Department of Health and Human Services
Part 1. Overview Information

 

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Center for Complementary and Integrative Health (NCCIH)

Funding Opportunity Title

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)

Activity Code

R21/R33 Phased Innovation Award

Announcement Type

Reissue of RFA-AT-18-001

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-AT-18-002

Companion Funding Opportunity

None.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

 93.213

Funding Opportunity Purpose

 The purpose of this FOA is to solicit applications to examine the impact of behavioral interventions within the context of states' plans for use of the SAMHSA Opioid STR grant funds authorized under the 21st Century Cures Act. Applications are encouraged for clinical trials or observational studies that examine the impact of interventions such as mindfulness meditation, cognitive behavioral therapy, or multi-disciplinary rehabilitation for primary or secondary prevention for opioid use disorder (OUD) or as an adjunct to medication assisted treatment (MAT) of OUD. Applications that emphasize treatment of the comorbidities of OUD and chronic pain are of particular interest.

Key Dates

 

Posted Date

November 16, 2017

Open Date (Earliest Submission Date)

December 18, 2017

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

January 18, 2018, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates. No late applications will be accepted for this Funding Opportunity Announcement.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

April 2018

Advisory Council Review

June  2018

Earliest Start Date

July  2018

Expiration Date

January 19, 2018

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Go to Grants.gov to download an application package to complete the application forms offline or create a Workspace to complete the forms online; submit your application to Grants.gov; and track your application in eRA Commons.
Learn more about the various submission options.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information


Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
 Background

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).

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). 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 their effectiveness for the comorbidity of OUD and chronic pain.

A State-of-the-Art conference focused on pain management was sponsored by the U.S. Department of Veterans' Affairs in March 2017, and presented recommendations for non-pharmacological approaches to chronic musculoskeletal pain management.  The conference summarized a wide-range of knowledge, gaps and opportunities (https://www.hsrd.research.va.gov/for_researchers/cyber_seminars/archives/video_archive.cfm?SessionID=1217).

Types of behavioral interventions for prevention of OUD or as an adjunct to Medication Assisted Therapy (MAT) for OUD that are of interest to NCCIH for the purposes of this FOA include, but are not limited to, the following: biofeedback, cognitive behavioral therapy, guided imagery, hypnosis, meditation (e.g., mindfulness meditation), mindful techniques and multi-disciplinary rehabilitation, progressive relaxation, tai chi, and yoga.

While there are effective FDA-approved medications for OUD including methadone, buprenorphine/naloxone, buprenorphine, and naltrexone, there are multiple barriers to this approach.  One is the lack of access to 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) recently released a funding opportunity announcement (State Targeted Response to the Opioid Crisis Grants, TI-17-014) designed to support states' responses to the opioid crisis. In addition to lack of access, challenges exist in uptake and adherence to these agents.

According to the SAMHSA funding opportunity announcement, at least 76% of the almost $500 million appropriated in FY17 is to fund state efforts to expand access to evidence-based treatment and recovery support services to individuals for whom other sources of payment do not exist. This includes individuals not covered by public or commercial health insurance programs, those for whom coverage has been formally determined to be unaffordable, those for whom services are not sufficiently covered by the individual's health insurance plan, and those for whom services or coverage for services are not available from other sources (e.g. State Block Grant Funds, Medicaid Funds or the Veterans Administration).

A second focus of the SAMSHA funding will be on programs to enhance primary or secondary prevention efforts. It will be important to assess the role of complementary behavioral interventions for primary prevention of OUD in patients who are considered at risk, and to assess its role in secondary prevention to reduce relapse in patients who are abstaining and who have a history of OUD.  While there is some evidence of benefit for some behavioral interventions in chronic pain patients, there are few studies of patients with both co-morbidities and behavioral interventions to study the effects of reducing pain to enhance treatment of OUD.

This unprecedented infusion of funds at a time of critical need could be transformative. For example, it could hasten the availability of MAT in the general health care sector.  It could also lead to a variety of psychosocial strategies as adjuncts to MAT, which may enhance adherence to MAT and opioid abstinence. In addition, these behavioral strategies may also be utilized as primary or secondary prevention strategies to reduce the number of people who develop OUD and/or decrease the rate of relapse in people who have a history of OUD.  

Research Goals

The purpose of this FOA is to solicit applications proposing to test approaches using behavioral interventions for primary or secondary prevention of OUD or as an adjunct to MAT for OUD in general healthcare in the context of states' plans for use of the funds authorized under the 21st Century Cures Act.  A primary goal of this FOA is to encourage studies evaluating whether select behavioral interventions may improve uptake or adherence to MAT, relapse prevention, or prevention of OUD in at risk people. 

The proposed projects must meet the following criteria:

  • Projects must leverage an opportunity made available by funding which individual U.S. states receive under SAMHSA TI-17-014. Link: https://www.samhsa.gov/grants/grant-announcements/ti-17-014/ and the projects funded by SAMHSA which can be found here: https://www.samhsa.gov/grants/awards/2017/TI-17-014
  • Project teams must include relevant state agency staff as key personnel (or other staff on the project) to ensure adequate input from state agencies to study design and planned outcomes
  • Projects must be designed to generate causal inferences on the effects of psychosocial approaches as an adjunct to MAT using FDA-approved medications for treatment of OUD, prevent development of OUD, or prevent OUD relapse to reduce: drug use and/or overdose deaths, length of time on medication, dropout, time to relapse, and at least one other physical or mental health or health-related outcome. 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, as long as the outcomes studied in the projects are those listed above. 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. 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.

Applicants proposing cluster-randomized trials are encouraged to consult relevant guidance documents issued by the NIH Health Care Systems Research Collaboratory:(http://rethinkingclinicaltrials.org/experimental-designs-randomization-schemes-top/experimental-designs-and-randomization-schemes-introduction/ )). 

Applications proposing observational studies should employ strong statistical methods designed to mitigate bias and support causal inferences. Observational studies that are purely descriptive and do not use methods to mitigate bias are not responsive to this FOA and will not be reviewed.

Applications proposing to study botanical products or non-FDA approved medications are not responsive to the FOA and will not be reviewed.

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 pain and OUD?
  • Does delivery of behavioral therapies in community settings, in outpatient settings, etc. enhance primary or secondary prevention of OUD compared to usual care?
  • What are effective implementation strategies to engage patients in behavioral interventions as an adjunct to MAT to sustain benefits?
  • Do behavioral therapies reduce relapse rates for patients with a history of OUD and prevent recurrence of opioid misuse?
  • What impact does high adherence to a behavioral intervention have on adherence to MAT?
  • Which behavioral therapies for treatment of chronic pain (e.g., CBT, hypnosis, biofeedback, Tai Chi, Yoga, relaxation therapies, manual therapies, or mindfulness meditation) provide better outcomes in patients with OUD and receiving MAT or for primary or secondary prevention of OUD?
  • Are non-pharmacological approaches to pain reduction (e.g., cognitive behavioral therapy, mindful mediation, mindful exercise, yoga, etc.) effective for primary prevention in reducing chronic pain and preventing onset of OUD? 
  • What is the best dose, frequency, intensity or session length for therapist or instructor led classes to treat pain or psychosocial issues that are co-morbid with OUD disorder and may enhance adherence to MAT or prevent OUD relapse?
  • Does incorporating patient choice in pain care 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 provider delivers a given treatment more effectively?
  • Do group versus individual treatment approaches to pain management (by providing CBT, hypnosis, biofeedback, Tai Chi, Yoga, relaxation therapies, manual therapies, or mindfulness meditation) as an adjunct to MAT provide better outcomes?
  • 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 patient characteristics predict response to a strategy (comorbidity, psychological characteristics, physical limitations)?

Applications proposing research topics not identified as high programmatic priority will be considered of lesser or low program priority, which will significantly reduce the likelihood of funding.  

Phases of Award

The R21 phase will support the development of preliminary data; feasibility studies; case report forms and other resources necessary for the performance of the study; further development and finalization of study partnerships including signed contracts with performing clinical sites; Institutional Review Board/Data and Safety Monitoring Board approval of the trial protocol, informed consent(s), and manual of operations. All regulatory approvals should be obtained prior to the end of the R21 award.

The R33 phase will support the conduct of the research study, including training of intervention providers, comparison group providers, or other resources required for study initiation.  These should be planned at the start of the R33 award to allow for the successful launch and execution of the proposed clinical study in the R33 phase. The R33 award is subject to NCCIH funding availability and scientific priorities. R33 awards will be made after administrative review with attention to the extent to which agreed upon milestones have been met. 

Milestones

Utilization of milestones is a key characteristic of this FOA. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. Plans must be guided by milestones that will be reached by the end of the R21 phase. Milestones are to be performance-based to achieve completion of the trial on time and on budget. The individual milestones must be quantifiable and measurable.  A summary of the milestones will undergo an administrative review to ascertain if each milestone proposed was or was not met.  Only R21 projects that have met milestones will deemed eligible to transition to the R33 implementation phase.

Special Considerations

National Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human Subjects:  The National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects.   Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects.  The guidelines are available on NIDA's Web site at  http://www.drugabuse.gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects.

Data Harmonization for Substance Abuse and Addiction via the PhenX Toolkit:  NIDA and NCCIH strongly encourage investigators involved in human-subjects studies to employ a common set of tools and resources that will promote the collection of comparable data across studies and to do so by incorporating the measures from the Core and Specialty collections, which are available in the Substance Abuse and Addiction Collection of the PhenX Toolkit (www.phenxtoolkit.org).  Please see NOT-DA-12-008 (http://grants.nih.gov/grants/guide/notice-files/NOT-DA-12-008.html) for further details.

Considerations for Selection of Study Design

For mind and body interventions that either are or can be delivered in groups, investigators should have a strong rationale for the choice among trial designs options. The selection of study design should be guided by decisions about how best to deliver the intervention and by concerns regarding contamination and logistics. 

In traditional randomized clinical trials (RCTs), individual participants are randomized to receive an intervention that is delivered individually (e.g. spinal manipulation, acupuncture, or individually delivered hypnosis). When an intervention can be delivered in a group format there are several methods of randomizing participants to the intervention. The first option is an individually randomized group treatment trial (IRGTs), where individual participants are randomized to one of the interventions but the intervention is delivered in small groups (e.g. yoga, Mindfulness Based Stress Reduction, or tai chi classes).  The second option is a group-randomized trial (GRTs), also called cluster-randomized trial (cRCTs), where groups of participants are randomized to study conditions, often defined by their workplace, school, primary care provider, or community. In cRCTs, the intervention provided to the randomized groups can be delivered individually, in small groups, or to the entire group.

The study team biostatistician will need to consider how the chosen study design led to the proposed data analysis and sample size estimates.  The justification should include consideration of the positive intra-class correlation expected in data obtained from participants in the same groups, or clusters.  In general, these types of studies need to consider how the data analysis and sample size address the extra variation expected in the data and the degrees of freedom available to estimate that extra variation. Failure to account for this variable in the sample size calculation can result in underpowered studies.  Link to Office of Disease Prevention website on group and pragmatic randomized trials free online training is available (https://prevention.nih.gov/resources-for-researchers/nih-methods-training/grt

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information
Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed

New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NCCIH intends to commit $1,500,000 (total costs) in FY 2018 to fund 3 - 4 awards.

Award Budget

Direct costs will vary with the scope of the project. Support for the R21 phase may not exceed $200,000 direct costs. The R33 phase direct costs must not exceed $500,000 per year.

Award Project Period

The project period is limited to 1 year for the R21 phase and to 2  years for the R33 phase, and the maximum project period must coincide with period of SAMHSA funding for TI-17-014.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o   Hispanic-serving Institutions

o   Historically Black Colleges and Universities (HBCUs)

o   Tribally Controlled Colleges and Universities (TCCUs)

o   Alaska Native and Native Hawaiian Serving Institutions

o   Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • U.S. Territory or Possession

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility
Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).
Section IV. Application and Submission Information
1. Requesting an Application Package

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

Martina Schmidt, Ph.D
National Center for Complementary and Integrative Health (NCCIH)
6707 Democracy Blvd, Suite 401
Bethesda, MD 20892 (Express Mail Zip: 20817)
Telephone: 301-594-3456
Fax: 301-480-1587
Email: schmidma@mail.nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.  

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.  

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Other Attachments

The following attachments must be included as a part of the application.  Attachments permit expansion of certain elements that cannot be appropriately described in the Research Strategy. All attachments listed below must be provided or the application will not be peer reviewed.

1. Clinical or Observational Protocol Synopsis

A Clinical or Observational Protocol Synopsis must be provided as an attachment called "Clinical Protocol Synopsis.pdf" and must not exceed 12 pages. The synopsis will provide a concise snapshot of the overall trial (whether clinical or observational). It will be considered by reviewers in addition to the components of the regular application.  It is meant to summarize the necessary elements of the clinical (or observational) study.

The Clinical or Observational Protocol Synopsis is expected to include the following information:

  • Brief and/or Official Protocol Title
  • Focus of the Study
  • Objectives: A brief description of objectives, including the primary objective and secondary objectives (in a few sentences).
  • Study Design: A brief description of the study design (e.g., observational, randomized, parallel group or factorial, double-blind, and the Phase)
  • Intervention to Be Tested: A description of the intervention to be tested, and a brief description of the protocol to be followed in each arm of the trial and the adherence assessment. Specify concomitant interventions, if applicable.
  • Primary and Important Secondary Endpoints: Specify the endpoints for the primary and, if applicable, important secondary endpoints.
  • Provide schedule of clinical and laboratory evaluations.
  • Study Population: A brief description of the study population, including the sample size, gender, age, demographic group, required health status, and geographic location.
  • Enrollment Sites: A list of enrollment/participating sites and their expected enrollment. Briefly describe plans for IRB approval.
  • Statistical Design and Power: Specify the number of subjects to enroll, the expected effect size, event rate, power and the statistical methods (per protocol, intent-to-treat) to compare groups with respect to the primary outcome measure. Specify criteria for intervention discontinuation and stopping guidelines.
  • Group Assignment: Methods of assignment of participants to study groups and of randomization
  • Subject Participation Duration: Time it will take for each individual participant to complete all subject visits.
  • Study Duration: Estimated time (in months) from when the study opens to enrollment until: (1) completion of data collection; and (b) final data analyses.
  • A Recruitment and Retention Plan describing the following:  1) the planned recruitment methods including use of contact lists, databases or other pre-screening resources, advertisements, outreach, media / social media and referral networks or groups; 2) if there are known participant or study-related barriers to accrual or participation (based on literature or prior experience), please list these barriers and describe plans to address them to optimize success; 3) contingency plans for participant accrual if enrollment significantly lag behind accrual benchmarks; 4) participant retention and adherence strategies; 5) possible competition from other trials for study participants; 6) safeguards for vulnerable populations as appropriate (e.g., children, pregnant women); and 7) strategies for outreach to minorities and women. Investigators are encouraged to review the NCCIH Study Accrual and Retention Plan (https://nccih.nih.gov/grants/policies/SARP).

2. FDA or Other Applicable Regulatory Agency Strategy and Communication(s)

A Regulatory Communication Plan must be provided as an attachment called "Regulatory Communication Plan.pdf" and must not exceed 3 pages of a written description.  Additional pages can include copies of correspondence from the FDA indicating whether the proposed study will require an IND/IDE. The Regulatory Communication plan should describe the process that will be used for attaining all necessary FDA or other applicable regulatory agency approvals necessary to the conduct of the trial, and associated timeline. For trials using an FDA-regulated product that requires an Investigational New Drug (IND)/IDE application, the grant application must include evidence regarding the outcome of a pre-IND meeting, or other evidence of communication with FDA. If the protocol is exempt from an IND/IDE, a copy of the exemption letter from the FDA should be provided.   If the proposed clinical study does not include a device or drug, this document should provide a brief statement as to why FDA regulation is not applicable.

3. Clinical or Human Subjects Research Experience   

Applicants must provide a detailed table listing the characteristics of trials or human subjects research that demonstrate experience in trial or human subjects conduct and/or coordination in the last 5 years. The table must be provided as an attachment called "Clinical Trial Experience.pdf" and must not exceed 3 pages.

The table columns should include:

Column A: clinical trial (or human subjects research) title

Column B: applicant's role in the trial (or human subjects research)  

Column C: a brief description of the trial design

Column D: planned enrollment

Column E: actual enrollment

Column F: number of sites

Column G: whether the trial(s) were completed on schedule or not

Column H: publication reference(s)

4. Timeline and Milestone Plan

A Timeline and Milestone Plan must be provided as an attachment called "Timeline and Milestone Plan.pdf". The milestone plan should describe the key milestones that need to be met for each phase of the application (R21 and R33). The first set of milestones must indicate what activities will be done during the R21 phase in order to transition to the R33 and the second set of milestones must include activities that will be done in the R33 phase to achieve study aims.  The applicants should include proposed milestones that describe key elements to ensure each phase's success; the processes that will be met; and a timetable identifying when each of these key milestones will be met.

Applicants should use the following definition of a milestone in their application: a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones must be relevant, achievable, and quantifiable. The Plan should propose at least 3 milestones for completion of the R21 phase, a discussion of the suitability of the proposed milestones for assessing success in the R21 phase, and a discussion of the implications of successful completion of these milestones for the proposed R33 study. Milestones should be specific, quantifiable, and scientifically justified; they should not be simply a re-statement of the R21 specific aims.  At least one milestone must involve an assessment of the continued feasibility and value of the proposed R33, using information obtained in the R21 phase, and specifically considering any changes in the Opioid STR program, other initiatives targeting pharmacotherapy for opioid use disorders in the State or States in which the intervention is being tested, or other relevant factors (e.g., state budgets) and their impact on the original research plan. 

The plan should include anticipated challenges to meeting milestones and propose potential mitigation or corrective actions strategies. Milestones should address overall recruitment and retention goals.  The Terms and Conditions under this FOA will include a milestone plan that is mutually agreed upon by the investigators and NCCIH, such as: a) obtaining regulatory approval of the final protocol; b) establishing agreements with participating industry partners, if indicated; c) finalizing the study procedures and training participating clinical site staff; d) enrolling 25%, 50%, 75%, and 100% of the targeted sample size; and (e) completing all subject follow-up and data collection activities.

Investigators must include a description of the milestones in the application, which may include, but are not limited to, the following: 

R21 phase:

  • Final study protocol submitted & approved by NCCIH (prior to starting R33 phase)
  • Final case report forms submitted & approved by NCCIH
  • Complete final Informed consent(s) and, if applicable, assent forms
  • Final Data and Safety Monitoring Plan approved by NCCIH prior to starting R33 clinical trial
  • Submission of an approved Study Accrual and Retention Planned by the Authorized Business Official for R33 (https://nccih.nih.gov/grants/policies/SARP)
  • Finalize and obtain NCCIH approval of the planned milestones that must be met in the R21 phase in order to submit a request to transition to the R33 phase. These milestones will undergo an administrative review. Milestone Criteria may include the following:
  • Comprehensive laboratory plan (as applicable)
  • Pharmacy/Laboratories Identification (as applicable)
  • Contracts/Third Party Agreements (if applicable)
  • Training plan for clinical site(s)
  • Data Completeness and Quality Monitoring Reporting Plan
  • Completion of regulatory approvals
  • IRB approval for clinical site(s)

R33 phase:

  • Assessment of site(s) protocol implementation performance
  • Collection of data related to primary and secondary endpoints and database lock
  • Submission of primary manuscript to peer-reviewed scientific journal
  • Submission of study results to ClinicalTrials.gov within 12 months of the primary completion date
  • Data sharing plan for study data and biospecimens (if applicable)
  • Obtain NCCIH approval for R33 phase protocol, data and safety monitoring plan, and study accrual and retention plan
  • Complete necessary regulatory approvals for proposed clinical trial (e.g., IRB, FDA IND). 

During the award phase, achievement of each milestone for the R21 and R33 phases will need to be communicated to the NCCIH Program Officer listed on the Notice of Award.  Award continuation, even during the period recommended for support, is conditional upon satisfactory progress. Continuation of the award is conditional upon satisfactory progress and if, at any time, recruitment, as defined in the NCCIH Study Accrual and Retention Plan for Human Subect Research (https://nccih.nih.gov/grants/policies/SARP), falls significantly below projections, or core milestones mutually agreed upon by the PD/PI and the NCCIH, are not met, the NCCIH may consider ending support and negotiating an orderly phase-out of the award. The NCCIH retains, as an option, periodic external peer review of progress. NCCIH staff will closely monitor progress at all trial stages including milestones, accrual, and safety.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed.  Project teams must include relevant state agency staff as key personnel (or other staff on the project) to ensure adequate input from state agencies to study design and planned outcomes

R&R Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

Budgets for both the R21 and R33 phases must be included in the application.

If parts of the costs of the trial are to be provided by sources other than NCCIH, these contributions must be presented in detail in the budget justification.

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

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.  

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: 

Specific Aims:

In the single attachment allowed for the specific aims, applicants should provide brief background information to define the proposed complementary or integrative health intervention that will be used for prevention or as an adjunct to MAT, justify the importance of the topic area, outline the knowledge gap relevant to the proposed study, and provide rationale for the proposed hypotheses.  This page should also include sections titled "R21 Specific Aims" and "R33 Specific Aims", and include the relevant aims or hypotheses associated with each set of specific aims.

Research Strategy:

The Research Strategy should be organized in a manner that will facilitate peer review. The body of the application should present an overview of the state of the science, current status and relevance of the trial, a discussion of the specific protocol, and the approach to data collection, analysis, and dissemination. The application should contain separate Approach sections for the R21 and R33 phases.

Separate, Significance and Innovation sections may be included, but they could also be combined into a single section within the R21 section as appropriate.  It is not necessary to repeat any information or details in the R33 section that are described in the R21 section.

The following criteria should be addressed:

Significance:  The significance of the proposed clinical trial and importance of the question should be clearly stated. If available, the application should provide rigorous preclinical or clinical preliminary data to support the study rationale. It is particularly important that there be a discussion of how the trial will test the proposed hypotheses and why there is clinical equipoise. The application should make clear the need for and timeliness of the study with emphasis on how the results will address an evidence gap and therefore advance our knowledge of theory and practice in this area.  A discussion of the costs and benefits of the study should be included for evaluation of the trial's significance. The applicant is expected to provide a precise response to these two questions:  Will the results be informative about the potential role of this treatment for prevention or treatment of OUD?  How will the results effect future care in the state where the research is conducted?

Innovation:  Explain how the application challenges and seeks to shift current research or clinical practice paradigms.

Approach: The research approach section should include a description of the supporting data, clinical trial experience, the experimental approach, and reference the Timeline and Milestone Plan.

Supporting Data: The studies that led to the proposed clinical trial should be presented. Data from pilot studies which show the need for and the feasibility of the trial should also be presented. Additional supporting data from other research should be included so that the approach chosen is clearly justified and adequately framed. The application should provide data which should demonstrate the plans for and the initial planning phase of the proposed early phase study (R21). Applications should address the rationale for choosing the planned specific behavioral intervention or approach. This may include public health impact if subsequent efficacy trials are conducted and positive; ethical dimensions; and/or patient perspectives on acceptability of the proposed intervention. Characteristics of any preliminary research results provided in support of the proposed project, whether conducted by the applicant or others, should be described in the application

Experimental Approach:  The proposed experimental approach should include an appropriate study design and the rationale for the design chosen. The experimental approach description should include:

  • A brief description of the project timeline referencing but not repeating the required attachment for Timeline and Milestone Plan as appropriate.
  • A description and rationale for the research hypothesis(es), methods of randomization if applicable, primary and secondary outcome measures, intervention(s), and participant follow-up procedures.
  • A description of the study population and why it is the most appropriate group to answer the question, and how or if results will generalize to a broader population.
  • For the R33 phase, describe the methodology including:  a) the scientific rationale for the measure(s) used to assess the impact of giving the behavioral intervention; b) the measure(s) proposed to assess the interventions effect on OUD. Information on measurement validity and reliability should be included in the application. Describe measurement schedules. The approach should be summarized clearly in the application, with specific references to the Clinical Protocol Synopsis to be submitted as an "Other Attachment".
  • Discussion of the challenges expected in implementing the research and how these might be overcome.
  • A discussion of potential challenges in implementing the research protocol and how they will be addressed.
  • The strategy for timely publication and dissemination of results
  • Data Management and Quality Control:  Details of efficient data management and methods for monitoring quality; Statistical Methods:  Discussion of sample size justification to be powered on changes expected in the effect size expected for primary outcome measure; study outcome measures; plans for interim (if any, with cogent justification) and final analyses powered to detect impact on each aim; methods of bias control (e.g. use of health education arm ); and methods for handling missing data.

Data and Safety Monitoring Plan:

In addition to the NIH application requirements for data and safety monitoring for clinical trials (NCCIH requires independent monitoring for research involving human subjects. Applicants should refer to NIH's policy on data and safety monitoring (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html), as well as the NCCIH Guidelines for Data and Safety Monitoring (http://nccih.nih.gov/grants/policies/data-safety-monitoring).  The Independent Monitoring Committee (IMC) or Data and Safety Monitoring Board (DSMB) will have the responsibility to review interim and final data, and recommend whether the protocol should be modified, and, at each meeting, whether the study should be continued or should be terminated early. Thus, its ethical responsibilities, to the participants as well as to the integrity of the study, are of paramount importance to the NCCIH. The IMC/DSMB will meet in person or by phone at least twice a year.  Applicants should not appoint IMC/DSMB members in advance of the peer review, or even inquire about the interest of possible DSMB members, because anyone so contacted would not be eligible to serve as a member of the peer reviewer committee that will evaluate the applications for scientific merit.

Letters of Support:

Letters of support from clinicians or clinical department chairs whose support is necessary to the successful conduct of the trial should be provided. Applicants are also encouraged to include documentation of the commitment of any subcontractors and consultants, as well as service agreements for personnel or facilities. Letters of commitment must be co-signed by the business official of the collaborating center.

If parts of the costs of the trial are to be provided by sources other than NCCIH, provide Letter(s) of Support signed by an authorized representative.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

  • Generally, Resource Sharing Plans are expected, but they are not applicable for this FOA.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Inclusion Enrollment Report

Use only for applications with due dates on or before January 24, 2018. When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide must be followed. 

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH's electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Funds may not be used to provide treatment or other services.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization's profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NCCIH Referral Office by email at schmidma@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.  

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information
1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The R21/R33 phased innovation grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. An R21/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data.  Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding, the likelihood achieving planned milestones will ensure investigators are ready to begin the R33 phase. Reviewers will assign a single impact score for the entire application, which includes both the R21 and R33 phases.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? 

Specific to this FOA:

How well does the project assess the impact of a behavioral intervention as an adjunct for MAT for Opioid Use Disorders (OUD) or for primary or secondary prevention of OUD in the state or states in which the intervention is being tested?

If the aims are achieved, how will the behavioral intervention as an adjunct to MAT for OUD (or as a stand alone for primary or secondary prevention of OUD) be expanded in the state or states in which the approach is being tested?

If the primary outcomes of the trial are achieved, how critical will the information be to address the evidence gap and advancing knowledge of theory and practice? How would the results of the trial have a significant influence on clinical care and improve health?  Is there sufficient demonstration for the presence of clinical equipoise? How strong is the body of preclinical and/or clinical research to support the study rationale and how rigorous are those data? 

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?  

Specific to this FOA:

How does the involvement of the Single State Agency staff enhance the feasibility, scientific impact, or relevance of the project?  How strong is the application in demonstrating that the PDs/PIs and Key Personnel have the experience and capability to conduct the proposed study and meet milestones and timelines? How well defined are their roles and responsibilities? What evidence is provided to ensure that the clinical centers will employ the appropriate personnel to recruit subjects and implement the clinical protocol? How well does the application provide evidence of necessary experience and expertise of the investigators with the psychosocial intervention, the study population, and the research methods to be employed? What evidence is provided to ensure that the investigators' clinical centers will employ the appropriate personnel to recruit subjects and design/implement the clinical protocol? Does the investigative team have a track record of publishing the results of clinical trials previously completed?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA:

How will the proposed clinical trial change clinical practice or practice guidelines? Does the proposed research have the potential to advance the field even if the proposed study design, methods, and intervention are not innovative?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

Specific to this FOA:

What strengths and weaknesses are there in the study design? For observational studies, have investigators proposed methods to mitigate bias and support causal inference? How appropriately is the study designed to answer the research question, test the proposed hypothesis/hypotheses, and collect the necessary data? How efficient is the trial design? How strong is the evidence for equipoise? How well does the Clinical Protocol Synopsis attachment describe the necessary elements of the clinical trial and how likely is it that the protocol can be efficiently implemented at all of the sites?   Is the psychosocial intervention appropriately characterized?  How well are the clinical outcome measures, dose/duration of intervention and follow up, appropriateness of inclusion/exclusion criteria, and sample size justified and explained? What evidence is there that the study population has been appropriately defined? How well does the Recruitment and Retention plan provide evidence that the accrual goals can be reached within the proposed timeline? How appropriate is the plan to monitor accrual? Is the study timeline appropriate to complete the goals and address the scientific question(s)? Are there plans for adverse events to be appropriately captured and monitored? How effectively does the Project Management Plan identify and describe risks to implementation and how well are contingency plans described?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?  

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? 

Specific to this FOA:

Does the application document the availability of the requisite eligible subject pool in proposed clinical site(s)? Is there documentation of the commitment of any subcontractors and consultants, as well as service agreements for personnel and facilities?  What facilities and resources are available to adequately coordinate study intervention? Is there strong evidence that the institutions have the available resources needed to conduct study with adequate number(s) of clinical sites?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Milestones

How strongly do the milestones address the specific aims of each phase? Are the listed milestones appropriate for the goals of the project? To what extent are the milestones relevant, measurable, quantifiable, result-focused and time-bound? Does the application address contingency plans in the event the R21 and/or R33 milestones are not achieved? 

Data and Safety Monitoring

Is the proposed Data and Safety Monitoring Plan appropriate for the proposed clinical trial? What is the quality of the DSM Plan to monitor sites/centers, and participating facilities (labs, pharmacies)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

Not Applicable.

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCCIH, , in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

  • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
  • Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.
3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information
1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee's business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person's race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator's scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements.  FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award.  An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS.  The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant's integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 "Federal awarding agency review of risk posed by applicants."  This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Scientific/Research Contact(s)

Robin Boineau, M.D., M.A.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-6286
Email:  robin.boineau@nih.gov

Peer Review Contact(s)

Martina Schmidt, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone:301-594-3456
Email: SchmidMa@mail.nih.gov

Financial/Grants Management Contact(s)

Shelley Carow
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3788
Email:  shelley.carow@nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.