Important statistical considerations in the evaluation of post‐market studies to assess whether opioids with abuse‐deterrent properties result in reduced abuse in the community

Purpose Abuse, misuse, addiction, overdose, and death associated with non‐medical use of prescription opioids have become a serious public health concern. Reformulation of these products with abuse‐deterrent properties is one approach for addressing this problem. FDA has approved several extended‐release opioid analgesics with abuse‐deterrent labeling, the bases of which come from pre‐market studies. As all opioid analgesics must be capable of delivering the opioid in order to reduce pain, abuse‐deterrent properties do not prevent abuse, nor do pre‐market evaluations ensure that there will be reduced abuse in the community. Utilizing data from various surveillance systems, some recent post‐market studies suggest a decline in abuse of extended‐release oxycodone after reformulation with abuse‐deterrent properties. We discuss challenges stemming from the use of such data. Methods We quantify the relationship between the sample, the population, and the underlying sampling mechanism and identify the necessary conditions if valid statements about the population are to be made. The presence of other interventions in the community necessitates the use of comparators. We discuss the principles under which the use of comparators can be meaningful. Conclusions Results based on surveillance data need to be interpreted with caution as the underlying sampling mechanisms can bias the results in unpredictable ways. The use of comparators has the potential to disentangle the effect due to the abuse‐deterrence properties from those due to other interventions. However, identifying a comparator that is meaningful can be very difficult.