Drug shortages. Part 1. Definitions and harms.

Drug shortages are repeatedly in the news. The earliest drug shortages were reported during the First World War, but the numbers of shortages have increased in recent years. In the first part of this two-part review we discuss definitions of drug shortages and so-called stock-outs, which are localized shortages, and the harms that they can cause. Drug shortages make it difficult or impossible to meet the therapeutic needs of individual patients or populations, but we lack an adequate definition. The problems are too complicated to be encompassed in a brief intensional dictionary-style definition, and that is reflected in the many different attempts at definition that have been proposed. We therefore propose an extensional operational definition that incorporates the processes by which products are manufactured, the causes of shortages, and the contributory factors. A definition of this sort allows one to identify the main causes of a particular drug shortage and therefore the remedies that might prevent, mitigate, or manage it. In the second part of the review we discuss the causes and solutions in more detail. Adverse drug reactions and medication errors attributable to shortages occur but are not often reported. Adverse reactions to substitute medicines are possible, and errors can occur because of unfamiliarity or unnecessary treatment with replacement medicines. Other harmful outcomes include withdrawal reactions, under-treatment, treatment delays and cancellations, failure of alternatives, and disruption of clinical trials.