Statistical considerations in the choice of endpoint for drug use disorder trials

To date, the US Food and Drug Administration (FDA) requires drug use disorder trials developing new medications to use abstinence, a clinically meaningful endpoint, as the primary outcome. Although abstinence is the gold standard, only a relatively small percentage of participants in drug use disorder trials ever achieve this endpoint. This has prompted clinical trialists to consider quantitative measures of frequency of use, recognizing that some reductions in drug use that fall short of complete abstinence may potentially represent clinically important improvements. While much of the discussion concerning alternative outcomes to abstinence has focused on their clinical relevance, there are important statistical considerations that should also be taken into account.

In this paper, we demonstrate and highlight the degree to which use of a quantitative measure of frequency of use, relative to a binary measure of abstinence, yields a very discernible increase in statistical power for assessing efficacy or effectiveness of treatments for drug use disorders.

While it is well established that dichotomizing a quantitative measure invariably results in loss of statistical power, what is less well recognized is the degree of loss in the context of drug use disorder trials. In some cases, the required sample size must be almost doubled to achieve the same level of power.