Analyzing quality of life among people with opioid use disorder from the National Institute on Drug Abuse Data Share initiative: implications for decision making.

PURPOSE: We aimed to estimate health state utility values (HSUVs) for the key health states found in opioid use disorder (OUD) cost-effectiveness models in the published literature. METHODS: Data obtained from six trials representing 1,777 individuals with OUD. We implemented mapping algorithms to harmonize data from different measures of quality of life (the SF-12 Versions 1 and 2 and the EQ-5D-3 L). We performed a regression analysis to quantify the relationship between HSUVs and the following variables: days of extra-medical opioid use in the past 30 days, injecting behaviors, treatment with medications for OUD, HIV status, and age. A secondary analysis explored the impact of opioid withdrawal symptoms. RESULTS: There were statistically significant reductions in HSUVs associated with extra-medical opioid use (-0.002 (95% CI [-0.003,-0.0001]) to -0.003 (95% CI [-0.005,-0.002]) per additional day of heroin or other opiate use, respectively), drug injecting compared to not injecting (-0.043 (95% CI [-0.079,-0.006])), HIV-positive diagnosis compared to no diagnosis (-0.074 (95% CI [-0.143,-0.005])), and age (-0.001 per year (95% CI [-0.003,-0.0002])). Parameters associated with medications for OUD treatment were not statistically significant after controlling for extra-medical opioid use (0.0131 (95% CI [-0.0479,0.0769])), in line with prior studies. The secondary analysis revealed that withdrawal symptoms are a fundamental driver of HSUVs, with predictions of 0.817 (95% CI [0.768, 0.858]), 0.705 (95% CI [0.607, 0.786]), and 0.367 (95% CI [0.180, 0.575]) for moderate, severe, and worst level of symptoms, respectively. CONCLUSION: We observed HSUVs for OUD that were higher than those from previous studies that had been conducted without input from people living with the condition.

Thus far, health-related quality of life estimates for patients with opioid use disorder in the United States are limited, and importantly, they were not generated from studies among people living with the condition. This study extracted data from six clinical trials providing data among 1,777 people with opioid use disorder, made publicly available by the National Institutes of Health, to produce estimates of health-related quality of life. Our study found higher health-related quality of life estimates as compared to previous studies, modest impact of medications for opioid use disorder and strong impact of withdrawal symptoms on this outcome. These higher values among people with opioid use disorder might reflect the very negative perception of this condition among members of the general population (among whom these estimates have been generated previously). However, these relatively high estimates could also reflect an adaptation to the condition or a lack of awareness of associated-health damage in the context of dependence. The low number of observations providing data on medications for opioid use disorder led to high uncertainty around related estimates of health-related quality of life, but our findings could also reflect real experiences by patients in the absence of the positive effects of non-medication opioids, which deserve more attention in clinical practice. Our study suggests that systematically measuring withdrawal symptoms and representing these in health economic models might provide a more accurate representation of health-related quality of life among people with opioid use disorder and therefore of the impact and cost-effectiveness of interventions.

Characterization of peer support services for substance use disorders in 11 US emergency departments in 2020: findings from a NIDA clinical trials network site selection process.

INTRODUCTION: Emergency departments (ED) are incorporating Peer Support Specialists (PSSs) to help with patient care for substance use disorders (SUDs). Despite rapid growth in this area, little is published regarding workflow, expectations of the peer role, and core components of the PSS intervention. This study describes these elements in a national sample of ED-based peer support intervention programs. METHODS: A survey was conducted to assess PSS site characteristics as part of site selection process for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) evaluating PSS effectiveness, Surveys were distributed to clinical sites affiliated with the 16 CTN nodes. Surveys were completed by a representative(s) of the site and collected data on the PSS role in the ED including details regarding funding and certification, services rendered, role in medications for opioid use disorder (MOUD) and naloxone distribution, and factors impacting implementation and maintenance of ED PSS programs. Quantitative data was summarized with descriptive statistics. Free-text fields were analyzed using qualitative content analysis. RESULTS: A total of 11 surveys were completed, collected from 9 different states. ED PSS funding was from grants (55%), hospital funds (46%), peer recovery organizations (27%) or other (18%). Funding was anticipated to continue for a mean of 16 months (range 12 to 36 months). The majority of programs provided "general recovery support (81%) Screening, Brief Intervention, and Referral to Treatment (SBIRT) services (55%), and assisted with naloxone distribution to ED patients (64%). A minority assisted with ED-initiated buprenorphine (EDIB) programs (27%). Most (91%) provided services to patients after they were discharged from the ED. Barriers to implementation included lack of outpatient referral sources, barriers to initiating MOUD, stigma at the clinician and system level, and lack of ongoing PSS availability due to short-term grant funding. CONCLUSIONS: The majority of ED-based PSSs were funded through time-limited grants, and short-term grant funding was identified as a barrier for ED PSS programs. There was consistency among sites in the involvement of PSSs in facilitation of transitions of SUD care, coordination of follow-up after ED discharge, and PSS involvement in naloxone distribution.

PERSPECTIVE: Health Economic Interests at NIMH and NIDA to Improve Delivery of Behavioral Health Services.

BACKGROUND: Effective financing mechanisms are essential to ensuring that people can access and utilize effective treatments and services. Financing mechanisms are needed not only to pay for the delivery of those treatments and services, but also ancillary costs, while also keeping care affordable. AIMS: This article highlights key areas of the interest of the National Institute of Mental Health (NIMH) and the National Institute on Drug Abuse (NIDA) in supporting applied health economics and health care financing research. Specifically, this article discusses the long-range impact of NIH's earlier investments in applied health economics research, and NIH's ongoing efforts to communicate its interests in health economics research. We discuss the 2023 NIMH-NIDA-sponsored health economics conference, and the ideas presented there for developing and assessing innovative behavioral health care financing models; three of the presented papers were recently published in the Journal of Mental Health Policy and Economics. METHODS: We describe the history and impact of NIMH- and NIDA-sponsored economic research and identify current research interests as identified in the NIMH and NIDA Strategic Plans and recent funding announcements. We examine themes presented at the NIMH-NIDA Health Economics conference. The conference included over 300 participants from 20 countries, from six continents. RESULTS: The topics highlighted at the conference highlight the ways in which NIH-funded research has promoted the development of innovative health care financing methods, both from the supply side (e.g., providers and payers) and demand side (e.g., service users and families). Invited speakers discussed the findings from NIH-supported research in the topic areas of payment and financing, behavioral economics and social determinants of health. Keynote speakers highlighted emerging topics in the field, including the economics of health equity, biases in mental health models in health care, and value-based insurance design. DISCUSSION: We demonstrate a resurgence of and explicit interest in health economics and policy research at NIMH and NIDA. However, more work is needed in order to design funding mechanisms that fully provide access to and facilitate use of effective evidence-based practices to improve mental health outcomes. For example, it is important that policy and health economic research projects include decision makers who will be the end users of data and study results, to ensure that results can be meaningfully put into practice. IMPLICATIONS FOR HEALTH CARE: Designing effective and efficient funding mechanisms can help ensure that service users have access to effective treatments and that clinicians and provider organizations are adequately compensated for their work. IMPLICATIONS FOR HEALTH POLICIES: Federal, state, and local policies, as well as policies of payers and health care organizations, can influence the type of care that is supported and incentivized. IMPLICATIONS FOR FURTHER RESEARCH: As demonstrated by the research interests as outlined in their respective Strategic Plans and funding announcements, NIMH and NIDA continue to fund health economic and policy research that aims to improve health care access, quality and outcomes for people with or at risk of developing behavioral health conditions in the US and around the world.

National Institute on Drug Abuse Clinical Trials Network Meeting Report: Managing Patients Exposed to Xylazine-Adulterated Opioids in Emergency, Hospital and Addiction Care Settings.

Used as a veterinary sedative and not approved for human use, xylazine has been increasingly linked with opioid overdose deaths in the United States. A growing number of people have been exposed to xylazine in the illicit opioid supply (especially fentanyl) or in other drugs, particularly in some areas of the Northeast. Xylazine is an α-2 adrenergic agonist that decreases sympathetic nervous system activity. When combined with fentanyl or heroin, it is purported to extend the duration of the opioid's sedative effect and to cause dependence and an associated withdrawal syndrome; however, data to support these concerns are limited. Despite the escalating frequency of detection of xylazine in people with nonfatal and fatal opioid overdose, direct links to these outcomes have not been identified. Because the strongest causal link is to fentanyl coexposure, ventilatory support and naloxone remain the cornerstones of overdose management. Xylazine is also associated with severe tissue injury, including skin ulcers and tissue loss, but little is known about the underlying mechanisms. Nonetheless, strategies for prevention and treatment are emerging. The significance and clinical effects of xylazine as an adulterant is focused on 4 domains that merit further evaluation: fentanyl-xylazine overdose, xylazine dependence and withdrawal, xylazine-associated dermal manifestations, and xylazine surveillance and detection in clinical and nonclinical settings. This report reflects the Proceedings of the National Institute on Drug Abuse Center for the Clinical Trials Network convening of clinical and scientific experts, federal staff, and other stakeholders to describe emerging best practices for treating people exposed to xylazine-adulterated opioids. Participants identified scientific gaps and opportunities for research to inform clinical practice in emergency departments, hospitals, and addiction medicine settings.

Research Priorities to Improve Treatment of Patients Exposed to Xylazine-fentanyl: Rapid Communication from a National Institute on Drug Abuse Center for the Clinical Trials Network Meeting.

ABSTRACT: In response to the rapid escalation in the detection of xylazine in the unregulated drug supply, in April 2023, the White House designated fentanyl contaminated with xylazine an "emerging threat." The National Institute on Drug Abuse Center for Clinical Trials Network convened a multidisciplinary meeting of stakeholders, federal staff members, researchers, and clinicians caring for patients with fentanyl and xylazine exposures. This convening focused on the most critical areas of concern with the goal of describing current practices and a xylazine-fentanyl research agenda. Discussions focused on the domains of epidemiology and laboratory detection, xylazine withdrawal and overdose, and dermal manifestations. The authors were involved in planning and moderating the program and providing a summary of the proceedings.

National Institute on Drug Abuse: Dissemination of Scientific Knowledge to Improve Adolescent Health.

The wide and effective dissemination of research findings is crucial to the mission of the National Institute on Drug Abuse (NIDA). This article describes NIDA dissemination efforts and resources that are available to inform clinicians, teens, families, and educators about youth and substance use. Resources that are available include content addressing facts about youth drug use, trends in use, and stigma, in addition to substance use disorder (SUD) prevention and treatment. Information is provided about resources such as infographics, research-based practice guides, training, educational events, and online videos. How input is solicited to inform dissemination efforts is described and future directions for NIDA's dissemination efforts are outlined.

The national institute on drug abuse diversity scholars network: success for a diverse addiction science workforce.

There is a well-known lack of diversity in many Science, Technology, Engineering, and Mathematics (STEM) fields. The gap in awarded National Institutes of Health (NIH) grants for scientists from underrepresented populations at the early stages of their careers contributes significantly to this lack of diversity. The National Institute on Drug Abuse (NIDA) Diversity Scholars Network (NDSN) program implemented a new model in 2016 to provide support to underrepresented early-career investigators (ECIs) by equipping them to navigate the competitive NIH grant process. NDSN has a demonstrable track record of providing equity through educational opportunities by enhancing the grant funding success of participants. Of 59 participants from 2016 through 2021, 53% received funding within the first two years after completing the program and 69% by four years. NDSN scholars surmount systemic funding barriers by building relationships with scientific coaches, mentors, NIDA Program Officials and intentionally engaging in network building, which all contribute to the funding success of ECIs. NIDA's NDSN program provides a model for retaining underrepresented ECIs that not only benefits individual scholars, but also the institutions they serve and society as a whole.

National Institute on Drug Abuse (NIDA) research priorities to support the development of incentive-based treatments for substance use disorders.

The purpose of this commentary is to highlight current research priorities of National Institute on Drug Abuse (NIDA) Division of Therapeutics and Medical Consequences (DTMC) regarding the development and testing of incentive-based interventions for the treatment of substance use disorders (SUDs). This manuscript summarizes the NIH Stage Model for behavioral intervention development, briefly reviews existing research on incentive-based treatments for SUDs that falls within the scope of DTMC at NIDA and highlights the development of digital therapeutics-based incentive interventions as an exemplar and high priority area. We briefly review how digital therapeutics approaches may address some common limitations to dissemination of incentive-based interventions and highlight opportunities for integrating incentive-based approaches into pharmacotherapy efficacy trials. Finally, we mention several related funding opportunities for researchers interested in developing incentive-based approaches for SUD treatment. The overall goal of this commentary is to inform the research community of current NIDA priority areas for intervention development and funding.

National Institute on Drug Abuse Clinical Trials Network Meeting Report: Advancing Emergency Department Initiation of Buprenorphine for Opioid Use Disorder.

Opioid use disorder and opioid overdose deaths are a major public health crisis, yet highly effective evidence-based treatments are available that reduce morbidity and mortality. One such treatment, buprenorphine, can be initiated in the emergency department (ED). Despite evidence of efficacy and effectiveness for ED-initiated buprenorphine, universal uptake remains elusive. On November 15 and 16, 2021, the National Institute on Drug Abuse Clinical Trials Network convened a meeting of partners, experts, and federal officers to identify research priorities and knowledge gaps for ED-initiated buprenorphine. Meeting participants identified research and knowledge gaps in 8 categories, including ED staff and peer-based interventions; out-of-hospital buprenorphine initiation; buprenorphine dosing and formulations; linkage to care; strategies for scaling ED-initiated buprenorphine; the effect of ancillary technology-based interventions; quality measures; and economic considerations. Additional research and implementation strategies are needed to enhance adoption into standard emergency care and improve patient outcomes.

NIDA Boosts Research and Development of Medical Devices for Substance use Disorder via the NIH Blueprint MedTech Initiative.

Background: Deaths from drug overdose have reached a crisis level, with more than 100,000 reported from April 2020 to April 2021. Novel approaches to address it are urgently needed. Objectives: National Institute on Drug Abuse (NIDA) is leading novel comprehensive efforts to develop safe and effective products that address the needs of the citizens affected by SUD. NIDA aims to support research and development of medical devices intended to monitor, diagnose, or treat substance use disorders. Results: NIDA participates in Blueprint MedTech program is part of the large NIH Blueprint for Neurological Research Initiative. It supports the research and development of new medical devices through product optimization, pre-clinical testing, and human subject studies, including clinical trials. The program is structured in two main components - Blueprint MedTech Incubator and Blueprint MedTech Translator. It offers free to the researcher services that are typically unavailable in academic environment - business expertise facilities and staffing to successfully develop minimum viable devices, pre-clinical bench testing, clinical studies, planning and executing in manufacturing, as well as regulatory expertise. Conclusions: Through Blueprint MedTech, NIDA provides innovators with expanded resources to ensure the success of the research.

National Institute on Drug Abuse: Dissemination of Scientific Knowledge to Improve Adolescent Health.

The wide and effective dissemination of research findings is crucial to the mission of the National Institute on Drug Abuse (NIDA). This article describes NIDA dissemination efforts and resources that are available to inform clinicians, teens, families, and educators about youth and substance use. Resources that are available include content addressing facts about youth drug use, trends in use, and stigma, in addition to substance use disorder (SUD) prevention and treatment. Information is provided about resources such as infographics, research-based practice guides, training, educational events, and online videos. How input is solicited to inform dissemination efforts is described and future directions for NIDA's dissemination efforts are outlined.

Increasing evidence-based substance use interventions globally: The National Institute on Drug Abuse postdoctoral fellowships.

As of April 2020, 121 individuals from 47 nations had completed 124 NIDA International Program INVEST Drug Abuse Research Fellowships. This is the first comprehensive effort to assess the fellowships from the combined perspectives of career outcomes, migration patterns, publications, cost per publication, and funding. We searched electronic sources such as university websites, ResearchGate, LinkedIn, PubMed, and NIH databases to find current curriculum vitae, journal articles published in 2018 and 2019, and funding records. We found electronic records for 94.2% of former NIDA INVEST fellows (n = 114); 55.5% were male (n = 67). The majority are at least partially involved in addiction research, prevention, or treatment (85.9%; n = 98), primarily at academic institutions (73.7%, n = 84) as faculty members (65.8%, n = 75) conducting research (86%, n = 98). Nearly three-fourths (74.6%, n = 85) are still working in their home countries; and 74.6% (n = 85) coauthored at least one research article indexed in PubMed during 2018 or 2019. Of the 656 unique research articles, 52.4% (n = 344) were published by multinational groups. The average cost to NIDA for each peer-reviewed publication was $19,677. More than half (53.5%, n = 61) of the fellows received funding through 431 unique grants-led by NIDA (55), other NIH Institutes and Centers (57) and other U.S. funders (55). Using the measures of career outcomes, migration patterns, publications, cost per publication, and funding INVEST fellowships are cost-effective mechanisms to advance scientific knowledge, build addiction research capacity, foster international cooperation, and promote adoption of evidence-based addiction policies and interventions around the world.

Research priorities for expanding access to methadone treatment for opioid use disorder in the United States: A National Institute on Drug Abuse Center for Clinical Trials Network Task Force report.

In the US, methadone treatment can only be provided to patients with opioid use disorder (OUD) through federal and state-regulated opioid treatment programs (OTPs). There is a shortage of OTPs, and racial and geographic inequities exist in access to methadone treatment. The National Institute on Drug Abuse Center for Clinical Trials Network convened the Methadone Access Research Task Force to develop a research agenda to expand and create more equitable access to methadone treatment for OUD. This research agenda included mechanisms that are available within and outside the current regulations. The task force identified 6 areas where research is needed: (1) access to methadone in general medical and other outpatient settings; (2) the impact of methadone treatment setting on patient outcomes; (3) impact of treatment structure on outcomes in patients receiving methadone; (4) comparative effectiveness of different medications to treat OUD; (5) optimal educational and support structure for provision of methadone by medical providers; and (6) benefits and harms of expanded methadone access. In addition to outlining these research priorities, the task force identified important cross-cutting issues, including the impact of patient characteristics, treatment, and treatment system characteristics such as methadone formulation and dose, concurrent behavioral treatment, frequency of dispensing, urine or oral fluid testing, and methods of measuring clinical outcomes. Together, the research priorities and cross-cutting issues represent a compelling research agenda to expand access to methadone in the US.

A mapping review of NIDA-funded implementation research studies on treatments for opioid and/or stimulant use disorders.

BACKGROUND: The biomedical research enterprise invests greatly in discovery-oriented science, but significantly less in how to implement the most effective of these innovations. The return on investment in public health benefit is therefore low. In the context of substance-related overdose epidemics, presently with opioids and/or stimulants, the gap in proven treatments and routine access is amplified. Implementation research is designed to deepen understanding of how best to scale-up proven treatments. This study assessed how implementation research has been deployed in the National Institute on Drug Abuse (NIDA) efforts to address the opioid and stimulant epidemics. METHODS: Adapting a procedure developed to categorize HIV-focused research, a four-stage systematic mapping review of NIDA-funded R01, R34, R61, and U studies pertaining to opioids and/or stimulants funded between 2015 and 2019 was performed. Abstracts were retrieved using NIH Research Portfolio Online Reporting Tools. Key study characteristics were abstracted and coded by two independent reviewers. RESULTS: An initial search across NIH institutes yielded 5963 relevant records. Of these, 666 (11.2 %) were NIDA funded. One-hundred-and-thirty-four (20.1 %) of the 666 studies were opioid and/or stimulant treatment related. Of these, 28 (4.2 %) were categorized as Implementation Preparation (IP), and 16 (2.4 %) were categorized as Implementation Research (IR). Over the five-year period, there was a gradual increase in both IP and IR studies. CONCLUSIONS: Implementation research is a small but slowly growing component of the federal portfolio to address substance-related public health issues. To more effectively respond to contemporary overdose epidemics, implementation research must take on an even more significant role.

The NIDA clinical trials network: evolving, expanding, and addressing the opioid epidemic.

Over the past two decades, the National Drug Abuse Treatment Clinical Trials Network (CTN), a program of the National Institute on Drug Abuse (NIDA), has expanded from the initial six Nodes to 16 Nodes, as a nationwide consortium of research scientists and treatment providers working together to improve care for substance use in the nation's communities. Encompassing both specialty care programs and general medical settings, the Network has become a unique resource for expertise on clinically focused research, bridging the gap between research and treatment delivery. Over 22 years, the CTN has completed 101 studies, resulting in 650 publications. In response to the opioid epidemic, a CTN task force generated a comprehensive list of research priorities in the areas of prevention, treatment, knowledge dissemination, and workforce training, to form the basis of the Network's opioid portfolio. The Network's opioid portfolio currently includes five main categories of studies: (1) large multi-site studies; (2) studies aimed at closing the treatment gap; (3) expansion of ongoing studies to improve service delivery and implementation; (4) studies to explore the use of substance use data in electronic health record systems; (5) training and dissemination projects to expand the research/health care provider workforce. With funding from the Helping to End Addiction Long-Term InitiativeSM (HEAL), the CTN established five new Nodes, which, along with the pre-existing Nodes, are distributed in every region of the nation and engage researchers and clinicians in areas that have been among the hardest hit by the opioid epidemic. Through this expanded network and its commitment to developing personalized, evidence-based treatments, the CTN is poised to address and provide solutions for the ongoing epidemic of opioid use and addiction.

Core outcomes set for research on the treatment of opioid use disorder (COS-OUD): the National Institute on Drug Abuse Clinical Trials Network protocol for an e-Delphi consensus study.

BACKGROUND: A lack of consensus on the optimal outcome measures to assess the efficacy and effectiveness of interventions for the treatment of opioid use disorder (OUD) has hampered the pooling of research data for evidence synthesis and clinical guidelines. A core outcome set (COS) is a minimum set of outcome measures that are recommended for all studies of a particular condition. The National Drug Abuse Treatment Clinical Trials Network (CTN) Core Outcome Set for OUD (COS-OUD) is a development study to identify core constructs, meaningful outcomes, and their optimal measurement for all efficacy and effectiveness studies of OUD treatment and service delivery. METHODS/DESIGN: Overseen by an expert workgroup, a modified, stepwise, e-Delphi methodology will be used to gain consensus among a panel of clinical practitioners and researchers involved in the treatment of OUD, who are members of the CTN. Sequential rounds of anonymous, online questionnaires will be used to identify, rate the importance of, and refine a core outcome set. A consensus threshold will be achieved if at least 70% of the panel rate the measure as critical for inclusion in the COS-OUD. Where consensus is not reached or there are suggestions for new measures, these will be brought forward to a further round of review prior to a consensus meeting. Products from this study will be communicated via peer-reviewed scientific journals and conferences. DISCUSSION: This initiative will develop a COS for OUD intervention trials, treatment studies, and service delivery and will support the pooling of research and clinical practice data and efforts to develop measurement-based care within the OUD treatment cascade. TRIAL REGISTRATION: http://www.comet-initiative.org/Studies/Details/1579.