Too stringent requirements for the publication of clinical-trial data in the European Union could put investment in early-stage research at risk, the head of the UK’s BioIndustry Association (BIA) has warned.

At a meeting held in London to discuss progress with the proposed regulation to revise the EU’s Clinical Trials Directive (2001/20/EC), BIA chief executive Steve Bates welcomed the proposals in general as “moving in the right direction”, particularly in relation to issues such as streamlining the submission and assessment procedures for clinical-trial applications.

All the same, Bates commented, there was “nervousness” among BIA members about the amendments on data transparency tabled in her rapporteur’s report by Labour MEP Glenis Willmott, who addressed last week’s meeting organised by the European Parliament’s Information Office in the UK.

The proposed regulation published by the European Commission last July would require sponsors to submit a “summary of results” to the EU’s clinical-trial database within one year of a clinical trial ending.

In her rapporteur’s report, which will be voted on in the European Parliament’s Committee on Environment and Public Health, Willmott has amended this provision to read: “Within one year from the end of a clinical trial, the sponsor shall submit to the EU database the clinical study report [CSR], including a lay summary of the clinical trial”.

Willmott’s report also argues that clinical trial data “should not be considered commercially confidential once a marketing authorisation has been obtained”.

Accelerate development

The MEP insisted that sharing more knowledge about clinical-trial results would “not only increase trust in medicines but will accelerate the development of lifesaving treatments”.

All the same, she acknowledged in London, there was likely to be a “big battle” over the precise criteria for transparency. Some stakeholders wanted to see raw data from trials made publicly available, while Willmott believed a CSR should be sufficient.

The CSR data would be fully accessible public-domain material, available from a single source, Willmott confirmed.  She also said the pharmaceutical companies she had met with “didn’t have a problem” with any of Willmott’s views on transparency.

Phase III perspective

Bates wondered, though, whether the tabled amendments did not reflect something of a “Phase III view of the world”.

He referred to the “fragile nature” of the coalitions formed to get Phase I and II trials up and running, as the changing nature of drug development put increasing emphasis on collaborations between industry, academia and charities.

Protection of know-how and intellectual property were “vital” to achieving these coalitions and underpinned the funding available for partnerships, Bates warned.

The risk, he told the meeting, was that a requirement for data transparency across the board would “make getting that funding for such risky work even harder”, leaving a shortfall that “cannot be made up by academic money alone”.

Timing and ability

Bates was backed up by an (unidentified) lawyer from Covington & Burling in London, who sits on the BIA’s regulatory working group.

Although “everyone accepts that transparency is essential”, the lawyer said, there was a danger that the provisions in the Willmott report could affect both the timing of patent filings and researchers’ ability to file patents.

For example, an academic researcher or university spin-out conducting a Phase I or early Phase II study would be obliged to file for a patent on their work before the trial data became public knowledge, he noted.

Given the time it took medicines to reach the market, mandatory early filing would not only eat into post-marketing patent protection but might undermine the value of the patent if, for example, there were little evidence of efficacy at that stage.

Willmott insisted, though, that the amendments as proposed would not compromise data protection in any way, as patients’ personal data would be anonymised and “truly commercially confidential information will be treated in line with existing legislation on access to documents”.

Transparency workload

Another objection to the amendments on transparency was that the workload involved would be too onerous for non-commercial organisations.

Sarah Meredith, deputy director of the Medical Research Council’s Clinical Trials Unit, said the MRC “fully supports” the transparency cause but “we do think that requiring study reports for all clinical trials is a sledgehammer to crack a nut”.

She estimated that putting together a clinical study report was three months’ work and wondered how charities and public research funders were going to resource that.

The way to go, Meredith suggested, was mandatory trial registration and summaries, but with the addition of publication and data access for “legitimate uses”.

The European Commission’s feeling, noted Stefano Soro, head of the Product and Service Safety Unit within the Directorate-General Health and Consumers, was that it had taken a “balanced” approach on data transparency.

Moreover, the proposed summary of results would not be “such a short summary”, he added, referring to those used on the database in the US.

Not life or death

Nonetheless, “I don’t think this is going to be a matter of life or death for the Commission”, Soro told the meeting.

While some concerns had already be expressed by non-commercial research charities, the “discussion is open” and “at the end of the day it’s a political choice”, he commented.

Retrospective reporting

Dr Síle Lane, campaigns manager for Sense About Science (part of the AllTrials campaign for data transparency), described the EU database and the Willmott amendments as “good steps forward” but wanted to know what was being done about retrospective registration and reporting of clinical trials.

The “vast majority” of drugs now prescribed in Europe were licensed 10-15 years ago, Lane pointed out. These medicines were now coming off patent and there might be other uses for them.

“Surely the regulators and researchers need to know all the trials that were done on these drugs and what was in them,” Lane commented.

As Soro observed, clinical trials conducted outside Europe or in the framework of a marketing authorisation had to comply with current legislation and be listed on a publicly available registry.

However, the proposed regulation to overhaul Directive 2001/20/EC did not deal with the marketing authorisation of medicines, nor was it just about drug development, he stressed. Rather, the intention was to create a framework for all types of trials.

Retrospective transparency might be problematic, Soro suggested: “It’s more difficult to deal; with the past than to deal with the future”.