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BOOST

The Buprenorphine Dosing for OUD Outcomes and Studying Treatment Episodes (BOOST) evaluation involves 10 research projects. The overarching aims are to evaluate the outcomes of episodes of care for Veterans receiving high-dose daily buprenorphine OUD treatment; examine trends in Veteran exposure to high-dose buprenorphine; and characterize features of patients and healthcare settings where high-dose buprenorphine occurs.

    High Dose Buprenorphine in the Context of Opioid Use Disorder Episodes of Care within the Veterans Health Administration: Characterization and Outcomes

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    The purpose of BOOST is to examine the effects, risks, and benefits of high-dose buprenorphine daily doses (BDD), defined as daily doses greater than 24 milligrams, among Veteran patients receiving OUD treatment.

    We will examine trends in the exposure of Veterans to high-dose BDD; characterize the course of treatment where Veterans are exposed to high-dose BDD; contrast patient and setting characteristics (e.g., settings of care, prescribers of that care) where high-dose BDD occur; and examine patient outcomes (e.g., benefits, harms) associated with high-dose BDD. We will accomplish these examinations in a phased approach with a goal of informing the VHA and its federal partners about the courses of care and patient outcomes—positive or negative—associated with high-dose buprenorphine daily doses.

    Phase 1

    Timeline: 0-6 months

    • Project 1 - Characterize VA Policy and Restrictions
    • Project 2 - Characterize Dose Patterns
    • Project 3 - Evaluate Average Daily Dose and Trajectories
    • Project 4 - Examine Overdoses and Mortality
    • Project 5 - Examine Prescriber Perceptions

    Goal:

    Characterize Veteran episodes of care regarding receipt of high dose buprenorphine daily doses

    Phase 2

    Timeline: 6-32 months

    • Project 6 - Patient-Level Covariates of High-Dose BDD
    • Project 7 - Time to B-MOUD Discontinuation
    • Project 8 - High- vs Lower-Dose BDD Patient Outcomes
    • Project 9 - Profiles of OUD Episodes of Care
    • Project 10 - Characterize Episodes of Care Outcomes

    Goal:

    Characterize patient outcomes of episodes of care regarding receipt of high dose buprenorphine daily doses

    Buprenorphine and the FDA

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    Buprenorphine, an effective treatment for opioid use disorder (OUD), is known to decrease mortality and provide other health and social benefits. The VA has offered buprenorphine medication for OUD (B-MOUD) since 2002. Since then, buprenorphine has become a first line treatment for Veterans with moderate to severe OUD diagnoses. Historically, the US Food and Drug Administration (FDA) has recommended a maximum daily dose of 24 milligrams of buprenorphine. However, this dosing guidance was supported by pilot imaging studies which did not account for patients with co-occurring pain syndromes and which were established prior to the emergence of high-potency fentanyl in the illicit drug supply.

    Emerging Research

    Prescribers have reported that higher average buprenorphine daily doses (A-BDD) are needed to control symptoms of withdrawal, cravings, and co-occurring pain among patients with OUD. Furthermore, observational and prospective studies have indicated that patients receive buprenorphine doses greater than 24 milligrams have increased retention to treatment and decreased cravings. However, it remains unclear whether the benefits of high-dose buprenorphine outweigh the potential harms. BOOST is committed to evaluating the risks and benefits of high-dose BDD and disseminating knowledge to federal partners and the public in order to improve OUD treatment for Veterans.

    October 2024

    At the beginning of Fiscal Year 2025, the initiation of BOOST gave rise to a new inter-agency evaluation between the FDA and the VA, with the goal of characterizing and improving buprenorphine treatment for Veterans with OUD.

    Head Evaluators

    VA research teams from Salt Lake City, West Haven, Little Rock, and Portland are collaborating to make this initiative possible.

    Anne Black, PhD

    West Haven VA

    Adam Gordon, MD, MPH

    Salt Lake City VA

    Corey Hayes, PhD, PharmD

    Little Rock VA

    Jessica Wyse, PhD, MA, MPP

    Portland VA

    William Becker, MD

    West Haven VA

    Affiliated Projects

      Phase 1 - Project 1

      Characterize VA Policy, Regulatory Environment, Restrictions, and Enablers of Prescribing Buprenorphine for the Treatment of OUD in the VA

      This narrative review will describe VA policy and regulatory environment to prescribe buprenorphine formulations for the treatment of OUD. The review will examine clinical practice guidelines, protocols, services, formulary information from FDA approval of buprenorphine and buprenorphine/naloxone since 2002. This review will update a recent review of Wyse, et.al. describing the history of MOUD in the VA. The review will describe the history of national initiatives to provide buprenorphine treatment in the VHA. Finally, the review will examine research gaps and opportunities to synergize operational initiatives to improve care.

      • Lead Site: Salt Lake City
      • Progress: Underway (Start: July 1, 2024)
      • Timeline: 0-9 months (End: June 30, 2025)
      • First Deliverable: July 1, 2025
      Phase 1 - Project 2

      Characterize Dose Patterns of Buprenorphine for Veterans with OUD (2006-2023)

      This analysis will (1) characterize the episodes of care of buprenorphine medication treatment for OUD (B-MOUD) within the VA. Annual trends of prescription patterns of buprenorphine daily doses (BDD) will be evaluated (range, mean, median, mode) and characterized along strata of a) >24mg BDD, b) 16 to 24mg BDD, c) 8-16mg BDD, d) <8mg BDD; (2) examine patterns of different formulations of buprenorphine (e.g., tablets, films, extended release products) regarding BDD and strata; (3) correlate changes in BDD (and strata) with VA policy changes (e.g., formulary designations, DATA 2000 changes, advanced practice clinician prescribing), (4) describe practitioner prescribing of B-MOUD regarding characteristics and strata.

      • Lead Site: Salt Lake City
      • Progress: Underway (Start: July 1, 2024)
      • Timeline: 0-18 months (End: March 31, 2026)
      • First Deliverable: April 1, 2025
      Phase 1 - Project 3

      Evaluate average Buprenorphine Daily Dose and Trajectories Within Episodes of Care 2006-2023

      This analysis will (1) identify trajectories for average buprenorphine daily dose (A-BDD) among Veterans initiating B-MOUD and (2) assess patient characteristics associated with each trajectory, particularly a high dose trajectory [i.e., average daily buprenorphine dose > 24 milligrams (mg) per day]. This study will include all B-MOUD episodes from Veterans diagnosed with OUD in the Corporate Data Warehouse from between fiscal years 2006-2020. The data used for this study, all from the Corporate Data Warehouse, will include Inpatient, outpatient, demographic, and outpatient pharmacy files.

      • Lead Site: Little Rock
      • Progress: Design phase (Start: January 1, 2025)
      • Timeline: 3-9 months (End: June 30, 2025)
      • First Deliverable: July 1, 2025
      Phase 1 - Project 4

      Examination of Fatal- and Non-Fatal Overdoses and Mortality

      This analysis will evaluate the association between the A-BDD trajectories identified in Project 3 and subsequent patient outcomes (i.e., fatal and non-fatal overdoses, overdose death, and all-cause mortality). Specifically, this study will combine data on inpatient care, outpatient care, and death certificate data from the Mortality Data Repository to identify relevant patient outcomes that may be associated with the differing dose trajectories.

      • Lead Site: Little Rock
      • Progress: Design phase (Start: January 1, 2025)
      • Timeline: 3-12 months (End: September 30, 2025)
      • First Deliverable: October 1, 2025
      Phase 1 - Project 5

      Examining the Prescriber Perceptions of High Dose Buprenorphine Prescribing

      This evaluation will utilize qualitative interviews with buprenorphine prescribers within VA to examine perceptions of, and experiences with, high dose BDD. We will utilize purposive sampling to recruit buprenorphine prescribers embedded within distinct clinical settings (mental health, SUD specialty, pain, infectious disease) and across prescriber roles (physician, advanced practice clinicians (e.g., nurse practitioners, physician assistants, pharmacists)). Participant selection will additionally aim to maximize variation across VA geographic region.  We will develop a semi-structured interview guide in collaboration with VA and federal stakeholders. Anticipated topics addressed within the guide will include perceptions and prescribing experiences with high dose BDD; clinical concerns and unanswered questions; and policy and practice considerations. We plan to conduct 40 interviews over a 8-month period. Transcription, data cleaning, coding and analysis will be on-going and complete by 12 months.

      • Lead Site: Salt Lake City
      • Progress: Underway (Start: October 1, 2024)
      • Timeline: 0-12 months (End: September 30, 2025)
      • First Deliverable: July 1, 2025
      Phase 2 - Project 6

      Patient-Level Covariates of High-Dose Buprenorphine Prescribing

      This analysis will (1) describe proportions of patients with OUD who filled high vs. low-dose B-MOUD prescriptions by year and patient characteristics, (2) compare patient groups defined by receipt of high-dose B-MOUD vs. lower-dose B-MOUD on clinical and sociodemographic characteristics, stratifying on pre/post 2021 removal of language related to >24mg BDD, (3) using multivariable logistic regression modeling, estimate the odds of high-dose B-MOUD dosing associated with patient clinical and sociodemographic characteristics in patients with OUD, stratifying on pre/post 2021 removal of guideline language on >24mg dose.

      • Lead Site: West Haven
      • Progress: Design phase (Start: April 1, 2025)
      • Timeline: 7-12 months (End: September 30, 2025)
      • First Deliverable: May 1, 2025
      Phase 2 - Project 7

      Time to B-MOUD discontinuation following initiation

      Replicating Chambers et al. (2023) with VACS National cohort data, among patients within VHA initiating B-MOUD between 2013-2023, conduct Kaplan-Meier and Cox regression survival analyses to estimate the association between buprenorphine dose and time to treatment discontinuation, controlling for potential informative censoring, and measured potential confounders. Consider inclusion of time-invariant (consistent with Chambers) vs. time-updated buprenorphine dose.

      • Lead Site: West Haven
      • Progress: Design phase (Start: March 1, 2025)
      • Timeline: 6-24 months (End: September 30, 2026)
      • First Deliverable: October 1, 2025
      Phase 2 - Project 8

      Time to high-dose buprenorphine following buprenorphine initiation

      Survival analysis assessing the association between B-MOUD start dose and time to >24 mg BDD, controlling for potential confounders, considering the effect of time-updated buprenorphine dose, co-prescription, and patient characteristics.

      • Lead Site: West Haven
      • Progress: Design phase (Start: June 1, 2025)
      • Timeline: 9-24 months (End: September 30, 2026)
      • First Deliverable: April 1, 2026
      Phase 2 - Project 9

      Propensity score-weighted comparison of high- vs. lower-dose B-MOUD exposure on patient outcomes

      Grouping patients by exposure to high-dose B-MOUD vs. lower-dose B-MOUD) compare the probability of opioid-related adverse events (overdose, withdrawal, fentanyl use, hospitalization), using propensity score weighting to control for potential confounders related to non-random assignment to treatment.

      • Lead Site: West Haven
      • Progress: Design phase (Start: October 1, 2025)
      • Timeline: 13-30 months (End: March 31, 2027)
      • First Deliverable: July 1, 2026
      Phase 2 - Project 10

      Propensity score-weighted comparison of high- vs. lower-dose B-MOUD exposure on patient outcomes

      Using latent class analysis, discrete courses of OUD treatment will be defined by type, combinations and/or sequences of treatments within episodes of care. Their associations with patient clinical and sociodemographic characteristics will be assessed.

      • Lead Site: West Haven
      • Progress: Design phase (Start: January 1, 2026)
      • Timeline: 16-30 months (End: March 31, 2027)
      • First Deliverable: September 1, 2026

      HAVE QUESTIONS?

      Contact us here:

      Jacob Baylis, MPH - Project Coordinator 

      Jacob.Baylis@va.gov  or Jacob.Baylis@utah.edu 

      Adam Gordon, MD, MPH - Principal Investigator 

      Adam.Gordon@va.gov or Adam.Gordon@utah.edu