Bad Pharma: How Medicine is Broken, And How We Can Fix It. Ben Goldacre

These local authorisations were then ‘copied’ to all other nations. The MHRA, the UK drugs regulator, held the information the researchers wanted, so they would have to approach it for a copy. The researchers dutifully wrote to the MHRA, asked for the reports on a drug called fluoxetine, and then waited patiently. Finally the answer came: the MHRA explained that it would be happy to hand over this information, but there was a problem.

      The documents had all been shredded.⁷⁵

      This was in keeping, it explained, with the agency’s retention policy, which was that such documents were only kept if they were of particular scientific, historical or political interest, and the files didn’t meet those criteria. Let’s just take a moment to think through what the criteria must be. The SSRI antidepressant drugs have seen many scandals on hidden data, and that should be enough on its own, but if you think back to the beginning of this chapter, one of them – paroxetine – was involved in an unprecedented, four-year-long investigation into whether criminal charges could be brought against GSK. That investigation into paroxetine was the largest investigation that the MHRA has ever conducted into drug safety: in fact, it was the largest investigation the MHRA has ever conducted, of any kind, ever. Quite apart from that, these original study reports contain vitally important data on safety and efficacy. But the MHRA shredded them all the same, feeling that they were not of sufficient scientific, historical or political interest.⁷⁶

      I can only leave you there.

      Where are we so far?

      The missing data saga is long and complex, and involves patients around the world being put at risk, and some major players which have let us down to an extraordinary extent. Since we are almost at the end of it, this is a good moment to gather together what we’ve seen so far.

      Trials are frequently conducted, but then left unpublished, and so are unavailable to doctors and patients. Only half of all trials get published, and those with negative results are twice as likely to go missing as those with positive ones. This means that the evidence on which we base decisions in medicine is systematically biased to overstate the benefits of the treatments we give. Since there is no way to compensate for this missing data, we have no way of knowing the true benefits and risks of the drugs doctors prescribe.

      This is research misconduct on a grand, international scale. The reality of the problem is universally recognised, but nobody has bothered to fix it:

       Ethics committees allow companies and individual researchers with a track record of unpublished data to do more trials on human participants.

       University administrators and ethics committees permit contracts with industry that explicitly say the sponsor can control the data.

       Registers have never been enforced.

       Academic journals continue to publish trials that were unregistered, despite pretending that they won’t.

       Regulators have information that would be vital to improve patient care, but are systematically obstructive:

       they have poor systems to share poor summaries of the information that they do have;

       and they are bizarrely obstructive of people asking for more information.

       Drug companies hold trial results that even regulators don’t see.

       Governments have never implemented laws compelling companies to publish data.

       Doctors’ and academics’ professional bodies have done nothing.

      What to do about all this?

      You will need to wait, because in the next section there are even greater horrors to come.

      Trying to get trial data from drug companies: the story of Tamiflu

      Governments around the world have spent billions of pounds on stockpiling a drug called Tamiflu. In the UK alone we have spent several hundred million pounds – the total figure is not yet clear – and so far we’ve bought enough tablets to treat 80 per cent of the population if an outbreak of bird flu occurs. I’m very sorry if you have the flu, because it’s horrid being ill; but we have not spent all this money to reduce the duration of your symptoms in the event of a pandemic by a few hours (though Tamiflu does do this, fairly satisfactorily). We have spent this money to reduce the rate of ‘complications’: a medical euphemism, meaning pneumonia and death.

      Lots of people seem to think Tamiflu will do this. The US Department of Health and Human Services said it would save lives and reduce hospital admissions. The European Medicines Agency said it would reduce complications. The Australian drugs regulator said so too. Roche’s website said it reduces complications by 67 per cent.⁷⁷ But what is the evidence that Tamiflu really will reduce complications? Answering questions like this is the bread and butter of the Cochrane Collaboration, which you will remember is the vast and independent non-profit international collaboration of academics producing hundreds of systematic reviews on important questions in medicine every year. In 2009 there was concern about a flu pandemic, and an enormous amount of money was being spent on Tamiflu. Because of this, the UK and Australian governments specifically asked the Cochrane Acute Respiratory Infections Group to update its earlier reviews on the drug.

      Cochrane reviews are in a constant review cycle, because evidence changes over time as new trials are published. This should have been a pretty everyday piece of work: the previous review, in 2008, had found some evidence that Tamiflu does indeed reduce the rate of complications. But then a Japanese paediatrician called Keiji Hayashi left a comment that would trigger a revolution in our understanding of how evidence-based medicine should work. This wasn’t in a publication, or even a letter: it was a simple online comment, posted underneath the Tamiflu review on the Cochrane website.

      You’ve summarised the data from all the trials, he explained, but your positive conclusion is really driven by data from just one of the papers you cite, an industry-funded meta-analysis led by an author called Kaiser. This, ‘the Kaiser paper’, summarises the findings of ten earlier trials, but from these ten trials, only two have ever been published in the scientific literature. For the remaining eight, your only information comes from the brief summary in this secondary, industry source. That’s not reliable enough.

      In case it’s not immediately obvious, this is science at its best. The Cochrane review is readily accessible online; it explains transparently the methods by which it looked for trials, and then analysed them, so any informed reader can pull the review apart, and understand where the conclusions came from. Cochrane provides an easy way for readers to raise criticisms. And, crucially, these criticisms did not fall on deaf ears. Tom Jefferson is an editor at the Cochrane Acute Respiratory Infections Group, and the lead author on the 2008 review. He realised immediately that he had made a mistake in blindly trusting the Kaiser data. He said so, without any defensiveness, and then set about getting the information in a straight, workpersonlike fashion. This began a three-year battle, which is still not resolved, but which has thrown stark light on the need for all researchers to have access to clinical study reports on trials wherever possible.

      First, the Cochrane researchers wrote to the authors of the Kaiser paper, asking for more information. In reply, they were told that this team no longer had the files, and that they should contact Roche, the manufacturer of Tamiflu. So naturally they wrote to Roche and asked for the data.

      This is where the problems began. Roche said it would hand over some data, but the Cochrane reviewers would need to sign a confidentiality agreement. This was an impossibility for any serious scientist: it would prevent them from conducting a systematic review with any reasonable degree of openness and transparency. More than this, the proposed contract also raised serious ethical issues, in that it would have required the Cochrane team to actively withhold information from the reader: it included a clause saying that on signing it, the reviewers would never be allowed to discuss the terms of this secrecy agreement; and more than that, they would be forbidden