Leading figures in the European Medicines Agency (EMA) have warned that a climate of risk-aversion in medicines regulation is threatening patient and public health.
In Nature Reviews Drug Discovery, EMA’s executive director Guido Rasi and senior medical officer Hans-Georg Eichler – along with other senior colleagues – suggest there has been a shift towards an intolerance to risk that is denying patients access to new treatments.
“The negative consequences of regulatory tolerance in allowing drugs onto the market that turn out to be unsafe are obvious,” write the authors. However, “the potential for adverse effects on public health owing to the absence of new drugs because of regulatory risk-aversion is less apparent,” they add.
The phenomenon is recognised in The Future of Pharma, a 2011 book by Prof Brian D Smith which suggests risk-aversion by regulators may be a symptom of a broader, societal intolerance of risk that has emerged alongside increasing affluence.
Coupled with an increasingly litigious culture which punishes companies when things go wrong, risk aversion is a major challenge for the pharma industry, argues Prof Smith, and being able to overcome regulatory burden is now a “significant fitness criteria” for pharma companies.
Drugs are approved by regulatory agencies on the basis of their assessment of whether the available evidence indicates that the benefits of the drug outweigh its risks, and in recent years agencies have been criticised both for being overly tolerant of risks or being excessively risk-averse.
That situation reflects the challenge in determining an appropriate balance between benefit and risk with the limited data that is typically available before a drug’s approval. A drug may be denied a marketing authorisation, be withdrawn from the market or restricted in use when it might in fact cause more good than harm, they note.
“There are no hard and fast rules, and different stakeholders may arrive at divergent conclusions when balancing the expected benefits of a drug against the harms it might cause once allowed onto the market,” note Eichler et al in the Nature article.
In turn, the unwillingness to accept uncertainty – for example by regulatory request for additional data before licensing – has a knock-on effect on pharmaceutical R&D. With finite resources available to drug developers, raising the hurdle too high can make other R&D programmes nonviable.
They call for greater involvement by patients to gauge the acceptable level of risk linked to a medicine – citing the case of Biogen Idec’s briefly withdrawn multiple sclerosis drug Tysabri (natalizumab) – and suggest new methodologies should be drawn up to combine patient views with hard data.
A key change would be to develop the concept of ‘tolerability of risk’ and the recognition that zero-risk does not exist in real life situations.
“Good drug regulation is more than just minimising risks; it is about maximising gains in public health,” conclude the authors.