LONDON – Long-awaited new rules on clinical trials in Europe will fail to deliver on the major objective of speeding up approvals, after a political compromise led the proposed timelines for authorizing trials to be extended.
The result would be that it could take more than 100 days to get the go-ahead for a trial. Given most member states currently have shorter timelines, the new rules – which are intended to create a harmonized and efficient framework for clinical research – will bring little or no overall improvement, and are likely to slow down the process of getting approvals for multinational trials.
For Belgium and the UK, which set the benchmark, both turning round approvals within a month, that represents a big step backward.
The agreement, reached Dec. 20, may have simplified the rules, but it “misses its initial goal,” according to the UK Bioindustry Association (BIA). The CEO of the BIA, Steve Bates, said, “I fear the compromise in extending the timelines for approval fails to improve the attractiveness of Europe and the UK as a location for global clinical trials.”
Under the new legislation, the European Union’s (EU) 28 member states will be required to grant approvals within 60 days, which is the same as under the current rules. However, that can be extended by a further 50 days for the advanced therapies category, into which many biotech products fall. Bates said increasing the timeline to more than 100 days “will result in a worse position for researchers in innovative bioscience companies, medical research charities and in hospitals and academia, than the UK consistently achieves at present.”
The European association Europabio echoed the BIA, saying the compromise text “is not ambitious enough” and signals that there is “little commitment” to restoring a competitive environment for conducting clinical research in Europe.
The European Federation of Pharmaceutical Industries and Associations (EFPIA) agreed, saying that “timelines that are too long contribute to higher clinical trials costs, which can lead to fewer clinical trials.”
In its original proposal made in July 2012, the European Commission – the body responsible for drawing up new legislation – set a deadline of 48 days for giving approvals, with an extension to 79 days for advanced therapies. For low-risk trials, such as Phase IV comparator studies of marketed drugs, the original draft proposed a deadline of 26 days.
The draft has been watered down because some countries said they could not meet the shorter timelines. EFPIA – whose members invest €2 billion (US$2.74 billion) per annum in clinical research in Europe – said it strongly supports the commission’s initial proposal. While recognizing the difficulties some member states would have in implementation, EFPIA Director General Richard Bergström pointed to Belgium and the UK as examples of best practice, saying the timelines set by the commission are achievable. “When adjustments in national regulatory systems are required, these should be regarded as an investment in the future,” he said.
Following the political approval between the member states and the European Parliament, the Clinical Trials Regulation now will go forward for formal ratification in March 2014. The measures are due to come into effect in 2015, replacing the much-maligned Clinical Trials Directive of 2001, which is blamed for creating a fragmented landscape and a huge bureaucratic overhead, placing a particular burden on academic trials.
It is significant that the new rules take the form of a regulation and not a directive since once a regulation is formally approved it is immediately applicable in every member state. Directives, on the other hand, have to be transposed into national laws, often leading to differences in interpretation between one country and another.
According to the European Commission, the 2001 directive resulted in a 25 percent decrease in the number of applications to carry out clinical trials in Europe between 2007 and 2011. Commenting on the agreement on the compromise text, EU Health Commissioner Tonio Borg said he “would have hoped for a more ambitious approach in line with [the European Commission’s] original proposal.”
If the new legislation singularly fails to deliver on the aim of speeding up approvals, it should meet the objective of reducing bureaucracy, with a streamlined application procedure. Rather than having to make separate – and often different – applications to each country for a multinational trial, there will be a single portal managed by the European Commission for submitting a standardized application.
One country will take the lead in assessing applications, taking in feedback from the other countries concerned. It is intended that a national approval would cover more than one site within a country. Ethical approvals will remain under the control of individual member states.
The new regulations also will create new requirements on transparency of clinical trials data, with a public central register of all trials and an obligation to publish a summary of results within one year of completion of a trial, and also to include a separate summary for non-experts.
The Alltrials campaign welcomed the agreement that all clinical studies conducted in Europe must be registered and the results reported. Ben Goldacre, co-founder of Alltrials and author of Bad Pharma, a book that catalogues lack of transparency around trials of currently marketed drugs, said, “This is great news and patients around the world should be grateful for all the fantastic work done on this by politicians in Europe.”
Glenis Willmott, the member of the European Parliament who is steering the legislation through Parliament, said, “For too long, unflattering studies on new medicines have gone undisclosed. Around half of all trials are never published, usually those with negative or disappointing results.”
EFPIA is currently at a standoff with the European Medicines Agency over the agency’s proposal to publish clinical study reports once the products they relate to are approved, arguing that will undermine commercial confidentiality. However, EFPIA welcomed the approach on transparency to be taken in the new clinical trials regulation, saying it respects the need to protect commercially sensitive information.