Causal inference for evaluating prescription opioid abuse using trend‐in‐trend design

Abstract

Purpose One response to the opioid crisis in the United States has been the development of opioid analgesics with properties intended to reduce non‐oral use. Previous evaluations of abuse in the community have relied on population averaged interrupted time series Poisson models with utilization offsets. However, competing interventions and secular trends complicate interpretation of time‐series analyses. An alternative research design, trend‐in‐trend, accounts for heterogeneity in per capita opioid dispensing and unmeasured time‐varying confounding, which provides a causal evaluation, provided that underlying assumptions are met. Methods Trend‐in‐trend can be modeled using a logistic regression framework. In logistic regression, exposure was any product‐specific outpatient dispensing by three‐digit ZIP code and calendar quarter, for 22 opioids. The outcome was any product‐specific abuse case ascertained from poison centers and drug treatment programs, covering 94% of the US population, between July 2009 and December 2016. Product‐specific odds ratios compared places without dispensing with places with any dispensing; the causal contrast represents the odds of product‐specific abuse in the community given exposure. Results Dispensing of new and low‐volume opioids varied considerably across the country, with no region showing high of all products. Of 22 opioids analyzed, the three with approved labeling as intended to deter abuse ranked near the lowest in both absolute (population‐adjusted rates: 1.7, 0.9, and 8.2 per million people per quarter, respectively) and relative measures (trend‐in‐trend ORs: 1.96, 1.79, 1.69, respectively). Conclusions Postmarketing studies of prescription opioid abuse may benefit by evolving from unadjusted surveillance rates to a causal inference approach.

Abuse-Deterrent Opioids: A Survey of Physician Beliefs, Behaviors, and Psychology

“…In our earlier study of national dispensing patterns, we noticed that new opioid analgesics were initially prescribed in locations that hosted phase III clinical trials for that product, tertiary care and teaching hospitals, and well-established advanced pain management clinics with multi-state catchment areas [ 30 ]. The hypothesis is also consistent with our previous analysis, where we found that early high-dispensing locations for new branded opioids was geographically concentrated and sometimes corresponded to phase 3 clinical trial sites [ 31 ], a phenomenon reported in a much earlier study [ 32 ] but given little attention until recently [ 33 ].…”

“…A common narrative has been that nonmedical opioid use increased in the United States because outpatient extended-release opioids became more widely used by those without formal pain management credentials or specialization [54][55][56][57]. From the findings of this survey and our previous work [31], we propose a complementary hypothesis that early adopters may have different approaches to opioid risk management. If confirmed by further investigation, this observation may impact the interpretation of FDA-mandated assessments of Risk Evaluation and Mitigation Strategies (REMS) that occur 18 months and 3 years after launch [58].…”

Indonesian New Exporter (INE) as a Training and Development Model Micro Small and Medium Enterprises (MSMEs) in The Field of Handicrafts

“…Current design trends and future development of craft require sustainable development strategies, explaining export opportunities and the situation when product creation is new, especially knowledge about trend craft design. Trends focus on standout products with an independent timeline in the global market (Dasgupta et al, 2019). Exploration of existing forms is the development of new products based on existing products.…”