rfa-ts-15-001.pdf

Centers for Disease Control and Prevention

Agency for Toxic Substances and Disease Registry Extramural Research Program Office

Analyze and Evaluate Potential Risk Factors for Amyotrophic Lateral Sclerosis (ALS)

RFA-TS-15-001

Application Due Date: 04/06/2015

Signature Date

Analyze and Evaluate Potential Risk Factors for Amyotrophic Lateral Sclerosis (ALS)

RFA-TS-15-001

TABLE OF CONTENTS

Part 1. Overview Information

Key Dates Required Application Instructions Executive Summary

Part 2. Full Text

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 1. Overview Information Participating Organization(s) Centers for Disease Control and Prevention Components of Participating Organizations Agency for Toxic Substances and Disease Registry Extramural Research Program Office (ATSDR ERPO) Agency for Toxic Substances and Disease Registry (ATSDR) National Center for Environmental Health (NCEH) Funding Opportunity Announcement (FOA) Title Analyze and Evaluate Potential Risk Factors for Amyotrophic Lateral Sclerosis (ALS) Activity Code Applications in response to this FOA will be funded using the R01 activity code.

Funding Opportunity Announcement Type New Funding Opportunity Announcement Number

RFA-TS-15-001

Catalog of Federal Domestic Assistance (CFDA) Number(s) 93.061 Category of Funding Activity:

Health FOA Purpose The purpose of this funding opportunity announcement (FOA) is to allow for investigator-initiated research that will further the understanding of potential risk factors for amyotrophic lateral sclerosis (ALS), while supporting the goals of the National ALS Registry. The Registry’s goals are to estimate the number of new cases of ALS each year, estimate the number of people who have ALS at a specific point in time, better understand who gets ALS and what factors affect the disease, and improve care for people with ALS.

ATSDR is seeking investigator-initiated research proposals that will provide a greater understanding of ALS etiology, especially the environmental contribution, that may lead to prevention or a possible cure.

The purpose of this FOA is to provide additional clarifying information based on questions received from potential applicants during the Pre-Application Conference Call or as a result of direct communication with the Scientific Program Official. A summary of the "questions and answers" and a list of changes made to the original FOA begins on page 31.

Key Dates Publication Date: To receive notification of any changes to RFA-TS-15-001, return to the synopsis page of this announcement at www.grants.gov and click on the "Send Me Change Notification Emails" link. An email address is needed for this service.

Letter of Intent Due Date: 02/27/2015

Application Due Date: 04/06/2015 http://www.grants.gov

On-time submission requires that electronic applications be error-free and made available to CDC for processing from eRA Commons on or before the deadline date. Applications must be submitted to and validated successfully by Grants.gov/eRA Commons no later than 5:00 PM U.S. Eastern Time. Note:

HHS/CDC grant submission procedures do not provide a period of time beyond the application due date to correct any error or warning notices of noncompliance with application instructions that are identified by Grants.gov or eRA systems (i.e., error correction window).

Scientific Merit Review: 06/30/2015 An approximate date, actual date may be between June and July, 2015.

Secondary Review: 07/22/2015 An approximate date, actual date may be between June and July, 2015.

Estimated Start Date: 09/30/2015 An approximate date, actual date will be in September, 2015.

Expiration Date: 04/07/2015 Due Dates for E.O. 12372: Due no later than 60 days after the application receipt date.

Required Application Instructions It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise in this FOA. 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.

Note: The Research Strategy component of the Research Plan is limited to 25 pages.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Telecommunications for the Hearing Impaired: TTY 1-888-232-6348

Executive Summary Purpose The purpose of this funding opportunity announcement (FOA) is to allow for investigator-initiated research that will further the understanding of potential risk factors for amyotrophic lateral sclerosis (ALS), while supporting the goals of the National ALS Registry. The Registry’s goals are to estimate the number of new cases of ALS each year, estimate the number of people who have ALS at a specific point in time, better understand who gets ALS and what factors affect the disease, and improve care for people with ALS. ATSDR is seeking investigator-initiated research proposals that will provide a greater understanding of ALS etiology, especially the environmental contribution, that may lead to prevention or a possible cure.

The purpose of this FOA is to provide additional clarifying information based on questions received from potential applicants during the Pre-Application Conference Call or as a result of direct communication with the Scientific Program Official. A summary of the "questions and answers" and a list of changes made to the original FOA begins on page 31.

Mechanism of Support. Grant

Funds Available and Anticipated Number of Awards. The anticipated number of awards to be issued http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf

Funds Available and Anticipated Number of Awards. The anticipated number of awards to be issued under this FOA is between one and three. The minimum award amount, per award, for the first 12-month budget period (including direct and indirect costs) will be $250,000. The maximum award amount, per award, for the 12-month budget period (including direct and indirect costs) is expected to be $400,000. The total award for the first year of funding will not exceed $1,200,000 (including direct and indirect costs).

Because the nature and scope of the proposed research is expected to vary from application to application, the size and duration of each award may also vary. The total amount awarded and number of awards will depend upon the number, quality, duration and cost of the applications received, and available funding.

Budget and Project Period. The budget period will be twelve months with an anticipated start date in September 2015. The project period will be from one to three years; the longest project period is anticipated to be from September 2015 to August 2018. The maximum estimated total funding (direct and indirect costs) for the first budget period is up to $400,000 (direct and indirect costs) per award. The estimated total funding (direct and indirect) for an award with a three year project period is expected to be up to $1,200,000 per award.

Applicants must specifically describe the level of annual funding and project period requested.

Application Research Strategy Length: Page limits for the Research Strategy are clearly specified in Secti on IV. Application and Submission Information of this announcement.

Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.

Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. NOTE: CDC does not make awards to individuals directly.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply.

The principal investigator or other key personnel must demonstrate previous research expertise, experience, and knowledge related to studies of large datasets, and to ALS epidemiologic demographic risk factors.

Expertise is illustrated by evidence of at least one peer-reviewed publication or serving as an investigator on a grant, cooperative agreement, or contract in these subject matter areas (include description and references in the biographical sketch).

The applicant must demonstrate well-defined working relationships with organizations expected to participate in the research. This should be demonstrated by letters of support detailing the nature and extent of the involvement from the grantee’s institution and outside organization (include in the appendices).

The applicant must demonstrate the ability to access or collect the data planned for use in the proposed research. This may be demonstrated by a memorandum of understanding or letter of agreement (include in the appendices).

Number of PDs/PIs. Applications may name more than 1 PD/PI. However:

One PD/PI must be designated as the contact person for all correspondence related to the application.

All PD/PIs must include their eRA Commons ID in the Credential fieldof the Senior/Key Person Profile Component of the SF 424(R&R) Application Package

Eligible researchers may only submit one application as a PD/PI

Number of Applications. Eligible applicant institutions may not submit more than one application.

Application Type. New

Special Date(s).

http://www.cdc.gov/od/pgo/funding/grants/additional_req.shtm#SectionIV http://www.cdc.gov/od/pgo/funding/grants/additional_req.shtm#SectionIV http://era.nih.gov/commons/index.cfm#SectionIII1A

Letter of intent, if it is submitted, is due 45 days after publication.

Pre-application teleconference calls will conducted on January 21, 2015, and February 18, 2015, from 2:00 – 3:30 pm Eastern Time to address prospective applicants’ questions regarding FOA TS15-001, Analyze and Evaluate Potential Risk Factors for Amyotrophic Lateral Sclerosis (ALS).

PARTICIPANT ACCESS INFORMATION

CALL DATE: January 21 and February 18, 2015 CALL TIME: 2:00 Eastern Time CALL DURATION: 1 hour 30 minutes CALL LEADER: Susan Neurath Toll-Free Number: (855)-644-0229 Local Number: (770)-488-3600 Passcode: 8636049 #

Application Materials. See Section IV.1 for application materials.

Hearing Impaired. Telecommunications for the hearing impaired are available at:

TTY: (770) 488-2783.

Part 2. Full Text Section I. Funding Opportunity Description

Statutory Authority

This program is authorized under Section 399S of the Public Health Service Act [42 U.S.C. Section 280g-7].

1. Background and Purpose

The purpose of this funding opportunity announcement (FOA) is to allow for investigator-initiated research that will further the understanding of potential risk factors for amyotrophic lateral sclerosis (ALS), while supporting the goals of the National ALS Registry. The Registry’s goals are to estimate the number of new cases of ALS each year, estimate the number of people who have ALS at a specific point in time, better understand who gets ALS and what factors affect the disease, and improve care for people with ALS.

ATSDR is seeking research proposals that will provide a greater understanding of ALS etiology that may lead to prevention or a possible cure.

ALS, also known as Lou Gehrig’s disease, is a progressive and often fatal neuromuscular disease. Most people die within 2–5 years of being diagnosed with ALS (1). ALS is not a nationally notifiable condition;

as a result, there is significant uncertainty about the incidence and prevalence of ALS in the United States, as well as the lack of knowledge about the etiology of the disease. A few researchers have described the incidence and geographical distribution of ALS in specific geographical areas, mostly in Europe (2-10). On the basis of those studies, the incidence rate of ALS across all ages is estimated to be 1.6 persons per 100,000 population, and the rate increases to five persons per 100,000 population in the seventh decade of life (11).

An estimated 5,000 persons receive a diagnosis of ALS each year in the United States, with an estimated prevalence of 12,000 cases (11). ALS is more prevalent in men than in women, with a typical age of diagnosis at age 55–75 years (1). A limited number of studies have evaluated possible risk factors such as family history of the disease, certain occupations (e.g., military service), exposure to heavy metals or http://grants.nih.gov/grants/ElectronicReceipt/submit_app.htm#SectionIV1 family history of the disease, certain occupations (e.g., military service), exposure to heavy metals or infectious agents, physical activity, and trauma (12-24).

The uncertainty in the incidence and prevalence of ALS, as well as the lack of knowledge about the etiology of the disease, has created a need for structured data collection. The ALS Registry Act (H.R. 2295), passed in October 2008, amends the Public Health Service Act to require the Secretary of DHHS, acting through the Director of CDC, to (1) develop a system to collect data on ALS; and (2) establish a national registry for the collection and storage of ALS data.

This FOA seeks research to learn more about how many people are affected by ALS and the risk factors for ALS. Eligible researchers are encouraged to learn more about the National ALS Registry and consider whether the information and tools contained in the Registry could augment their proposal.

In October 2010, CDC through the federal Agency for Toxic Substances and Disease Registry (ATSDR) launched the National ALS Registry. The National ALS Registry’s mission is to better describe the incidence and prevalence of ALS in the US; examine factors, such as environmental and occupational, that might be associated with the disease; better outline key demographic factors (such as age, race or ethnicity, gender, and family history of individuals diagnosed with ALS) associated with the disease; and facilitate examination of the connection between ALS and other motor neuron disorders that can be confused with ALS, misdiagnosed as ALS, and in some cases progress to ALS.

The development, surveillance findings, use, and future enhancement of the registry is described in ATSDR’s first National ALS Registry report Prevalence of Amyotrophic Lateral Sclerosis – United States, 2010-2011 (25) (Available at: http://www.cdc.gov/mmwr/pdf/ss/ss6307.pdf .)

As described in the report, the registry takes a two-pronged approach for tracking ALS cases in the US by using 1) existing national administrative databases, and 2) a secure web portal that allows patients to self-enroll and take brief risk factor surveys. The first approach uses records from four existing national administrative databases (Medicare, Medicaid, the Veterans Heath Administration, and the Veterans Benefits Administration [VBA]) to identify ALS cases on the basis of an algorithm developed through pilot projects. The algorithm uses variables such as the International Classification of Diseases Ninth Revision (ICD-9) 335.20 and VBA 8017 codes, a prescription for Riluzole, and the frequency of visits to a neurologist to categorize patients as “definite ALS”, “possible ALS”, or “not ALS”. Those determined to be “possible ALS” will be reevaluated as additional years of data become available. Pilot tests indicate the algorithm had a sensitivity of 87% and specificity of 85%.

Because not all persons with ALS can be identified through the use of the national databases due to eligibility requirements, a second approach is also used. A secure web portal was created to help identify ALS cases not found in the administrative databases. To enter the National ALS Registry through its web portal, patients must answer a series of validation (screening) questions. These validation questions were obtained from the Veterans Administration’s ALS Registry (which is no longer enrolling persons with ALS) and were found to be very accurate; 93.4% of those who passed the screening questions were determined by a neurologist to have ALS or a motor neuron disease.

ATSDR’s first National ALS Registry report estimates that over 12,000 people in the United States live with the disease. ALS prevalence estimated from registry data was consistent with findings from long-established European registries and smaller-scale epidemiologic studies previously conducted in the United States.

Survey results of registry participants cover questions about sociodemographics, occupational history, military history, physical activity, alcohol consumption, cigarette smoking, and family history of neurodegenerative diseases, among others. Initial reviews of the data have identified potential future research topics. These include, but are not limited to, a more detailed analysis of whether a correlation exists between ALS and specific occupations or industries, caffeine consumption, or reproductive history (for females only).

Another way the Registry is being used to facilitate ALS research is through the Registry’s research notification mechanism (available at: http://wwwn.cdc.gov/ALS/ALSClinicalResearch.aspx). Approximately http://www.cdc.gov/mmwr/pdf/ss/ss6307.pdf http://wwwn.cdc.gov/ALS/ALSClinicalResearch.aspx

22,000 e-mail messages have been sent to portal registrants about clinical trials and studies in which they are eligible to participate. These studies have ranged from randomized control trials/studies of drug efficacy and safety, psychological well-being, treatment of muscle cramps, and risk-factor analysis.

ATSDR is currently engaging in a series of activities to enhance the National ALS Registry. Examples already underway include creating new survey modules to help identify additional potential risk factors for ALS, undertaking comprehensive surveillance activities in select states and large metropolitan areas to help test the completeness of the Registry, and evaluating the feasibility of establishing a complementary national biorepository for patients enrolled in the Registry. More information about the National ALS Registry and its new initiatives can be found at http://www.cdc.gov/mmwr/pdf/ss/ss6307.pdf .

References

1. Mitsumoto H, Chad DA, Pioro EP. Amyotrophic lateral sclerosis. Philadelphia, PA: F.A. Davis Company; 1998.

2. Anonymous. The Scottish Motor Neuron Disease Register: a prospective study of adult onset motor neuron disease in Scotland. Methodology, demography and clinical features of incident cases in 1989. J Neurol Neurosurg Psychiatry 1992;55:536–41. Available at http://www.ncbi.

nlm.nih.gov/pubmed/1640227.

3. Bettoni L, Bazzani M, Bortone E, Dascola I, Pisani E, Mancia D. Steadiness of amyotrophic lateral sclerosis in the province of Parma, Italy, 1960–1990. Acta Neurol Scand 1994;90:276–80.

4. Chiò A, Cucatto A, Calvo A, Terreni AA, Magnani C, Schiffer D. Amyotrophic lateral sclerosis among the migrant population to Piemonte, northwestern Italy. J Neurol 1999;246:175–80.

5. Guidetti D, Bondavalli M, Sabadini R, et al. Epidemiological survey of amyotrophic lateral sclerosis in the province of Reggio Emilia, Italy: influence of environmental exposure to lead.

Neuroepidemiology 1996;15:301–12.

6. Huber S, Henn V. Unchanged incidence and prevalence of amyotrophic lateral sclerosis in the canton of Zurich. Schweiz Arch Neurol Psychiatr (Bucur) 1995;146:52–4.

7. Mandrioli J, Faglioni P, Merelli E, Sola P. The epidemiology of ALS in Modena, Italy. Neurology 2003;60:683–9.

8. Mitchell JD, Gibson HN, Gatrell A. Amyotrophic lateral sclerosis in Lancashire and South Cumbria, England, 1976–1986: a geographical study. Arch Neurol 1990;47:875–80.

9. Traynor BJ, Codd MB, Corr B, Forde C, Frost E, Hardiman O. Incidence and prevalence of ALS in Ireland, 1995–1997: a population-based study. Neurology 1999;52:504–9.

10. Tysnes OB, Vollset SE, Aarli JA. Epidemiology of amyotrophic lateral sclerosis in Hordaland county, western Norway. Acta Neurol Scand 1991;83:280–5.

11. Hirtz D, Thurman DJ, Gwinn-Hardy K, Mohamed M, Chaudhuri AR, Zalutsky R. How common are the “common” neurologic disorders? Neurology 2007;68:326–37.

12. Armon C, Kurland LT, Daube JR, O’Brien PC. Epidemiologic correlates of sporadic amyotrophic lateral sclerosis. Neurology 1991;41:1077–84.

13. Kamel F, Umbach DM, Munsat TL, Shefner JM, Hu H, Sandler DP. Lead exposure and amyotrophic lateral sclerosis. Epidemiology 2002; 13:311–9.

14. Roelofs-Iverson RA, Mulder DW, Elveback LR, Kurland LT, Molgaard CA. ALS and heavy metals: a pilot case-control study. Neurology 1984;34:393–5.

http://wwwn.cdc.gov/ALS/ALSClinicalResearch.aspx http://www.cdc.gov/mmwr/pdf/ss/ss6307.pdf metals: a pilot case-control study. Neurology 1984;34:393–5.

15. Nicholas JS, Lackland DT, Dosemeci M, et al. Mortality among US commercial pilots and navigators. J Occup Environ Med 1998;40:980–5.

16. Schulte PA, Burnett CA, Boeniger MF, Johnson J. Neurodegenerative diseases: occupational occurrence and potential risk factors, 1982 through 1991. Am J Public Health 1996;86:1281–8.

17. Sutedja NA, Fischer K, Veldink JH, et al. What we truly know about occupation as a risk factor for ALS: a critical and systematic review. Amyotroph Lateral Scler 2009;10:295–301.

18. Okamoto K, Kihira T, Kondo T, et al. Lifestyle factors and risk of amyotrophic lateral sclerosis:

a case-control study in Japan. Ann Epidemiol 2009;19:359–64.

19. Wang H, O’Reilly EJ, Weisskopf MG, et al. Vitamin E intake and risk of amyotrophic lateral sclerosis: a pooled analysis of data from 5 prospective cohort studies. Am J Epidemiol 2011;173:595–602.

20. Beghi E, Logroscino G, Chio A, et al. Amyotrophic lateral sclerosis, physical exercise, trauma and sports: results of a population-based pilot case-control study. Amyotroph Lateral Scler 2010;11:289–92.

21. Fang F, Chen H, Wirdefeldt K, et al. Infection of the central nervous system, sepsis and amyotrophic lateral sclerosis. PLoS ONE 2011;6:e29749.

22. Okamoto K, Kihira T, Kobashi G, et al. Fruit and vegetable intake and risk of amyotrophic lateral sclerosis in Japan. Neuroepidemiology 2009;32:251–6.

23. Piazza O, Siren AL, Ehrenreich H. Soccer, neurotrauma and amyotrophic lateral sclerosis: is there a connection? Curr Med Res Opin 2004;20:505–8.

24. Woolsey PB. Cysteine, sulfite, and glutamate toxicity: a cause of ALS? J Altern Complement Med 2008;14:1159–64.

25. Mehta, P; Antao, A; Kaye, W; et. al.; MMWR July 25, 2014; 63 (SS07); 1-14. Available at: https://wwwn .cdc.gov/als/Download/Prevalence%20of%20Amyotrophic%20Lateral%20Sclerosis%20—;%20United%20Sta tes,%202010–;2011.pdf.

Healthy People 2020 and other National Strategic Priorities

This study directly supports several of the United States Health and Human Services’ (HHS) Healthy People 2020 goals and objectives. Specifically the goals for promoting high-quality, longer lives free of preventable disease, and the objectives of EH21 (improve the quality and utility of existing information systems for environmental health).

Public Health Impact

ALS is a progressive and often fatal neuromuscular disease that affects over 12,000 people, and their families, in the United States. Yet, little is known about the incidence, prevalence, or etiology of the disease.

This research will expand our current understanding of the potential risk factors for ALS.

Relevant Work https://wwwn.cdc.gov/als/Download/Prevalence%20of%20Amyotrophic%20Lateral%20Sclerosis%20⠎%20United%20States,%202010⠍2011.pdf https://wwwn.cdc.gov/als/Download/Prevalence%20of%20Amyotrophic%20Lateral%20Sclerosis%20⠎%20United%20States,%202010⠍2011.pdf https://wwwn.cdc.gov/als/Download/Prevalence%20of%20Amyotrophic%20Lateral%20Sclerosis%20⠎%20United%20States,%202010⠍2011.pdf

ATSDR launched the National ALS Registry in October 2010. The Registry tracks ALS cases in the United States by using existing national administrative databases and a secure web portal that allows patients to self-enroll and take brief risk factor surveys. In July 2014, ATSDR released the first National ALS Registry report (Mehta, P; Antao, A; Kaye, W; et. al.; Prevalence of Amyotrophic Lateral Sclerosis – United States, 2010-2011; MMWR July 25, 2014; 63 (SS07); 1-14). The report is available at https://wwwn.cdc.gov/als /Download/Prevalence%20of%20Amyotrophic%20Lateral%20Sclerosis%20—;%20United%20States ,%202010–;2011.pdf.

2. Approach

The research conducted shall be innovative and expand our current knowledge of ALS etiology. Information gleaned from this research and other research areas will help ATSDR better understand the etiology and epidemiology of ALS and prioritize topics for possible future risk factor surveys that persons with ALS will be able to take through the National ALS Registry web portal.

Objectives/Outcomes

The following items represent possible study objectives. Applicants are not expected to address all of the objectives but are encouraged to propose research that addresses or complements at least one of the following objectives.

Provide greater understanding about the geographical distribution of ALS in the US.

Identify potential risk factors for ALS. Areas of particular interest include, but are not limited to:

Environmental and occupational risks Infectious agents and viruses Nutritional intake Physical and sports activities Pharmaceutical use (e.g., statins) Trauma experience

Prospective cohort studies are preferred. However, retrospective case-control studies or ecological studies may also be considered. Analyses of existing datasets, such as from large observational studies, may also be proposed.

The applicant should consider submitting research topic areas not currently being studied/funded by the National ALS Registry. Examples of previous ALS research funded by ATSDR can be found at https://wwwn.cdc.gov/als/ALSExternalResearchfundedbyRegistry.aspx.

Target Population

While this research is being conducted to benefit all ALS patients, the researchers are encouraged to include the National ALS Registry enrollees, as appropriate, in their research plan.

Collaboration/Partnerships

Although not required, the applicant is encouraged to consider submitting an application to use ATSDR’s Research Notification tool to recruit ALS patients from the National ALS Registry. The tool can be found at http://wwwn.cdc.gov/als/ALSClinicalResearch.aspx . Using this tool, researchers can have email notifications about their approved studies sent to persons with ALS who are enrolled in the Registry.

Evaluation/Performance Measurement https://wwwn.cdc.gov/als/Download/Prevalence%20of%20Amyotrophic%20Lateral%20Sclerosis%20⠎%20United%20States,%202010⠍2011.pdf https://wwwn.cdc.gov/als/Download/Prevalence%20of%20Amyotrophic%20Lateral%20Sclerosis%20⠎%20United%20States,%202010⠍2011.pdf https://wwwn.cdc.gov/als/Download/Prevalence%20of%20Amyotrophic%20Lateral%20Sclerosis%20⠎%20United%20States,%202010⠍2011.pdf https://wwwn.cdc.gov/als/ALSExternalResearchfundedbyRegistry.aspx http://wwwn.cdc.gov/als/ALSClinicalResearch.aspx

Applicants should include analytic plans that describe the research design and hypotheses, data collection measures, and methods to evaluate the effectiveness of the proposed research strategy to address the hypotheses within the project period. Outcomes to be evaluated should be clearly specified.

Translation Plan

Research findings should be disseminated through publications, including articles in peer reviewed journals and “Research Briefs” for diverse audiences, as well as presentations at professional conferences and other venues. An explanation for how the scientific findings could be translated into public health programs, policies or practice should be included in the application.

Section II. Award Information

Funding Instrument Type: 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 - An application that is submitted for funding for the first time. Includes multiple submission attempts within the same round.

Estimated Total Funding: $1,200,000

Maximum estimated funding for the first 12-month budget period, per award.

Anticipated Number of Awards: 3

The budget period will be twelve months with an anticipated start date in September 2015. The project period will be from one to three years; the maximum project period is anticipated to be from September 2015 to August 2018. The estimated maximum total funding (direct and indirect costs) for the first budget period is up to $400,000 (direct and indirect costs) per award. The estimated total funding (direct and indirect) for the project period is expected to be up to $1,200,000 per award.

The actual number of awards and award amounts are contingent upon availability of funds and a sufficient number of meritorious applications. Because the nature and scope of the proposed research is expected to vary from application to application, the size and duration of each award may also vary. The total amount awarded and number of awards will depend upon the number, quality, duration and cost of the applications received, and available funding.

Awards issued under this FOA are contingent on the availability of funds and submission of a sufficient number of meritorious applications.

Award Ceiling: $400,000 Per Project Period Award Floor: $250,000 Per Project Period Total Project Period Length: 3 year(s) Throughout the project period, CDC's commitment to continuation of awards will depend on the availability of funds, evidence of satisfactory progress by the recipient (as documented in required reports), and CDC’s determination that continued funding is in the best interest of the Federal government.

HHS/CDC grants policies as described in the HHS Grants Policy Statement (http://www.hhs.gov/ asfr/ogapa/aboutog/hhsgps107.pdf) will apply to the applications submitted and awards made in response to this FOA.

http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf

Section III. Eligibility Information

1. Eligible Applicants Eligibility Category: State governments

County governments City or township governments Special district governments Independent school districts Public and State controlled institutions of higher education Native American tribal governments (Federally recognized) Public housing authorities/Indian housing authorities Native American tribal organizations (other than Federally recognized tribal governments) Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education Nonprofits without 501(c)(3) status with the IRS, other than institutions of higher education Private institutions of higher education Others (see text field entitled "Additional Information on Eligibility" for clarification) Unrestricted (i.e., open to any type of entity above), subject to any clarification in text field entitled "Additional Information on Eligibility"

The following types of Higher Education Institutions are always encouraged to apply for CDC 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

Nonprofits Other Than Institutions of Higher Education:

Nonprofits (Other than Institutions of Higher Education)

Governments:

Eligible Agencies of the Federal Government U.S. Territory or Possession

Other:

Native American tribal organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Regional Organizations Foreign Organizations: a Foreign Organization is a public or private

Foreign Organizations: a Foreign Organization is a public or private organization, whether non-profit or for-profit, located in a country other than the United States (U.S.) and its territories that is subject to the laws of the country in which it is located, irrespective of the citizenship of project staff or place of performance. Delete when Foreign Organizations are not allowed to apply Bona Fide Agents: a Bona Fide Agent is an agency/organization identified by the state as eligible to submit an application under the state eligibility in lieu of a state application. If applying as a bona fide agent of a state or local government, a legal, binding agreement from the state or local government as documentation of the status is required. Attach with "Other Attachment Forms" when submitting via www.grants.gov.

Federally Funded Research and Development Centers (FFRDCs): FFRDCs are operated, managed, and/or administered by a university or consortium of universities, other not-for-profit or nonprofit organization, or an industrial firm, as an autonomous organization or as an identifiable separate operating unit of a parent organization. A FFRDC meets some special long-term research or development need which cannot be met as effectively by an agency's existing in-house or contractor resources. FFRDC's enable agencies to use private sector resources to accomplish tasks that are integral to the mission and operation of the sponsoring agency. For more information on FFRDCs, go to http:// ecfr.gpoaccess.gov /cgi/t/text/ text-idx?c=ecfr& sid=512ff78311f427c00454772dcf21523a&rgn=div8 &view=text&node=48:1.0.1.6.34.0.1.18& idno=48

2. Foreign Organizations Foreign Organizations are eligible to apply.

Foreign (non-US) organizations must follow policies described in the HHS Grants Policy Statement (http ://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf), and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide. International registrants can confirm DUNS by sending an e-mail to ccrhelp@dnb.com, including Company Name, D-U-N-S Number, and Physical Address, and Country. Special Instructions for acquiring a Commercial and Governmental Entity (NCAGE) Code: https ://eportal.nspa.nato.int/AC135Public/Docs/US%20Instructions%20for%20NSPA%20NCAGE.pdf .

Foreign components of U.S. Organizations are eligible to apply.

For this announcement, applicants may include collaborators or consultants from foreign institutions. All applicable federal laws and policies apply.

3. Special Eligibility Requirements

N/A

4. Justification for Less than Maximum Competition

5. Responsiveness http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr&sid=512ff78311f427c00454772dcf21523a&rgn=div8&view=text&node=48:1.0.1.6.34.0.1.18&idno=48 http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr&sid=512ff78311f427c00454772dcf21523a&rgn=div8&view=text&node=48:1.0.1.6.34.0.1.18&idno=48 http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr&sid=512ff78311f427c00454772dcf21523a&rgn=div8&view=text&node=48:1.0.1.6.34.0.1.18&idno=48 http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf mailto:ccrhelp@dnb.com https://eportal.nspa.nato.int/AC135Public/Docs/US%20Instructions%20for%20NSPA%20NCAGE.pdf https://eportal.nspa.nato.int/AC135Public/Docs/US%20Instructions%20for%20NSPA%20NCAGE.pdf

Applications must meet the following criteria to be considered ‘responsive’ and eligible for consideration by peer review:

Proposed award amount must not exceed $400,000 for the first year.

The Research Strategy of the Research Plan shall not exceed 25 pages.

The Principal Investigator (PI) and/or senior researchers have previous research expertise, experience, and knowledge related to studies of large datasets, and to ALS epidemiologic demographics and risk factors, as demonstrated by authoring at least one recent relevant scientific journal publication or serving on at least one previous relevant scientific grant. This information must be included in the appropriate biosketch. Applications where the Principal Investigator or key personnel do not meet these requirements will be considered nonresponsive.

The applicant must include letters of support detailing the nature and extent of the working relationships and involvement that can be expected from organizations outside the grantee’s institution that will participate in the research. This information should be organized in an appendix. Applications that do not include letters of support from participating organizations will be considered nonresponsive.

The application must include memoranda of understanding, letters of agreement, or other documentation demonstrating that the data to be used in the proposed research will be available to complete the proposed project. This documentation should be included in an appendix. Applications that do not include documentation of access to project data will be considered nonresponsive.

6. Required Registrations Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

(Foreign entities only): Special Instructions for acquiring a Commercial and Governmental Entity (NCAGE) Code: https://eportal.nspa.nato. int/AC135Public/Docs/US%20Instructions%2 0for%20NSPA%20NCAGE.pdf System for Award Management (SAM) – must maintain current registration in SAM (the replacement system for the Central Contractor Registration) to be renewed annually, https://www.sam.gov/portal/SAM/#1.

Grants.gov eRA Commons

All applicant organizations must register with Grants.gov. Please visit www.Grants.gov at least 30 days prior to submitting your application to familiarize yourself with the registration and submission processes.

The “one-time” registration process will take three to five days to complete. However, it is best to start the registration process at least two weeks prior to application submission.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization. All registrations must be successfully completed and active before the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

7. Universal Identifier Requirements and System for Award Management (SAM) https://eportal.nspa.nato.int/AC135Public/Docs/US%20Instructions%20for%20NSPA%20NCAGE.pdf https://eportal.nspa.nato.int/AC135Public/Docs/US%20Instructions%20for%20NSPA%20NCAGE.pdf https://www.sam.gov/portal/SAM/%231 http://www.Grants.gov https://public.era.nih.gov/commons/public/login.do?TYPE=33554433&REALMOID=06-1edb031f-46c7-44b3-b803-60b537de74d2&GUID=&SMAUTHREASON=0&METHOD=GET&SMAGENTNAME=-SM-938PYmoLVb4VrDeXo04LZUDVDvc%2b3899ByInEAjuSUvWNIGfB2zRpWiCivYGCogG&TARGET=-SM-http%3a%2f%2fpublic%2eera%2enih%2egov%2fcommons http://www.Grants.gov

7. Universal Identifier Requirements and System for Award Management (SAM) All applicant organizations must obtain a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements.

The DUNS number is a nine-digit number assigned by Dun and Bradstreet Information Services. An AOR should be consulted to determine the appropriate number. If the organization does not have a DUNS number, an AOR should complete the US D&B D-U-N-S Number Request Web Form or contact Dun and Bradstreet by telephone directly at 1-866-705-5711 (toll-free) to obtain one. A DUNS number will be provided immediately by telephone at no charge. Note this is an organizational number. Individual Program Directors/Principal Investigators do not need to register for a DUNS number.

Additionally, all applicant organizations must register in the System for Award Management (SAM).

Organizations must maintain the registration with current information at all times during which it has an application under consideration for funding by CDC and, if an award is made, until a final financial report is submitted or the final payment is received, whichever is later. SAM is the primary registrant database for the Federal government and is the repository into which an entity must provide information required for the conduct of business as a recipient. Additional information about registration procedures may be found at the SAM internet site at https://www.sam.gov/index.html.

If an award is granted, the grantee organization must notify potential sub-recipients that no organization may receive a subaward under the grant unless the organization has provided its DUNS number to the grantee organization.

8. Eligible Individuals (Project Director/Principal Investigator) in Organizations/Institutions Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) 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 HHS/CDC support.

9. Cost Sharing This FOA does not require cost sharing as defined in the HHS Grants Policy Statement (http:// www.hhs.gov/ asfr/ ogapa/ aboutog/ hhsgps107.pdf).

10. Number of Applications As defined in the HHS Grants Policy Statement, (http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf), applications received in response to the same funding opportunity announcement generally are scored individually and then ranked with other applications under peer review in their order of relative programmatic, technical, or scientific merit. HHS/CDC will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application.

Only one application per institution (normally identified by having a unique DUNS number) is allowed.

Eligible researchers may only submit one application as a PD/PI.

Section IV. Application and Submission Information

1. Address to Request Application Package Applicants must download the SF424 (R&R) application package associated with this funding opportunity from www.Grants.gov.

If access to the Internet is not available or if the applicant encounters difficulty accessing the forms on-line, contact the HHS/CDC Procurement and Grants Office Technical Information Management Section (PGO TIMS) staff at (770) 488-2700 or pgotim@cdc.gov for further instructions. Hours: Monday - Friday, 7am – 4:30pm U.S. Eastern Standard Time. CDC Telecommunications for the hearing impaired or disabled is available at: TTY 1-888-232-6348.

http://fedgov.dnb.com/webform https://www.sam.gov/index.html http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.Grants.gov mailto:pgotim@cdc.gov

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/ 424/SF424_RR_Guide_General_VerC.pdf), 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.

The forms package associated with this FOA includes all applicable components, mandatory and optional.

Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow the instructions in the SF 424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

In conjunction with the SF424 (R&R) components, CDC grants applicants should also complete and submit additional components titled “PHS398.” Note the PHS398 should include assurances and certifications, additional data required by the agency for a complete application. While these are not identical to the PHS398 application form pages, the PHS398 reference is used to distinguish these additional data requirements from the data collected in the SF424 (R&R) components. A complete application to CDC will include SF424 (R&R) and PHS398 components.

3. Letter of Intent Due Date for Letter of Intent: 02/27/2015

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 CIO staff to estimate the potential review workload and plan the review.

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

Name of the Applicant

Descriptive title of proposed research

Name, address, and telephone number of the PD(s)/PI(s)

Names of other key personnel

Participating institutions

Number and title of this funding opportunity

The letter of intent should be sent to:

Susan Neurath, PhD Scientific Program Officer National Center for Injury Prevention and Control Centers for Disease Control and Prevention (CDC) 4770 Buford Hwy, NE Mailstop F-63 Atlanta, GA 30341

Telephone: 770-488-3368 Email: SFN8@cdc.gov

4. Required and Optional Components mailto:SFN8@cdc.gov

4. Required and Optional Components A complete application has many components, both required and optional. The forms package associated with this FOA in Grants.gov includes all applicable components for this FOA, required and optional.

5. PHS 398 Research Plan Component The SF424 (R&R) Application Guide includes instructions for applicants to complete a PHS 398 Research Plan that consists of 16 components. Not all 16 components of the Research Plan apply to all Funding Opportunity Announcements (FOAs). Specifically, some of the following 16 components are for Resubmissions or Revisions only. See Part I, Section 5.5 of the SF 424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf) for additional information. Please attach applicable sections of the following Research Plan components as directed in Part 2, Section 1 (Funding Opportunity Announcement Description).

Follow the page limits stated in the SF 424 unless otherwise specified in the FOA. As applicable to and specified in the FOA, the application should include the bolded headers in this section and should address activities to be conducted over the course of the entire project, including but not limited to:

1. Introduction to Application (for Resubmission and Revision ONLY) - provide a clear description about the purpose of the proposed research and how it addresses the specific requirements of the FOA.

2. Specific Aims – state the problem the proposed research addresses and how it will result in public health impact and improvements in population health.

3. Research Strategy – the research strategy should be organized under 3 headings: Significance, Innovation and Approach. Describe the proposed research plan, including staffing and timeline.

4. Inclusion Enrollment Report (Renewal and Revision applications ONLY)

5. Progress Report Publication List (for Continuation ONLY)

Human Subjects Section

6. Protection of Human Subjects

7. Inclusion of Women and Minorities

8. Targeted/Planned Enrollment Table (for New Application ONLY)

9. Inclusion of Children

Other Research Plan Sections

10. Vertebrate Animals

11. Select Agent Research

12. Multiple PD/PI Leadership Plan.

13. Consortium/Contractual Arrangements

14. Letters of Support

15. Resource Sharing Plan(s)

16. Appendix

Component 4 (Inclusion Enrollment Report) applies only to Renewal and Revision applications for clinical research. Clinical research is that which is conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Patient-oriented research includes: (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical trials, and (d) development of new technologies). Follow the page limits in the SF 424 unless otherwise specified in the FOA.

All instructions in the SF424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_VerC.pdf) must be followed along with any additional instructions provided in the FOA.

6. Appendix

6. Appendix Do not use the appendix to circumvent page limits. A maximum of 10 PDF documents are allowed in the appendix. Additionally, up to 3 publications may be included that are not publically available. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

7. Page Limitations All page limitations described in this individual FOA must be followed. For this specific FOA, the Research Strategy component of the Research Plan narrative is limited to 25 pages. Supporting materials for the Research Plan narrative included as appendices may not exceed 10 PDF files with a maximum of 60 pages for all appendices.

8. Format for Attachments Designed to maximize system-conducted validations, multiple separate attachments are required for a complete application. When the application is received by the agency, all submitted forms and all separate attachments are combined into a single document that is used by peer reviewers and agency staff. Applicants should ensure that all attachments are uploaded to the system.

CDC requires all text attachments to the Adobe application forms be submitted as PDFs and that all text attachments conform to the agency-specific formatting…