Notice of Intent to Publish a Funding Opportunity Announcement for Behavioral Research to Improve MAT: Behavioral and Social Interventions to Improve Adherence to Medication Assisted Treatment for Opioid Use Disorders (R61/R33, Clinical Trials Optional)

Notice Number: NOT-AT-19-006

Key Dates

Release Date: November 02, 2018
Estimated Publication Date of Funding Opportunity Announcement: December 08, 2018
First Estimated Application Due Date: February 08, 2019
Earliest Estimated Award Date: September 01, 2019
Earliest Estimated Start Date: September 01, 2019

Related Announcements
NOT-AT-19-007

Issued by
National Center for Complementary and Integrative Health (NCCIH)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism ( NIAAA)

Purpose

The National Center for Complementary and Integrative Health (NCCIH), along with partnering Institutes/Centers/Offices intends to promote a new initiative by publishing a Funding Opportunity Announcement (FOA) to solicit applications to examine the impact of behavioral and social interventions designed to improve adherence to Medication Assisted Treatment (MAT) for persons with Opioid Use Disorders (OUD). Applications are encouraged for fully powered effectiveness and/or implementation studies that will examine whether combining MAT with behavioral and/or social interventions (e.g., mindfulness meditation, cognitive behavioral therapy, or multi-disciplinary rehabilitation) can improve adherence to MAT and, at the same time, may prevent substance abuse relapse, and improve long-term abstinence from illicit opioids. Studies that address adherence determinants at more than one level of ecologic influence (including the patient, caregiver/family, providers and/or healthcare system, and community levels) are of higher priority.

The FOA is expected to be published in the Fall of Fiscal Year (FY) 2019 with an expected application due date in the Winter of FY 2019

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This Notice encourages investigators with expertise and insights into behavioral and social interventions to improve medication assisted therapy (MAT) to begin to consider applying for this new FOA.

 

This FOA will utilize the R01 activity code. Details of the planned FOA are provided below.

This study is part of the of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative will bolster research across NIH to: (1) improve treatment for opioid misuse and addiction, and (2) enhance pain management. More information about the HEAL Initiative is available at:  https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative.

Research Initiative Details

Although there are safe and effective FDA-approved pharmacotherapies for OUD (e.g., buprenorphine, and methadone), relapse prevention of OUD (e.g., depot naltrexone), opioid withdrawal (e.g., lofexidine), and opioid overdose (e.g., naloxone), their outcomes are less than optimal. There are multiple factors associated with these suboptimal outcomes. Some social and behavioral interventions have shown scientific evidence of efficacy in the treatment of OUD but not used as an adjunct to MAT. However, these interventions are not widely utilized. This may be, in part, due to many of these behavioral/social interventions not having been systematically studied in conjunction with different clinical targets of OUD pharmacotherapies. For example, although depot naltrexone is safe and effective for relapse prevention of OUD, there are no psychosocial interventions that have been methodically evaluated to determine whether they would improve long-term outcomes to reduce substance abuse relapse. There is significant clinical evidence that pharmacotherapy can be more effective when combined with behavioral/social interventions in other areas such as smoking cessation. However, the evidence for the effectiveness of these interventions combined with OUD pharmacotherapy is insufficient. At the same time, the labeling for these pharmacotherapies include a recommendation that patients also receive psychosocial interventions. Therefore, there is an urgent need to evaluate if psychosocial interventions can improve adherence of MAT for OUD and, at the same time, enhance the treatment intervention and long-term outcomes, including a reduction in drug abuse relapse.

Adherence

Adherence is increasingly understood as a multifaceted concept. Adherence to MAT involves three dimensions: initiation (i.e., starting the MAT regimen), implementation (i.e., executing the MAT dosing schedule), and persistence (i.e., length of time on MAT before discontinuation). Each dimension of adherence may have unique determinants, and each may require distinct behavioral and social interventions. Additionally, for many OUD patients MAT is part of a treatment regimen, which may include inpatient or outpatient substance abuse treatment, social supports such as 12-step programs, or professional therapy. Persons with OUD often experience multiple comorbid conditions which may require different and concurrent courses of therapy, or present unique cognitive, emotional, or social challenges that can interfere with adherence.

Adherence to MAT and other OUD treatments is dynamic with the potential to change over time. Some health care professionals and researchers may view adherence as a stable and dichotomous property of individuals; i.e., "there are adherent patients, and there are non-adherent patients." This misses how adherence to MAT may vary in response to disease activity, treatment methods, and the course of psychosocial or illness comorbidities. The dynamic nature of adherence underscores the challenges of improving adherence to MAT over the course of care. This is also an opportunity to re-examine and/or adapt evidence-based behavioral and social interventions that have not previously been used to support MAT adherence.

Determinants of adherence and non-adherence span a broad ecologic spectrum. They may be influenced by the severity of addiction; the complexity of MAT combined with concomitant treatments; stigma associated with OUD; individual factors such as sociodemographic characteristics, comorbidities, cognitive functioning, mental health status, health literacy, self-efficacy and motivation for self-management; aspects of the person-provider relationship; social and factors such as an individual’s access to social support, relationships and gender dynamics, and culture; and successively larger structural influences, including factors related to health economics (MAT cost, insurance coverage, access to transportation, and cost-sharing) and the characteristics of MAT delivery approaches. These multilevel adherence determinants invite a range of interventions that target individuals, families, caregivers, health-care providers, communities, and/or healthcare system delivery methods.

New developments and innovations provide opportunities to advance MAT adherence research. Advances in mobile health (mHealth) technologies and informatics provide opportunities to monitor MAT adherence, improve measurement precision, and to deliver individualized interventions that are timely, tailored, and interactive. Attention to patient-centered care and shared decision-making models that include the person, family, and caregiver as part of the care team further broadens targets for improving adherence. Growing attention to health behavioral economic approaches suggest new ways to "nudge" behavior in helpful directions. Additionally, healthcare coverage models that are designed to incentivize the delivery of high-quality and cost-efficient care are becoming increasingly common.

Regardless of focus or approach, the MAT adherence research will benefit from high scientific rigor and innovative study designs. Applications submitted in response to this FOA are encouraged to propose well-powered trials with appropriate sample sizes that employ and describe objective measures, centralized randomization procedures, and blinded outcome assessors. Applications that propose novel research designs, including sequential randomized designs are also encouraged.

Chronic Pain

Chronic pain is an important co-morbidity in patients with OUD. Twenty to 30 percent of US adults report chronic pain (Nahin, 2015). Treatment of acute and chronic pain conditions with opioids is contributing to the OUD epidemic. Pain patients at increased risk of developing OUD are those with pain that is inadequately controlled, exposed to opioids during acute pain episodes, and/or chronic pain in patients with a history of substance abuse.  Among patients with OUD treatment and chronic pain, barriers to patients actively engaging in treatment include fear of inadequately treated pain and depression. (Stumbo et al, 2017). A number of behavioral interventions have shown value for management of chronic pain. Recent American College of Physician guidelines for management of chronic back pain include recommendations to consider interventions including mindfulness-based stress reduction, multidisciplinary rehabilitation, meditative exercise such as tai chi and yoga, progressive relaxation, operant therapy and cognitive behavioral therapy (CBT) (Qaseem et al., 2017 [ACP guidelines]). However, there are relatively few studies evaluating effectiveness of these nonpharmacologic interventions when used to treat the comorbidity of OUD and chronic pain.

Research Goals

The goal of this FOA is to solicit applications proposing to test approaches using behavioral and/or social interventions to improve adherence to MAT for OUD and, at the same time, may provide additional therapeutic benefit to improve long-term outcomes such as stress reduction, and opioid abstinence. Projects are strongly encouraged to leverage funding which individual U.S. states receive under SAMHSA awards in the last few years to enhance OUD treatment. A primary goal of this FOA is to encourage studies evaluating whether behavioral and/or social interventions may improve uptake or adherence to MAT, relapse prevention for OUD, or improve abstinence for persons engaged in OUD treatment.

The proposed projects must meet the following criteria:

  • Project teams must include relevant stakeholders as key personnel or other staff on the project to ensure adequate input to study design and planned outcomes. For example, a project that proposes to integrate an intervention into a healthcare system must include a representative from that healthcare system as key personnel or other staff.
  • Projects must be designed to generate causal inferences on the effects of behavioral/social approaches as an adjunct to MAT using FDA-approved medications for treatment of OUD, or prevent OUD relapse to reduce: drug use and/or overdose deaths, length of time on medication, dropout, time to relapse.
  • Designs may include: observational studies, randomized controlled explanatory trials, randomized controlled pragmatic trials, or other types of controlled designs employing statistical approaches that mitigate bias and support causal inferences. Hybrid effectiveness-implementation designs may also be appropriate. Projects may incorporate randomization approaches appropriate to the research question, such as by cluster or timing of implementation. If another method is used to generate the comparison group, perhaps by staged assignment or staged implementation of the approach, it should provide comparable rigor to randomization. Randomization may occur at the patient, provider, clinic, or community level, as is appropriate to the research question.
  • PDs/PIs must plan to use some of the funds awarded by this FOA to attend an annual meeting of investigators funded under the FOA and engage in other activities, such as periodic conference calls, designed to facilitate appropriate standardization of measures, collaboration and other mechanisms for maximizing the scientific yield from this FOA.

Research topics (scientific questions of interest) may include, but are not limited to, the following:

  • What is the effectiveness of integrated treatments as an adjunct to MAT versus MAT alone for persons with chronic pain and OUD?
  • What are effective implementation strategies to engage patients, providers, healthcare systems, and communities to increase use of effective behavioral and/or social interventions as an adjunct to MAT to sustain benefits?
  • Do behavioral therapies in combination with MAT reduce relapse rates for patients and prevent recurrence of opioid misuse?
  • What impact does high adherence to a behavioral or social intervention have on adherence to MAT?
  • Does improving patient and provider shared decision making in pain care treatments lead to better adherence to MAT or OUD relapse rates?
  • Do specific settings (residential treatment, outpatient, intensive inpatient, community centers,
  • telehealth, etc.)  for delivery of behavioral interventions provide better outcomes? Is it better to have single provider or multiple providers?  What type(s) of provider(s) delivers a given treatment more effectively?
  • What are the incremental benefits of combined approaches relative to a single approach as an adjunct to MAT (e.g., psychological/behavioral [P/B] alone vs. P/B + physical activity [yoga, tai chi, or exercise] to treat pain)?
  • What characteristics predict better response or adherence to MAT for patients (comorbidity, psychological characteristics, physical limitations), providers (training/education, certifications, experience treating OUD), communities (social supports, treatment resources, stigma), and healthcare systems (access to care, reimbursement)?

Funding Information

Estimated Total Funding $3,600,000 in FY2019.
Expected Number of Awards 8
Estimated Award Ceiling $300,000 in direct costs
Primary CFDA Numbers 93.213; 93.866; 93.273

Anticipated Eligible Organizations

Public/State Controlled Institution of Higher Education
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education)
Small Business
For-Profit Organization (Other than Small Business)
State Government
Indian/Native American Tribal Government (Federally Recognized)
County governments
City or township governments
Special district governments
Independent school districts
Public housing authorities/Indian housing authorities
Indian/Native American Tribally Designated Organization (Native American tribal organizations (other than Federally recognized tribal governments)
U.S. Territory or Possession
Indian/Native American Tribal Government (Other than Federally Recognized)
Regional Organization

Applications are not being solicited at this time.

Inquiries

Please direct all inquiries to:

Dave Clark, DrPH
National Center for Complementary and Integrative Health (NCCIH)
301-827-1916
dave.clark@nih.gov



NCCIH HEAL Initiatives
National Center for Complementary and Integrative Health (NCCIH)
Email: NCCIHHEAL@mail.nih.gov