Specialists attack drug agency’s fast track approval scheme

BMJ 2016; 353 doi: (Published 01 June 2016) Cite this as: BMJ 2016;353:i3060
  1. Nigel Hawkes
  1. London

A plan to fast track the approval of new medicines in Europe has been criticised by a group of leading specialists in pharmacology and public health.

They argued in a letter to top officials at the European Medicines Agency (EMA) that the “adaptive pathways” pilot, which aims to speed the adoption of new drugs and reduce their cost, is based on flawed assumptions that lack a proper evidence base.

Among the signatories were Martin McKee, of the London School of Hygiene and Tropical Medicine; Peter Gøtzsche, of the Nordic Cochrane Centre in Copenhagen, Denmark; Tom Jefferson, honorary fellow at the Centre for Evidence-Based Medicine at Oxford; and Richard Thompson, past president of the Royal College of Physicians.

The EMA’s plan was also attacked by the European Public Health Alliance, a European non-governmental organisation, in a briefing note that made many of the same points as the letter. The letter and the note were posted on 26 May on the alliance’s website.1

Critics of the EMA plan have been galvanised by two developments: the disclosure at a London conference on 4 May that what had been described as a pilot is to be integrated into EMA’s routine approval process, even though the report of the pilot has yet to be published; and an article in the New England Journal of Medicine by EMA’s executive director, Guido Rasi, and others, claiming that the adaptive pathways approval route would reduce drug prices.2

Jefferson told The BMJ that many questions about the plan remained unanswered. He was surprised that an organisation that had led the world in achieving transparency in its operations had on this occasion functioned in secrecy. “The pilot is finished, but where is it?” he said. “How were the drugs selected, and which drugs were selected? We don’t know anything about it, which is extraordinary given EMA’s previous great achievements in opening up their regulatory archives.”

EMA’s pilot was designed to speed up the approval of new drugs by requiring less trial evidence before marketing approval, making up for it by intensive post-marketing surveillance to confirm efficacy and safety as the use of the drugs expanded. This process was originally aimed at areas of unmet need, but its critics were alarmed that the NEJM article seemed to expand it to all new medicines and to claim that it could cut drug prices—normally considered not to be a regulator’s job.

The implication, said the European Public Health Alliance briefing paper, is that fast track, light regulation will be applied to approvals for all new medicines—“a fundamental regulatory change through the back door.”

A second concern is that the proposal abandons the gold standard for medical evidence, the randomised controlled trial, and replaces it with observational trials and post-marketing surveillance. Jefferson warned of a huge literature going back to the late 1980s that observational evidence overestimated or gave the wrong answers when compared with randomised controlled trials.

And, even if that evidence put the drug in a bad light, the letter said, “once market entry is achieved it may be difficult to temper demand even if the drug is revealed to be less effective or more harmful than initially believed.” Jefferson said that it was “extraordinary” that the names of the drugs so far considered in the programme were not known.

The letter also sought reassurances that, if any drug is authorised, the post-surveillance plan must be agreed and legally binding and must follow an agreed protocol, and that the EMA will inform the public of any sanctions taken against companies that fail to comply. It acknowledged that adaptive pathways could be beneficial but emphasised a need to communicate the uncertainty involved to any patients receiving the treatment, since they will occupy an intermediary role between patients and research participants. “We expect all documents relating to adaptive pathways to be made public expeditiously,” the letter added.

An EMA spokeswoman told The BMJ that it would publish the letter on its own website, together with a response, in the next two to three weeks.


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