Excessive risk aversion in regulatory decision-making on medicines is not in the best interest of patients and public health, according to an article published today in Nature Reviews Drug Discovery by members of the European Medicines Agency (EMA) staff, including its Executive Director and Senior Medical Officer, chairs and members of EMA scientific committees, and representatives of national authorities. “The negative consequences of regulatory tolerance in allowing drugs onto the market that turn out to be unsafe are obvious, but the potential for adverse effects on public health owing to the absence of new drugs because of regulatory risk-aversion is less apparent”, highlight the authors.
In ‘The risks of risk aversion in drug regulation’, the authors argue that risk aversion could lead to denying a marketing authorisation to a medicine, withdrawing it from the market or restricting its use when it would in fact have caused more good than harm. They also highlight the ‘opportunity costs’ associated with the unwillingness to accept some uncertainty, as resources for research and development (R&D) are finite and a regulator’s request for additional data might have the unintended consequence of making resources unavailable for R&D programmes on other medicines that could have brought public health gains.
Therefore, the authors make the following suggestions to best align acceptance of risk and uncertainty by regulators with the best interests of public health:
- Define ways to systematically include the patient view on the level of acceptable risk linked to a medicine, which may be different to regulators’ assumptions;
- Reflect on methodologies to combine value judgements, including patients’ values, with interpretation of ‘hard’ data;
- Develop the concept of ‘tolerability of risk’ thresholds for medicines evaluation, recognising that zero risk situations do not exist in real-world conditions;
- Take into account the shift in medicines regulation towards an emphasis on surveillance of safety and effectiveness in the real world. Development of robust tools to enable real-time knowledge generation, faster decision-making and opportunities for risk minimisation measures should reduce the perceived need for risk aversion at the initial stage of licensing;
- Allow medicines regulators to factor ‘opportunity costs’ into standards for evaluation of the benefit-risk of medicines and in individual marketing-authorisation decisions.