'Flood' of disclosure of clinical study reports curbed for now

The opinions of advocate general (AG) Gerald Hogan suggest that detailed clinical study reports (CSR) and other pre-clinical or clinical documents featuring know-how or details of expensive and time-consuming product safety testing will not be automatically subject to disclosure by the European Medicines Agency (EMA), said Nicole Jadeja and Catherine Drew of Pinsent Masons, the law firm behind Out-Law.

CSRs are prepared by businesses undertaking clinical trials to support the development of new medicines. They often contain a vast amount of detail relating to the nature of the trials, the methodology underpinning them and the results achieved. CSRs will be submitted by those businesses to regulators to support their application for marketing authorisation for the new products developed. The data contained in the CSR supports the positive risk:benefit for the product.

In two cases before it, the Court of Justice of the EU (CJEU) has been asked to determine, principally, whether the commercial interests of pharmaceutical companies in the CSRs they produce are protected by a general presumption of confidentiality. The court has also been asked to consider circumstances in which pre-clinical or clinical documents are not protected by a presumption of confidentiality but where exceptions to the disclosure may still arise.

In his opinions, AG Hogan considered how competing EU laws which apply in the context of the disclosure of clinical documents should be interpreted.

EU 'freedom of information' (FOI) laws, which concern public access to documents held by EU institutions, mandate disclosure upon request subject to exemptions applying. A separate EU regulation confirms that the rules on public access to documents apply to the EMA, and further require the EMA to "adopt rules to ensure the availability to the public of regulatory, scientific or technical information concerning the authorisation or supervision of medicinal products which is not of a confidential nature".

The EMA, the body responsible for considering applications for European marketing authorisation for medicines, has developed such a document disclosure policy and has claimed that it in many areas goes beyond what the law requires, so that it "can provide as much information to the public as possible". It has cited the publication of clinical data submitted by industry to support marketing applications as an example of this.  

In one of the cases before the CJEU, the EMA was asked to disclose the CSR prepared by an applicant for marketing authorisation for a novel treatment for a rare disease.  Disclosure was requested by a rival pharmaceutical company. The other case concerns a request to the EMA for the disclosure of toxicity study reports relevant to a veterinary medicine.

The EMA decided that the documents could be disclosed in redacted form, especially since part of the documents had already been published in a European Public Assessment Report (EPAR). EPARs are published for every human or veterinary medicine application that has been granted or refused a marketing authorisation and essentially summarise the EMA's findings on the risk:benefit of the product.

The owner of the documents challenged the EMA's views on disclosure, claiming that the documents contained confidential, commercially sensitive information and as such should not be disclosed in their entirety. In considering the companies' appeals, however, the EU's General Court upheld the EMA's view that the documents did not fall within a category of documents in which a general presumption of confidentiality has been recognised. It is these decisions of the General Court which have been appealed to the CJEU.

In his non-binding opinion on the cases, AG Hogan determined that the General Court had made a number of errors in the way it had applied the law. He said the documents are of the type to which the general presumption of confidentiality should apply and that they do contain commercially sensitive information.

Despite the protection provided by market exclusivity in the EEA, he said there were circumstances in which protection for the document in third countries such as Australia, Brazil and China would fall away if the data in the CSR enters the public domain.

Catherine Drew of Pinsent Masons said the opinions attached some weight to the time, cost and effort put into generating the data within the CSRs and toxicity reports.

"The CSR contained know-how which was the product of years of research and which represented an economic investment of several hundred million US dollars," Drew said. "The toxicity report in the second case contained the details of expensive and time consuming safety tests. These facts were undoubtedly relevant to the AG’s analysis, in determining whether the information was confidential, commercially sensitive. It raises interesting questions as to the extent to which the fact that the tests were expensive and time consuming is relevant in the assessment as to whether or not information is commercially confidential."

Drew said some stakeholders advocate that only if the methods used and disclosed in the CSRs were particularly innovative – perhaps even warranting intellectual property protection – would that make the content of the CSRs confidential, commercially sensitive information. Others would support the view of the AG that the information does not have to be "novel" to warrant protection. 

AG Hogan determined that the disclosure of the CSR would undermine the commercial interests of the document owner and provide a considerable advantage to any potential competitor.  He was persuaded by the costs and complexities of the clinical trial process and the nature of the information, which included methodologies and analysis, disclosed in the CSR. He said that even though a competitor would still have to conduct clinical studies and trials of their own prior to developing a rival medicinal product, and would benefit from a period of market exclusivity, this did not mean that access to the report would not be of considerable benefit to that business.

The AG rejected arguments raised against disclosure which were rooted in claims that the EMA's grant of a conditional marketing authorisation was part of an ongoing decision-making process. An exception written into EU FOI laws requires the refusal of disclosure of documents in cases where there has been no decision on the matter to which the document relates "if disclosure of the document would seriously undermine the institution's decision-making process, unless there is an overriding public interest in disclosure".

Nicole Jadeja of Pinsent Masons said: "The AG resolutely agreed with the General Court that the grant of a conditional marketing authorisation is a final and separate decision, based upon the recommendation of the EMA. It is not, therefore, open to argument that disclosure of the document should be refused on the basis either that it relates to a matter where a decision has not been made by the EMA or the disclosure would seriously undermine the EMA’s decision-making process."

Jadeja said: "There has been a long-standing tension between stakeholders in the industry over where the balance should lie between openness and transparency in the regulatory system, the need to provide adequate protection to the fruits of complex and expensive research and the need to make data available to stimulate competition by generic medicines."

"The opinion, if followed, will prevent the opening of floodgates for requests for disclosure of pre-clinical and clinical documents such as CSRs. However, the AG has rightly recognised the need for each set of documents to be assessed specifically and a decision made by the EMA on the merits of particular facts. The AG has said the CJEU should not just quash the decisions of the General Court but should refer the cases back to the General Court for re-examination of the documents at issue in light of his reasoning."

"Whilst the AG has struck at least a temporary blow to the EMA’s policy, it seems he has tried to strike a sensible balance between the likely positions of the innovator and generic stakeholders," she said.

There has been a sustained push over time by legislators and policy makers in favour of a more transparent regulatory process. As part of this, EU regulations were introduced in 2014 which concern the authorisation, conduct and results of clinical trials, although delays in the development of a fully functional EU portal and database mean the rules have yet to take effect.