Key data-transparency amendments introduced in the European Parliament have made it through to the final stage of the legislative process for the European Union’s proposed regulation on clinical trials for medicinal products.
The compromise version of the draft regulation endorsed at the end of last week by the EU Member States’ Committee of Permanent Representatives (COREPER I), following agreement between Parliament and the Lithuanian presidency of the EU Council, retains provisions inserted last May by the European Parliament’s Committee on Environment and Public Health.
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30 days after the MA has been granted, the decision-making process on the MA application completed, or the application withdrawn by the sponsor.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 political agreement is subject to technical finalisation and to formal approval by the Council and the European Parliament at plenary level. A first reading in Parliament has been scheduled for 10 March 2014.
The proposed regulation, which will repeal the much-criticised clinical-trial Directive, 2001/20/EC, sets a deadline of 60 days for approving standard trial applications. This deadline may be extended by up to 50 days for more complex medicinal products.
The European Commission’s original proposals included an approval deadline of 48 to 79 days maximum, depending on the type of clinical trial, with a 26-day timeline for low-risk trials subject to a complete application and with no grounds for delay or additional requests.
The extended deadlines in the compromise package have disappointed the UK’s BioIndustry Association, whose chief executive officer Steve Bates warned that they failed “to improve the attractiveness of Europe and the UK as a location for global clinical trials”.
In particular, Bates added, “increasing the timeline to over 100 days for clinical trial approvals for advanced and innovative therapies is unlikely to boost clinical research” in the European Union.
“I fear this will result in a worse position for researchers in innovative bioscience companies, medical research charities and in hospitals and academia who are developing innovative treatments, than the UK consistently achieves at present,” he said.
There was a more resigned response from the European Federation for Pharmaceutical Industries and Associations (EFPIA), which has also lobbied hard for more competitive trial timelines.
While Federation and its membership “strongly support the timelines put forth by the Commission in its initial proposal, EFPIA recognises the difficulties faced by some Member States in implementation”, it stated.
“The legislation agreed upon today remains a positive step towards a more streamlined scientific and ethical process for clinical trials approval.”
The data-transparency provisions in the compromise legislation also include the possibility of fines if trial sponsors do not comply with the reporting requirements.
Article 89a of the proposed regulation as it stands says Member States “shall lay down rules” on “effective, proportionate and dissuasive penalties” for infringement of the new rules.
This would include non-compliance with the regulation’s provisions on “submission of information intended to be made publicly available to the EU database”.
CCI and privacy
The compromise regulation does make some concession to concerns expressed by industry over data privacy and commercially confidential information (CCI) in clinical-study reports.
In the preamble to the regulation, Recital 20a states that “in general” the data included in clinical study reports “should not be considered commercially confidential once a marketing authorisation has been granted, the decision-making process on the application for a marketing authorisation has been completed, or an application for marketing authorisation has been withdrawn”.
Moreover, the Recital says, “the main characteristics of the clinical trial, the conclusion on Part I and the decision on the authorisation of the clinical trial, the substantial modification of the clinical trial, and the clinical trial results including reasons for temporary halt and early termination, in general should not be considered confidential”.
In the main body of the legislation, however, Article 78 on the proposed EU clinical-trial database stipulates that public access may be waived where confidentiality is justified on the grounds of:
- protecting personal data in accordance with Regulation (EC) No 45/2001;
- protecting commercially confidential information (CCI), “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”;
- protecting confidential communication between Member States in relation to the preparation of the assessment report;
- ensuring effective supervision by Member States of the conduct of a clinical trial.
These exceptions were not mentioned in the generally enthusiastic welcome given to the legislative compromise by supporters of wider access to clinical-trial data.
Yet EFPIA applauded the legislators’ approach to transparency, saying it “respects the need to protect personal patient data and commercially-sensitive information”, while the BIA listed “more transparency on the conduct and results of the clinical trial” among the positive outcomes of the political debate.
No CCI definition
A more cautious note was sounded by the Ethical Medicines Industry Group (EMIG), the research-based biopharmaceutical trade association representing the interests of mainly small to medium-sized enterprises in the UK.
As EMIG pointed out, the text adopted by Committee of Permanent Representatives does not include any definition of what should be considered CCI.
And while the assumptions about commercially confidential information in Recital 20a are not legally binding, they could “serve as a means of interpretation of the binding provisions on public access to the database in the Regulation and also in relation to the ongoing discussions concerning the EMA policy on the publication of clinical-trials data”, EMIG warned.
This makes the as yet uncertain outcome of the court proceedings brought by InterMune and AbbVie against the European Medicines Agency over its disclosure of clinical-trial data on request “even more important since it has to be expected that the Court will also give some general guidance how this data must be protected against unjustified disclosure”.
AllTrials co-founder Dr Ben Goldacre had one complaint about the transparency provisions in the compromise package, which is that they remain non-retroactive.
“The vast majority of medicines prescribed today came on the market five, 10, or 20 years ago,” Goldacre commented.
“This new law will do nothing to improve the evidence base for those treatments. We still cannot get all the results of all the trials on even the simplest everyday treatments, the antidepressants, the statins, the blood pressure treatments, and more.”
These are the drugs “that doctors are using right now, and will continue to use for at least a generation”, Goldacre added. “Notably, the law would also do nothing to ensure that researchers and doctors can access all the results of trials on controversial drugs such as Tamiflu.”
Recital 20 of the regulation as it stands does state that clinical-trial data based on studies conducted before the regulation’s application date “should be registered in a public register which is a primary or partnered registry of the international clinical trials registry platform of the World Health Organisation”.