Clinical trial data: a culture of transparency
It’s becoming clear that some of healthcare’s biggest challenges, including the continuing battle against antibiotic resistance, are going to require a collaborative approach in the industry.
The recent trend of mergers and acquisitions in pharmaceuticals highlights the industry’s newfound appetite for cross-licensing and sharing knowledge. Just two decades ago, when rivalry between the big pharma companies was at its peak, this would have been unheard of.
But in the last 12 months we’ve seen some of the largest pharmaceutical companies demonstrating their openness to change as they engage in patent licensing agreements and deals to meet their goals.
Much of a company’s commercial clout is seated in its patents, which are published for all to see, but there’s also a great deal of valuable information in the data yielded by clinical trials.
This information is usually kept secret, but after growing concerns about drug safety and efficacy, and in order to promote a culture of transparency and trust in the industry, the European Medicines Agency (EMA) announced in October that, from next year, pharma companies will be required to release the clinical trial data used to support the marketing authorisation (MA) applications for their drugs.
On the one hand, this transparency looks as though it will make the pharma industry far more efficient. There’s less chance of the same costly trials being carried out by different companies and, by examining the data in existing trials, companies can learn from the mistakes of others and redesign their trials accordingly.
In fact, a handful of companies have already embraced this culture of transparency. In the last couple of years, some of the world’s largest pharma companies, including Pfizer, Johnson & Johnson and GlaxoSmithKline, have announced that they will make their clinical trial data available to researchers.
"Once information within the MA application has been disclosed, it becomes prior art and cannot then serve as the basis for an invention and patent application."
But the move appears to be counterintuitive—in an industry where recouping the huge costs of drug development is paramount, the confidential information contained within clinical trial data is what gives companies their competitive edge.
Furthermore, clinical trial data may include privileged information, such as know-how, trade secrets or information that is protected by IP, which if disclosed could compromise a company’s commercial position.
So, after the EMA’s new transparency policy on clinical trial data comes into force next year, how can companies ensure their sensitive information is protected?
Balancing act
On October 2 the EMA announced that from January 1, 2015 all pharma companies with approved medicines in the EU after that date will be required to make the data that supported those medicines’ approval available to the public.
The EMA said it embarked on the process to introduce the policy because “it believes that the release of data, making it accessible to all who wish to see it, is about establishing trust and confidence in the system”.
The finalised policy has been in the making for longer than two years, and takes on board views and concerns of hundreds of stakeholders and organisations. However, before the current policy was a glimmer in the EMA’s eye, it was clear it might run into problems.
In early 2013, US-based pharma companies AbbVie and InterMune filed lawsuits against the EMA to stop it granting other companies access to information that supports MA applications for their drugs.
AbbVie, seeking to protect its $3 billion-a-year Crohn’s disease drug Humira (adalimumab), filed two complaints at the EU General Court in January 2013. It argued that the agency’s decision to grant this access violated AbbVie’s “fundamental right to the protection of confidential commercial information”.
Similarly, in its February 2013 complaint that focused on lung medicine Esbriet (pirfenidone), InterMune accused the EMA of failing to engage in the “balancing exercise” which, it said, is required when assessing whether there is any public interest in disclosing disputed information that overrides the need to protect its commercial interests.
AbbVie’s suits have since closed, but InterMune’s still stands and is awaiting guidance from the Advocate General of the Court of Justice of the EU (CJEU).
These lawsuits demonstrate just how long a tightrope promoting transparency may be. AbbVie and InterMune both told the Bloomberg news organisation that they were in favour of transparency but opposed the release of certain privileged information, often described as “commercially confidential information” (CCI).
Commercially confidential
One of the key concerns that emerged from the EMA’s invitations to comment on preliminary drafts of the transparency policy was the concept of CCI, and how to protect it from unfair commercial use by other companies.
The EMA defines CCI as “any information contained in the clinical reports submitted to the agency by the applicant/marketing authorisation holder (MAH) that is not in the public domain or publicly available and where disclosure may undermine the legitimate economic interest of the applicant/MAH”.
However, CCI appears to be in the eye of the beholder. A paper titled Open Clinical Trial Data for All? A View from Regulators was the first to outline the EMA’s proposed transparency policy back in 2012. The article, written by a group of regulators including the EMA’s director Guido Rasi, discusses the failed attempt by medical journal BMJ and independent organisation, the Cochrane Collaboration, to access clinical study reports about flu treatment Tamiflu (oseltamivir phosphate) from its manufacturer Genentech.
The authors agreed with the BMJ and Cochrane, believing that trial data should not be considered CCI as “most patients enrolling in clinical trials do so with an assumption of contributing to clinical knowledge”. Quoting the BMJ’s paper, they added: “Non-disclosure of complete trial results undermines the philanthropy.”
The EMA admits that in stakeholders’ competing interests, a compromise had to be made. It says that the “overwhelming majority” of data in clinical reports is not CCI.
It includes a provision whereby sponsors may propose which parts of their applications should be redacted, along with justifications on why those parts should be redacted, although it will make the final decision on what information should be removed.
But what if the agency and company do not agree on what information should be redacted? Information considered confidential may enter the public domain and damage the MA applicant’s market position.
To avoid problems later, companies may have to rethink their patenting strategies now.
A matter of time
“The agency’s proactive publication policy could prejudice later patent filings on subsequent inventions made on known products,” says Diana Heimhalt, a senior associate in Taylor Wessing’s Munich office.
Once information within the MA application has been disclosed, it becomes prior art and cannot then serve as the basis for an invention and patent application, she explains.
“MA applicants would no longer be able to use the currently confidential information to obtain patents for the inventions relating to the information in an MA application if it is disclosed to the public.”
She adds that companies will have to make a judgement on when it is more profitable to file their MA application in the EU. If they find that the most profitable option is to apply for an MA outside the EU first, it could delay the progress of medicines in the EU market as well as EU patients’ access to new drugs, Heimhalt warns.
Stephanie Pilkington, a partner at Potter Clarkson in the UK, agrees that timing is key and recommends that drug companies review their strategies for managing their patent portfolios in light of the changes.
“Prudent innovators certainly should consider how changes to the EMA’s policy might affect their plans for portfolio management and securing the strongest position from the research and development they undertake,” she says.
“Careful coordination between regulatory and IP functions should allow innovators to continue to be able to secure useful protection, but thorough and timely analysis of material submitted to the EMA will be more important than ever to make sure that protection has been sought before material potentially enters the public domain.”
What’s next?
The EMA’s policy, due to come into effect on January 1, 2015, will apply to any new MA applications made after that date.
However, uncertainties remain. Heimhalt says there are some concerns about how the policy might affect bilateral agreements, which protect partnerships and often contain confidentiality clauses.
There is also the question of whether there will be any copyright in the data submitted, she adds: “At the moment it is unclear whether or not copyright applies due to jurisdictional differences.”
Pilkington says that innovator drug companies may feel uncertain, as the EMA could make further changes to the policy in the coming months.
“Uncertainty about what the EMA will do is likely to be drug companies’ biggest concern, which has an unsettling effect, and the possibility that EMA changes in policy might have retroactive effects.”
There also remains the spectre of the CJEU’s pending opinion in InterMune v EMA, which could prompt amendments to the policy.
However, Pilkington says, continued discussion will give the EMA a better understanding of what information is commercially valuable, and the CJEU’s opinion may further clarify this understanding.
As the major challenges in healthcare evolve, so will strategies for tackling them. Such a dramatic shift in thinking from confidentiality to transparency was never going to please all parties, but if this approach proves to have a positive effect on companies’ drug pipelines, it is likely that transparency will become the way forward.
