By Jerome Burne
21 Sep 2015
It’s generally agreed that the NHS is not in good health but there’s no clear diagnosis. There are plenty of suggestions – lack of funding, uncompassionate nurses or box-ticking managers. But I want to suggest another one: the crisis in evidence based medicine (EBM).
Everyone agrees EBM is a good idea – running trials to test treatments before they are given to patients– but EBM has been allowing in dangerous and unreliable results for years and badly needs an upgrade. It may seem a geeky topic but if you are put on a drug for life, you really want to know that it has been properly tested. The collateral damage from bad drugs is huge. A new book calculates that psychiatric drugs alone are the third leading cause of death.
One attempt to fix the problem is campaign called AllTrials which demands that drug companies to allow researchers access to the raw results of their trials, which is a start but it’s not enough.
What’s needed is Jeremy Corbyn. After all who could be a more appropriate saviour of the NHS than an unassuming and committed socialist? A common jibe is that he’s reprising the brief flowering of socialism immediately after the war when the modest Clement Atlee, having led a radical labour government to an unexpected landslide victory, created the NHS.
Drug for kids makes suicide for likely
There’s no shortage of evidence that EBM is in trouble. A vivid example was published last week in the British Medical journal (BMJ). It set out in forensic detail how a clinical trial, supposedly showing that the antidepressant Seroxat was safe and effective when given to depressed children, actually found quite the opposite – that the drug didn’t improve their depression and made them more likely to commit suicide.
The BMJ’s investigation makes it clear that far from being a piece of serious research, the trial was effectively no more than a cynical marketing exercise. Although there were 23 authors listed, many eminent and respected psychiatrists, none of them had actually seen the results. They hadn’t even taken part in writing them up. That had been done by an employee of the company, GlaxoSmithKline (GSK) as it is now called. The academics had the same relationship to the product as celebrities do to the perfume or skin cleansers they endorse.
A system that is supposed to provide reliable information for doctors and patients to decide on treatment but which ends up encouraging doctors to give drugs to children that will make a few more likely to commit suicide is clearly not fit for purpose. It’s also makes it obvious what the problem is: EBM has been entirely hijacked by commercial interests. If EBM is going to deliver useful results the systems for delivering it have to become independent. Easy to say, much harder to do.
As the BMJ investigation also makes clear, it wasn’t just GSK that had been bending the science. A number of academics, a respected journal and a university were also involved in the deception. However, even though the BMJ re-analysis makes it unarguable that the trial data was deliberately falsified; none of the major players have been prepared to make any kind of retraction or amends.
Drug company refuses to correct untruthful article
For example when GSK was asked by the BMJ team if it would now publish a corrected version of the article, it refused, saying that the original article: ‘accurately reflects the honestly held views of the clinical investigating authors’. What’s more GSK does not agree that the article was false, fraudulent or misleading,
This is an implausible claim since, as the article points out, the company had used the study – known by the sinister title of: Trial 329 – as part of an illegal marketing campaign for which it was fined a record $3 billion dollars in 2012. The campaign claimed that Trial 329 had demonstrated that Seroxat had ‘remarkable efficacy and safety.’ Since it had been published in a top journal – The Journal of the Academy of Child and Adolescent Psychiatry – this was widely believed and two million prescriptions were written for children in the following year.
It’s the continuing refusal to admit there is anything wrong that has made the BMJ’s investigation essential. The original trial was done over a decade ago and concerns about its reliability surfaced very quickly but since then the other individuals and institutions involved have proved equally intransigent. As the BMJ puts it: ‘None of the paper’s 22 mostly academic university authors, nor the journal’s editors, nor the academic and professional institutions they belong to, have intervened to correct the record.’
For patients and doctors alike this is the really disturbing message of the investigation, just pointing the finger at the drug companies’ data manipulation is to miss the point. The AllTrials campaign has been focused on getting drug companies to make the raw material they gather from trials available to independent researchers. That’s a worthwhile aim but it doesn’t begin to tackle the scale of the problem if other medical institutions, usually dependent on drug company funding, are prepared to collude with drug company deceptions.
The watchdog that doesn’t bark or bite
And on the rare occasions they do allow external researchers in, such as the data GSK provided the BMJ, they can do it in such a way that the data is virtually unusable. When the team asked GSK for 70,000 pages of patient reports (these trials generate a vast amount of paper) they were allowed to see them via a computer link that only allowed you to see one page at a time. No printing or downloading, you had to make notes about each page by hand. That’s transparency very lite.
And then there’s another party involved in delivering EBM – the regulatory authorities, such as the MHRA (the UK drug watchdog). They are there to protect the public but the MHRA is totally funded by the drug companies whose products it licences.
But the very existence of the quixotic BMJ trial raises the query about the dog that didn’t bark. Why was it necessary to have a group of concerned independent researcher devote a year or more to minute scrutiny of literally tens of thousands of documents to discover exactly how a negative trial result was turned into a positive one? Why wasn’t this done by the regulatory authority?
It was a huge project. It involved such laborious and painstaking tasks as reclassifying all the reported side-effect so their description reflected what the patients had actually described. In the original journal article, for example, when patients said they had self-harmed or tried to commit suicide, this was classified under the anodyne and highly misleading term – ‘emotional lability’. That’s how a serious side effect is magicked away.
Why we need Jeremy Corbyn
And this is the story of just a single trial. Dozens of new drugs come on the market every year, a few show up as particularly dangerous and are withdrawn (although never for being ineffective) and some details come out but for the most part the way the raw data may have been massaged for public consumption lurks under a blanket of secrecy that would be the envy of an offshore bank. Certainly the MHRA let no light into the workings of Trial 329. Why?
All this carefully amassed evidence for deliberate deception plus the refusal of the major players, even now, to acknowledge that there really is a problem, gives more weight to the proposal that some independent body without any commercial interest in the outcome of drug trials should now be set up to run them.
‘The reanalysed data from study 329 sets the record straight and shows the extent to which drug regulation is failing us,’ says Dr Fiona Godlee, BMJ editor-in-chief. ‘We need independent trials and legislation to ensure that the results of all clinical trials are made fully available and the individual patient data are available for legitimate independent third-party scrutiny.’
And this of course is where Jeremy Corbyn comes in. For years the neo-liberal consensus has favoured light touch regulation of business and financial industries and privatisation programs. Big clinical trials, regarded as the cornerstone of EBM are done by the companies that make the drugs. A publically run program to test new treatments would fit easily in Corbyn’s plans for some re-nationalisation.
The need for legislative muscle
Light touch regulation of the financial sector has fallen heavily out of favour but it is still flourishing in the pharmaceutical industry and it is a set to become even lighter. There’s a sense in the BMJ investigation that just setting out the details of how trials can be perverted and how to stop it is enough encourage an EBM U-turn so protecting patients becomes the priority.
But it won’t happen without some legislative muscle, which no government for over 30 years has been remotely interested in even proposing. Corbyn’s election at least opens up the possibility of change. Without it a bill currently going through Congress in America provides a clear picture of what is likely to happen here instead.
It’s called the 21st Century Cures Act and it’s the brain child of the Manhattan Institute, a free market think tank that aggressively pursues a neo-liberal agenda. The passage of the bill has been helped by an army of nearly 1200 lobbyists. Its stated aim is to encourage innovation and speed up the time it takes to get new and effective drugs out to people who desperately need them.
An Act that will leave patients more vulnerable to drug damage
A spokesperson for the Manhattan Institute explained why it is needed: ‘The enormous cost and risk of phase III trials creates an incentive for researchers and investors to avoid work on medication for the chronic conditions that pose the greatest threat to American people. The cost of a trial to determine safety and efficacy is not worth the money.’
American drug experts see it as a dangerous move. ‘The emphasis has been on getting drugs and devices onto the market quickly not on making sure they are safe,’ says Dr Rita Redberg, a cardiologist from the University of California Medical Centre. ‘The 21st Century Cures Act will severely weaken the FDA’s already ineffective regulatory scheme for medical devices.’
Details on what the Act is proposing were set out in in an Editorial in the New England Journal of Medicine back in June. There Jerry Avorn, Professor of Medicine at Harvard Medical School writes: ‘Speeding up approval for new drugs, does of course mean less time for checking and assessing them. Already a drug only needs just one trial of around 750 patients, treated for six months or even less to get a licence’
He goes on to explain that the new act proposes that trials could be allowed on the market with even shorter and smaller trials. Use of ‘gold standard’ RCTs are to be cut back and companies will be able to show that drugs safe and effective by pointing to ‘evidence from clinical experience’ (what doctors report) and observational studies – tracking the effects of treatment on a group to see what the longer term effects are.
Why light touch regulation has been a disaster
I asked Professor John Abraham a sociologist at King’s College London about the likely effect of even less regulation. His special area is pharmaceutical drugs and the way regulation affects safety, effectiveness and the rate at which innovative new drugs are developed.
He said: ‘The neo-liberal consensus since Thatcher has believed in setting business free. The belief is that left to their own devices drugs companies will innovate more and bring more effective drugs to market.
‘In fact my research shows just the opposite happens. When you reduce the amount of oversight you get more drugs having to be withdrawn because of the harm they are doing, which is not a surprise, but the rate at which effective new drugs come to market also drops.’
The attitude which allowed Trial 329 to be run and then for no one to be held to account is not going to be changed by the introduction of the sort of drug licencing process set out in the 21st Century Cures Act. Jeremy Corbyn the NHS needs you.