Clinical-trial data regarded as commercially confidential information (CCI) will be exempt in some circumstances from public disclosure under the new EU clinical-trials Regulation adopted by plenary vote in the European Parliament last week.

The issue is particularly sensitive in light of the proceedings brought by InterMune and AbbVie against the European Medicines Agency (EMA) over its disclosure of clinical-trial data on request.

Last week AbbVie withdrew its two court cases against the EMA after reaching a compromise in which the agency accepted “an entirely new set of redacted documents and related justification for redaction proposed by the company” (see separate story on today’s clinical e-lert).

The two developments in combination were interpreted by some news outlets – apparently taking their cue from initial comments by the AllTrials data-transparency campaign – as meaning that commercial confidentiality is no longer a valid argument for withholding any clinical-trial data from the public.

Statements from industry, though, as well as actual provisions in the text adopted by European Parliament, suggest otherwise. 

In response to a request for clarification, AllTrials acknowledged that the relevant post on its website “attempted to summarise this complex issue and was perhaps overly broad in that instance”. The campaign said it would duly amend the reference to CCI and Clinical Study Reports.

Full functionality

MEPs voted by 594 to 17 against, with 13 abstentions, to adopt the European Parliament’s  position on the new regulation, which will repeal the much-criticised clinical-trials Directive, 2001/20/EC.

The Regulation now has to be formally adopted by Council and published in the EU’s Official Journal.

Its implementation depends on the EMA achieving full functionality with the EU portal and database under development to address requirements for clinical-trial approvals and data transparency in the new regulation. Accordingly, the regulation is expected to take effect in mid-2016 at the earliest.

In line with a compromise version agreed last December, the approved text retains provisions inserted last May by the European Parliament’s Committee on Environment and Public Health under the guidance of rapporteur Glenis Willmott.

Notably, these include the obligation for clinical-trial sponsors to submit a results summary, regardless of the study outcome, to a publicly accessible EU database within one year of the trial ending, as well as an additional summary understandable to lay people.

Where the purpose of the trial is to obtain a marketing authorisation (MA), the applicant will also have to file the clinical-study report to the EU’s database 30 days after the MA has been granted, the decision-making process on the MA application completed, or the application withdrawn by the sponsor.

The new Regulation also makes provision for “effective, proportionate and dissuasive” penalties where clinical-trial sponsors do not comply with the transparency or other requirements.

Key provisions

Among other key features of the approved Regulation, as detailed by the European Commission, are:

  • A streamlined authorisation procedure, allowing for a “fast and thorough assessment” of clinical-trial applications by all Member States concerned and resulting in a single assessment outcome.                                                                                     
  • Simplified reporting procedures, so that researchers will no longer have to submit “largely identical information” on clinical trials separately to various bodies and Member States.                                                                                                              
  • The responsibilities and detailed composition of ethics committees will continue to be determined independently by each EU Member State.                                                          
  • Extending the concept of tacit agreement in the assessment phase of a clinical-trial application to all assessors.                                                                                     
  • A risk-based approach to clinical-trial regulation, including a lighter touch for ‘low-intervention’ trials.  

Clear statement

Willmott, who is leader of the European Parliamentary Labour Party and Labour member of the European Parliament for East Midlands in the UK, took a similar line to AllTrials on the vexed issue of data transparency and CCI.

The regulation as adopted by plenary vote includes “a clear statement that Clinical Study Reports should not be seen as commercially confidential”, she declared.

“This is vital in supporting the European Medicines Agency as they try to publish the data they hold on old trials.”

The European Ombudsman, Emily O'Reilly, noted that over the last five years her office had dealt with “several complaints from citizens who were refused access to clinical-trials data”.

During the same period, the Ombudsman has conducted more than a dozen inquiries into the EMA, many involving “refusals to make public documents regarding the authorisation and regulation of medicines by the Agency”.

Thanks to the Ombudsman’s intervention, the EMA had agreed it should release these documents on request, and had declared that it would “make all similar information publicly available proactively”.

“The Ombudsman strongly supports this aim and will work tirelessly to ensure that it is achieved,” it stated.

CCI exemption

According to AllTrials, the approved regulation “says that information from Clinical Study Reports of trials should not be considered commercially confidential”. 

However, the published text approved by the Parliament only stipulates, in its preamble  (Recital 68), that “in general” the data included in a clinical-study report “should not be considered commercially confidential once a marketing authorisation has been granted, the procedure for granting the marketing authorisation has been completed, [or] the application for marketing authorisation has been withdrawn”.

Moreover, the “main characteristics of a clinical trial, the conclusion on Part I of the assessment report for the authorisation of a clinical trial, the decision on the authorisation of a clinical trial, the substantial modification of a clinical trial, and the clinical-trial results including reasons for temporary halt and early termination, in general, should not be considered confidential”, it adds.

The approved text goes on to state, in detailing the provisions for a publicly accessible EU database of clinical-trial data (Article 81 (4)), that the database “shall be publicly accessible unless, for all or part of the data and information contained therein, confidentiality is justified on any of the following grounds:

  • protecting personal data in accordance with Regulation (EC) No 45/2001;
  • protecting commercially confidential information, in particular through taking into account the status of the marketing authorisation for the medicinal product, unless there is an overriding public interest in disclosure”.

Ian Bushfield, campaigns support officer at Sense About Science (which is backing the AllTrials initiative), said MEPs had “fought very hard to get the Regulation to reflect the EU Ombudsman’s ruling that public interest generally overrides commercial interests” in terms of disclosing trial data

“With this Regulation and the EMA’s work it seems that sharing Clinical Study Report information will be the default,” he added. “This is good news because recent work has shown that CSRs contain a lot more, and a lot more useful, information than published papers from trials “.

Compromise version

The CCI provisions were already in place last December, when a compromise version of the draft regulation was endorsed by the EU Member States’ Committee of Permanent Representatives (COREPER I), following agreement between Parliament and the Lithuanian presidency of the EU Council.

At that point – as with the European Parliament’s plenary vote last week – the exceptions for disclosure of CCI were not mentioned in the generally enthusiastic welcome given to the legislative compromise by supporters of wider access to clinical-trial data.

Clearly the industry sees things differently. In response to the plenary vote, the European Federation of Pharmaceutical Industries and Associations (EFPIA) welcomed “the legislation’s approach to transparency, which respects the need to protect personal patient data and commercially confidential information”.

Similarly, the Association of the British Pharmaceutical Industry commended “the progress all parties have made in reaching an agreed European position, which also reflects a commitment to the protection of personal patient data and commercially confidential information”.

Retroactive lack

While AllTrials hailed the transparency provisions adopted by the Parliament as “fantastic”, it again bemoaned the lack of any requirement to publish trial data retroactively.

The new legislation “is only concerned with new trials, said AllTrials co-founder Dr Ben Goldacre.

“It does not address the far bigger problem, that we still don’t have full reporting for all trials on the medicines we are using right now, today, medicines which we will continue to use for the foreseeable future.”

Doctors and patients “simply cannot make informed decisions about which treatment is best, when the evidence on the treatments they are using is still being routinely and legally withheld”, Goldacre stated.

Implementation concerns

Industry also voiced some concerns, specifically around implementation of the new provisions at Member-State level.

While EFPIA, for example, believes the new legislative framework will facilitate a more streamlined and harmonised approach to clinical trials in the European Union, it also complains that some of the initial objectives in overhauling the Clinical Trials Directive “have been only partially achieved”.

The goal, EFPIA says, was to improve the efficiency of processes for authorising and conducting clinical trials in the EU and, in turn, to boost the region’s competitiveness as a clinical research hub, “encouraging more efficient patient access to innovative medicines in the EU”.

In this respect, the association insists, it is “critical that the [European] Commission and EMA interpret the Clinical Trial Regulation in a manner that respects patient privacy, the integrity of regulatory decision-making, and incentives for companies to make long-term investments in biomedical research”.

Applied in practice

According to EFPIA director general Richard Bergstrom, the success of the regulation will “depend on how it is applied in practice”.

It will be “essential to collaborate with relevant stakeholders and ensure they have the opportunity to provide input”, he stressed. “This is a must if we are to achieve a system that will foster the innovation we need to improve patient outcomes”.

That includes promoting collaboration between ethics committees and ensuring that clinical-trial applications are assessed “in the shortest time frame possible”.

The UK’s BioIndustry Association (BIA) echoed these sentiments, saying it “remains committed to ensuring that the new legislation delivers what it was intended to do - to improve Europe’s attractiveness as a location for clinical research”.

For that to happen, though, “we now need to ensure the legislation delivers simplification, efficiency, standardisation and speed in starting clinical trials”, BIA noted.

As such, the regulation must be “adopted and implemented in a practical and consistent way”, the association added, promising to work with regulators including the EMA and the UK’s Medicines and Healthcare products Regulatory Agency “to ensure the future EU Portal system is efficient, user-friendly and secure”.

As the regulation will be taking effect in 2016, “I would encourage companies planning trials in the next couple of years to use the Voluntary Harmonisation Procedure for multinational clinical trials and engage with the BIA as we consult members on implementation measures”, stated Steve Bates, the association’s chief executive officer.