A recent publication in the British Medical Journal (BMJ), documenting a three-year battle with the European Medicines Agency (EMA) for access to pharmaceutical data, is high-profile evidence that revised guidance is having a positive effect.
Years of debate among doctors, patients, pharmaceutical companies and regulatory agencies culminated last year in a modification to EU policy that the EMA considers acceptable.
In the BMJ article, which was published on the BMJ website on 11 May 2011, Professor Peter Gotzsche and Anders Jorgensen documented their extensive applications to the EMA for the clinical study reports of the anti-obesity drugs rimonabant and orlistat.1 The Danish researchers say they were determined to uncover these details because anti-obesity pills are controversial.
“The effect on weight loss in the published trials is small, and the harms are substantial,” said Gotzsche and Jorgensen. “People have died from cardiac and pulmonary complications or have experienced psychiatric disturbances, including suicidal events, and most of the drugs have been deregistered for safety reasons.”
The EMA refused access to the requested data after multiple appeals. In their first letter to the EMA, Gotzche and Jorgensen argued that biased accounts of drug trials are frequently published, and that withholding data strengthens this position, against the interests of patients.
After a first refusal in which the EMA said that the data release “would undermine commercial interests”, Gotzche amd Jorgensen appealed to Thomas Lönngren, the Executive Director of the EMA at the time, who said they could “institute court proceedings against the EMA” or complain to the European ombudsman.
Dr Hans-Georg Eichler, the Senior Medical Officer of the EMA, explained the long-standing motivation of the EMA to preserve confidential information.
“We recognise that pharmaceutical companies are in competition,” he said. “We acknowledge that intellectual property that has a high value riding on it is required to stimulate drug development.”
In the course of Gotzsche and Jorgensen’s appeals, the EMA refused access, quoting a series of different arguments. The main explanation was the protection of commercial interests. Other arguments included the assertion by the EMA that there was “no over-riding public interest”; the administrative burden of releasing the data; and the claim that the data sought would be of no value after the redactions by the EMA had been made.
On 8 October 2007, Gotzsche and Jorgensen sent their first communication to the European ombudsman, who subsequently wrote multiple letters of appeal to the EMA and proposed a “friendly solution” on two occasions.
On 31 August 2009, almost two years after their initial contact with the ombudsman, Gotzsche and Jorgensen informed the ombudsman that they had accessed data on the anti-obesity drug sibutramine from the Danish Medical Agency.
By 7 June 2010, the European ombudsman accused the EMA of “maladministration because of its refusal to grant access” in a press release.2
Within three months of the accusation, on 31 August 2010, the EMA informed the ombudsman that it would provide access.3
Dr Eichler says that the same debate has been going on in the United States and other jurisdictions. He said: “The US has ‘freedom of information’. If you ask the FDA for clinical trial reports, you will receive them, possibly after redactions, after a certain amount of time.
Comments from the UK Medicines and Healthcare Regulatory Agency (MHRA) suggest that it has undergone a similar evolution.
A spokesperson for the MHRA said: “Requests for information are dealt with under the Freedom of Information Act, one exemption of which is Section 43. Section 43 precludes release of information of a commercially sensitive nature where disclosure would, or would be likely to, damage commercial interests.
“We have applied S43 787 times since January 2005. Only one case got as far as an ICO [Information Commissioner’s Office] referral overturning our decision, which indicates that we are applying it correctly and proportionately.”
Gotzche and Jorgensen believe that publication of their experience and its eventual resolution “set an important precedent”. However, Dr Eichler suggests that the EMA has been reconsidering its standpoint at the same time “like every other agency and everybody else, through an evolution of thinking”.
He continues: “In the middle of last year, we resolved that we cannot maintain a position that clinical trial data are commercially confidential information.
“So we have gradually revised our policy and come out publicly with an access to documents policy on our website.
“The overarching principle is that, while a drug is still under consideration, we want to protect the process. We do not want undue influences from whichever side to influence the decision making that should be guided by the science and not by external influences.
“That is why we do not wish to make data public during the deliberations.
“However, once a decision has
been reached – be it positive or negative – then we will make the relevant information public.”
Andreas Potts, Acting Executive Director of the EMA, authored a response to the article by Gotzsche and Jorgensen that was published on the BMJ website on 13 May.
He said: “The authors make what appears to be a compelling call for more transparency by the regulatory authorities.
“However, they do so by ignoring the steps taken by the European Medicines Agency since it was established in 1995 and the latest actions and policy adopted over the last few years.
“The European Medicines Agency has taken important steps towards increasing its transparency over recent years.
“Mr Gotzsche and Mr Jorgensen themselves have acknowledged that the Agency’s new access to documents policy, which became effective in November 2010, has pushed transparency further forward than in most other drug regulatory authorities.”
Dr Eichler said: “With the benefit of hindsight, one could say, it would have been better if we had reacted somewhat faster.”
He continues: “I wish it had been a bit faster. But we also are an organisation that has to consider many stakeholders. There are other issues in there, not just commercially confidential information but also information relating to personal data.
“To give you an example, in a clinical trial report, usually there are appendices. An appendix may have the curriculum vitae of an investigator. In that will be personal information. That’s nothing to do with the trial. That’s not commercially confidential. But we have an obligation to protect that commercially.
“It could be the birth date, the private phone number of an investigator, that should not be in the public domain. So there were several considerations that we needed to resolve and that is why it did take a little while.”
When the EMA announced its new guidelines, Noël Walthion, Head of Patient Health Protection at the EMA, said: “Openness and transparency are enshrined as fundamental values in the agency’s regulatory framework.
“They allow our stakeholders to understand the basis for the agency’s scientific decision making and provide for the basis on which patients and healthcare professionals can have confidence in our opinions and information relating to medicines.”
It was reported on 7 December 2010, again in the BMJ, that Nikiforos Diamandouros, the European ombudsman, welcomed the EMA’s revised guidelines.
He said: “The EMA’s work has a direct impact on the health of European citizens. It is, therefore, crucial that EMA give the widest possible access to documents and pursue a proactive information policy for the benefit of citizens.”
Dr Eichler agreed. He said: I think the position where we are now is in everybody’s interests and should fulfill the information needs of all those who are concerned.”
- Gotzsche P and Jorgensen A. Opening up data at hte European Medicines Agency. BMJ 2011; 342: d2686
- Andreas Pott response: http://www.bmj.com/content/342/bmj.d2686/reply
- European Medicines Agencywidens access to its documents. BMJ 2010; 341: c7039. http://www.bmj.com/content/341/bmj.c7039