NIH – HEAL Initiative Limited Competition: Behavioral Research to Improve MAT: Ancillary Studies to Enhance Behavioral or Social Interventions to Improve Adherence to Medication Assisted Treatment for Opioid Use Disorders (R01 Clinical Trial Optional)

December 17, 2018 by

There is an opioid crisis in the United States. More than 4 million people in the United States report using opioids for non-medical purposes in the past month, and almost 2 million report symptoms consistent with an opioid use disorder (OUD) (National Survey on Drug Use and Health [NSDUH]).  Fewer than half of those with an OUD receive treatment (Volkow et al., 2014) and even fewer receive treatment of adequate duration.  The number of drug overdose deaths involving opioids has quadrupled between 1999 and 2015, to more than 33,000 annually (Rudd et al., 2016).

While there are effective FDA-approved medications for OUD including methadone, buprenorphine/naloxone, buprenorphine, and naltrexone, there has been a lack of access and limited utilization of these treatments. The 21st Century Cures Act addresses one significant barrier: insufficient funding for medication assisted treatment (MAT). The Substance Abuse and Mental Health Services Administration (SAMHSA) released two funding opportunity announcements designed to support states’ responses to the opioid crisis (TI-17-014“State Targeted Response to the Opioid Crisis Grants”, and TI-18-020 “Opioid State Targeted Response (STR) Supplement”).

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 this 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). Several 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]). Additionally, a recent systematic review on Noninvasive Nonpharmacological Treatment for Chronic Pain from the Agency for Research on Quality and Health (AHRQ) concluded, “Exercise, multidisciplinary rehabilitation, acupuncture, CBT, and mind-body practices were most consistently associated with durable slight to moderate improvements in function and pain for specific chronic pain conditions.” (Skelly et al., 2018) However, there are relatively few studies evaluating their effectiveness for the comorbidity of OUD and chronic pain.

To build upon the state’s infrastructure developed through SAMHSA grants funded under TI-17-014 “State Targeted Response to the Opioid Crisis” Grants the National Center for Complementary and Integrative Health (NCCIH) and the National Institute on Drug Abuse (NIDA) published three Funding Opportunity Announcements:

RFA-AT-18-001 “Behavioral Interventions for Prevention of Opioid Use Disorder or Adjunct to Medication Assisted Treatment-SAMHSA Opioid STR Grants (R21/R33)” and RFA-AT-18-002 “Clinical Trials or Observational Studies of Behavioral Interventions for Prevention of Opioid Use Disorder or Adjunct to Medication Assisted Treatment-SAMHSA Opioid STR Grants (R21/R33)” supported applications to assess the role of complementary behavioral interventions for primary prevention of OUD in patients who are considered at risk, and to assess the role of these interventions in secondary prevention to reduce relapse in patients who are abstaining and who have a history of OUD. Applications were also encouraged to examine if these complementary approaches enhanced adherence to MAT.

RFA-DA-18-005 “Expanding Medication Assisted Treatment  for Opioid Use Disorders in the Context of the SAMHSA Opioid STR Grants (R21/R33)” supported applications to test approaches for expanding MAT for OUD in the general health care sector or linking individuals with OUD who receive naloxone for the reversal of overdose to MAT in the context of states’ plans for use of the funds authorized under the 21st Century Cures Act.

This study is part 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:

Research Goals

With SAMHSA’s continued support of state’s opioid crisis response, we invite NIH grants funded through RFA-AT-18-001, RFA-AT-18-002, and RFA-DA-18-005 to submit research project grant (RPG) applications that will support ancillary research activities to substantially enhance and/or expand the aims of the funded parent grants.

Additional activities that may be supported by this FOA include, but are not limited to: adding evidence-based behavioral or social interventions to studies that, to date, are only expanding MAT availability or access, adding additional study sites, increasing total sample size, increase efforts to increase recruitment of under-represented populations, add additional data collection points, longer follow-up time points, and addition of new outcome measures.

Activities not responsive to this FOA

The following types of activities will be deemed nonresponsive to this RFA and withdrawn without review:

  • Adding a clinical trial component to an observational study
  • Adding activities to develop a novel behavioral intervention, which was not included in the parent award
  • Addition of elements that would require the trial be conducted under an IND or IDE, such as drug or device safety trials

In addition to the above description of the scientific objectives, resources communicating scientific interests of selected NIH I/C’s are summarized below. Applicants are encouraged to contact the Scientific/Research contact of the intended I/C to ensure that the aims of the proposed project are consistent with I/C mission.

National Center for Complementary and Integrative Health (NCCIH).  The mission of NCCIH is to define, through rigorous scientific investigation, the usefulness and safety of complementary and integrative health interventions and their roles in improving health and health care. NCCIH supported R21/R33 applicants are encouraged to use this funding opportunity to increase the number of sites and to include additional populations to increase statistical power, increase generalizability, and decrease sampling bias. Applicants are encouraged to discuss the goals of their ancillary study with NCCIH staff prior to submission.  Please note:  Support of a scientifically meritorious ancillary project grant, submitted under this FOA, is contingent upon successful transition to the R33 phase for the currently supported R21/R33 project grant.

National Institute on Drug Abuse (NIDA).  The mission of NIDA is to advance the science on the causes and consequences of drug use and addiction and to apply that knowledge to improve individual and public health. In addition to supporting and conducting basic and clinical research, it also seeks to ensure the effective translation, implementation, and dissemination of scientific research findings to improve the prevention and treatment of substance use disorders. NIDA supported R21/R33 applicants are encouraged to use this opportunity to expand their research activities in ways that will allow for more rapid dissemination and implementation of successful interventions. Applicants also encouraged to discuss the rationale for and goals of their ancillary study with NIDA staff prior to submission.  Please note: Support of a scientifically meritorious ancillary project grant, submitted under this FOA, is contingent upon successful transition to the R33 phase of the originally supported R21/R33 project grant.

Deadline:  February 13, 2019 (letters of intent); March 15, 2019 (full proposals)


Filed Under: Funding Opportunities