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. In recent years, regulatory agencies have been criticized both for being overly tolerant of risks or being excessively risk-averse, which reflects the challenge in determining an appropriate balance between benefit and risk with the limited data that is typically available before drug approval. 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. Here, we discuss the consequences of regulatory risk-aversion for public health and suggest what might be done to best align acceptance of risk and uncertainty by regulators with the interests of public health.
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The authors wish to thank H. Parkinson for her invaluable technical assistance in the production of this article.
Sir Alasdair Breckenridge is a partner with NDA Partners, a US consulting firm specializing in expert product development and providing regulatory advice to medical products industries.
- Disability-adjusted life year
(DALY). One DALY can be thought of as one lost year of 'healthy' life.
- Discrete choice experiment
A quantitative technique for eliciting preferences that involves asking individuals to state their preferences for hypothetical alternative scenarios, goods or services. Each alternative is described by several attributes and the responses are used to assess whether preferences are influenced by the attributes and also the relative importance of the attributes.
- Framing effects
A concept that describes how different ways of presenting the same information often evoke different emotions and decisions. For example, the statement that “the likelihood of survival 1 month after surgery is 90%” is typically considered more reassuring than the equivalent statement that “mortality within 1 month of surgery is 10%”.
- Orphan drug
Drugs that are intended for the diagnosis, prevention or treatment of life-threatening or very serious diseases that are also rare. Definitions of 'rare' vary in different regions; for example in the European Union, the definition is diseases that affect not more than 5 in 10,000 persons.
- Precautionary principle
A strategy to cope with possible risks in which scientific understanding is incomplete. In the literature and in international treaties and declarations, various definitions can be found. Some consider it to be “a need to err on the side of caution because of uncertainties about the safety of technologies or infrastructure” or “when human activities may lead to morally unacceptable harm that is scientifically plausible but uncertain, actions shall be taken to avoid or diminish that harm”, whereas others consider it to mean that “where there are threats of serious or irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost-effective measures to prevent [environmental] degradation.”
- Priming effects
A concept that describes how the activation of one thought (for example, through exposure to an image) may trigger related thoughts that influence subsequent actions or decisions. For example, in experimental settings, people primed with thoughts of money were less willing to help others with a particular task.
- Quality-adjusted life year
A measure of disease burden that includes both the quality and the quantity of life.
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Eichler, HG., Bloechl-Daum, B., Brasseur, D. et al. The risks of risk aversion in drug regulation. Nat Rev Drug Discov 12, 907–916 (2013). https://doi.org/10.1038/nrd4129
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