Clinical Trials
Funding and publishing trials
Running large well-designed trials costs a lot of money – though as some people pointed out, trials can also save money in the long run.
Drugs are a huge cost to the NHS. By reducing unnecessary treatments, trials can make savings as...
Drugs are a huge cost to the NHS. By reducing unnecessary treatments, trials can make savings as...
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I guess so from a, a money point of view I know these drugs are hugely expensive and if we continue the NHS as we want it to continue, you know, any savings that can be made on these thousands and thousand of pounds into new breast cancer drugs and all sort of things, I think that’s only a good thing. And the less time you have to be on chemotherapy and go through this, because it is like putting your life on hold for six months and then it, you know, going back to work, how you’re going to feel afterwards, you know. So the less time you spend doing all of that I think would be fantastic.
Funding for trials can come from a range of sources, including:
• The NHS and the National Institute for Health Research (NIHR)
• Government-funded research councils such as the Medical Research Council (MRC)
• Major research charities such as Cancer Research UK
• Commercial companies
The patient information leaflet you are given when a trial is explained to you should always make clear who is funding the research.
A few people we talked to were not aware that the NHS funds trials. One person thought the trial she was in was funded by a drug company. She said, “It’s self-explanatory really... I mean, where else would the money come from?” When she was told that many trials are NHS-funded, her surprised reply was “Really? Goodness me, heavens!” (The trial she was in was in fact funded by the NHS).
By contrast, Marie assumed the trial she was asked about must be NHS research because she was approached through her consultant in an NHS hospital. She was worried to find it was not.
She had heard bad things about commercial trials. She thought a trial in an NHS hospital would be...
She had heard bad things about commercial trials. She thought a trial in an NHS hospital would be...
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The only information that I heard about clinical trials was bad information. And the few, about a year ago when all those boys had clinical trials* and they all went wrong and I know that they’re still fighting for compensation, trying to prove it with the drug companies, and I don’t agree anybody would ever be able to fight drug companies. They have too much money behind them. I knew that, but had I have known it was a foreign drug company and not my NHS research team, I wouldn’t have agreed. But I just thought that it was because I knew nothing about trials and it was put to me from an NHS hospital that it would be NHS. I don’t know why I thought that because I was totally ignorant about trials but I thought it would be done through my local hospital research.
*FOOTNOTE: Marie 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. A copy of the Inquiry Report of this incident can be downloaded from the Department of Health website.
Marie referred to a Phase 1 trial at a commercial research unit based at Northwick Park Hospital in 2006, when 6 healthy volunteers became extremely ill. Many people said they were a bit suspicious of commercially run trials, and the belief that they might be more risky than publicly funded research was often given as a reason. This was certainly the view held by Leslie, who became seriously ill during a trial.
However, others took the view that all trials are well regulated, whoever funds them.
Drug companies will of course research products in order to make money, but the UK has a good...
Drug companies will of course research products in order to make money, but the UK has a good...
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One of the challenges for trials, I think, is that it’s highly unlikely we’ll ever see dramatic results. It’s all about making improvements on the periphery. If the, you know, penicillin’s already been found. I don’t imagine, although I’m not a medical person, that there’s many more penicillins about, you know? So therefore if you’re going into a trial, you shouldn’t expect a eureka moment. It’s going to be improvements on the margins. And so your expectations should be placed like that accordingly, I think, really. I think some people get very nervous and concerned about trials sponsored by drug companies. Well, drug companies are set up to make money for their shareholders. I quite understand that. And so therefore the work they do will be about trying to find a therapy that is so good that they make a lot of money out of it. Nothing wrong with that, really, as long as they don’t take chances with wild cards that affects people’s health, on the hope that it might do something. Now that would be a fear of a lot of people. My view on that is that within the country you have sort of a very strong ethics governance and the risks of that happening are very, very low.
What I do think is important, though, for drug companies is if they do a trial and it doesn’t work, they publish that as well. Because you can learn as much about what doesn’t work than you can - I mean, that’s a trite phrase, but you can. And I think whilst it would be a heck of a disappointment for them, I think it’s just a civil duty to share that with everybody.
Lester raises two further concerns affecting levels of trust in commercial research: the profit motive, and the question of whether trial results are fully published. Taking the profit motive first, several people expressed worries about the pharmaceutical industry’s need to make money out of drugs and how this affected the kind of research carried out. Celia wanted more government research funding instead, whereas Julian felt this was unlikely to be achieved.
Celia argues for more government research funding. She feels drug companies tend to fund research...
Celia argues for more government research funding. She feels drug companies tend to fund research...
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Well, yes, I mean I think more money does need to be put into research definitely. When you think of all the money that they waste on Trident and wars and all the rest of it. You know, I just think there’s so many more important things in life. And more money does need to be put - and, you know, they, they rely so much on the charitable organisations, Cancer Research and all the different charities - which are great and we need them, and that’s all right, because that also spreads the word to ordinary people about research, when they hear about what the charities are doing. But I still think it’s the government’s responsibility. And they have the access to the really big amounts of money.
What about drug company-funded trials? Do you have any worries about that?
Yes, I mean obviously, because they’re only interested in making money, as far as I’m concerned, which is okay, again, if they do get a breakthrough and, and, and come up with some really good treatment. But the trouble with them is that they put money into providing treatments for the same diseases. In other words, they just change, you know - for instance look at high blood pressure. There’s so many different treatments for high blood pressure, and, and we don’t need them all, do we? As far as I know we don’t need all of these different treatments, and they only go in for new treatments for the same disease because they can make more money out of it.
The costs of developing new drugs are high, so Julian thinks investment from drug companies is...
The costs of developing new drugs are high, so Julian thinks investment from drug companies is...
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Some people worry about trials being funded by drug companies. Is that an issue for you or does it not worry you at all?
No, I don’t think there’s any way of avoiding that. I mean, the sums involved in developing a new drug are enormous, so the estimate is for every drug that succeeds - I mean you must know this better than I do - every drug that succeeds and makes it to market, the cost is something like half a billion pounds, depending a little bit.
So that’s an enormous cost which is paid by the drug company that develops the drug. And I suppose you could have government financing that, but as things are, without enormous restructuring of the way that medical services and medical research are funded, it’s unavoidable that drug companies must foot the bill.
I suppose the thing that I do worry about, that again is being tackled now in various ways, is the unfairness of allocation of resources. So there are drugs which are desperately needed to treat infectious disease in the third world, for instance, which could benefit enormous numbers of people, which, until recently, have not been developed because the rewards from developing drugs for poor people in poor countries are rather small, even though the benefit of the drug may be huge. But I think foundations like the Gates Foundation are beginning to remedy that problem by providing incentives for drug companies to develop those drugs.
However, Caroline noted that funding priorities are influenced not only by drug companies but also by powerful charities with interests in specific conditions. (See also ‘Under-researched topics/priorities for other research’).
Some people argued that investment from drug companies was vital, and said they had few concerns about their involvement, or at least wanted to keep an open mind. Anthea commented particularly on Phase 1 trials, “If the companies weren’t funding them, they wouldn’t be being done. There’s no way that the National Health Service or anybody else could afford to do these trials.”
Tony thinks there are conspiracy theories about the role of the pharmaceutical industry, but he...
Tony thinks there are conspiracy theories about the role of the pharmaceutical industry, but he...
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I know that there is a great, shall we say, conspiracy theory [laughs] about big pharma, and up to a point I keep an open mind about this. It is big business. There are multi millions of pounds involved. And I don’t for one second begrudge the profits that the big pharmaceutical companies make, because I know how much it costs them to start new drugs. Whether they sometimes abuse the relationship they have with some medical practitioners, I’m in no position to judge or pass comment. I can see that it could happen.
Another concern raised by Lester (above) is the issue of publishing trial results. There are concerns that research teams are less likely to publish the results of trials which show the intervention did not have the effects they hoped it would have. (These results are sometimes called ‘negative findings’). Many people think drug companies have an extra reason to keep negative findings quiet, because it may affect their sales and profits. There was a lot of support for regulations to insist that all results are made public.
Amanda worries that commercial trials may suppress negative' findings. Good research is not...
Amanda worries that commercial trials may suppress negative' findings. Good research is not...
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Well, most trials, drug trials, are funded by the pharmaceutical industry, and I find that very worrying because they own the data then, and they can control the data. There was one rheumatoid arthritis drug called anakrina, for example, that we systematically reviewed, looked at the scientific evidence, and the drug company had suppressed some of the evidence. There were three trials that they used to get the drug licensed with about a thousand people in, which suggested it worked, and then after it was licensed for use there was a great big trial, bigger than the other three trials put together, a safety trial, in which they wouldn’t publish whether it worked or not, the efficacy data. In fact they claimed they hadn’t measured it, but we did have the protocol so we knew that wasn’t true. And it turned out, you know, they, they just suppressed that data. They claimed it hadn’t been measured. They said, “Oh well, you couldn’t, this was a trial done in a different population. This was now done in a standard rheumatoid arthritis population instead of a highly selected population, and therefore it was too confounded to be usable.” But it was a randomised controlled trial, so the two groups were comparable. So my conclusion was that actually this didn’t work, if you use it in ordinary people, a drug that they were trying to promote for use in ordinary people. So yeah, the fact that trials are published by the pharmaceutical industry our defence has to be that the data is made public domain. But I, I think the government should be funding more trials. I think participation in research should be just built in to the health service, in such a way that it becomes very cheap and painless. You know, there’s not huge costs because part of the way we routinely collect data anyway.
What are the obstacles to that at the moment, do you think?
Research is not cheap. It costs. I mean, it isn’t cheap because it has to be done well. I think there’s absolutely no point doing research badly. I mean, I’ve seen people put together protocols and then cut down their sample size* calculations because it’s coming out at too costly. But I actually think what’s, you know, £2 million sounds like a lot of money, but if you’re preventing a lot of deaths it actually becomes quite trivial in terms of health costs. So no, I think it should be nationally funded, and I think it, more should be funded.
*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 if you are looking for fairly small changes in outcome you will need large numbers of participants to pick these up reliably.
Amanda was a member of a research ethics committee and was surprised it was not seen as not part...
Amanda was a member of a research ethics committee and was surprised it was not seen as not part...
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I think it’s desirable that people should know the results, I mean, that’s why we go into it. I personally feel worse, what’s worse, and is for a trial to come out and then not get published at all, you know, rather than the individuals being informed. And interestingly enough on the research ethics committee I’ve sat on and I’ve tried to bring up, “They have no publication policy, they have no strategy for publishing this trial” and being told that we’re not allowed to discuss that. Whereas I always think it ought to be built in that this data will be put into the public domain. I mean, I have a colleague who works in another country who was part of a multicentre trial for a major pharmaceutical company, and in the trial protocol it said results will be published within, I think it was 24 months of the close, after recruitment of the last patient. And they added into their, their centre, “Should the results not have been published within 24 months of the closure of the trial, our centre reserves the right to publish the results for this centre”, and they were excluded from the trial, because they insisted on that. They were told that could not be put in. Well, if they’re going to be published within 24 months, why could that not be put in? And so they refused to do the trial without that in. And they, and they - so that’s, that’s an insight. So who owns the data? I think the data ought to be owned by the people who are in the trial.
So I like the new strategies that are coming out, that data has to be put into the public domain and it should be a prerequisite, certainly for funding from government bodies. You know, if our government’s going to fund a trial, well, let’s have the results, and I - more than just the results, let’s have the data, suitably anonymised to protect patient confidentiality, in the public domain to be re-analysed, because even in the analysis there could be bias. So, I’m a great believer in transparency.
However, Kate, who works for a healthcare charity, thinks that drug companies have acquired an unfair reputation. Most research teams will want to publish their findings as articles in academic medical journals, which get independent experts to review the articles before they are accepted (a system known as peer review). Kate thought sometimes peer reviewers were more likely to find fault with drug company research because there is “a bit of a stigma attached to pharmaceutical companies”.
Problems in publishing ‘negative’ findings may not be simply to do with who funds the research, however. Publicly funded researchers may also find it difficult to be honest about ‘negative’ findings, as they may feel it will affect their career and their academic reputation. They may feel very passionate about a new treatment they have developed and be unwilling to admit that their hopes for it have been disappointed.
It takes a long time for most trial results to be published. Sometimes when results seem...
It takes a long time for most trial results to be published. Sometimes when results seem...
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The trial that I was involved with lasted for three years and it’s finished now. And what happens is that all the data is collected. It’s anonymised, that’s to say none of us ever know who the individuals were. It’s just on numbers and averages. And that goes through an independent committee. And then the results are published, really.
Now, there are quite a lot of issues with all of that. Number one, it takes a long time for data to be published in a trial. And that’s one of my disappointments, if you like, that because people quite rightly are frightened to jump to early conclusions, they say, “Oh, we’ve got to get all the data in before we publish.” Well, sometimes if you’ve got a three-year trial or a four-year trial, you might know after a year what’s really going on, but people very rarely publish it. And that then puts the people going into the trial at years two, three and maybe four at a disadvantage, because more is known about the likelihood of success than what they may be told. So I wish there were ways in which data could be more freely available. I think - and I’m not talking necessarily about my own experience - but I think one of the risks is, if you’ve got a group of people who are absolutely passionate about a trial for a therapy that might work, if in the early part it isn’t giving them what they expect, there was a very natural, understandable reluctance to publish that or to tell anybody. You just sort of keep on, “Well, maybe this is a bit of a tweak. Maybe it will get better.” I feel almost guilty saying that, because that’s making them feel that they’re less than honest. They’re not. They’re just human. And I think it’s absolutely understandable. I could sort of take it back to my time in the bank. If we were trying to sell a particular - if my team, my colleagues were trying to sell a particular mortgage and it wasn’t selling, you wouldn’t sort of very often look back and say, “Gosh, is the mortgage right?” You’d just try and keep selling it a bit harder and hope it would go through and ignore the customer complaints. You know, you’d set up a call centre. It’s human nature. You don’t do it out of nastiness. It’s just how it is.
FOOTNOTE' Researchers are right to be cautious about jumping to conclusions too early in a trial. Large trials can take a long time to get enough people and enough data to draw reliable conclusions. However, sometimes results are so obvious that a trial has to be stopped early, either because the one of the treatments is strikingly better than the other, so it becomes unethical to withhold it, or because risks are revealed that are too great.
(There is a dilemma here – researchers are right to be cautious about jumping to conclusions too early in a trial. Large trials can take a long time to get enough people and enough data to draw reliable conclusions. However, sometimes results are so obvious that a trial has to be stopped early, either because one of the treatments is strikingly better than the other, so it becomes unethical to withhold it, or because risks are revealed that are too great).
Even if researchers do submit reports of ‘negative’ findings, academic journals are sometimes less likely to accept them for publication compared to articles reporting ‘positive’ findings. New breakthroughs may be seen as more exciting reading than a report that a treatment does not have the effects hoped for and is not worth pursuing.
But ‘negative’ findings are just as important and valuable as ‘positive’ findings. They can mean that future patients are not exposed to unnecessary risks from treatments which do not work, and that money can be better spent elsewhere. In recent years there have been a lot of efforts to encourage researchers and journals to think differently about ‘negative’ findings.
See also ‘Feedback of trial results’.
Last reviewed September 2018
Last updated July 2011
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