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.

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

This Funding Opportunity Announcement (FOA) invites applications from clinical investigators to participate in the National Drug Abuse Treatment Clinical Trials Network (CTN). NIDA intends to continue to develop and test interventions to address a variety of substance use problems via collaborative partnerships among NIDA, clinical research investigators, and healthcare providers and institutions.

NIDA’s National Drug Abuse Treatment Clinical Trials Network (CTN) was established in 1999 to bridge the gap between research and practice to improve substance use disorder (SUD) treatment. Through the collaborative partnership of scientists, treatment providers, and other community stakeholders, the CTN seeks to address critical research questions with direct relevance to clinical practice and the needs of patients. Over the last two decades, the CTN’s research infrastructure and agenda have evolved to reflect the changing landscape of the SUD treatment community, transformation of health care systems, and emerging scientific advancements. With the 2015 applications and awards, the Network's research portfolio began to expand beyond specialty SUD treatment settings into general medical settings and healthcare systems.

The CTN currently is comprised of two coordinating centers and 18 Nodes. Each Node is a primary performance site, with numerous affiliated clinical research sites. The CTN program is administered within NIDA through the Center for the Clinical Trials Network (CCTN). NIDA plans to continue supporting the CTN research infrastructure to build on the broad portfolio of research conducted in the CTN. Applications proposing new Nodes and continued support of existing Nodes are encouraged. Applications proposing Multiple Principal Investigator (MPI) collaborations, including collaborations among institutions in different states, are encouraged. NIDA has an interest in extending the reach of the CTN to regions of the country that are heavily impacted by substance use and not currently represented in the Network.

Applications responsive to this FOA should address how their infrastructure, including the expertise of investigators and institutional resources, could address key and emerging substance misuse/SUD issues in a variety of healthcare settings, in accordance with the objectives and research topics outlined below. Applicants should propose a research agenda likely to have substantial public health significance and impact on clinical practice. The proposed research agenda will not necessarily be conducted in the CTN but could constitute one source of research ideas to be considered during the project period. The proposed infrastructure and research agenda should illustrate how the proposed Node could contribute and participate in the research network to improve SUD treatment and advance research in the field. Incomplete and/or non-responsive applications will be withdrawn prior to review.

• Test strategies for the integration of SUD prevention and treatment into specialty and general medical settings (such as in primary care, emergency care, and HIV and other infectious disease settings) including strategies for linking these medical settings to SUD specialty care settings or vice versa;
• Evaluate comprehensive SUD treatment models that address co-occurring medical and mental health conditions;
• Evaluate telehealth and other innovative technologies for improving and implementing evidence-based SUD treatment;
• Promote use of learning healthcare system principles and practices through research that embeds research in clinical care and leverages electronic health record data and other existing datasets;
• Ensure that SUD treatment research encompasses diverse populations such as racial and ethnic minorities, women, youth, and other understudied populations;
• Generate evidence that addresses sustainability and will inform and support healthcare policy decisions and clinical guidelines in healthcare settings; and
• Develop a health data science and information technology research portfolio aimed at enhancing the efficiency and breadth of SUD treatment research.

NIDA’s priorities for treatment research topics vary over time, largely in response to public health needs and impacted by substance use trends, community demands and stakeholder policies. Examples of high priority research topics include, but are not limited to:

• Testing new medications, therapeutics, and behavioral strategies to address use of substances with rising use rates including, but not limited to, methamphetamine, marijuana, opioids, and cocaine;
• Developing and testing the efficacy and effectiveness of telehealth, digital and other therapeutics to improve patient engagement and retention in treatment;
• Developing and testing innovative and pragmatic treatment models (e.g. chronic care models incorporating measurement-based care) that have high potential for adoption and sustainability in various specialty and health care settings (e.g. hospitals, general medical settings, EDs);
• Developing and testing adjuncts to clinical care to improve treatment engagement and outcomes (e.g. technologies, peer support, pharmacists, case management);
• Developing and testing interventions in patients with SUD and co-occurring health conditions, such as psychiatric disorders, chronic pain, suicidality, infectious disease (e.g. HIV, Hepatitis C), and other medical conditions (e.g. cardiac diseases and metabolic diseases);
• Studying strategies for managing subthreshold and low risk SUD through prevention and/or early interventions;
• Studying strategies that address challenges to delivering care in underserved and minority populations; and
• Leveraging healthcare data, creating longitudinal SUD patient registries, exploring linking data sources (such as EHRs, claims, death records, prescription monitoring and other available datasets), and applying artificial intelligence approaches to predict risk and guide clinical decisions.

Nodes: The Node is the functional unit within the CTN and resides within the grantee institution of the cooperative agreement award. The Node:

• Provides scientific leadership and core functions for the clinical research conducted within the CTN;
• Builds partnerships with the research organizations (clinical research sites) within the Node and seeks collaborative opportunities with other established networks, such as the CTSAs, SIREN, and the PCORnet, and other relevant research projects;
• Proposes, plans, and coordinates the research, training, and dissemination activities of the network, in collaboration with NIDA and other Nodes;
• Works collaboratively with the CTN Clinical Coordinating Center (CCC) and Data and Statistics Center (DSC);
• Works within the CTN with each collaborating research organization as an equal partner.

Research Agenda: Node investigators develop research concepts for potential CTN research projects in close partnership with the clinical and research personnel within the Node, NIDA, and colleagues across the CTN. Nodes submit research proposals to the Research Development Committee (RDC, a subcommittee of the CTN Steering Committee) for discussion and review.

Each collaborating Node agrees to:

• Designate the Director (or other senior official) of each research site to represent the site for CTN activities and to ensure fulfillment of CTN obligations;
• Participate fully in the development of research concepts and protocols for studies (in collaboration with the CCC/DSC) to be conducted in the CTN;
• Participate in clinical studies and adhere fully to Good Clinical Practice (GCP) and to the specific protocol and operations manual applicable to each study;
• Cooperate with periodic on-site audits by NIDA or its designees to ensure appropriate use of investigational drugs, compliance with all applicable federal, state and local regulations for research on human subjects, including Institutional Review Board (IRB) approval and informed consent (e.g., 45 CFR 46), compliance with protocol specifications, quality assurance and accuracy of data recording and completeness of reporting of adverse drug reactions;
• Coordinate all data collection and statistical analysis with the DSC and within the parameters and guidance outlined in the CTN policy and procedures.

Training Agenda: The CTN structure provides many opportunities for pre-doctoral, post-doctoral and junior faculty researchers to gain valuable hands-on experience in designing, participating in, and managing complex clinical trials and other clinical studies.

Principal Director(s)/Principal Investigator(s) (PD(s)/PI(s)). Nodes are led by the PD(s)/PI(s), who should be able to make a substantive and long-term commitment of effort to CTN responsibilities. The PD(s)/PI(s) are responsible for all projects conducted within their Node.

Center for the Clinical Trials Network (CCTN). The organization within NIDA responsible for scientific collaboration, administrative oversight, budgetary management, and operational management of the CTN research program.

Data and Statistics Center. The entity established under a contract awarded by NIDA to provide data management and analysis systems as required to implement and support standards established by NIDA's CCTN. The major tasks of the DSC are to:

• Establish systems for the collection, management and storage of study data;
• Plan and perform statistical analyses;
• Review and monitor the quality of study data;
• Monitor trial progress;
• Prepare reports for the Data and Safety Monitoring Board (DSMB);
• Provide expert consultation and support services as directed by NIDA.

Clinical Coordinating Center. The entity established under a contract awarded by NIDA to provide certain resources and services for CTN clinical trials and other clinical studies, including support for regulatory requirements and oversight functions mandated by NIH and DHHS. The major tasks of the CCC are to:

• Provide support for the development and maintenance of protocols;
• Provide support and expertise for regulatory affairs and protection of human subjects;
• Provide on-site monitoring of clinical study sites and quality assurance support;
• Serve as NIDA's safety officer for CTN studies;
• Provide central pharmacy services for medication packaging, shipping, and inventory control;
• Provide clinical laboratory support and drug testing;
• Coordinate the distribution of trial supplies, medications, forms, and manuals;
• Provide regulatory, quality assurance and training plans for protocols;
• Provide training in a variety of venues;
• Provide other expert consultation and support services as needed.

CTN Steering Committee. The Steering Committee (SC) constitutes the primary governing body of the CTN, with representation from each of the Nodes, NIDA, the CTN Clinical Coordinating Center, and the CTN Data and Statistics Center. The SC uses both established and ad hoc committees and workgroups (e.g., Research Development Committee, Publications Committee) to assist it in carrying out its functions. The SC meets in person at least annually, and via webinars as the need arises.

Funding to carry out the network's research agenda falls into two categories:

Core Funds. NIDA will provide core funds directly to the Nodes on an annual basis. Core funding is the initial fixed-base funding and provides infrastructure and salary support that is not protocol-specific. Examples include, but are not limited to:

• Principal Investigator and Co-Investigator effort
• Community engagement activities
• Clinical trials quality management activities
• Travel to attend clinical trials network meetings
• Mentoring and training of staff
• Record retention to meet regulatory requirements

Study Funds (SF). NIDA will provide SF to the Nodes on an annual basis. SF provides support to conduct studies, including study-specific infrastructure or other requirements needed to conduct studies at a site. SF varies annually, depending on costs of ongoing protocols and will be awarded to cover expenses attributable to study development, implementation or close-out of a clinical trial. Study funds include, but are not limited to, the following study-specific expenses:

• Personnel salary (study-specific)
• Study required tests and evaluations
• Travel for study-specific personnel, as required by network, to attend clinical trials network meetings
• Travel to attend study-specific trainings
• Equipment and supplies
• Study specimen shipment and storage

NIDA expects that equipment and services funded via Core or SF will be made available, as appropriate, for other NIDA-funded network activities regardless of how funds were initially provided to purchase those items.

Based on communications with Study Lead Investigators, affiliated sites, and the DSC/CCC, the Nodes will estimate study funding needs (salary and non-salary SF) annually and submit a budget request to NIDA. NIDA will then determine the amount of SF to be provided in the coming grant year. Adjustments in SF allocation may be made at regular intervals during each budget period, based on both performance and availability of funds.

Distribution of Study Funds to Network-Affiliated sites

SF will be distributed to the sites from the Nodes prior to enrollment of study participants following the process described above.

SF may be provided to the Node for its use and distribution to the sites to provide additional support for study-related expenses for activities that are not directly related to participant accrual.

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.

Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants: The National Advisory Council on Drug Abuse (NACDA) encourages NIDA and its grantees to consider the points it has set forth regarding existing or prospective sponsored research agreements with tobacco companies or their related entities and the impact of acceptance of tobacco industry funding on NIDA's credibility and reputation within the scientific community. Please see http://www.drugabuse.gov/about-nida/advisory-boards-groups/national-advisory-council-drug-abuse-nacda/council-statements/points-to-consider-regarding- for details.

Data Harmonization for Substance Abuse and Addiction via the PhenX Toolkit: NIDA strongly encourages investigators involved in research with human subjects 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 (https://grants.nih.gov/grants/guide/notice-files/NOT-DA-12-008.html) for further details.

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

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

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:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• 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

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.

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.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. 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.

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.

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

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).

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace 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.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, 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.

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: [email protected]

Applicants are encouraged to send the letter of intent by email to the email address above, but as an alternative, the letter may also be sent to:

Office of Extramural Policy and Review
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Suite 4243, MSC 9550
Bethesda, MD 20892-9550

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

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.

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

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

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

Facilities and Other Resources. Briefly describe proposed partnerships with healthcare organizations explaining how productivity of the network will be increased and how the partnerships will advance the objectives of the program. Specialty programs should be able to describe their relationships with primary care programs or the available integrated medical services. In addition, programs should be able to describe how they will integrate existing EHR data with proposed research projects.

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

Biosketches of applicants must describe their recent experience and participation in randomized clinical trials, preferably of a multicenter nature. Specific roles (PD/PI, participating site, leadership committee, lead investigator, trial design and development) should be described for each study. Publications that resulted from participation in the studies should be listed. Applicants are expected to provide evidence of their unique strengths, accomplishments and capabilities to contribute to shared CTN activities. Applicants should provide evidence of expertise in the conduct of clinical trials, particularly pragmatic, randomized clinical trials. Persons responsible for participant recruitment, enrollment, data collection and data management should be shown to have extensive experience and high qualifications.

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

The application should only request Core funding. Core funding is the initial fixed-base funding and provides infrastructure and salary support that is not study-specific. Examples include, but are not limited to:

• Principal Investigator and Co-Investigator effort
• Community engagement activities
• Clinical trials quality management activities
• Travel to attend clinical trials network meetings
• Mentoring and training of staff
• Record retention to meet regulatory requirements

Study Funds (SF) should not be requested; SF will be determined and provided as protocols are initiated through a collaborative process between the NIDA and awardees. The process for proposing research to be conducted in the CTN is for investigators to submit a study concept for peer review to the CTN Research Development Committee (RDC), a sub-committee of the CTN Steering Committee. The CCTN Director reviews the RDC’s recommendations and makes final approval decisions in consultation with NIDA leadership. If a concept is approved to move forward, a team comprised of CTN investigators, NIDA Scientific Officer(s), and Data and Statistics Center and Clinical Coordinating Center staff members is convened to develop a study protocol. An independent Protocol Review Board (PRB) reviews the protocol(s) and provides recommendations to NIDA. The CCTN Director considers PRB recommendations and makes final decisions regarding protocol approval for implementation or disapproval. Applicants should describe in their application how they will comply with this review procedure.

Each PD/PI must expend 2.4-4.2 (CY) person-months effort annually on the award over the entire period of support.

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

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

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

Research Strategy:

Applications should propose infrastructure, including expertise of investigators and institutional resources, and a broad research agenda. The proposed infrastructure and research agenda should illustrate how the proposed Node could contribute and participate in the research network to improve substance use disorder treatment and advance research in the field. Research sites must describe their previous experience and success in conducting multi-site clinical trials.

Applications should propose core faculty with extensive SUD expertise; expertise in successfully leading multi-site clinical trials; bioinformatics expertise; familiarity with state-level SUD treatment policies; and demonstrated active and ongoing collaboration with health systems and/or research networks.

The research plan must include the following features of collaborating sites and research networks: 1) capacity to support large-scale trials of treatment and prevention interventions with an emphasis on sustainability to answer important SUD research questions, 2) collaboration with health systems and settings that can embed research in clinical care, 3) ability to use electronic health record system (EHRs) data collected within typical clinical visits to simplify clinical trial implementation, including the identification, assessment, monitoring, and follow-up of SUD patients, 4) willingness to participate in collaborative studies with data sharing as part of a national clinical research infrastructure, and 5) ability to engage diverse patients in areas highly impacted by substance use.

Applicants should describe how the communities served by organizations in their proposed Node have been impacted by addiction. Applicants must cite specific measures and their data sources to justify the impact of addiction such as overdose deaths per capita or rates of methamphetamine use disorder.

Proposed research sites must have previous experience and success in conducting multi-site clinical trials. Applicants should provide evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure.

Node organizational structure should be described. The capacity to expand, as needed, for the conduct of specific scientific projects and related activities should be described. Applicants are encouraged to describe novel approaches or methodologies for improving the efficiency of conducting pragmatic trials in the CTN. Applicants are encouraged to describe mechanisms for leveraging novel strategies for effective collaboration and study oversight. Applicants are encouraged to use existing Federal and other resources (e.g., CTSAs, practice-based research networks, administrative databases or patient registries) to increase study efficiencies.

Applicants should provide a detailed description of a research agenda likely to have substantial public health significance or impact on clinical practice and consistent with the goals and objectives of this FOA (see Section 1., Priority Research Topics), which could be carried out to take advantage of the unique capabilities of the CTN. The proposed research agenda is not meant to be limited to the description of a single study; rather it must encompass a broader set of research ideas that address current public health needs related to substance use and describe how knowledge gaps would be filled if the agenda were to be accomplished. This research agenda is not expected to be a detailed concept for a research protocol, and the proposed research agenda will not necessarily be conducted in the CTN. The proposed vision for a CTN research agenda could constitute one source of research ideas to be considered during the project period. It should include high priority projects that will provide needed evidence to help decision makers and providers in health care settings and patients/caregivers make better-informed decisions. The proposed research agenda should describe critical research questions that the applicant asserts must be addressed to advance scientific knowledge and have an impact on curtailing addiction related morbidity and mortality.

Each of the specific research areas within the proposed agenda should include: scientific rationale and significance, main research questions; explanation of reliance on electronic health records (if applicable), feasibility for execution in the CTN; public health impact; and plans for dissemination and implementation of findings.

The application should describe the strengths and weaknesses in the rigor of the prior research (both published and unpublished) that serves as the key support for the proposed project(s) or research agenda. The application should discuss plans to address weaknesses in the rigor of the prior research that serves as the key support for the proposed project(s) or research agenda.

The application should include a discussion of the feasibility of the proposed research agenda and its relevance to the treatment field, research methods that might be used, patient populations that might be studied, cost-efficiencies, potential for implementation and adoption by health care systems, and how potential findings would lead to changes in clinical practice.

The discussion should also address how the applicant proposes to work collaboratively at all levels (including with other network members and NIDA and on projects proposed by other Nodes) to advance CTN research. In previous years, successful applicants have typically emphasized their capacity to conduct multi-site clinical trials and have provided brief descriptions of 2 - 4 projects they could lead as part of the proposed research agenda.

History of Collaboration

Applicants must describe any relevant collaborative research activity undertaken between the applicant institution and the proposed healthcare organizations (or healthcare system networks). Contributions and collaborations in areas such as protocol design, study recruitment, data analysis and interpretation, publication and dissemination should be highlighted. Documentation of recruitment and retention rates in clinical trials should be provided.

Population Available for Clinical Trials

Applicants must describe populations who are available to them. Investigators must demonstrate the ability to recruit and retain diverse participants, including racial and ethnic minorities and women, from populations served by their proposed healthcare providers. Potential challenges and corresponding solutions should be discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls).

Letters of Support

Applications indicating opportunities to conduct research in multiple types of medical settings and healthcare organizations are preferred. Letters of support from all healthcare organizations outside of the awardee institution with whom the applicant desires to collaborate in conducting CTN-sponsored research should be included. These letters should summarize the organizations' research experience and demonstrate their capacity to conduct research. These letters should also be coupled with evidence of support for these activities from leadership of the collaborating organizations.

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:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

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

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed. Since only delayed onset studies are expected, do not complete a full study record.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

Both Renewal and New Applications must add and complete the Delayed Onset Study record and must check box "Anticipated Clinical Trial?".

Study Title-- use: "Multiple Delayed-Onset Studies"

Justification Attachment: Indicate each clinical study protocol developed during the project period will be subject to approval through a procedure that involves an initial concept submission and subsequent review by the Research Development Committee (RDC, a subcommittee of the CTN Steering Committee). If the concept receives approval, the next stage will be development of the protocol, which also must undergo review and approval prior to implementation.

Single IRB

Participating institutions must agree to acceptance of oversight by a single IRB of record for multi-site studies per NIH policy, rather than local IRBs, to standardize the oversight for protection of human subjects in CTN trials, especially those operating in multiple states (https://grants.nih.gov/policy/clinical-trials/single-irb-policy-multi-site-research.htm). Include information in the application regarding how the study will comply with the NIH single Institutional Review Board (sIRB) policy prior to initiating any multi-site study in the delayed onset study justification.

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

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

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.

This initiative is not subject to intergovernmental review.

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.

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 How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. 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 NIDA, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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.

Only the review criteria described below will be considered in the review process.

Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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).

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.

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? 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?

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

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? Does the applicant demonstrate previous experience, leadership, and success with large scale projects?

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed 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?

Does the applicant demonstrate the capability to develop and conduct studies using artificial intelligence in the analysis of large healthcare datasets? Will results provide relevant information and adequate data for general medical settings to determine applicability for adoption?

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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Does the application adequately address the following, if applicable?

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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? Does the applicant describe and justify a streamlined research infrastructure with the capacity to expand, as needed, for the conduct of specific scientific projects and related activities? Does the description of the Node infrastructure demonstrate core capabilities and expertise (e.g., clinical investigators and informaticists, etc.) for satisfactory conduct of CTN research activities and efficient implementation of pragmatic trials in general medical settings? Are the partner healthcare organizations well suited to contribute to research studies aimed at improving SUD clinical practices? Have partner healthcare organizations demonstrated the capability to leverage electronic health record systems and other health information technology (HIT) resources to facilitate research designs that make use of data collected during routine clinical care? Does the application include documentation from the partner healthcare organizations that outlines strong commitment to the project planning and implementation?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

For research that involves human subjects but does not involve one of the 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 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.

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 individuals of all ages (including children and older adults) 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.

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.

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.

Not Applicable

For Renewals, the committee will consider the progress made in the last funding period. For Renewal applications, did the Node initiate and effectively lead studies in the Network? If a Renewal application, did the Node have substantial participation in Network research and demonstrate leadership in dissemination of research?

Not Applicable

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.

Not Applicable

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).

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).

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.

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIDA, 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 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 National Advisory Council on Drug Abuse. 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.

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.

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.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC or a central IRB. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement (NIH UG1), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project, although specific tasks and activities may be shared among the awardees and the NIH as defined above.

The PD(s)/PI(s) will have the primary responsibility for:

The Program Director/Principal Investigator (PD/PI) and collaborating investigators will have the primary responsibility for defining the details for the project within the guidelines described in the Request for Applications DA-20-024 and for performing the scientific activity. The PD/PI and collaborating investigators agree to accept close coordination, cooperation, and participation of NIDA Program staff in those aspects of scientific and technical management of the project described in these terms and conditions. The PD/PI and collaborating investigators agree to accept close coordination and to cooperate fully with NIDA designated coordinating centers and contractors. The PD/PI further agrees to participate fully in the activities of the Clinical Trials Network (CTN) Steering Committee and in other committees and workgroups as formed.

Awardees will retain custody of and have primary rights to the data under these awards, subject to Government rights of access consistent with current DHHS and NIH Policies.

a. Generally, Awardees under this agreement have the following rights and responsibilities:

Provide leadership for their Node. The Node refers to the combination of the awardee organization and the partnering health care organizations. The awardee provides scientific leadership and management of clinical trials as well as administrative and study operations services for the Node. The awardee agrees to negotiate and establish formal working relationships with healthcare organizations such as SUD specialty treatment centers, hospitals, healthcare networks, Federally Qualified Healthcare Centers (FQHCs), patient-centered medical homes (PCMHs), accountable care organizations (ACOs), or other entities to participate in CTN activities and conduct research and training projects. These agreements will include, at minimum: 1) a statement of work defining the goals and objectives of the research projects to be undertaken under this cooperative agreement; 2) a budget for support of the research projects that clearly identifies the personnel, equipment, materials, and other costs required to successfully conduct high quality research according to the requirements of specific protocols approved for implementation by the CTN Steering Committee and NIDA; and 3) a financial and program reporting requirement, including access to data and materials, to facilitate CTN program operation and research project oversight and monitoring. Initial agreements between the awardee institution and healthcare organizations may be more general as specific details will depend on the research projects and participating sites. The awardee will also agree to follow all CTN standards as established by the Steering Committee.

Core functions - This includes but is not limited to 1) arranging and managing the participation of partnering healthcare organizations; 2) providing scientific and technical expertise for protocol development and research operations; 3) coordinating and providing resources for activities within the Node; 4) collaborating with NIDA and other Nodes to publish and disseminate findings from CTN research projects; and 5) working with the CTN Clinical Coordinating Center and Data and Statistics Center. The Principal Investigator agrees to provide adequate support for Node personnel participation in Steering Committee and other CTN meetings as required.

Research Concept Development and Implementation - In close partnership with the partnering healthcare organizations, and in collaboration with other CTN members, the awardee develops research concepts for potential CTN trials and submits them to the CTN Research Development Committee for discussion and review, and to NIDA for approval.

b. Data Rights:

The NIH expects investigators supported by NIH funding to make their research data available to the scientific community for subsequent analysis based on a data sharing plan approved as part of the award; see the NIH data sharing policy website at https://grants.nih.gov/grants/policy/data_sharing. The CTN is intended as a national resource for the advancement of treatment for individuals with SUD and other affected persons. The Awardee of this agreement acknowledges that NIH has access to any and all data generated under this cooperative agreement and the Awardee agrees to provide royalty-free, nonexclusive, and irrevocable license for the government to reproduce, publish, or otherwise use the material and data derived from research conducted under this cooperative agreement. The Awardee agrees to register studies in the clinicaltrials.gov database and submit results according to NIH policy http://clinicaltrials.gov/ct2/manage-recs/fdaaa. The Awardee also agrees to cooperate with NIDA’s contracted Data and Statistics Center as requested by the CCTN with regard to (1) collection and analysis of data generated under the CTN, including but not limited to collection of PhenX Toolkit Core Tier 1 measures (https://www.phenxtoolkit.org/) and NIDA CTN common data elements (CDEs); and (2) providing timely, accurate, and complete data for purposes of monitoring the safety and progress of research projects conducted within the CTN. For each protocol, NIDA will appoint a Lead Investigator (LI). Data from all participating sites will be included in a single dataset and the dataset will be provided to the study LI. At the end of each protocol, the LI will be required to make available a public use file of all related participant-level study data. Exceptions may be made for certain types of studies or health system data; a data sharing plan must be provided and approved by the CCTN in these instances. The awardees will retain custody and primary rights to their Node data consistent with current DHHS and NIH policies, including a policy to provide public access to selected, significant data sets generated with the use of public funds, within a reasonable period after primary analysis or publication by the CTN. The awardee must agree to retain records for each completed study for a minimum of 3 years (or more if necessary) after study data lock. Each site must also comply with their respective IRB and other regulatory entities regarding records retention.

c. Study Management:

The awardee is responsible for the proper conduct of CTN studies at each site within their Node. All studies conducted in the CTN are subject to the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. The awardee must provide resources to ensure that (1) staff receive adequate training and resources to conduct the studies; (2) the studies are conducted according to the protocol and applicable regulatory requirements; (3) the studies recruit and retain participants per approved recruitment plans, including appropriate number of women and minorities per NIH policy; (4) staff perform adequate data entry; (5) corrective actions are implemented when appropriate; (6) study materials and records are kept and/or disposed appropriately; and (7) study personnel participate in study related activities as planned by the Lead Investigator, NIDA Center for the Clinical Trials Network (CCTN) and/or Coordinating Centers. Each study site must agree to monitoring activities that will be specified in each protocol.

d. Reporting Requirements:

In addition to periodic financial and administrative reports required by NIH for administration of this cooperative agreement, the Awardee agrees to furnish the following reports according to the schedule indicated:

Investigational New Drug (IND) Reports: Awardees are required and agree to provide reports according to regulations and guidelines established by the Food and Drug Administration (FDA).

Final Study Report: Study Lead Investigators are required to provide CCTN with a Final Study Report within 120 days of data lock upon completion of the protocol. In addition, the Lead Investigator will present primary outcome results to the study DSMB or monitor(s) (if applicable), the participating sites, and the Steering Committee prior to publication.

e. Publication of Data:

Prompt and timely presentation and publication in the scientific literature of findings resulting from research undertaken in the CTN is required. It is expected that the Lead Investigator will complete and submit the initial outcome paper to an appropriate peer-reviewed scientific journal within 180 days of study data lock. The Awardee agrees to acknowledge NIDA support in the publications and oral presentations resulting from research conducted under this cooperative agreement. Review and approval by the Publications Committee will be required for all analyses prior to publication or presentation. The Awardee agrees to present all CTN manuscripts to the CTN Publications Committee for review and approval prior to journal submissions.

f. Protocol Closure:

Throughout the term of the cooperative agreement NIDA may request that a research project or study site be terminated for reasons including but not limited to: 1) insufficient participant accrual; 2) poor performance in conducting the protocol; 3) safety of the participants in the study; 4) achievement of conclusive study results; 5) emergence of new information that diminishes the scientific importance of the study question; 6) misuse of federal funds; and 7) shortfalls in appropriated funds available to pursue the study. Financial support from NIDA and access to further investigational drug supplies through this cooperative agreement will cease upon project closure, except that funds and other resources may remain available for participants already enrolled in the study.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The Center for the Clinical Trials Network (CCTN) is the organization within NIDA responsible for the scientific collaboration, administrative oversight, and operational management of the CTN research program funded by NIDA.

NIDA Program staff has substantial scientific and programmatic involvement throughout this cooperative agreement through technical assistance, and advice and coordination extending beyond normal program stewardship for grants as described below.

a. NIDA s Scientific Role

The Director of the CCTN will appoint NIDA Program Officers and Scientific Officers with expertise in clinical research to participate in the development of study plans and protocols, and to coordinate projects across scientific disciplines and CTN Nodes. NIDA Scientific Officers may initiate or participate in publications in accordance with established professional and NIH guidelines for authorship.

The CCTN Director, and/or designated staff, will work closely with the CTN Steering Committee to ensure that CTN efforts are consistent with NIDA’s research objectives and complement other clinical research activities supported by NIDA and other organizations.

NIDA will appoint advisory boards within and outside of the CTN as deemed necessary during the development and progress of protocols and studies.

For ongoing research projects NIDA Scientific Officers and NIDA's CCC and DSC will monitor study progress through incremental review of case report forms. NIDA and the CCC and DSC and/or the LI will prepare periodic reports profiling the conduct of the study including the safety of study participants for review by the CTN Data and Safety Monitoring Board (DSMB) and/or other monitoring bodies as applicable. The DSMB may recommend to NIDA a need to alter, suspend, or close an ongoing study due to safety concerns, study performance issues, or early evidence of efficacy or futility.

b. NIDA s Role in Protocol Review and Approval

In order for a CTN research project to be initiated, a research concept must be reviewed by the CTN Research Development Committee and approved by the NIDA CCTN. Once a concept is presented for consideration, NIDA will evaluate the proposed project according to: NIDA’s research agenda; potential impact on the science and public health; relevance to current national priorities; likelihood for timely completion; participant safety; compliance with Federal regulatory requirements; an estimated budget; and resource requirements. If a concept is approved to move forward, a team comprised of CTN investigators, NIDA Scientific Officer(s), and Data and Statistics Center and Clinical Coordinating Center staff members will be convened to develop a study protocol. The CCTN Director will appoint a Protocol Review Board that will review protocols as needed and provide recommendations to the CCTN Director. The CCTN Director will consider PRB recommendations and will make final decisions regarding protocol approval or disapproval. To maximize resources, the NIDA CTN DSMB Charter could include the role of scientific protocol review. NIDA will provide no study materials or permit expenditure of CTN funds unless and until the proposed protocol is officially approved by NIDA.

c. NIDA Access to Data

The CCTN Director, and/or designated staff or agents, shall have access to all data generated under this cooperative agreement. Monthly reports on trial progress for studies that are monitored will be prepared by the Data and Statistics Center and reviewed by CCTN, the CTN Steering Committee, and the study Lead Investigator. Data must be available for external checking against original source documents as required by NIDA, and Federal regulations pertaining to the responsibility of NIDA as an IND sponsor.

Monitors from the Data and Statistics Center and the Clinical Coordinating Center will perform periodic review of data recorded on clinical source documents, case report forms, or in electronic form. Both the Data and Statistics Center and the Clinical Coordinating Center are established under contracts awarded by NIDA to provide certain resources and common services for CTN clinical trials or clinical studies, as needed, including support for regulatory requirements and oversight functions mandated by NIH and DHHS.

d. NIDA Monitoring of Trials

All CTN studies are subject to monitoring according to protocol-specific monitoring plans. The Node must agree to periodic monitoring by Clinical Coordinating Center and Data and Statistics Center representatives. In addition, formal site audits will be conducted if necessary. The monitoring may include periodic on-site visits and remote document reviews by staff from the Node and the NIDA appointed Coordinating Centers to assess the following: (1) investigational drug accountability; (2) compliance with applicable federal, state and local regulations for Human Subject Research, including Institutional Review Board (IRB) approval and informed consent (compliance with 45 CFR 46); (3) compliance with protocol specifications; quality control and accuracy of data recording; and (4) completeness of reporting adverse events. Monitoring is conducted to assure that: the rights and well-being of participants are protected; the reported trial data are accurate, complete, and verifiable from source documents; and the conduct of the trial complies with the currently approved protocol/amendment(s), with GCP, and with all applicable regulatory requirements. Reports of all monitoring activities and audits will be reviewed by the CCTN and study performance will be reported to the DSMB. Summary reports from DSMB meetings will be provided to the Lead Investigator, who in turn will provide necessary documentation to other entities, as needed. Finally, NIDA program and grants management staff will review study accrual, and fiscal and administrative procedures. NIDA reserves the right to discontinue site participation in protocols based on poor performance.

e. NIDA Review of Performance

CCTN will periodically review the performance of the CTN as a whole and of individual Nodes. The review will be based on information provided in periodic trial progress reports compiled from data on recruitment, retention, follow-up, treatment exposure, monitoring reports, and other factors, as well as from evaluations of site performance conducted by the CCTN staff. Insufficient patient accrual, substandard data quality, inadequate progress in executing the research agenda, or noncompliance with the Terms and Conditions of Award may result in a reduction in budget, withholding support, suspension, or termination of award.

f. Normal Program Stewardship

A separate NIDA Program Official other than the CCTN Director will be responsible for the normal programmatic stewardship of the award and will be identified in the Notice of Grant Award.

Areas of Joint Responsibility include:

CTN Steering Committee. The Steering Committee constitutes the primary governing body of the CTN. Membership shall comprise voting representation from each of the Nodes, the CCTN, the Clinical Coordinating Center, and the Data and Statistics Center. The Steering Committee uses both established and ad hoc committees and workgroups (e.g., Research Development Committee, Publications Committee) to assist it in carrying out its functions. By accepting a Cooperative Agreement award, all participating Nodes must agree to abide by the policies and By-laws approved by the Steering Committee. The Steering Committee shall meet face-to-face at least once each year and via webinar/conference call as necessary during the year.

Protocol Review Board (PRB). An independent expert board, appointed by and reporting to the CCTN Director, that reviews proposed protocols and informed consent documents. To minimize delay and provide continuity, this board may be combined with a DSMB (see below) for a given study.

Data and Safety Monitoring Board (DSMB). An independent expert board, appointed by and reporting to the CCTN Director, that oversees and monitors the conduct of multi-site clinical trials and other clinical studies as needed to ensure the safety of participants and the validity and integrity of data. The DSMB may conduct a scientific review of a protocol if necessary (see above). The DSMB also makes an independent assessment of the research and recommends whether studies undertaken in the CTN that are monitored should continue.

Single IRB of record (IRB). To reduce the burden on local IRBs and to standardize the oversight for protection of human subjects in our trials, the use of a single IRB for CTN research studies is required unless an exception is granted (https://grants.nih.gov/policy/clinical-trials/single-irb-policy-multi-site-research.htm).

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to dispute resolution. A Dispute Resolution Panel composed of three members will be convened. The three members will consist of a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two. In the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure in no way affects the Awardee’s right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and DHHS regulations 45 CFR Part 16.

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.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and 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)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Betty Tai, Ph.D.
NIDA Center for Clinical Trials Network (CCTN)
Telephone: 301-443-2397
Email: [email protected]

Gerald McLaughlin, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-5819
Email: [email protected]

Jennifer Schermerhorn
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-6704
Email: jen.schermerhorn@nida.nih.gov

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.

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.