# Assessing real-world evidence of the effects of opioid analgesic tapering on substance-related problems

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2024 · $349,045

## Abstract

Project Summary/Abstract
 Against the background of major efforts to alleviate the adverse effects of long-term opioid therapy (LtOT)
for chronic pain, there is great concern about the risk of unintended harmful consequences among those
tapering opioid dosage or discontinuing LtOT. For this reason, a 2020 National Academy of Medicine
discussion paper and multiple other recent commentaries have highlighted the urgent need for real-world
evidence regarding the benefits and harms of LtOT tapering. The overall objective of this proposal is to
leverage large-scale healthcare data and rigorous pharmacoepidemiologic designs to strengthen the evidence
base concerning the extent to which LtOT tapering affects risk of 4 substance-related outcomes: overdose,
opioid use disorder (OUD), other substance use disorder (SUD), and intentional overdose/other self-harm. The
central hypothesis is that there are minimal adverse effects of tapering compared with maintaining LtOT—and
that the effects are limited to certain clinical contexts and subgroups. The proposal’s rationale is that combining
design-based and statistical control of confounding with rigor in measurement of LtOT, tapering, and
substance-related outcomes is essential to strengthening evidence on LtOT tapering. The project will evaluate
its central hypothesis in 2 specific aims: (1) estimate the effects of LtOT tapering on serious substance-related
outcomes, and (2) identify patient groups more vulnerable to the estimated effects of LtOT tapering. Both aims
will involve the analysis of patients receiving LtOT in nationwide, longitudinal data from commercial and
Medicare Advantage healthcare insurance claims. In aim 1, the project will estimate the extent to which LtOT
tapering is associated with risk of substance-related outcomes (overdose, OUD, other SUD, and intentional
self-harm). The primary analytic approach will be a within-individual design that rules out confounding from all
time-stable factors by capitalizing on intra-individual variability over time, complemented with statistical
covariates to help account for time-varying confounding. Aim 2 will employ this within-individual approach in
subgroups to determine whether tapering-related harms are greater among individuals (a) with longer-duration
LtOT, (b) with higher-dose LtOT, (c) experiencing more rapid tapering, (d) with pre-existing SUD or other
mental health conditions, or (e) from marginalized (Black or Hispanic/Latino/a) racial and ethnic groups. The
innovation of the proposal is in its (a) rigorous research designs to reduce confounding and other biases, (b)
consideration of heterogeneity in tapering effects, and (c) interdisciplinary, international research team. The
proposal is significant because it will guide harm-benefit calculations and best practices (e.g., tapering rates)
for policy, as well as for individual patients. Without this information, tapering recommendations must still be
made using evidence that has been repeatedly ...

## Key facts

- **NIH application ID:** 10876998
- **Project number:** 5R01DA059026-02
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Patrick Donovan Quinn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $349,045
- **Award type:** 5
- **Project period:** 2023-07-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876998

## Citation

> US National Institutes of Health, RePORTER application 10876998, Assessing real-world evidence of the effects of opioid analgesic tapering on substance-related problems (5R01DA059026-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10876998. Licensed CC0.

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