Expired PAR-13-188: Reducing the Duration of Untreated Psychosis in the United States (R34)

Part 1. Overview Information

Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Mental Health (NIMH)
Funding Opportunity Title	Reducing the Duration of Untreated Psychosis in the United States (R34)
Activity Code	R34 Clinical Trial Planning Grant Program
Announcement Type	New
Related Notices	May 17, 2016 - This PA has been reissued as PAR-16-264. NOT-OD-16-004 - NIH & AHRQ Announce Upcoming Changes to Policies, Instructions and Forms for 2016 Grant Applications (November 18, 2015) NOT-OD-16-006 - Simplification of the Vertebrate Animals Section of NIH Grant Applications and Contract Proposals (November 18, 2015) NOT-OD-16-011 - Implementing Rigor and Transparency in NIH & AHRQ Research Grant Applications (November 18, 2015) September 25, 2014 - See Notice NOT-MH-14-033. Notice of Information on High-Priority Research Areas to Understand and Reduce Mental Health Disparities. June 3, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same. August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications. May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.
Funding Opportunity Announcement (FOA) Number	PAR-13-188
Companion Funding Opportunity	PAR-13-187, R01 Research Project Grant
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.242
Funding Opportunity Purpose	Approximately 100,000 adolescents and young adults in the United States experience a first episode of psychosis (FEP) every year. The early phase of psychotic illness is widely viewed as a critical opportunity for indicated prevention, and a chance to alter the downward trajectory and poor outcomes associated with serious mental disorders such as schizophrenia. Multi-element FEP specialty care programs can produce a range of positive clinical and functional outcomes. The timing of treatment is critical; short and long-term outcomes are better when individuals begin treatment close to the onset of psychosis. Numerous studies find a substantial delay between the onset of psychotic symptoms and the initiation of treatment; in the U.S. treatment is typically delayed between one and three years, suggesting that many FEP persons are missing a critical opportunity to benefit from early intervention. Early identification, rapid referral to specialty FEP care, and engagement in phase-specific treatment are essential to shortening the duration of untreated psychosis (DUP) and pre-empting functional deterioration. The World Health Organization advocates reducing DUP to 3 months or less by addressing bottlenecks in the pathway from early psychosis identification to initiation of specialty care. Accordingly, this Funding Opportunity Announcement (FOA) will support R34 grants that (1) identify a baseline rate of DUP in community treatment systems that include evidence-based specialty care programs for FEP; (2) map referral pathways to FEP care, (3) identify gaps and bottlenecks in the referral pathway, and (4) develop and pilot test feasible strategies for substantially reducing DUP among persons with FEP.

Key Dates

Posted Date	April 10, 2013
Open Date (Earliest Submission Date)	June 1, 2013
Letter of Intent Due Date(s)	30 days prior to the application due date
Application Due Date(s)	July 1, 2013 and Standard dates thereafter, by 5:00 PM local time of applicant organization. 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	Standard dates apply
Advisory Council Review	Standard dates apply
Earliest Start Date	Standard dates apply
Expiration Date	May 8, 2016
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the 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.

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

Approximately 100,000 adolescents and young adults in the United States experience a first episode of psychosis (FEP) every year (calculated from McGrath, Saha, Chant, et al., 2008). The early phase of psychotic illness is widely viewed as a critical opportunity for indicated prevention, and a chance to alter the downward trajectory and poor outcomes associated with serious mental disorders such as schizophrenia. Compared to traditional treatment approaches, programs that integrate pharmacologic, psychological, and rehabilitation interventions for FEP are associated with a range of positive outcomes, including remission of psychotic symptoms, lower-rates of re-hospitalization, shorter hospital stays, improved quality of life and social functioning, increased cognitive performance, and reductions in substance use (Penn, Waldheter, Perkins, et al., 2005). The timing of treatment is critical; short and long-term outcomes are better when individuals begin treatment close to the onset of psychosis (Marshall, Lewis, Lockwood, et al., 2005; Perkins, Gu, Boteva, et al., 2005).

International consensus statements from the World Health Organization recommend that specialty care for FEP start within 3 months of illness onset (Bertolote and McGorry, 2005). However, more than two dozen studies conducted worldwide have observed a substantial delay (on average 2 years) between the appearance of psychotic symptoms and the initiation of appropriate treatment (Marshall et al., 2005). Two influential meta-analyses have clearly established that the duration of untreated psychosis (DUP), the time between the onset of psychosis and initiation of appropriate treatment, is correlated with poor outcome (Marshall et al., 2005; Perkins et al., 2005). In the United States, DUP ranges between one and three years (e.g., Hass and Sweeney, 1992; Ho, Andreasen, Flaum, et al., 2000), suggesting that many persons with FEP are missing a critical opportunity to benefit from early intervention.

Research suggests that DUP can be reduced within healthcare systems by enhancing early detection and treatment referral mechanisms (Melle, Larsen, Haahr, et al., 2004). Reducing DUP in the United States from current levels of 1-3 years to the international standard of no more than 3 months should be a major focus of applied research efforts. Research to improve FEP case identification and referral in the United States is a logical complement to other NIMH initiatives on improving outcomes for people with FEP, such as the Recovery After an Initial Schizophrenia Episode (RAISE) initiative.

Nature of the Funding Opportunity

This FOA aims to support research that will (1) investigate early links in the FEP case identification and referral chain in the United States, and (2) develop feasible strategies for reducing delays in early detection, speedy referral, and rapid initiation of stage-specific treatment. The target population is not limited to first episode schizophrenia, but includes all persons experiencing a first episode of psychosis regardless of presenting DSM-IV diagnosis. Applications submitted to this FOA are encouraged to base research activities in settings that link to treatment systems with evidence-based specialty care programs for FEP. A variety of configurations are possible, but evidence-based treatment programs typically feature use of single antipsychotic medications, prescribed in low doses; family psychoeducation; and supported employment (Addington, McKenzie, Norman, et al., 2013), along with cognitive-behavioral therapy, assertive case management, and continuity of care across inpatient and outpatient treatment settings (Bertolote and McGorry, 2005). Coordination of these treatment elements is also an important feature of specialty care programs for FEP.

For the initial benchmarking phase of the research, applications submitted to this FOA should (1) specify a scientifically acceptable operational definition of DUP; (2) use reliable measures to quantify overall DUP among persons who enroll in FEP specialty care; (3) map the various referral pathways that channel persons with FEP to specialty care programs; and (4) identify gaps and bottlenecks in these referral pathways, including barriers that impede the following:

time to first recognize psychotic symptoms
time to refer to mental health treatment
time to enrollment in FEP specialty care programs
time to initiate stage-specific FEP treatment

Applications submitted to this FOA are encouraged to develop and test the feasibility of strategies for reducing contributors to DUP within the selected care setting, based on results of the benchmarking activities. It is expected that pilot data from feasibility tests will be used to support applications for subsequent R01 intervention studies that will compare alternative methods for reducing DUP in community service settings. The strategies proposed to reduce DUP should aim to close gaps as well as remove significant bottlenecks in the referral pathway to specialty FEP care. NIMH encourages applications that explore approaches for producing one or more of the following:

Better signal detection of psychosis onset, or symptoms suggesting high clinical risk of psychosis, within primary care settings, schools, child/youth mental health services, college counseling centers, emergency departments, criminal justice agencies, and/or other community settings;
Methods to achieve expeditious referral of persons with FEP, or those at high clinical risk of psychosis, to an appropriate specialty care treatment program; and
Strategies for achieving rapid engagement and initiation of stage-specific FEP treatment

Applications submitted to this FOA should consider supply side approaches (e.g., targeting clinical and community systems), such as the development and testing of strategies for training primary care physicians and nurses, school and college counselors, emergency department staff, police, and mental health generalists to recognize signs of early psychosis, and the improvement of referral networks to fast-track the on ramp to FEP care initiation. This FOA is also intended to encourage demand side approaches (e.g., engaging people with FEP, and their family members, friends, caregivers, etc.) to improve help-seeking, access, and engagement in care for persons with FEP and/or youth at high clinical risk for psychosis, through education, decision-support systems, and other tools, such as social media.

Research to reduce DUP requires expertise on the characteristics of service delivery systems and community settings in which DUP reduction strategies would be embedded, as well as expertise on the needs, life circumstances, and diversity of the population of young people with FEP and/or at high clinical risk of psychosis. Investigators should convey knowledge of DUP assessment strategies and factors that may contribute to treatment delays in the U.S. health care system (see Compton & Broussard, 2011). Multi-disciplinary research teams with complementary areas of expertise are encouraged. NIMH encourages applications that involve collaboration with stakeholders from multiple clinical or community practice settings, as well as consumers of services and their family members and social contacts. In addition, NIMH welcomes applications proposing to leverage existing practice research infrastructures such as the Mental Health Research Network (MHRN), the Clinical Translational Science Awards Program (CTSA) and other research and practice networks looking to conduct studies to reduce DUP. NIMH also welcomes coordination of DUP research with other public and private initiatives that specifically address early identification and treatment of young people at high risk for mental illness.

This R34 FOA, and the related R01 FOA, PAR-13-187, support experimental and quasi-experimental studies focused on designing, refining, and testing algorithms of practical and accurate case identification of persons with FEP and/or at high risk of psychosis within a myriad of possible clinical and community contexts, and strategies that promote rapid referral to the appropriate stage-specific specialty care.

Research Topics

Applications to this FOA should focus on substantial DUP reduction for persons with FEP. The NIMH encourages applications in which referral to appropriate stage-specific care is feasible. This FOA supports studies on the research topics listed below, which are intended to be illustrative, not exhaustive:

Testing the effectiveness of strategies to improve identification and referral of patients with FEP within emergency service systems to appropriate stage-specific care.
Improving case identification of FEP within non-specialty clinical and community systems (e.g., primary care, high schools, justice settings, college campuses, or workplace).
Improving access and engagement in care of persons in the high-risk state for psychosis, resulting in rapid FEP identification and entry into specialty FEP care.
Improving identification of symptoms and help-seeking behavior among people with FEP and those at high risk of psychosis by targeting these individuals, their family members, and/or their social networks.
Developing and testing decision-support tools for improving the matching of symptomatic and functional deficits with available service systems within a catchment area.
Assessing the impact of high risk of psychosis/FEP public awareness campaigns on initiation of treatment and DUP.
Social networking approaches to identify persons at high risk of psychosis or with FEP and link to treatment.

It is expected that applications submitted to this FOA will identify other important, innovative and impactful research topics. Investigators considering applying to this FOA are encouraged to contact the Scientific/Research Contact for this FOA for additional guidance prior to submitting an application. Investigators who have already completed significant developmental or pilot work in this area should consider an application to PAR-13-187 (R01).

The sections on pilot testing for effectiveness and on innovative services research found in PAR-12-279 can serve as a useful guideline for the development of such studies under this FOA. The R34 should propose the developmental work to be performed that would enhance the probability of success in a larger study. Designs need not be reduced scope versions of the anticipated larger study, but should instead attempt to develop and refine the research strategies to be utilized in the subsequent large-scale study. NIMH recognizes that while the scope of interest for this R34 FOA is consistent across both this and the companion R01, PAR-13-187, FOA, there are specific research topics for which the field may not yet be ready for a large-scale trial. The R34 provides the opportunity for high risk, high reward studies that may be of high priority to the NIMH.

Thus, appropriate research activities for this R34 FOA might include: refining and pilot testing strategies for reducing DUP among people with FEP; working out the details of the study protocols and randomization procedures (if appropriate); examining the feasibility of recruiting and retaining participants into the study conditions; and/or developing supportive materials and resources. In addition, collection of preliminary data regarding feasibility, acceptability, safety, tolerability, and target outcomes are also appropriate. Given the intended pilot nature of the R34 mechanism, conducting a formal test of outcomes is not required and obtaining an estimate of an effect size may not be possible.

References

Addington DE, McKenzie E, Norman R, Wang JL, Bond, GR. Essential evidence-based components of first-episode psychosis services, Psychiatric Services in Advance, February 1, 2013; doi: 10.1176/appi.ps.201200156).

Bertolote J, McGorry P. (2005). Early intervention and recovery for young people with early psychosis: Consensus statement. British Journal of Psychiatry, 187 (suppl. 48):s116 s119.

Brunet KB, Lester M, Thornhill HK. (2007). Delays in mental health services and duration of untreated psychosis. Psychiatric Bulletin;31:408-10.

Compton MT & Broussard B. (2011). Conceptualizing determinants of DUP. Current Psychiatry Reviews, 7(1):1-11.

Haas G, Sweeney JA. Premorbid and onset features of first-episode schizophrenia. Schizophrenia Bulletin. 1992;18:373-386.

Ho B, Andreasen NC, Flaum M, Nopoulos P, Miller D. Untreated initial psychosis: Its relation to quality of life and symptom remission in first-episode schizophrenia. American Journal of Psychiatry 2000;157:808-815.

Marshall M, Lewis S, Lockwood A, Drake R, Jones P, Croudace T. (2005). Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: A systematic review. Archives of General Psychiatry, 62:975-983.

McGrath J, Saha S, Chant D, Welham J. (2008). Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiologic Reviews, 30:67-76.

Melle I, Larsen TK, Haahr U, Friis S, Johannessen JO, Opjordsmoen S, Simonsen E, Rund BR, Vaglum P, McGlashan T.Melle I, Larsen TK, Haahr U, et al. (2004). Reducing the duration of untreated first-episode psychosis: effects on clinical presentation. Archives of General Psychiatry, 61:143 150.

Penn D, Waldheter E, Perkins D, Mueser K, Lieberman J. (2005). Psychosocial treatment for first-episode psychosis: A research update. American Journal of Psychiatry,162:2220 2232.

Perkins D, Gu H, Boteva K, Lieberman J. (2005). Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: A critical review and meta-analysis. American Journal of Psychiatry, 162:1785 1804.

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 Resubmission Revision The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The NIMH intends to commit approximately $2,000,000 in FY 2013 to fund between 3 and 4 grants Future year amounts will depend on annual appropriations.
Award Budget	Direct costs are limited to $450,000 over the R34 project period, with no more than $225,000 in direct costs allowed in any single year.
Award Project Period	The total project period for an application submitted in response to this FOA may not exceed 3 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to 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:

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)
Eligible Agencies of the Federal Government
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 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.
System for Award Management (SAM) (formerly CCR) 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 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 and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
Of an application with a changed grant activity code.

Section IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the 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.

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 NIMH 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:

Susan T. Azrin, Ph.D.
Division of Services and Intervention Research
National Institute of Mental Health
6001 Executive Boulevard, Room 7145, MSC 9631
Rockville, MD 20892-9631
Rockville, MD 20852 (for express/courier service)
Telephone: 301-443-3267
Email: [email protected]

Page Limitations

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

Required and Optional Components

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

SF424(R&R) Cover