Today, the European Medicines Agency for the first time ever proactively releases key documents that will allow independent researchers to verify pharmaceutical companies’ claims about the safety and effectiveness of new medicines. Clinical Study Reports, as the documents are called, provide detailed information on the methodologies and results of clinical trials. Today’s release represents a victory for patient advocates and a huge step forward for transparency in medical research. The European Medicines Agency’s new transparency policy only applies to documents it has received since 1st January 2015.
Dr Síle Lane, director of campaigns and policy at the charity Sense about Science which runs the AllTrials campaign for clinical trial transparency, said:
It is very welcome news that the European Medicines Agency is starting to publish all Clinical Study Reports it receives. The 700 organisations in the AllTrials campaign, who between them represent hundreds of millions of people worldwide, have been calling for this. We all now hope that other global medicines regulators will follow the European Medicines Agency’s great lead. The European Medicines Agency’s new policy means there will be a lot more information about our future medicines available for scrutiny. This is fantastic. However, the majority of medicines we use now, and will continue to use for years to come, were approved in the past. And it’s the information on these medicines that remains hidden. Regulators like the European Medicines Agency need to do everything they can to ensure all information about all our medicines is available to doctors and researchers.
April Clyburne-Sherin, campaign manager of AllTrials USA, said
Lack of access to important clinical trial information is a problem that hinders clinical and policy decision making globally. Building trust in clinical research and improving the efficiency and efficacy of drug development requires that policy leaders in each country work to improve access to Clinical Study Reports. In the US, around half of clinical trials are never published, motivating a growing community of stakeholders, including policy makers, researchers, medical staff, and patients, to call for greater clinical trial transparency and access to clinical trial data. Recently, the US Food and Drug Agency responded by clarifying and expanding the requirements for clinical trial registration and sharing of results on ClinicalTrials.gov. The European Medicines Agency policy on the publication of clinical data presents a further step forward, and serves as an example for the US medical community.
The US Food and Drug Agency does not release Clinical Study Reports. Dr Erick Turner of the Center for Ethics in Health Care at Oregon Health & Science University explained to AllTrials that:
The FDA posts documents on Drugs@FDA; these are reviews that summarize the data in CSRs [Clinical Study Reports]. Researchers who have the time and interest to take a deep dive into the data will want access to the CSRs themselves, but CSRs are not made available on Drugs@FDA. Perhaps one can get (redacted) CSRs from the FDA by making a Freedom of Information request— I doubt it but I never tried it myself.
Numerous groups and individuals have expressed their support for today’s move by the European Medicines Agency. Peter Doshi of the Department of Pharmaceutical Health Services Research at the University of Maryland School of Pharmacy called on other regulators to follow suit:
The launch of EMA’s much discussed Policy 0070 marks the second of the European regulator’s landmark — and still unparalleled — achievements in democratizing access to clinical trial data and other regulatory documents. Whereas other regulators have taken a ‘hands off’ approach, the EMA has proactively re-examined its approach to claims of commercial confidentiality – and generally moved in favor of public health. Policy 70 promises a near barrier-free way for anybody with an internet connection to access clinical study reports of trials for new medicines. It confirms the EMA’s conviction that the transparency of clinical study reports and regulatory documents is fundamental to achieving its public health mission. Other regulators should take heed.
Seth Berkley, CEO of Gavi, the vaccine alliance, noted that
Opening up access to trial results has the potential to boost knowledge sharing, drive innovation and ultimately accelerate the development of lifesaving drugs and vaccines.
In a press release, the European Medicines Agency announced that
As a first step, EMA is publishing today data for two medicines, representing approximately 260,000 pages of information for over 100 clinical reports. Data will be progressively added online for all applications concerned since the policy entered into force [in January 2015]… Once the process is fully implemented and the backlog has been dealt with, EMA aims to publish the reports 60 days after a decision on an application has been taken, or within 150 days after the receipt of the withdrawal letter. EMA is committed to these timelines… According to current forecasts, EMA expects to offer access to approximately 4,500 clinical reports per year.
An European Medicines Agency webpage states that
For every new medicine, citizens, including researchers and academics, will be able to directly access thousands of pages from clinical reports submitted by companies to EMA in the context of marketing-authorisation applications. EMA is the first regulatory authority worldwide to provide such broad access to clinical data.
Professor David Webb, the president of the British Pharmacological Society, noted the potential benefits for trial participants:
The reports offer us new opportunities for increasing the effectiveness of clinical trial design and minimising the risk to volunteers and patients who participate in clinical studies.
In the past, Clinical Study Reports submitted to the European Medicines Agency could only be accessed through Freedom of Information requests, a process that could take years because drug companies at times tried to block access through the courts. Two companies are currently attempting to stop the European Medicines Agency from releasing a different set of medical research documents. Today, Richard Bergström, director general of the European Federation of Pharmaceutical Industries and Associations (EFPIA), a pharmaceutical industry group, described the new policy as “a major step forward”.
One group of independent experts recently examined Clinical Study Reports for a slimming drug obtained through a Freedom of Information request and concluded that “[the publicly available] reports of these trials seemed to have systematically understated adverse events,” suggesting that pharmaceutical companies do not always tell regulators, doctors and patients the full story about the negative side effects of the drugs they sell. In 2010, the US Food and Drug Administration found that a pharmaceutical company had failed to adequately disclose potentially lethal side effects of a diabetes drug that had been detected during clinical trials; that single drug has been estimated to have subsequently caused 100,000 heart attacks in the US alone.
During the lengthy consultation process preceding today’s release, AllTrials and many of the groups and individuals supporting the campaign submitted hundreds of comments advocating for greater transparency, keeping redactions to a minimum, and facilitating access to documents by independent researchers.
The European Medicines Agency has provided a video of the press briefing it gave on the day of the release:
Covering the European Medicines Agency’s move in FierceBiotech, Ben Adams reported that
Unhappy pharma companies, many of which have resisted the calls for transparency, have over the past four years fought back against the EMA [European Medicines Agency], hence the delays and compromises over the release of data.
The EMA said that its guidance “makes clear that the vast majority of the information contained in clinical reports is not considered CCI [commercial confidential information].” But where this might be the case, companies will need to submit to EMA for review a table justifying why such data have been redacted.
The new guidance clarifies which type of data EMA would typically refuse as being CCI and how the redaction of such data will be handled. The use of CCI was originally absent in the 2012 plans for transparency but crept into its final policy after voices from pharma swayed the agency.
Meanwhile, Alison Abbott writing in Nature observed that
In the 260,000 pages released on 20 October, almost all the redactions are made to anonymize patient data; only two pages included redactions for commercially confidential information.
The Regulatory Affairs Professionals Society published a news item quoting EMA Deputy Executive Director Noël Wathion as follows:
The amount of commercial confidential information in clinical reports is extremely limited … out of the 260,000 pages which we will release today, only two pages contain commercial confidential information that has been redacted… There can be no general presumption of confidentiality, so there can be no blanket protection as such… [O]n the redactions that are being proposed in terms of commercial confidential information, the approach of the EMA is not different in terms of access to documents [through Freedom of Information requests] versus this proactive publication of clinical data.
FierceBiotech’s Ben Adams wrapped up his article with a note of cautious optimism.
There is also concern that almost all of the data for the drugs used by doctors and patients will not be made public under the EMA’s rules, as they are only active back to drug applications from the beginning of last year.
But what has been achieved is nothing short of a major shift, in just a few years, from a paternalistic attitude from both pharma and the EMA that believed the data need only be seen by these two groups, to a proactive stance by the regulator and even by some (though not all) in pharma to share this information more widely.
Meanwhile, one early user speculated that the new EMA platform may still need some work.
— Cormac Sheridan (@Cormac_Sheridan) October 21, 2016
When we flagged this potential barrier with the EMA, their press office explained via email that
Testing the new platform for Applied Clinical Trials, journalist Peter O’Donnell managed to gain access and found what he described as an “Ali Baba’s Cave” of trial data:
As the EMA claims, the information is comprehensive… What is surprising is the public availability of this detail and extent of information. Anyone wanting to do so can consult any one of hundreds documents, ranging from the clinical overview addendum and clinical justification to detailed errata.
Patients and healthcare professionals will now be able to access more information about the data underpinning the approval of the medicines they are taking, or prescribing, thus enhancing the understanding of the use of these medicines and bolstering trust in the regulatory process.
The data can also be used for independent re-analysis by academics and researchers after a medicine has been approved, and help medicine developers learn from the experience of others, potentially leading to more treatments being developed more efficiently.