PA-13-168: Secondary Analyses of Existing Data Sets and Stored Biospecimens to Address Clinical Aging Research Questions (R01)

Part 1. Overview Information

Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute on Aging (NIA)
Funding Opportunity Title	Secondary Analyses of Existing Data Sets and Stored Biospecimens to Address Clinical Aging Research Questions (R01)
Activity Code	R01 Research Project Grant
Announcement Type	Reissue of PA-09-265
Related Notices	December 16, 2016 - This PAR has been re-issued as PA-17-088. 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) June 4, 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	PA-13-168
Companion Funding Opportunity	Not Applicable
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.866
Funding Opportunity Purpose	This funding opportunity announcement (FOA)) invites applications employing secondary analysis of existing data sets or stored biospecimens, to address clinically-related issues on aging changes influencing health across the life span, and/or on diseases and disabilities in older persons. This FOA will support activities addressing specific hypotheses in clinical aging research and/or to inform the design and implementation of future epidemiologic or human intervention studies, or current geriatric practice in maintenance of health, management of disease, and prevention of disability. Existing data sets may also be used to develop and test new statistical analytical approaches. Costs for archiving of data to be made publicly available may be included in the budget, as long as the archival activities are pertinent to the proposed secondary analyses.

Key Dates

Posted Date	March 29, 2013
Open Date (Earliest Submission Date)	May 5, 2013
Letter of Intent Due Date(s)	Not Applicable
Application Due Date(s)	Standard dates apply, 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)	Standard AIDS dates apply, by 5:00 PM local time of applicant organization.
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

Clinical trials and epidemiologic research projects (case-control or cohort studies) typically generate data with potential utility beyond the specific hypotheses and questions for which they were originally designed. There is considerable potential in using secondary analyses of existing clinical data sets and biorepositories to explore important research issues regarding biological changes affecting health across the life span and on disease and disability in old age. Secondary analyses of existing data sets and stored biospecimens are also a cost-effective means to explore new hypotheses on such issues and for informing the design of future studies in clinical aging research.

In addition to data bases and biospecimen repositories generated by clinical research, information collected through health administration activities may also provide a rich source of data relating to health maintenance and disease prevention practices; the incidence and prevalence of chronic conditions and diseases (including multiple morbidities); patterns of geriatric care and medication use; health outcomes (including disabilities) resource utilization (including comparative effectiveness research) and economic impact. These administrative data sets have potential advantages in availability; large size and representativeness; breadth of medical and demographic information; localization of care (community, hospital, and long-term facilities); and suitability for linkage with other data sets. In some settings, such as disease prevention or screening programs, results of clinical studies or stored specimens may also be available.

This funding opportunity will support activities addressing specific hypotheses in clinical aging research and/or inform the design and implementation of future epidemiologic or human intervention studies, or current geriatric practice in maintenance of health, management of disease, and prevention of disability. Applicants are encouraged to use data from a variety of sources, including those supported through investigator-initiated research activities, cooperative agreements, and contracts from public or private sources. Examples include:

Longstanding observational cohorts, with periodic assessments and/or biospecimens, investigating a broad range of risk/protective factors or pathophysiological mechanisms related to chronic diseases of the elderly (e.g., Alzheimer's disease) or to functional and cognitive decline in aging.

Observational cohorts assembled to address a specific question and followed prospectively over time with periodic assessments and/or biospecimens (e.g., Study of Osteoporotic Fractures, Study of Women's Health Across the Nation, Multicenter Osteoarthritis Study, Health ABC, etc.).

Family-based studies. Observational studies of siblings, parent-offspring, and twin pairs.

Cohorts from large clinical trials testing disease prevention or screening interventions (e.g., WHI); behavioral or medical interventions targeting disease management; or multi-component interventions to ameliorate geriatric conditions or disability trajectory.

Data set and stored biospecimens from a clinical trial of sustained caloric restriction in humans (i.e., CALERIE trial; Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy).

Groups identified by disease or non-disease status for comparison analyses (e.g., hip fracture patients) either retrospectively for risk factors (e.g., case-control studies) or prospectively for health-related outcomes.

Groups defined by administrative data bases to explore specific hypotheses regarding aging changes across the lifespan or diagnosis and management of medical conditions common among the elderly (e.g., CMS data, managed and/or accountable care organization data, health insurance data bases, electronic health records, etc.)

Specialized data sets collected to address specific questions (e.g. FDA Critical Path Initiative drug data bases to evaluate analgesic efficacy.)

Investigators are also encouraged to augment existing data sets as appropriate and feasible to address their study hypotheses. For example, new analyses performed on existing biospecimens, electronic linkage with or among administrative data bases, or primary collection of new information could increase the utility of the data for answering relevant clinical questions. Comparison between existing data bases or within merged data sets (e.g., young adults with mid-life, mid-life with older adults, etc.) is also encouraged as appropriate to address the study question, especially to address specific research hypotheses related to aging changes across the life span.

Costs for archiving of data to be made publicly available may be included in the budget, as long as the archival activities are related to the proposed secondary analyses. Plans for creation of a publicly archived database must include adequate data set documentation and instructions for use by investigators not affiliated with the original study. Provision for easy accessibility of archived datasets is required.

Potential applicants may also wish to review the following links to identify observational cohorts or clinical trials from which valuable data and/or biospecimens may be analyzed to address clinical aging research questions:

NIH Clinical Trials.gov: http://clinicaltrials.gov/

NIA Trial- Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) http://calerie.dcri.duke.edu/

NIA Population Studies Database: http://nihlibrary.ors.nih.gov/nia/ps/niadb.asp

The Osteoarthritis Initiative (OAI): http://oai.epi-ucsf.org/datarelease/

NIH Research Portfolio Online Reporting Tools (RePORT): http://projectreporter.nih.gov/reporter.cfm

NCI Surveys and studies: http://appliedresearch.cancer.gov/surveys/

The Kaiser Permanente Resource for Genetic Epidemiology Research in Adult Health and Aging: https://rpgehportal.kaiser.org

Applicants are responsible for adhering to the individual study policies governing ancillary projects and access to clinical trials data and/or biorepository samples. The application should include a letter of support from the relevant study committee granting access to data sets and/or repository (if application involves analysis of stored samples) and approval of the proposed secondary analysis study.

Research Objectives

Secondary analyses of clinical data sets or stored biospecimens may include, but are not limited to:

Physiological factors affecting aging changes (e.g., endocrine, musculoskeletal health, reproductive aging) at different points in the life span, including factors contributing to healthy aging across the life span.

Variability in rates of aging changes and its determinants (e.g., genetic and other factors influencing slow rates of change in body composition/muscle mass, bone density, etc., with age).

Genetic and other determinants of exceptionally healthy aging, such as protective factors that prevent or slow common adverse age-related changes or events.

Differences in risk factors for age-related conditions at different ages, at different stages of disease progression, and in the presence or absence of co-existing conditions.

Early-life changes (e.g., during pubertal transition, adolescence) that influence health, either increased or decreased risk for diseases, in young adulthood or at later stages of life.

Complex effects of sustained caloric restriction in humans on protective and risk factors for aging processes and diseases associated with aging.

Physiologic, molecular, cellular and genetic mechanisms of sustained caloric restriction in humans.

Long-term health effects of interventions that are administered over a large part of the life span (e.g., antihypertensives, lipid lowering agents, analgesics).

Long-term effects of physical activity and lifestyle on health and functional outcomes throughout the life span.

Factors contributing to decline in functional status, development of disability, and loss of independence that are potential targets for interventions (1) in different care settings (community/outpatient; acute-care/hospital; long-term care facilities) and transitions between settings, and (2) in sub-groups of elders with special needs (e.g., cognitive impairment, vision or hearing loss, economic hardship).

Effects of specific combinations of two or more comorbid conditions or combinations of medications on risks for specific beneficial and/or adverse health outcomes.

Public health and cost impact of specific combinations of two or more chronic conditions.

Differences in health outcomes (effectiveness and safety) between alternative treatment regimens or health care management strategies for older patients with specific common conditions in old age, or with specific combinations of two or more chronic conditions.

Interactions among medications, disease processes, and health outcomes in complex older patients with multiple chronic conditions.

Validation, revision, or development of new phenotypes for geriatric syndromes and conditions in older populations and population subgroups.

Occurrence and management of geriatric complaints, syndromes, or multi-factorial problems (e.g., fatigue, pain, frailty, unexplained anemia, urinary incontinence, falls, mobility disorders).

Potential differential effects of interventions due to age, race, gender or other factors through subgroup analyses of data from completed clinical trials.

Exploratory analyses, including assays on stored biospecimens, to explore effects of interventions on additional outcomes.

Analysis and meta-analysis of existing data sets to inform designs of future clinical trials (e.g., to determine prevalence of a disease or condition, or a combination of conditions in a population of interest; to estimate effects size of an intervention and duration of treatment in a population of interest, etc.)

Analysis or meta-analysis of existing data sets to explore opportunities for and determine the need for comparative effectiveness clinical trials in a topic area.

Methodology development. Single or multiple data sets may be used to develop and test new analytic approaches for any of the above topics. Methodological studies that address inferential issues in observational data on treatment effects, such as confounding by indication.

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 number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Award Budget	Application budgets are not limited, but need to reflect the actual needs of the proposed project.
Award Project Period	The scope of the proposed project should determine the project period. The maximum period is 5 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
Non-domestic (non-U.S.) Entities (Foreign Institutions)

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are 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.

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