The EU Moves To Open Up the World of Clinical Trial Data

The EU Medicines Agency (EMA) has, after 18 months of twists and turns, approved a new framework designed to ensure access to unpublished clinical trial data. The EMA rules are the first of their kind worldwide, "setting a new standard for transparency," boasted the agency's director Guido Rasi at a Parliament event for International Right to Know Day. A step forward, yes, but advocates are still leery given the leeway afforded drug companies to redact "commercially sensitive" information.

The rules, pushed by the advocacy group AllTrials and others, come almost comically late given the magnitude of the trial data problem worldwide. Basically, the status quo allows pharmaceutical researchers to trash clinical trial data if it's not to their liking.

Say that you, a pharmaceutical company, have a new drug and want to test it out. Maybe it's something new to treat high-blood pressure—a "new and improved" version of one of the current stand-by medications. You get a bunch of people together with high blood pressure and maybe a few without, and set them up on a regimen of your pill or a regimen of some placebo pill. You dutifully record the results.

At the end of the trial, you look at the results and … sad trombone. Not only has the drug not done a whole lot for high-blood pressure, it's had some pretty serious side effects.

It might seem obvious that the drug should be scrapped or at least reconfigured. You are in the business of helping people, after all. But … but all of that time and money. Instead of scrapping the drug, you scrap the study. It just gets buried. Meanwhile, a new study is conducted, perhaps tweaked a bit in its methodology, and maybe this one is a bit more positive. This more positive study is the one that gets rushed off to publication.

When regulators are then deciding to approve a drug and later when health care providers are deciding whether that drug should be recommended, they see only positive studies. The people that matter most in determining whether this particular pill should go inside of your body are none the wiser about any unpublished negative trials.

Increasingly, funding organizations in the US (like the NIH) and elsewhere are requiring the registration of clinical trials before the trial is set to begin. If you want to test something, the test needs to be made public before it has a chance to fail and be stuffed away. This doesn't force the drug company to publish the results in a journal, but it ensures that those results won't be able to just disappear. The EU Clinical Trials Regulation, a complementary set of rules to the new disclosure policies, forces researchers to register all trials as a prerequisite for drug approval.

The new EMA rules in effect force the publication of unpublished trials. This goes for any data considered during the drug (or medical device) approval process, which eventually will be all data given the new registration requirements. Once a decision is made as to whether a drug can be marketed, the data is published online.

"[The] EMA expects the new policy to increase trust in its regulatory work as it will allow the general public to better understand the Agency's decision-making," an agency press release offers. "In addition, academics and researchers will be able to re-assess data sets. The publication of clinical reports will also help to avoid duplication of clinical trials, foster innovation and encourage development of new medicines."

Several concerns persist, however, in the minds of open-data advocates. For one, the new rules offer little for drugs and devices already approved. Suffice it to say, the vast majority of drugs administered are not brand new and this makes the promised land of open clinical data a very, very distant prospect.

"The EMA's plan is to start making clinical study reports available from January 2015, and by recognizing the importance of this data, it sets a standard for data transparency now and in the future," said Carl Heneghan, director of Oxford's Centre for Evidence Based Medicine, in a statement posted to the AllTrials website. "However, what it also clearly demonstrates is the need to ensure clinical study reports are made available for all of those drugs that are in use today and predate this ruling."

A second problem is the matter of redaction. Drug companies get to black out information deemed to be commercially sensitive and that could mean a whole lot of missing data. Ben Goldacre, author of Bad Pharma and one of the principles behind the AllTrials campaign, noted that, "there are serious concerns around the redactions process."

"For this, we can only go on recent performance, which is not encouraging," Goldacre said. "EMA reached an agreement this year with AbbVie to censor information on protocol changes from the public release of a CSR. Protocol changes in a trial are precisely the kind of information that researchers need, to make an informed decision about whether that trial was a 'fair test' of the treatment."

Still, we're clearly getting somewhere. Transparency advocates now at least have a foothold, but still, the climb toward an open system of research is just getting started.