PROJECT SUMMARY/ABSTRACT Representing ~3% of the U.S. population, non-elderly disabled Medicare beneficiaries (henceforth “disabled beneficiaries”) account for ~25% of overdose deaths and hospitalizations related to prescription opioids. Among disabled beneficiaries, opioid-related harms are concentrated in the 20-25% who are prescribed long- term opioid therapy, primarily for chronic pain. We will first examine effects of a recent, important policy intervention – Medicare Part D opioid safety edits – on an understudied, high-risk cohort of disabled beneficiaries who are prescribed long-term, high-dose opioid therapy (Aim 1). Effective January 1, 2019, Medicare Part D plans are required to incorporate a set of enhanced safety edits into their drug utilization review systems. The most salient is a “care coordination edit” alerting pharmacists when daily doses of opioid prescriptions exceed 90 morphine milligram equivalence. The new Medicare Part D opioid safety policy is intended to identify overprescribing through pharmacist-prescriber consultation without directly restricting patient access (intended beneficial effect). It may also encourage the initiation of buprenorphine for opioid use disorder treatment in lieu of high-dose opioid regimes (beneficial spillover effect). However, the possible misinterpretation of the 90-MME threshold as a “hard stop”, coupled with administrative burdens, may prompt rapid dose reduction and abrupt discontinuation (unintended detrimental effect). Furthermore, overrepresented among disabled beneficiaries, racial/ethnic minority patients and rural patients may be less likely to benefit from the Medicare Part D opioid safety policy and more susceptible to unintended harms (Aim 2). The Medicare Part D opioid safety policy is now playing out against a backdrop of the COVID-19 pandemic. To minimize potential disruptions to health care, the federal government has made temporary changes to the Medicare telehealth and opioid regulations, which may facilitate the beneficial effects of the Medicare Part D opioid safety policy and alleviate the detrimental policy effects (Aim 3). We will use 2017-22 Medicare claims data and a quasi-experimental design. We will assess appropriate opioid tapering (intended beneficial effect), inappropriate opioid tapering (unintended detrimental effect), buprenorphine initiation (beneficial spillover effect), and opioid-related adverse events in emergency department and inpatient settings (downstream effect). We aim to: 1. Examine effects of the first-year, pre-pandemic implementation of the Medicare Part D opioid safety policy on disabled beneficiaries who are prescribed long-term, high-dose opioid therapy; 2. Compare racial/ethnic and rural-urban differences in policy effects; 3. Extend Aims 1 and 2 to the pandemic and post-pandemic eras to elucidate the interaction of the Medicare Part D opioid safety policy with flexibilities provided during the COVID-19 emergency and beyond. Our findings ...