Purpose: Long-term opioid therapy (LTOT) has been shown to be associated with opioid overdose, but the definition of LTOT varies widely across studies. We use a rigorous LTOT definition to examine risk of opioid overdose by duration of treatment. Methods: Data were from a large private health insurance provider in North Carolina linked to mortality records from 2006-2018. Eligible patients were adults (18-64) newly initiating opioid therapy after a pain diagnosis or surgery. We defined LTOT as ≥1 opioid prescription per month totaling ≥60 days’ supply within 90 days. We used inverse probability- (IP) weighted cumulative incidence functions to estimate three-year risk of opioid overdose and IP-weighted Fine-Gray models to estimate subdistribution hazard ratios, comparing LTOT to short- to medium-term opioid therapy (SMTOT). We also examined modification by derived indication of acute pain or surgery versus chronic pain. Results: We identified 491,369 patients, and 1.7% were exposed to LTOT. The three-year risk of opioid overdose was 0.3 percentage points (RD w= 0.003, 95% CI: 0.001, 0.005) higher in LTOT patients compared to patients with SMTOT. The weighted hazard of opioid overdose was 4.4 times as high (HR w 4.42, 95% CI 2.41, 8.11) among patients exposed to LTOT versus SMTOT. We did not find meaningful modification by clinical indication for opioid therapy. Conclusions: Exposure to LTOT was associated with increased risk of opioid overdose in this population of privately insured patients using a rigorous definition of LTOT. These findings confirm the importance of guidelines to minimize duration of opioid therapy whenever possible.

Purpose: Impact of policies limiting opioid prescribing for acute and post-surgical pain among racially minoritized populations are not well understood. We evaluated the impact of two North Carolina (NC) policies on outpatient opioid prescribing among injury and surgical patients by race, ethnicity, age, and sex. Methods: We conducted controlled and single series interrupted time series using electronic health data from two integrated healthcare systems in NC, among >11 years-old patients having acute injuries and surgery between April 2014 to December 2019. The policy interventions were safe opioid prescribing investigative initiative (SOPI, May 2016) and NC law limiting opioid days’ supply (STOP Act, January 2018). Outcomes included, proportion of patients receiving index opioid prescription after surgery or injury event, receipt of subsequent opioid prescriptions, days’ supply, and milligrams of morphine equivalents (MME). Results: Of the 621,997 surgical and 864,061 injury patients, 69.4% and 19.7%, respectively, received an index opioid analgesic prescription. There were sustained declines in index opioid prescription among post-surgical patients after SOPI [-2.7% per year (-4.6, -0.9)] and STOP act [-4.1% (-5.9, -2.2)], but no change among injury patients. Policy-related opioid prescribing declines were larger among black, native American, and Hispanic post-surgical patients than whites and Asians. Index and subsequent opioid days’ supply showed sustained declines after SOPI and STOP Act among post-surgical patients. There was no policy impact on MME. Conclusions: Policies were associated with reductions in opioid prescribing, particularly in post-surgical patients, however, racialized disparities likely reflect implicit and explicit racialized biases in pain management practices.

Purpose: In drug studies, research designs requiring no prior exposure to certain drug classes may restrict important populations. Since abuse-deterrent formulations (ADF) of opioids are routinely prescribed after other opioids, choice of study design, identification of appropriate comparators, and addressing confounding by “indication” are important considerations in ADF post-marketing studies. Methods: In a retrospective cohort study using claims data (2006-2018) from a North Carolina private insurer [NC claims] and Merative MarketScan [MarketScan], we identified patients (18-64 years old) initiating ADF or non-ADF extended-release/long-acting (ER/LA) opioids. We compared patient characteristics and described opioid treatment history between treatment groups, classifying patients as traditional (no opioid claims during prior six-month washout period) or prevalent new users. Results: We identified 8,415 (NC claims) and 147,978 (MarketScan) ADF, and 10,114 (NC claims) and 232,028 (MarketScan) non-ADF ER/LA opioid initiators. Most had prior opioid exposure (ranging 64-74%), and key clinical differences included higher prevalence of recent acute or chronic pain and surgery among patients initiating ADFs compared to non-ADF ER/LA initiators. Concurrent immediate-release opioid prescriptions at initiation were more common in prevalent new users than traditional new users. Conclusions: Careful consideration of the study design, comparator choice, and confounding by “indication” is crucial when examining ADF opioid use-related outcomes.