In the event I realised that I was in fact on the placebo, because there was no possible recognisable benefit derived during the many months on which I was on this trial. And I suppose one can say that the only beneficial side effect is that after the trial per se had finished, all persons who had entered into the trial, whether or not they had been on the original drug or on the placebo, were for several months provided with the actual drug itself, prior to its having come onto the market.

When you started to think you were on the placebo, did you raise that with anybody running the trial?

No. It was totally pointless. There were regular questionnaires which were required to be completed after each session, after each – I forget for how long it went, I forget whether it was a month or two months or what will you. And these questionnaires included whether there was any noticeable effect, what one’s psychological view was, whether one felt – how one felt – whether one felt that one was losing one’s manhood, one’s masculinity, all sorts of things of that nature. They were very interesting psychological questions actually. But it didn’t worry me in any way.

And did they actually confirm to you afterwards that you were on the placebo? Or did you never ask, you just assumed?

It was proven to me when I was given the real drug, because that did have an effect [laughs].

[laugh] Right, yeah, fairly conclusive proof then. When you realised you were on the placebo, did you think about pulling out, withdrawing from the study?

Oh, not at all. If I’m part of a clinical trial I know that it, one has to go ahead with it. One undertakes these things seriously. it’s not a lightly taken decision.

it’s quite important if one is doing a test to see to what extent we know that a particular drug has an impact on the people who are taking it, and you must have a control group who are given a placebo, who are given something other than the drug, against which to compare those results. The fascinating thing of course is the number of times that people on the placebo have satisfied themselves that they have received some beneficial effect.

And they told you, you’d been taking the tablet, not the placebo?

Later on when we finished, when we finished everything.

Did you notice any difference?

Not at all, not at all, not at all.

Do you know what the results of the trial were? Did they–?

Well, they, I suppose they sent us a letter, probably the standard one, quite happy with the results of the trial. And besides thanked us or thanked me, thanked me. They told me, By the way you have been given a, a proper tablet. You’re one of the, the lucky persons Anyway but I can’t say that it was better for my condition, or worse. I never had any difference in my symptoms with this new tablet.

Did they take regular blood tests?

As well, yes. That was part of the trial after – twice, every two, every month we had to go back to the hospital for a blood test. And with a special recommendation, any problem we had to get in touch with the – we were given a telephone number, which – but in my case and I suppose the rest of the other group we didn’t have, in that particular research we didn’t have any problem at all.

But it, presumably they thought it worked for someone if they —

Yes, probably. But in not my case. It was —

And it didn’t make any difference to your blood glucose?

No, no, not at all. No, no, no. No, no, no. So I consider myself, I talked to my GP and he, he said, Well, probably it’s another tablet, but similar to the one you are taking now So probably he, I didn’t ask my GP which kind of tablet was it. But we were given enough information in general from the research. So we accept, because we knew the situation that may happen. We were aware and we were told about that.

One thing that I’d like to go back to is that this was going to be a placebo control trial–

Yes, yes.

— and what your thoughts were about being randomised and perhaps ending up in the placebo group – would that have mattered to you?

I thought about it and I think the answer, it didn’t matter to me from the point of view of taking part in the trial. I think it would have been interesting to me to know how I would react in that situation, because they do say that you are – how shall we say – influenced by, you know, your mental state at the time as much as anything else. So I’d be interested to know whether I was one of those people that was influenced or not. So it didn’t concern me, and I did think about it and I made a positive decision to go ahead regardless.

And you wouldn’t have known during the trial whether you were on the placebo. Do you know if they’d have told you at the end?

They would have told me, I think when I asked a question of the doctor at the time, they would let you into it at the end, obviously not during the course of it.

They would have told you. I would like to think I would have been aware [laughs], because I actually asked the question what happens, you know, if things weren’t happening, because, you know, it’s these moments when they come you want to take advantage of them [laughs]. And if it wasn’t working then I’d want to take some other form of help and basically they said you could drop out of the trial at any stage, and so that satisfied me on that particular question.

What kind of trials have you been in, what kind of treatments have they been comparing, can you remember?

Well, what it is normally, it’s some sort of a tablet. They said, Well, we’ve got this new tablet, so we’ll try it out As mine is a mental problem, it’s normally done by a mental hospital, or an organisation like the Institute of Psychiatrists. They’ll advertise and I go along and sit for interview and they will say to me Well, this is the tablet, these are the side effects Some will say, No, you will be given this tablet Some will say, No, it’s a blind study. You won’t know whether you get the actual tablet or the placebo I wasn’t very keen to take the placebo, because already I’m suffering. I don’t want the ruddy placebo. Then I shall tell them quite up front. No, if you’re giving the real tablet I will take it, but if you’re going to give me the placebo, goodbye I’m only volunteering because I’m suffering. I’m not volunteering for the money.

So have you ever taken part in a trial where there’s a placebo?

Oh, whenever they told me I just walked out. I’ve only taken part in trials where they said they’re going to give me the actual medicine.

I had a lumpectomy, had the bit taken out, and then I was asked if I would like to go onto a clinical trial. I’m strongly in favour of clinical trials. I think they’re the only way you can ever find out what works and what doesn’t, and I think it’s very important. So in theory I was strongly predisposed to do that, would want to help in any way I could. But when it was explained to me what the trial involved, I had deep doubts about it. The trial, basically I was being asked to be randomly put into a group of people who would not have tamoxifen, which was an anti-breast cancer drug, or into a group that would have tamoxifen, and it would just be random. So if I agreed to go on the trial I might well fetch up in the group that didn’t have it. I’d have a placebo, I’d have a little white sugar pill, and I would never know whether I’d actually had the tamoxifen or not. I knew a bit about tamoxifen and a bit about breast cancer, partly because it had been in my family. And anyway it’s the sort of subject that I was writing about and interested in. So I did a bit of investigation, rang round a few people, talked to a few people. Tamoxifen had already been widely used. There had already been a very large trial in the United States, which had shown that it seemed to have a very strong positive effect. It seemed from this large trial as if it might improve your chances of not recurring, not getting another episode of breast cancer, by about 30 per cent, which is, you know, a very strong positive effect. So I then became very worried at the idea of going into a trial where I might not be given it, and I might never know whether I’d had it or not. So I talked to the doctors about it and they said, Well, the trouble is, you know, we do need more research. We do need more evidence to be absolutely sure. That was American research. We need British research. We need to find out more details But when it came to it, I felt that we already did know pretty much. And every doctor and other people and other sources I looked at, everybody was really positive about tamoxifen.

That particular hospital already had quite a lot of people on it. And I thought to deny myself tamoxifen for the sake of a, you know, just a rather academic study, I thought that the disbenefit to me would be much greater, really, than the extra little bit of knowledge that would be acquired on top of the knowledge they already had. I felt badly about it because, you know, obviously we need more and more knowledge as time goes on about exactly what drugs work and how well they work. But I just felt on this occasion that we already knew a lot.

Oh, if tamoxifen had only been available as a clinical trial I would certainly have gone for it in the hope that I might have had it. Of course I probably would have been more nervous, because we also at that early stage wouldn’t have known whether or not it might have other alarming side effects. But I think if the doctor had said, Well, you know, we have high hopes of this dru I think I would have gone into it, though I think it does make you uneasy not to know, and never to know, whether you had a drug or not. But certainly if that had been your only chance, I’d have taken it.

I feel that the placebo effect is so well understood now. We all know. We are all easily fooled [laughs]. And, and doctors make us feel better, and being given pills and treatments make us feel better. And whether it’s some homeopathic bit of nonsense or whether it’s a, a genuine drug there is that plus effect. And I accept that about myself. So I would, I wouldn’t be worried about the idea of taking a placebo. I suppose you always feel uneasy about whether you’re missing out on a drug that might do you good. Or alternatively of course [laughs] you might be feeling worried about taking a drug that nobody knows quite yet what its side effects might be. I would want to look into it very carefully. I don’t see anything wrong with the principle of it, but as long as people, patients really, really know what they’re getting into, understand why, and think that the trial is worth it, that the knowledge they’re going to get is worth either giving or denying you the chance of a particular drug. And I think in the end that’s something you have to weigh up carefully. I think I would suggest all patients always try and get a second opinion, go back to their GP, talk to somebody else, these days, you know, look up on the Internet for all of the valid information from responsible sources that they can find. And there is a lot of information around now.

What would you think about placebo trials? Would you be willing to even think about it?

Well, my cousin’s husband has got MS and it’s very, very progressed now. But I know he’s been on, he was on a clinical trial and he was on a placebo, and I think he was really miffed about that [laughs].

That’s quite interesting, so that experience in your own family might make you think–

Yeah.

–differently about it?

Yes, it would. It would. I don’t think I’d like it at all, actually.

That’s interesting. Even though you’re, I mean most of the, what you were taking part in research for was to benefit other people really rather than benefiting yourself, apart from the two weeks, obviously.

Yes.

But there’s something different about a placebo trial for you.

Yes, definitely, definitely. Especially if cancer is involved. I think that, I think that’s an issue as well. If it was to test in-growing toenail creams or something like that then, you know, or something – I mean it’s very painful but, you know, something that wasn’t life threatening. But as soon as somebody says, Cance it changes everything. You just, it’s like having an intruder in your house, you just want it gone and out and finished with, and I just want to get on and not have it. I mean, I’m not in a state of complete panic or anything like that. I have complete confidence that this will sort it out and it’ll be gone. But then again there’s so many different types of cancer, and I know some people are on this watch and wait’, so maybe, maybe that would be different.

If I was experiencing a particular condition, is there anything I wouldn’t want to get involved in? o, there isn’t. If I’ve got the condition and I want it to be treated… mind you, I’d have to be absolutely convinced, like with an aneurysm, I’d have to be convinced that it was going to treat me. I wouldn’t want to just sort of sign up for it because, you know, it was going to pay me £20, or something stupid like that. I would want to – it’s the quality of the care that I would get that would be vital, and the background knowledge that I was going to be given that would be vitalespecially for aneurysm.

So for instance a placebo-controlled trial, how would you feel about being offered that, where you might be randomised to getting a placebo or you might get the treatment?

I wouldn’t want to do that – if it was so vital that I had the treatment. For – I can’t even think in what context I would, it would be okay to have a placebo rather than the actual product, if it was going to work. Because if I, even if I’d scratched myself, I wouldn’t want to have a placebo dressing and then someone else gets, you know, an all -singing all-dancing dressing that heals them in two days, or something like that, so.

I suppose the problem with trials is by definition you don’t know if the intervention is actually going to be any better than the placebo. But there’s something that worries you about
There is, yeah. Because, I think, of the fact that I’ve had this neurosurgery*, I’m thinking, you know, I wouldn’t want to be involved in anything that was potentially – I mean, okay, fine, if all the products are going to sort me out, or potentially going to sort me out – mind you, placebo might as well, mightn’t it, because it might just sort of, you know, the fact that you’re taking something or you’re sticking something somewhere might just be the thing that you need to get you through. I don’t know.

But for that to work you’ve got to believe it’s something that’s actually an intervention?

Yes, but as well I would – would I know the difference? I probably wouldn’t know the difference, if I wasn’t told it. I’d think, Oh this, you know, I’ve got to take it td [three times a day] or whatever, and that’s it, and I’ll do it. You know, I’m very regular with what I do, you know. I’m very sort of emphatic about times and all this sort of thing, and if I thought it was going to work I’d blooming take it.

* FOOTNOTE’ Jenny has recently had surgery for a cerebral aneurysm (an abnormal bulge in an artery in her brain).

Were you worried about being given the placebo and not getting the real drug?

Not at all, at that, at that time. Later on, one or two years ago, perhaps you know, there was an ex-, a research in London, I think it was in London, and some people, they were affected for some experimental tablet. It was a famous case.* So since then of course I, I was more comprehensive, more aware that I have to be, to be careful if I participate in other, another research. But until that moment I trust completely. I think it was a gen-, a mistake, understandable, whatever the result’s awful. But I suppose it’s part of the research in general, mistakes, everybody can make mistakes.

So in a way that’s made you more worried about the thought that you might get a dangerous drug rather than getting a placebo? Because sometimes people —

Yes.

— worry the other way, that they’re not going to get something that might help them.

Yes. I suppose so. And, what can I say? I thought at the beginning when this problem happened with the mistaken, mistaken tablets, medicine they were giving to some people, well, they, I do remember that those people were in hospital for the trial, I think for two or three weeks, some time. But I’ve never been in hospital for a trial, just some couple of hours or whatever. Or only hospitals that’s in particular areas, not to stay for more than four hours, to say. And, and the, the only once, the time that I participated in this research with tablet, I suppose I was completely, I trust. I trust, I trust completely the research. But, as I say, with this other case later on I am, I could be more aware to make sure. But at the same time I’m sure the, the people who make, organise the trial or the research, they have to be more careful because it was a, this situation affected everyone, the people that could participate in the research and the organiser as well. Loss of trust, something like that. So, but in general I do support research, investigation, whatever.

And the idea of being randomised doesn’t worry you?

No, no, no, not at all, no.

*FOOTNOTE’ Sergio 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. Most of the people we talked to took part in trials of treatments which had already been tested in humans before. A copy of the Inquiry Report of this incident can be downloaded from the Department of Health website.

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?’).