Then, almost two years into this process, the EMA changed tack. Suddenly, it began to argue that study reports contain personal data about individual patients. This argument hadn’t been raised by the EMA before, but it’s also not true. There may have been some information in some whole sections of the study reports that gave detail on some individual participants’ odd presentations, or on possible side effects, but these were all in the same appendix, and could easily be removed.
The EU Ombudsman’s conclusions were clear: the EMA had failed in its duty to give an adequate or even coherent explanation of why it was refusing access to this important information. He made a preliminary finding of maladministration. After doing that, he was under no obligation to offer any further opinion on the weak excuses offered by the EMA, but he decided to do so anyway. His report is damning. The EMA had flatly failed to address a serious charge that its withholding information about these trials was against the public interest, and exposed patients to harm. The Ombudsman also described how he had gone through the study reports in detail himself, and had found that they contained neither any commercially confidential information, nor any details about the commercial development of the drugs. The EMA’s claims that answering the request would have put it under an inappropriate administrative burden were untrue, and it had overestimated the work this would have involved: specifically, he explained, removing any personal data, where it did sometimes appear, would be easy.
The Ombudsman told the EMA to hand over the data, or produce a convincing explanation of why it shouldn’t. Amazingly, the EMA, the drugs regulator covering the whole of Europe, still refused to hand over the documents. During this delay, people certainly suffered unnecessarily, and some possibly also died, simply for want of information. But the behaviour of the EMA then deteriorated even further, into the outright surreal. Any scrap of the company’s thinking about how to run the trial, it argued, which could be intuited from reading the study reports and protocols, was commercially sensitive with respect to its thoughts and plans. This was true, the EMA said, even though the drugs were already on the market, and the information was from final clinical trials, at the very end of the commercial drug-development process. The researchers responded that this was perverse: they knew that withheld data is often negative, so if anything, any other company seeing negative data about these drugs would be less likely to try to get a competitor to market, if it appeared that the benefits of the drugs were more modest than had been thought.
That wasn’t the end of it. The EMA also grandly dismissed the idea that lives were at risk, stating that the burden of proof was on the researchers to demonstrate this. To me this is – if you can forgive me – a slightly contemptuous attitude, especially given what happens in the next paragraph. It’s plainly true that if doctors and patients are unable to see which is the best treatment, then they will make worse decisions, exposing patients to unnecessary harm. Furthermore, it is obvious that larger numbers of academics making transparent judgements about publicly accessible trial data are a much more sensible way of determining the risks and benefits of an intervention than a brief blanket ‘yes or no’ edict and summary from a regulator. This is all true of drugs like orlistat and rimonabant, but it’s also true of any drug, and we will see many cases where academics spotted problems with drugs that regulators had missed.
Then, in 2009, one of the two drugs, rimonabant, was taken off the market, on the grounds that it increases the risk of serious psychiatric problems and suicide. This, at the same time that the EMA was arguing that researchers were wrong to claim that withholding information was harming patients.
And then the EMA suddenly claimed that the design of a randomised trial itself is commercially confidential information.
In case it needs reiterating, let me remind you that the first trial appears in the Bible, Daniel 1:12, and although the core ideas have certainly been refined over time, all trials are essentially identical experiments, generic across any field, with the basics of a modern trial sketched out at least half a century ago. There is absolutely no earthly sense in which anyone could realistically claim that the design of a randomised controlled trial is a commercially confidential or patentable piece of intellectual property.
This was now a farce. The researchers opened all barrels. The EMA was in breach of the Declaration of Helsinki, the international code of medical ethics, which states that everyone involved in research has a duty to make trial findings public. The researchers knew that published papers give a flattering subset of the trial data, and so did the EMA. Patients would die if the EMA continued to withhold data. There was nothing of serious commercial value in there. The EMA’s brief public summaries of the data were inaccurate. The EMA was complicit in the exploitation of patients for commercial gain.
It was now August 2009, and the researchers had been fighting for more than two years for access to data on two widely prescribed drugs, from the very organisation that is supposed to be protecting patients and the public. They weren’t alone. The French ‘prescribers’ bulletin’ Prescrire was trying at the same time to get the EMA’s documents on rimonabant. It was sent some unhelpful documents, including the rather remarkable ‘Final Assessment Report’, from the Swedish agency that had handled the drug’s approval much earlier. You can read this PDF in full online. Or rather, you can’t. On the following page you can see exactly what the scientific analysis of the drug looked like – the document the EMA sent to one of France’s most respected journals for doctors.73 I think it tells a rather clear story, and to add to the insult, there are sixty pages of this in total.
In the meantime, the Danish Medical Authority had handed over fifty-six study reports to Cochrane (though it still needed more from the EMA); a complaint from the drug company about this had been rejected by the Danish government, which had seen no problem with commercial information (there was none), nor administrative hassle (it was minimal), nor the idea that the design of a randomised trial is commercial information (which is laughable). This was chaos. The EMA – which you may remember was responsible for EudraCT, the transparency tool that is held in secret – was going out on a very peculiar limb. It seemed that it would do anything it could to withhold this information from doctors and patients. As we shall see, sadly, this level of secrecy is its stock in trade.
But now we come to the end of this particular road for the EMA. It handed the full, final study reports over to the Ombudsman, reminding him that even the table of contents for each was commercial. Once he had had these documents in his hand, his final opinion came swiftly. There was no commercial data here. There was no confidential patient information here. Hand it over to the public, now. The EMA, at glacial pace, agreed to set a deadline for delivering the data to the researchers, doctors and patients who needed it. The Ombudsman’s final ruling was published at the end of November 2010.74 The initial complaint was made in June 2007. That is a full three and a half years of fighting, obstruction and spurious arguments from the EMA, during which one of the drugs had to be removed from the market because it was harming patients.
After this precedent had been set, things had to shift at the EMA; it was forced to revise its approach, and study reports were briefly made more widely available under a new policy (this window has just been shut down, in 2013, as you will read in the Afterword). But even this policy of sharing reports did not solve the problem of access to all information about a trial: the EMA often doesn’t hold all the modules, of all the reports, for all the uses of all the medicines it has approved. And it only holds records for the most recent few years, which is hopelessly incomplete, since in medicine we use treatments that have come on the market over the past few decades. In fact, this loophole is illustrated by the very first request made by the Cochrane researchers who won this great breakthrough with the Ombudsman. They applied for documents on antidepressants: a good place to start, since these drugs have been the focus of some particularly bad behaviour over the years (though we should remember that missing trial data pervades every corner of medicine). What happened next was even more bizarre than the EMA’s three-year battle to withhold information on orlistat and rimonabant.
The researchers put in their request to the EMA, but were told that the drugs had been approved back in the era when marketing authorisations were given