Lethal Secrets

ABC | 16 April 2015

British doctor Ben Goldacre on his campaign to stop drug companies burying the results of their clinical trials.

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TONY JONES, PRESENTER: Just how much do you know about whether the prescription drugs you’re taking are really as effective as they claim and whether or not you might be hit by adverse side effects? Well according to a global coalition of doctors and public health experts, none of us know anywhere near enough. The UK-based group AllTrials says drug companies have hidden the results for around half of all clinical trials. It now wants them to come clean. Case in point: Tamiflu, which was heavily promoted as a new and more effective treatment of influenza.

PETER COLLIGNON, INFECTIOUS DISEASES, ANU: Tamiflu first became available, it looked like it was great. I mean, I took the view, “Hey, this is like a new antibiotic equivalent. We’ve got a bacterial infection; we can kill it with an antibiotic.” Here is a virus we have not been able to kill and we can kill it.

TONY JONES: Well the Federal Government spent more than $200 million stockpiling Tamiflu and pharmaceutical giant Roche enjoyed a $4 billion global sales spike when swine flu hit back in 2009.

But a group of prestigious health researchers from the Cochrane Collaboration realised that Roche had not published all of its results.

CHRIS DEL MAR, Cochrane Collaboration: There was some data missing and not published. When we looked carefully at the data, we became anxious that there might have been some cherry picking of the trials that had been published, and the ones that hadn’t been published, we wondered about how many trials had never been published.

TONY JONES: Well it took nearly four years, but eventually Roche released all its data, and after reviewing it all, the Cochrane Collaboration reported last year that Tamiflu fell well short of the hype.

CHRIS DEL MAR: It does help control symptoms by about a bit less than a day. It reduces the time to full recovery. The big thing that we did find was that it didn’t help the complications, the hospitalisations, any of the complications we were particularly interested in and are particularly important for this drug – it’s one of the reasons for having it – didn’t seem to work.

TONY JONES: Well it has to be said that another report has since claimed Tamiflu does reduce complications and hospitalisations, although Cochrane reviewers pointed out to the ABC’s Catalyst program that the study was indirectly funded by Roche. Roche has had no influence over the results. Its position on Tamiflu remains unchanged.

Well, Ben Goldacre is a British physician, academic and science writer. He’s a founder of AllTrials, the campaign to get all information from clinical trials made public. He describes himself as a nerd evangelist and he joins us now from Oxford to spread the word.

Ben, thanks for being here.


TONY JONES: Let’s start with the Tamiflu story. Did Roche break any laws when it withheld the full details of its trials from the public and from the medical establishment?

BEN GOLDACRE: No. Roche broke no laws and that’s the most extraordinary thing about this situation. We know that the results of clinical trials are routinely, but also legally withheld from doctors, researchers and patients and this is a problem that’s been going on for decades and decades now. The first quantitative evidence, the first good quality academic study showing that trial results are withheld and that that harms patient care was published by actually an Australian researcher called Dr Simes in 1986 and we’ve been failing to fix the problem for over three decades now.

TONY JONES: So it’s obviously not news at all. But tell us, if you can, who this Cochrane group is because it ended up taking them to breach the Roche company’s secrecy walls and get the full data.

BEN GOLDACRE: Well, so in medicine we do randomised controlled trials to find out which treatment works best and those are the most fair tests we have. But unfortunately, we can’t rely on the results of just one clinical trial. There’ll be lots and lots of clinical trials done on a treatment, and to avoid any risk of cherry picking or selective referencing, what we do is something called a systematic review where we gather together all of the trials that have ever been done and add together all the results in effectively one big spreadsheet to get the best overall summary of all the data that’s been collected. So the Cochrane Collaboration is a global non-profit collaboration of over 10,000 academics now and it really is the gold standard for producing these systematic reviews of the evidence and they’re used pretty much by all doctors around the world is the best summary of what works in medicine. So, the Cochrane Collaboration were commissioned by both the Australian and the British Government to look at the evidence on Tamiflu and what happen next I think’s a really interesting example of science at its best, because they were criticised by actually a very junior Japanese physician who’d read their report and said, “Look, I think actually it looks to me like you’re missing some of the evidence.” And the Cochrane reviewers, instead of trying to squash criticism, said, you know, “Let’s have a look. Let’s see if you’re right.” And they began to dig deeper. And eventually what happened was really just because of the tenacity of the British and Australian Cochrane researchers on the team, Roche’s drug, Tamiflu, became probably the single most well-documented case so far of missing and withheld information on the methods and the results of clinical trials. But I think it’s important to recognise that I think Roche were unlucky. I don’t think Tamiflu is by any means the worst case for withheld data, it’s just the place where researchers were sufficiently motivated and dogged to look the hardest.

TONY JONES: The interesting thing is though they didn’t just put their hands up and say, “Well you’ve got us there. Fair cop, Gov’,” they’ve come out with yet another report. Now they claim that report proves that the other report was wrong. So, these companies are very well-resourced; they’re not exactly going to just sit down and allow themselves to be criticised, are they?

BEN GOLDACRE: Yeah, so the subsequent report that Roche are relying on is not a collection of randomised controlled trials. It’s observational data, it’s just looking at what happened to people in hospital who had Tamiflu. Now the trouble with that is that people who were treated with Tamiflu are likely to be different to people who aren’t treated with Tamiflu if you’re not looking at randomised trial data. So that’s much less reliable information, and I think every doctor, anybody who knows about evidence-based medicine, would recognise that that data that Roche is citing is much less reliable. But equally, I think it’s really important that we do have public critical discussion about the quality of evidence for different treatments and I’d welcome Roche getting involved in that critical discussion. But we can only have that kind of critical discussion if we have access to all the information, and at the moment, unfortunately, we know that the results of clinical trials are routinely withheld.

Now there’s actually one crucial extra problem which I think is often missed, which is: this isn’t just about drug companies. Academic researchers, people receiving government funding for clinical trials, those academic researchers are often just as bad as drug companies and in some studies they’re worse than drug companies for failing to make the results of their trials available. So this is a problem that cuts right across the board, whether it’s industry or non-industry. It’s a huge cultural failing in medicine.

TONY JONES: Yeah. Ben, I’ll talk to you a little more about what can be done about that. Just go back just for a moment though to the Tamiflu thing. I mean, Australia spent hundreds of millions of dollars, Britain spent hundreds of millions of pounds, the – globally, billions of dollars.

BEN GOLDACRE: Half a billion.

TONY JONES: Yeah. Half a billion in the UK. So globally billions of dollars was spent stockpiling Tamiflu in case there was a global flu pandemic of a killer flu. Are those stockpiles now worthless? Is that what’s being said here?

BEN GOLDACRE: So, I wouldn’t want to get into the business of adjudicating on any one particular drug. I think we just need to have the evidence so that we can have a conversation about which drugs are worth spending money on. I think when it comes to pandemic planning, I can understand that there are probably more considerations actually than even just the evidence. And I think governments feel an obligation to be seen to be doing something. I think sometimes in an atmosphere of popular panic, normal spending priorities can be distorted. We know from the way that people prioritise cancer spending, for example, over mental health spending, that the public’s priorities, that the media’s priorities can have an impact on spending. So, I’m not sure I would necessarily say that if we’d all the evidence, people wouldn’t have bought Tamiflu, but I can say for definite that we’d have been much less likely to buy Tamiflu. And also, crucially, it wasn’t just doctors, researchers and patients who didn’t have sight of all the information on Tamiflu; we’ve now got fairly clear evidence from Cochrane to show that the European Medicines Agency, for example, didn’t have all of the methods and results of all of the trials which have been conducted. And it’s not even just the results that matter; it’s also seeing the methods, it’s seeing exactly what was done in the trials because you need to know the finer detail of how a trial was conducted in order to make a decision about whether it really was a fair test or whether it was flawed by design in such a way that it would have exaggerated results. Now, even if regulators see that information …

TONY JONES: Sorry, Ben. Yeah, go ahead. Finish your point.

BEN GOLDACRE: Well, even if regulators see all of that information, I think that’s still not enough because regulators can sometimes miss things, not because they’re malicious or incompetent, but because, you know, medical statistics, evidence-based medicine is a difficult business, and like all data in science, it benefits from having many eyes on it to try and detect signals of risk and also signals of benefit.

TONY JONES: So Ben, how important is this week’s WHO statement which says the registration of all trials, there’s a scientific, ethical and moral responsibility and that sets definitive timetables for how quickly these big pharma companies, or any company really that’s creating a new drug, has before it has to release all its data on trials?

BEN GOLDACRE: So on the one hand, obviously, it’s fantastic news. It’s great to see the world’s biggest – the global public health organisation standing up and saying, “This is a real problem and this really matters,” and they’re absolutely right to do so. We cannot make informed decisions about which treatment is best when a third half of the information is withheld from us. But at the same time, I think we need to recognise that people withholding information on clinical trials are already in breach of multiple (audio problems) all around the world including even the Declaration of Helsinki, which is the fundamental ethical regulatory document for pretty much all trials around the world. There’s also even a law called the FDA Amendment Act, 2007, which is America-only, but says that anybody who fails to report the results of certain classes of clinical trials in America within 12 months can be subject to a $10,000-a-day fine, but the problem is nobody’s enforcing that, so firstly nobody has ever had a fine imposed upon them, even though when there’ve been independent audits, we’ve seen that between 80 and 50 per cent of trials that should be covered by that law are failing to report results. But also, we don’t have data on who’s transgressing, and this, I think, is a really cheap, straightforward, easy thing that health services in Australia, in Europe, in America can do for themselves – very cheap, very cost-effective. We need to do an audit where we take all of the registry entry, so all of the trials that we know have been conducted and completed and then we need to look and see if they’ve reported results. And if we do that comprehensively in a rolling audit all of the way through the past 10 or 20 years of medical trials, then we can say definitively: the following companies are the best and the worst for withholding data, and that’s important because if we assume good faith, we would say companies that are doing badly would want to learn from the companies that are doing well. We can also say the following drugs are the best and worst for missing data, and then doctors can use that information in their prescribing decisions. I think it’s very wrong for a doctor to allow their politics to get in the way of their prescribing decisions, but if there are two apparently equally effective drugs and one comes from a company with a proven track record of being almost perfectly transparent and the other comes from a drug company with a proven track record of withholding information, suing regulators to force them to withhold information, then I think the clinically cautious thing for a doctor to do is to prescribe the drug that comes from the company that’s more transparent.

TONY JONES: Ben, that was almost an entire TED talk, that last answer, and it’s – it brilliantly took us out to the end of our program, but we’ll have to leave you there. We’ll come back to you another time and there’s many more questions to ask you. We’ll come back and do that another time. Thanks very much for being there.

BEN GOLDACRE: Any time. Thank you. AllTrials.net

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