a supervised study, monitoring effectiveness and side effects - an ‘open label expanded access’ study. (‘Open label’ means both the patient and doctor know what the drug is that is being taken).

Pam could only get lapatinib through an open-label expanded access study. She'd have joined a...

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Age at interview: 70

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If - this was an experimental treatment and you could only get it if you took part in the trial. If this had been set up as a randomised trial where you might get it or you might not, how would you have felt about taking part in that?

Oh, I would have gone for it definitely. Oh yes. If there was some treatment available which would be helpful, then I would definitely take it.

And how would you have felt if you’d been randomised to the group that didn’t get it?

Would I have known that is was the group that didn’t get it?

You might or you might not - depends whether the trial is blinded or not.

Mmmm, [sigh] well, I suppose it’s a bit like entering a competition and not winning. I’d have felt, “Well, that’s just the way the cookie crumbles.” It would have been helpful if I’d had the trial. If I couldn’t have the trial, then hopefully there’s a different treatment that could deal with me. But with this particular trial it’s been going on for a long time, and it’s very well established, and it will eventually, hopefully sooner rather than later, for the benefit of other people in my position, be approved by NICE [National Institute for Health and Clinical Excellence]. And hopefully it will be available in hospitals, so people don’t have to go through that terrible, terrible stress of deciding to pay for a treatment and then being landed with the whole of the costs of the NHS, which is diabolically unfair. Because when you have cancer it’s very stressful, you don’t need the added stress of the financial worry. That is really a life sentence. I feel that if the people who are in charge, all the bureaucrats, if they were in our position they wouldn’t behave like that. And I really feel that so strongly. And if there was something, you know, one could do about it, like petition or something - I know there are doctors who are very involved and being very cross about it as well, and doing something about it.

I suppose that what they would argue is that they don’t yet know whether it’s safe and whether it works, and that that’s what this trial is trying to find out before they make it available to everyone.

Yes, I’m sure that’s right. But it is, it is available. It’s available in America, and the Americans, of course, have a very good track record of cancer treatment, better than here, as I understand it.

Mmm, so there is some evidence actually over there?

Yes absolutely, absolutely. And also I think with this particular hospital I’m at and with the consultants I’m under, they wouldn’t recommend anything that wasn’t appropriate. Because there’s another thing - people can take the same drug but the side effects can be different, because everybody is different. People can react differently. The way the drug reacts on your cancer can be different, one person to another, so that’s another thing. It’s all very complicated.

Footnote' Licensing for use in the UK was approved in July 2008 shortly after Pam's interview.

Sometimes with diagnostic or surgical procedures non-randomised studies are done to check if the procedure is safe and effective.

Judith was asked about a trial of a new fibre-optic camera to be used by the anaesthetist during...

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Age at interview: 45

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Well, that was on the morning of my operation. I went in the night before. It was a little bit more vague, because it was just, the ward was hotter than Hades, it was just so hot. And I hadn’t slept well and the bed was uncomfortable. And they’d said, “You mustn’t have anything to eat or drink after midnight.” And then in the morning it turned out I was third on the list, so they said it would be about half one by the time I had the operation [laughs]. Then the breakfast trolley came round and I thought, “Oh God.”

And I had a headache. And then she, the, I think she was a registrar anaesthetist suddenly appeared and said that they were doing a clinical trial on a new device to, it was a camera to put down your throat to see whether, the improvement in sore throats afterwards. And also it gave them a better view of the larynx. And so I quickly read through it and said, “Oh yes, that’s fine.” Because I thought, “Well, if I’m under an anaesthetic anyway, frankly I don’t really mind.” And if it’s something that gives them a better view of everything, then if there was any problems anywhere they would, they would be able to pick it up. So again it wasn’t a huge decision to make. But she did go through it all and there’d already been a study in Pakistan and Gloucester [laughs], which seemed odd, but yes, and she said that it, she’d, so far it seemed that things were improving. But it just seemed such a minor thing that frankly I didn’t mind at all.

What about the timing of that? Because that sounds like you were feeling quite vulnerable already at that point. Was it a good time to raise that or should it have been discussed at a different point?

I think, I think that was fine for what it was. If it had been something, you know, more, that I felt would have had more of an impact than that. But like I say, if you’re under anaesthetic anyway it can’t be that different to what they’re already doing. They’ve already done it on eight hundred people so, yes, it was fine. And then she came after the operation when I was just coming round and said, “How’s your throat? Is it sore?” And it wasn’t sore, so that was it.

So that’s partly what they were looking for?

Yes.

What else were they looking for?

Because they said it gives them an improved view of the larynx and the throat and that type of thing.

And are there any other safety concerns that they’re testing while they’re doing this?

I don’t think so, no. I think it is just a new piece of equipment that they’re trying out.

Kate took part in an experimental non-randomised study of a new type of hip surgery. It is only...

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Kate took part in an experimental non-randomised study of a new type of hip surgery. It is only...

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Age at interview: 38

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I ran the London Marathon in 2007 and either the repetitive motion of running created a lump on the neck of my femur which damaged the cartilage in the hip joint, or the lump was already there and it was the increase in running miles that led to the damage. The surgeon suggested that if I were a couch potato who wasn’t particularly active, then it probably wouldn’t bother me. But because I like to keep fit and do lots of exercise it was impacting quite heavily on my day-to-day-life. I wasn’t able to run any more. Cycling was awkward. And I commute by bike, so it was really having quite an effect. So they decided that they should look at the surgical options. And it wasn’t the same sort of situation where I was randomised to either receive the surgery or not receive the surgery. It’s a new way of doing an old surgical technique. They used to basically cut you open and dislocate your hip joint to get into the hip, to tidy up the mess of the cartilage. Instead they’ve started doing this by arthroscopy. So they make the three little incisions near the injury, and they insert a camera into one, and then the other two are used for inserting tools. And they basically watch what they’re doing on a TV screen. And so they were able to remove the lump that was there, and they were also able to cauterise all the damage that had been done to the cartilage, without actually having to cut me open. You know, it’s just three little holes. I was in traction for the surgery as they do have to pull the bone out of the socket so they can get into the joint. But the device that they use, I think it means the surgery lasts for an hour and a half and you’re in traction for about half an hour of that, whereas previously you were in traction for about three hours. So the damage to the surrounding tissue of being in traction is lessened under this new technique.

And I met with the surgeon and he saw the tests that I’d done and all the results, and he did some functional tests and sort of moving my leg around, and he could feel there was definitely an impingement in the hip. So he told me my options and he said that I was an ideal candidate for this new type of surgery. And he explained to me that it was new, experimental, hadn’t been approved by the government as yet, but the government were interested in approving it. So NICE, the National Institute of Clinical Excellence, had published a whole lot of information for both surgeons and for patients, explaining what the possible risks were, what the benefits were. And so I had to go away and read all that information and come back to him with any questions. And then if I was happy to go ahead with it, I signed a consent form. And I went ahead.

The way I understand it is that they’re going to carry out a certain number of operations and monitor the outcomes. And if it’s shown to be of benefit then they will make this operation available widely on the NHS. Currently you can only get this operation if you agree to take part in the study.

Do you know if they intend to make it a randomised controlled trial before they get to that point?

I don’t know, I don’t know. Yeah, because there is potential for bias, you know, obviously if they only choose the easy cases it is more likely to be seen as successful. So mine I believe was quite straightforward. It was quite a small lump.

And, you know, if I hadn’t been so active and so keen to be active again, then it probably wouldn’t have bothered me whether or not I had the surgery. So I guess my case was an easy case. And if they just choose people like me to put forward then it’ll look like it’ll be highly beneficial [laughs], because it certainly worked for me.

Kate was unsure whether this type of surgery would eventually be tested in randomised controlled trials. She wondered if otherwise the type of patients selected might make the results look better than they would be for a wider group of people.

Unlike drugs, the success of a surgical intervention depends on the skill of the doctor as well as the type of procedure, so further studies may be needed to check that individual surgical teams have acquired the necessary skills to carry it out. Shirley was asked to take part in a study of a technique called sentinel node biopsy to check whether breast cancer has spread into the lymph nodes. The sentinel node is the first lymph node to be affected. If it can be found and removed, and is not cancerous, then other lymph nodes will not need to be taken out, avoiding some unpleasant side effects. The technique has already been found effective in randomised clinical trials, and many hospitals now want to offer it to their patients. But before they can do so the surgeons must demonstrate they can find the sentinel node accurately. The study Shirley was asked to join was part of a national programme to ensure local surgeons could perform the procedure and needed 30-40 women to join.

The surgical study Shirley was invited to join was to check that local surgeons could perform a...

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Age at interview: 72

Sex: Female

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The result [of a breast core biopsy] was inconclusive still, and I was then booked in for wide excision on a wire guideline, which happened on October 1^st …I had to go in and have a sort of scan and the wire inserted… And I was in and done terribly quickly, and out the next day. And it was actually remarkably pain free and good, because it was only a tiny little bit, I think, removed.

So I was home on the third. I went back on the 18^th to the [specialist hospital], saw the second-in-command again, and the result was positive. And having been told it was positive I was sort of - it would be unkind to say bombarded, but I was asked more or less immediately if I’d take part in the Sentinel Node Trial, and I said, “Yes”, because it seemed pointless not to and it might help other people etcetera.

And he said, “Do you mind? We have to get forty people into a trial, and discover if it’s going to be a good thing just to take out four, or up to four [lymph nodes].” They might get it down to just one, I think. And I didn’t feel that there in fact was any justification to say no, because I was going to have to have it done anyway, and if it helped others, it was, you know, why not?

The sentinel node biopsy involved little apart from being injected with a dye which showed...

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To have it done, one had to go in and have a dye put in. And the dye was, I think, injected. I think it was injected during the operation which pinpointed the nodes. And amazing dye. I think the blue’s only just gone [laughs]. And it didn’t hurt at all.

Could you see it through your skin, you mean, the dye or?

Oh yes, I was completely blue for months afterwards [laughs].

[Laughs] I thought when you said that you meant blue as in bruised. I hadn’t realised you meant the dye?

No, no. The first time, sort of after the core biopsy, it was black and blue from awful bruising, and the dye just was remarkably good dye [laughs]. And it lasted for, I suppose, almost sixteen months, fourteen months.

They were doing it in order to save people later on who sort of had the same thing. Because I believe that the normal thing is to take out all the lymph nodes, and you’re going to get sort of horribly swollen arms and water retention and etcetera etcetera.

I think they were attempting to achieve a reduction in having to take out all the lymph nodes, with all the possible difficulties I gathered might happen. And that by taking out only four, it would make life a whole heap more comfortable and easier for patients… I think it’s good, and much, much better for people if it’s only the one, obviously.

And in your case it was an operation you were going to have anyway.

Yes, completely. There wasn’t any options at all. And luckily, I think, because

I suppose one would have gone on thinking, “Have I? Haven’t I? Has it got to a node?” And it was immensely reassuring to be told it hadn’t.

It didn’t in fact involve me in anything that was not going to happen, and if by having done it, basically, if I’ve helped other people in the future, and particularly with daughters, daughters-in-law and grandchildren, you know, if it benefits any of them it’s a good thing. And others of course [laughs].

And in your case it wasn’t, there wasn’t any question of it being of benefit to you personally.

Absolutely not. No.

If you’d been asked to be in a trial where they were comparing one group against another and you wouldn’t be able to say which group you’d be in, they’d just randomly put you in one, how would you have felt about that?

I think differently, in fact, because I suppose there’d always have been a sort of feeling at the back of one’s mind that, “I wonder which? And if I’d had the other it would have been better or--” Actually, I don’t think I’d have liked that.

Last reviewed September 2018.
Last updated July 2011