Clinical Trials
Different types of clinical trial
Clinical trials cover a broad range of different types of research (see also our introductory explanation in ‘What are clinical trials and why do we need them?’) Trials are often used to test new medicines or vaccines but can also be used to look at new combinations of existing treatments or to test whether giving a treatment in a different way will make it more effective or reduce any side effects. Here Phil describes a trial comparing different medications for treating high blood pressure and cholesterol, and Wendy describes a trial comparing different chemotherapy regimens for bowel cancer.
Phil explains what the blood pressure trial was comparing and how people were allocated at random...
Phil explains what the blood pressure trial was comparing and how people were allocated at random...
SHOW TEXT VERSION
PRINT TRANSCRIPT
Well, there were two different types of pill they were trying. There was the old type, which is a beta blocker, and some of the newer pills, I think they’re called ACE inhibitors and calcium blockers. And they were trying to see the difference between the two types, whether one was more effective, whether the new type of pills was more effective than the old type. And the other thing they were doing was looking into how important cholesterol was, controlling cholesterol. And that I’d be on a, whatever combination of pills plus a placebo, which may or may not have been a cholesterol-lowering pill. As it turned out, it was, and my cholesterol came right down. So that was another, another benefit.
So there were two sets of comparisons --
Yeah.
-- going on?
Yeah.
So the first one was comparing just the hypertension treatments?
That’s right, yes, yeah.
And the second one was cholesterol?
Yeah.
Okay. Did they, how did they explain which group you were going to be put in and how that was going to be decided?
That was totally at random. It was just like a, put your name in a hat and whichever one came out that’s what you’d be doing.
You’re told right at the outset that if you’ve got, if there are any problems, let them know straight away, or after the six-week period and you’ll be taken off.
They, they wouldn’t let you do anything that would endanger you at all. You know, your life wouldn’t be at risk. So I never felt worried unduly, you know. I wasn’t, I was quite confident that I’d be, end up on a right, right combination, yeah.
What do you feel about the, the kind of information that you were given at the time?
Well, it was explained basically what the trial was about, and the type of pills they were. It was explained to you that all the, the pills being used were all tried and tested. They weren’t completely new. You weren’t like a guinea pig to that extent. You know, the main thing was to compare the newer type of pill with the old beta blocker, and to see what sort of results they got from that, plus the, what effect the lowering of cholesterol had. Because apparently, although they knew about, about the effects of cholesterol, it had never really been properly tested in conjunction with blood pressure reduction. So, you know, the whole thing was a new, new experiment, but it was all done with using drugs that had been used at least, you know, for some time. So I was always quite happy. I always felt I was in good hands and never really worried at all, you know.
Wendy was asked to take part in a year-long trial of chemotherapy for bowel cancer. She thought...
Wendy was asked to take part in a year-long trial of chemotherapy for bowel cancer. She thought...
SHOW TEXT VERSION
PRINT TRANSCRIPT
Just before Christmas I went to a major hospital away from where we lived, and I had an appointment there to see one of the oncology team. I also saw a professor, who was leading a trial. They explained about the facts up until - you know, went over all the surgery I’d had, reiterated all the things the surgeon had told me, but added into that the news that out of the fourteen lymph nodes two had cancerous activity. I didn’t know at that stage whether that was good, bad or indifferent, but I wasn’t, you know, I wasn’t very happy about that. Based on that, that’s why I was offered the chemotherapy, because there is a strong possibility if it’s reached the lymph nodes it’s on its way elsewhere. So I was then told the, the plan was to have six months of chemotherapy. Alongside that I was offered the chance, if I wanted to, to go into this clinical trial. And whilst I’d been waiting in the waiting room I’d read up about clinical trials, so I knew exactly what they were talking about. I asked a few pointed questions. It was all taped, by the way, so we could take the tape away, listen to all the questions, listen to all the things the professor had mentioned. We also had it all in writing as well, so we could read it. Which was really, really helpful, because I asked a friend who’s a doctor of our, a doctor friend of ours to read through it.
She did some research. We researched it and we had about, I think, two weeks. We went back to see him, at which point he wanted an answer as to whether we were going to go through with it or not. We were explained to us that it’s a six-month chemo anyway, but the trial would be a twelve-month trial. So for the first six months I’d be on both, for the latter six months just the clinical trial. They explained all the side effects and everything. And after much discussion in the family, thinking about the impact on the children, and if all these side effects did materialise what impact that would have on us as a family with no extended family to call upon, I thought it was too selfish of me to ask for that. But my children said, “Look, Mum, we’d put our lives on hold for a year if it means that you’re going to be better at the end, if you’ve got a better chance of survival.” So I ended up deciding to go into that.
At that point we were told it’s 50% of the people that are picked go on the trial, 50% don’t. It wasn’t a placebo, nothing like that. You’re either on it, or you’re on the trial but you’re not having the drug. They wanted to compare the two. It was a drug that has been used very, very successfully in advanced bowel cancer patients and they now want to trial it to see what the implications are of it on other bowel cancer patients.
FOOTNOTE' Randomised trials are done when we don’t know which treatment is best, in other words when the relative merits and disadvantages of different treatments are uncertain. Of course trials are done because there is a possibility that a new treatment will be better than the standard or control treatment, and it may have already been shown to work for other conditions or groups of patients. However, trials are just as likely to find that new treatments are no better, or indeed worse.
Some trials are designed to try out ways to prevent a particular disease in people who have never had the disease, or to prevent a disease from returning. The treatments being tested in these types of studies can include vaccines, but may also involve drugs or dietary supplements such as vitamins and minerals. Amanda took part in a trial testing whether yoghurt could help prevent irritable bowel syndrome (see also ‘Blinded trials’). She is a public health doctor and has also developed proposals to test the effectiveness of selenium in preventing cancer.
Amanda describes a double-blind trial of pro-biotic yoghurt to control irritable bowel syndrome....
Amanda describes a double-blind trial of pro-biotic yoghurt to control irritable bowel syndrome....
SHOW TEXT VERSION
PRINT TRANSCRIPT
And then the last trial was very recently, which is, I have irritable bowel syndrome, not - it comes and goes, I mean, I can be perfectly normal for months, and then I can get attacks. And so there was a local researcher in the university I was working who was doing a trial of pro-biotic yoghurt versus plain yoghurt, not pro-biotic yoghurt, to see whether it controlled the symptoms of irritable bowel, and I was eligible and I signed up for it and it required you to drink, to eat two cartons of yoghurt a day for six months, I think it was, or - I can’t even remember. It was a long time, I remember feeling quite yoghurted-out by the end of it. And you’d just pick up your yoghurts in boxes with a number, you know, LR0911 on the top or whatever it was, and had to fill in a diary about how you felt. And I was interested in doing this trial because I’m interested, I’m actually interested - I’ve just switched jobs - I’m interested in the public running trials on themselves, you know. So people who like myself were interested in generating knowledge, we’d get together and we’d do it. And I just wanted to see how easy it was, and actually it’s, it’s quite difficult. You forget to fill in the diary and you think, “Oh, what was it last Wednesday?” or you scribble it on a piece of paper because you don’t have your book with you because you’ve gone away and, you know, you really don’t feel like a yoghurt but you have to eat it, and I was very compliant, I’m sure I was much more compliant than most people, just because there’s part of me that’s a bit of a researcher and so it makes you realise just how much noise or rubbish must be put into trials really because you’re thinking, you know, “What was it?” And then I’d think, “Oh, well, I remember” and then I’d find my bit of paper and it wasn’t true. Then I’d have to go back and change it, you know. So, but if I hadn’t found the piece of paper that misinformation would then have been put in. You had to, how many stools did you pass and what, how firm were they. There was a little chart where you had to categorise your, [laughs] your stool and this sort of thing. And actually during the whole period I was asymptomatic, and I was actually quite interested in how the research nurse dealt with me, because she, I think she was frustrated because there were no symptoms.
And also I was neither better nor worse and so the other half of her was wanting me to say I was better, when I didn’t necessarily feel I was better, I just felt I was unchanged. And I felt people were wanting a certain result, I really did get that impression, so I thought it’s, you know, it’s really important that staff are blinded as well. They can’t, you can’t help but want a result, that what nobody wanted to hear was, “Well, I’m just the same. You know, I haven’t noticed any change at all”, you know, so which is, was my situation. Later they told me that I had been on, on the pro-biotic yoghurt, which was a good thing because I was asymptomatic and I remained asymptomatic. So, who knows? Well, I say it was a good thing, but who knows whether that was, I haven’t seen the results of the trial yet, so….
Very difficult isn’t it? Particularly with those self-report kind of conditions--
Yeah,
--where there’s no sort of objective kind of, you know, like a tumour size shrinking is in a way easy to measure, isn’t it, but something like that?
I really think these things have to be blinded from staff as well, because you can’t help, I mean, if you’re running a trial, I want to run a trial, you can’t help wanting the result, because you, you wouldn’t be doing the trial unless you believed your intervention was effective, really, I think. Although they say you’re supposed to be in equipoise*. I don’t think you would ever begin a trial unless you actually believed there was good grounds to think that this will work.
* FOOTNOTE: ‘Equipoise’ means a situation where clinicians are uncertain which treatment is best – literally it means they are balanced equally between them.
* FOOTNOTE: ‘Equipoise’ means a situation where clinicians are uncertain which treatment is best – literally it means they are balanced equally between them.
She has been trying to set up a trial on the internet to test if selenium supplements prevent...
She has been trying to set up a trial on the internet to test if selenium supplements prevent...
SHOW TEXT VERSION
PRINT TRANSCRIPT
I’ve actually put together a protocol for a trial that we want to do on the internet that’s looking at selenium as a food supplement, as a tablet, for preventing cancer. Now the observational data is quite powerfully suggestive that it’s preventive of cancer, but we know from lots of studies that things that look good, like HRT for women and preventing breast cancer, when you actually did the trial they’re not. So I think researchers have to be sceptical, but you wouldn’t even start thinking about it unless there was some reason to think it was doing good.
I mean, I have actually shown my trial proposal to colleagues [laughs]. One colleague, who’s a researcher in this building, actually turned round and said, “Well, I’m going to take selenium. You know, until you get the results of this trial this is such powerful evidence.” But it could easily not be true. We need to do the trial.
Only I heard yesterday that we didn’t get funding for that either. And the evidence base is so powerful for that, I’m not quite sure why. They won’t tell you why, but we will pursue that one because it’s a really, really important trial.
So with that one you would have recruited through…?
The internet, we would have just got the people. We’d say, you know, “Here’s a food supplement, you know, you’ve got a 50% chance of getting that or something that looks identical but which is inactive, a placebo, you know. Here’s, this is why we’re thinking of doing it, this is why we think it protects against cancer.” People would sign up, we’d either mail them the drug, the tablet, which is just like a vitamin tablet, or the placebo, and they’d take it. And the thing is it’s a very simple trial to do because we can just flag people for death or cancer in registries, in fact people don’t have to then do anything else. We’d like them to keep coming back on the internet and giving us information about their health, but if they don’t, if they never reappear again, we’ve still got their outcomes about whether they get cancer or die.
Drug trials, especially in cancer, are probably the most familiar type of trial for many people, but clinical trials are not always about testing medicines. They can be used to test ‘interventions’ aimed at changing a person’s behaviour or lifestyle. This could include an educational programme designed to improve a person’s understanding of their medical condition and help them to manage it more effectively, or a psychological treatment for mental health problems.
Fenella describes a trial testing the effectiveness of a computerised behavioural therapy...
Fenella describes a trial testing the effectiveness of a computerised behavioural therapy...
SHOW TEXT VERSION
PRINT TRANSCRIPT
There was, there have been clinical trials. There was one called IPCRESS, which looked at the use of computerised behavioural therapy for the management of anxiety disorders. And it basically involved people sitting in front of a computer using an evidence-based computer programme, and receiving sort of so many sessions of structured help using a computer programme. And they were supported by an assistant psychologist through, through that process. And then of course you have another group who might just have some counselling, and seeing which gets the better outcome. Now the aim isn’t to replace - with horror I can see people thinking, “But, you know, we’ve got therapists out there. Why do we need computers?” Some people initially might be very reluctant to come forward, but they might be very happy to sit in front of a computer initially. And it’s a gentle introduction to some, a behavioural method that has been tried and tested. And I think it’s not just about the fact that it was rigorously tested by one university and various Royal Colleges, it was more about actually that it was for a certain group of people, because different treatments can suit different people. But it may not be the way the treatment is presented. I think that some people want treatment in primary care, some people do want to go and see the hospital specialist, and some people just want to sit in front of a computer if they’ve got busy lives. So this was quite innovative.
And the original work, there was an original package that was developed at the University of Leeds, and then further packages were developed in other academic settings. And I think this was quite remarkable. So what the trial looked at was how effective in early-onset anxiety disorders this treatment was. And what we now have of course is - and of course there were good outcomes, people, you know, a certain group of people were helped fundamentally and found that treatment really did help them, whereas other people needed to go onto more structured face one-to-one therapy. The benefits of that is that it’s very low cost, the licensing of the equipment, of the programme is, is inexpensive, whereas to employ one psychologist, one CBT therapist might be £30-40,000 a year - plus you’ve got the accommodation problems and fitting it into people’s lives, not taking time off work or whatever - is that you can have a programmer, a stand-alone machine, and that machine can be used all day, 24/7.
You know, or people can access the programme through their computer at home. And I think that there’s something quite innovative about that.
The trial Jenny took part in was comparing the effectiveness of two different types of medication and an intra-uterine device (IUD or coil) as a way of reducing heavy periods.
Jenny was pleased to be invited by her GP to take part in a trial of different treatments for...
Jenny was pleased to be invited by her GP to take part in a trial of different treatments for...
SHOW TEXT VERSION
PRINT TRANSCRIPT
My GP asked me to be in a trial because I was having major bleeding, absolutely awful, it was about every two weeks. I was bleeding so heavily and I was going through so much, so much sanitary protection it was unbelievable, and he just suggested that I went in for the trial, because he wanted to put me on mefenamic - or no, he wanted to give me options as to what I was going to have, you know. Either it was, I think it was three items. It was either the coil, another drug, and mefenamic acid, and I obviously got selected for the mefenamic acid. But that’s why I went in for the trial, because I was just in such, such pain with the, with the periods.
I was given a leaflet with the ECLIPSE* logo on the front and all the data about why they were doing the trial and what products were included in the trial, and everything about the trial. You know, it was all sort of randomised, and it wouldn’t, nothing would be, nothing would be associated with me personally. It would all be sort of like patient A, B or C, you know. I wouldn’t be defined as in my name or anything like that. And - but to be honest I would have been quite happy to do anything, because I was that desperate. You know, I would have been quite happy to just put my name to anything.
* ECLIPSE = Effectiveness and Cost effectiveness of Levonorgestrel containing Intrauterine system in Primary care against Standard treatment for MEnorrhagia
FOOTNOTE' It is important to remember that you can have treatment anyway outside the trial and do not have to consent to a trial in order to be treated. Sometimes a new treatment will only be available as part of the trial, but in most cases there will be other treatments available.
Trials of different surgical procedures are not as common as drug trials, but they are becoming more frequent. Surgical trials may, for example, compare different types of surgery, or they may compare surgery with a non-surgical treatment.
Merilyn was quite pleased when she found out which type of by-pass surgery she had been allocated...
Merilyn was quite pleased when she found out which type of by-pass surgery she had been allocated...
SHOW TEXT VERSION
PRINT TRANSCRIPT
I actually went and had the bypass in November 2004. When I went into the ward, I was approached by one of the consultant’s nurses, who asked me if I’d be prepared to do a clinical trial. I didn’t really understand anything about it. It was called ART, Arterial Revascularisation Trial. And usually in a layman’s term what it meant was, the usual way of doing a bypass, they take veins from the leg or the arms and do the bypass with that. The actual ART trial meant that they didn’t do this. They actually took the arteries from your chest wall. And what it, what they explained to me was it would be done randomly. You might have it done that way or you might not, you wouldn’t know until you woke up. So it wasn’t until I woke up that I realised that I’d actually had the one, the arterial revascularisation. And it, when I had it all explained to me it sounded quite logical. It seemed that obviously an artery is bigger than a vein, and hopefully I might never need another bypass or I might, it might take me a long time to have another bypass. I’m crossing fingers [laughs]. I feel pretty good [laughs]. And as I said I’ve had this four years now. I’ve had no problems, no angina, I’ve had no time off of work and I feel great.
And when she explained to you that you would be put at random into either the group getting the vein from the leg or the trial--
Yeah.
--group, were you worried about that?
No, not at all. I just hoped I had the one from the chest, so I didn’t have another scar, because I knew I was going to have a big scar, but obviously the less scarring you’ve got the better, so I was pretty glad when I woke up to find out I’d had it done that way.
What do you think you’d have felt if you’d woken up and found it was the other way?
It wouldn’t have bothered me, no. I had to have it done. Obviously there was a problem, and I wanted to get the problem sorted out, so, no.
Alex understood doctors were unsure whether to recommend surgery for heel fracture or not. He had...
Alex understood doctors were unsure whether to recommend surgery for heel fracture or not. He had...
SHOW TEXT VERSION
PRINT TRANSCRIPT
Well, as I said, I had a slight preference. I can’t even call it that - but I had an idea that maybe, well, it hurts enough that maybe [laughs], maybe an operation would be better than no operation. But this was just, this wasn’t any rational, rational thought. This was just a feeling. So no, I mean, I understand what randomisation means and I understood that, that it could go either way and I was prepared for that, and it went the way I was sort of feeling, but I realise there was a fifty-fifty chance that it would so, yeah.
What do you think you would have felt if you’d been randomised to the other group?
Oof.
Would you have stayed in the trial?
I think so, yes, yes.
I didn’t see any reason why I shouldn’t do it, right? And there maybe there may well be other cases. There may well be other cases where people feel they don’t want to do it or they shouldn’t do it for all kinds of reasons. I can’t even list in my mind all the possible reasons. Maybe they just, maybe it would take much more time than it took in my case. Maybe it would be against their wishes in some sense. Maybe it would be against their religion, I don’t know, or against their convictions. So it’s everybody’s decision. It’s obviously up to them.
In my case it was an easy decision. There were two ways of treating my condition. I was explained that the doctors are not clear themselves about which treatment is better, in general, let alone which treatment is better for myself. So another way to put it, they probably would have to do something like random choice anyway, even if it’s not random choice, but they would have to decide somehow among two very close possibilities, among two very equally weighted possibilities. So it wasn’t going to make it any worse for me. It was probably going to do the tiny bit I did to help the doctor understand, the doctors understand this condition better, so I gladly and easily agreed to that.
So everybody’s situation is different. While I hope, I hope people don’t get into serious troubles, and if they do then they consider taking part in medical trials if they can.
Some trials are set up to evaluate screening and diagnostic tests, such as the UK Clinical Trial of Ovarian Cancer Screening. This aims to analyse whether either a blood test (for the tumour marker CA125) or an ultrasound scan are sufficiently accurate in detecting ovarian cancer to be worth offering to all women.
Joanna describes the ovarian cancer screening trial, comparing no screening, a blood test and a...
Joanna describes the ovarian cancer screening trial, comparing no screening, a blood test and a...
SHOW TEXT VERSION
PRINT TRANSCRIPT
Let’s start with the ovarian cancer, and just tell me how you came to be approached in the first place.
The GPs I think must have been recruited worldwide, as it were, or nationwide, and sent out letters. And they must also have had an age moment at which they sent it out, because half my friends in the area got the same request to be part of the trial, which is a three-arm trial. And they’re not all on the same - or were, I mean I’m finished now - but they’re not all on the same arm. Because there was a do nothing, just watch; there was an internal scan with a, you know, a wand, a uterine scan; and a blood test. And I have friends doing each bits of those, and I was having the scan. And at the time I already knew quite a lot about trials because my husband was actually involved in all sorts of trials. So I thought, “Well, this makes sense. It’s a screening trial. It’d be jolly nice to have a good screening system. So why not do it?” I mean, I had very little to lose basically. So I went along and I got the regular screening. And it was, involved two things. It was asking both the question, you know, which of these screening techniques was worth having, if any, but also how did screening affect the people who were being screened? So they had a massive long questionnaire that you were expected to fill in and tick boxes about how you felt about this, that and the other.
And I went through the whole process, which actually I failed to remember was a six-year process, which has just come to an end. So I’ve had, I’ve been doing it every year for six years. I get a letter, called up to the hospital. And on two occasions they get you to fill in the questionnaire, right at the beginning and then somewhere halfway through.
FOOTNOTE' This is the UKCTOCS trial looking at ovarian cancer screening in women in the general population between the ages of 50 to 74. There were 3 trial groups.
- In group 1, women were given a yearly blood test for the tumour marker called CA125, and then, if that is abnormal, a vaginal ultrasound scan
- In group 2, women were given a yearly vaginal ultrasound and then, if that is abnormal, a CA125 blood test
- In group 3, the women were not given any screening tests
Iain Chalmers, one of the authors of the book 'Testing Treatments' (a web resource is available at www.testingtreatments.org), explains why screening tests may be problematic, using the example of prostate cancer. Further trials may be needed to reduce uncertainty about which treatment to offer once people have been screened and a problem detected. In prostate cancer, the trial is comparing very different types of intervention: active monitoring, surgery, and radiotherapy.
Iain explains the worry that screening tests may raise anxiety, especially if it is unclear what...
Iain explains the worry that screening tests may raise anxiety, especially if it is unclear what...
SHOW TEXT VERSION
PRINT TRANSCRIPT
Well I’d be worried first of all about the side effects of a positive test, and the biggest side effect is probably anxiety. And it’s, I think, probably not sufficiently taken into account that some people, and I’m one of them, can be quite anxious faced with the result of a test which isn’t certain, and then go on to have other tests which are more invasive, if you like, than a simple blood test. So people need to know about that, but in particular they need to know well if it does turn out that this test identifies a cancer that’s there, a real cancer that’s there, what are the treatment options and what difference do they make to, for example my life expectancy, as one example, and what are the side effects of the treatments as well. And when not enough is known about those one can find oneself being treated for a disease and being labelled as being a cancer sufferer if you like, a good deal earlier than might otherwise have been the case and you want to be very clear that that’s got advantages as compared with, for example, going to your doctor when you’ve got some troubling symptoms, and then the doctor examines you and does things in response to the fact that you’ve gone to the doctor rather than the doctor has offered a screening test in spite of the fact that you appear to be well.
I mean there are some conditions, blood pressure, raised blood pressure is a good example, where you may not have any symptoms and because there are important and effective treatments for them it is a good idea for a doctor to check your blood pressure and see whether it’s raised and if it is, may be to do some further investigations and to invite you to consider going on treatment. Because we know that treating high blood pressure can reduce your risk of stroke, which is a very serious condition. But the situation with PSA [prostate specific antigen] screening is not like that yet, may be it will become that, but the evidence that’s so far available doesn’t put it in that class of a screening test at all.
Treatment for prostate cancer can have unpleasant side effects. Because the best way of treating...
Treatment for prostate cancer can have unpleasant side effects. Because the best way of treating...
SHOW TEXT VERSION
PRINT TRANSCRIPT
Would you like to go back to prostate cancer, what is the evidence at the moment about treatments?
Well one of the reasons that there is uncertainty is that prostate cancer is quite common, far more common than people realise, but it doesn’t kill people. In other words, you can die with prostate cancer but not of prostate cancer. So it’s quite important, given that fact, that one is very clear about the quality of the evidence upon which you intervene early with some of the quite radical things which people are intervening with. For example radical prostatectomy, quite a major operation, to remove a prostate with some cancer in it, has side effects. It can cause incontinence, men can become impotent as a consequence of it and then of course it has the risks associated with any large operation, those associated with the anaesthesia or bleeding and so on.
And then there is treatment given with radiotherapy as an alternative to that. There again there are problems which can be associated with the radiotherapy, so some people say, even when they know there is cancer there, well actually let’s just watch the situation and if it does seem to be deteriorating fast only then intervene with one of these more radical treatments. And that uncertainty is currently reflected in the fact that men are participating in this country in a very big controlled trial comparing those three different options, the radical surgery, the radical radiotherapy and active monitoring of the situation. And as a result of that study and other similar studies, although I think the British one is probably the biggest and the best, people like me are going to be in a far better position to take an informed decision if we find ourselves in the circumstances where we do have an early prostate cancer diagnosed. And indeed, if I went to my doctor with symptoms and it did lead to a diagnosis, I think I would want to be invited to participate in that controlled trial. It’s a way of hedging my bets because we don’t know which is best, but also helping to produce the information that will make decision making in future by people in my position more informed than it would otherwise have been.
There is also growing interest in testing different ways of giving people health information, to see which is most helpful to them in making decisions or understanding and managing their condition.
It was explained clearly to Sue that there was a trial comparing the effect of different types of...
It was explained clearly to Sue that there was a trial comparing the effect of different types of...
SHOW TEXT VERSION
PRINT TRANSCRIPT
She explained to me that it was a trial of people who’d already had one caesarean, and how that they, how they wished to proceed with the second birth, or the following birth. And she told me that there would be different, there would just be different questions, different facts, you would have, be given more information, and that - to help you make your decision. And that she said that I would be interviewed by people, and she told me that if I wanted to pull out at any time I could. If I, you know, wanted it to stop, I could.
And obviously everything would be treated confidentially. And then she asked me to, as I wanting to go forward with it, you know, to take this piece of paper away, read all about it and then sign it, and, you know, send it back in, which I did. I mean, well, I actually just signed it there. I mean, I read through it there, and then signed it, so again, so...
And so did, did she say what the different groups were going to be in the trial, and how you’d be allocated to one group or another?
I can’t remember if she said it then, or whether it was… later, I really can’t remember. I was told - actually it was on the information sheet that I was given, that there would be three different groups. One - and I can’t remember the exact things - but one would be, you know, different decisions and different, there would be three different segments of how the trial would be run, and you would be allocated into one of the groups, and that was actually written down in the thing.
If you are asked to take part in a trial, the UK Clinical Research Collaboration booklet on ‘Understanding Clinical Trials’ (see Resources), has a checklist of the kind of questions you might like to ask about how the trial is organised and what it involves. It also contains information on different types of trial and why they are needed.
Several people noted how important it is for trails to be well-designed, build on previous research, measure things that matter to patients, and include enough people to get reliable results. The number needed – the ‘sample size’ - will vary from trial to trial, depending on the condition, the treatment being tested and how big or small an effect the treatment is expected to have. The sample size is proposed by statisticians doing ‘power calculations’. In some cases a small number of participants may be enough, but as Sir Richard Doll explains below, if you are looking for fairly small changes in outcome you will need large numbers of participants to pick these up reliably.
It is vital that trials are well designed and build on existing knowledge, and that they focus on...
It is vital that trials are well designed and build on existing knowledge, and that they focus on...
SHOW TEXT VERSION
PRINT TRANSCRIPT
We just have to advance by comparing in a very rigorous way how we go forward with treating patients, otherwise we’re going to be stuck in not knowing. So yes, I thought trials were a wonderful idea, but it did occur to me that if I’d been on the trial working party, I would have some things to say about the information sheet. I would have had things to say about the end points. I would have had things to say about the possible outcomes, and about the feasibility of this trial. Because a huge amount of money was spent on it. It was a very costly trial, because of all the contention, I suppose. So there are economic aspects that need taking account of. Yes, I’m totally for clinical trials but they must be good quality clinical trials.
And, as I found with the people that I have spoken with and worked with, and indeed the clinicians more locally, I think it can only come about by a partnership between patients and health professionals, because we each have something different to give to, to devising any project, concept, trial that needs to be done. And the prior-, prioritisation of topics as well. You know, what is important to patients? What do they, what would really make a difference to their care? What do they want to know? Because they’re at the sharp end. They know what they want to know. They know what research would benefit.
And I think those patients that have become involved in this are able to stand back. They don’t do it - they do it based on their own experience because they know what it feels like - but they do it in a sort of detached manner. They have to become professional in their own way, in order to realise that this is an activity that’s undertaken on behalf of future patients. You do it on the basis of what you’ve learned today, what you’re learning today, but you’ve got to go forward and I think to do it in partnership is really the only way to do it. So yes, I’m totally for it. But the trial has to be well designed, well balanced, and presented in such way as to make sense to those who are going to participate. Otherwise it’s pretty futile if they don’t understand what’s happening.
What do you think are the characteristics of a good, well-designed trial?
Hmm. It’s easier to describe a bad one, isn’t it? And this is why I got involved, because I was invited to participate in one that was not balanced. The first thing that springs to mind is of course that it should be, let’s call it a legitimate comparison. It has to be utterly legitimate. In other words it has to be a comparison with, that is based on first of all the best standard treatment, a thorough overview of what is known on that topic - you can’t just have a bright idea and plunge in and ask for money. You have got to do your homework and find out what is known about this particular topic, before you even go, go there. I think I suppose the next requirement is to sort out, prioritise the question itself. In other words, how are you going to frame the question? It has to, I think, accommodate what are the important things about the thing you’re researching.
So framing the question that means something to both the clinician - in other words the sort of scientific, clinical treatment aspects - together with the aspects that the patient wants to find out. It’s, I think, no good having a trial that’s got an outcome that is meaningless. How are you going to get people to participate if they can’t identify with the purpose of the whole comparison? So it has to be a fair comparison.
Sir Richard Doll explains why it can be useful for trials to compare several things at once and...
Sir Richard Doll explains why it can be useful for trials to compare several things at once and...
SHOW TEXT VERSION
PRINT TRANSCRIPT
Yes. There are two things I’d like to mention.
One was something that, I pressed very hard but I wasn’t the first person to do it. That was that if you’re going to do a clinical trial then it takes a lot of organisation and a certain, lot of working and it takes time. For goodness sake, test two or three things at once. Don’t just one, just test one thing. So we introduced the factorial trial, in which two treatments can be used at once was for, in, in, in four groups of treatment. Both having A, both having B having A and B and having neither so we introduced this trial. This type of trial had been introduced by somebody else, I forget whose name, in the 40s but I got very keen on that and expanded that. And the second thing was, occurred a good deal later, was Peto’s realisation that the great majority of trials that were being carried out were too small to give a clear answer and as a result people were not convinced about the results because one person would carry out the trial of a new drug, get a positive effect and somebody else would do a trial and wouldn’t get a significant effect and they’d say “Oh, there’s a conflict”. Peto said, “Look, the trouble is you’re treating a hundred patients, or a few hundred, even a thousand. You’ve got to treat ten thousand to get a clear answer if you’re going to have moderately small, moderate effects which can be very important for a common disease like myocardial infarction.” And Peto’s insistence that you needed a very large number to get clear answer and his demonstration that you could do this and he, he in the so called ISIS series of controlled trials Oxford, he had 20-30,000 patients in a trial. So I think that was the next most important development and it’s got absolutely clear answers and people’s treat- prescribing habits changed overnight when you got the results of these very large trials.
FOOTNOTE' The number needed for each trial (the ‘sample size’) is proposed by statisticians doing ‘power calculations’. In some cases a small number of participants may be enough, but as Sir Richard explains, if you are looking for fairly small changes in outcome you will need large numbers of participants to pick these up reliably.
Sir Richard Doll was a pioneer of clinical trials in the twentieth century.
See also ‘What are clinical trials and why do we need them?’ and ‘Under-researched topics/priorities for other research’.
Last reviewed September 2018.
Last updated September 2018.
Copyright © 2024 University of Oxford. All rights reserved.