dd11-002 foa final 11.18.10.doc

Part I Overview Information

United States Department of Health and Human Services (HHS) Issuing Organization

Centers for Disease Control and Prevention at (CDC) at http://www.cdc.gov

Participating Organizations Centers for Disease Control and Prevention at (CDC) at http://www.cdc.gov

Components of Participating Organizations National Center on Birth Defects and Developmental Disabilities (NCBDDD/CDC) at http://www.cdc.gov/ncbddd/ Title: Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE): Study to Explore Early Development (SEED) II (U01)

The policies, guidelines, terms, and conditions of the HHS Centers for Disease Control and Prevention (CDC) stated in this announcement might differ from those used by the HHS National Institutes of Health (NIH). If written guidance for completing this application is not available on the CDC website, then CDC will direct applicants elsewhere for that information.

Authority: This program is authorized under Section 317C of the Public Health Service Act (42 U.S.C. 247b-4) and Section 301(a) of the Public Health Service Act (42 U.S.C. 241(a)).

Announcement Type: New Instructions for Submission of Electronic Research Applications:

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

This FOA must be read in conjunction with the application package instructions included with this announcement on Grants.gov/Apply for Grants (hereafter referred to as, Grants.gov/Apply.)

A registration process is necessary before submission, and applicants are strongly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.

Two Steps Are Required For On-Time Submission:

1) The application must be successfully submitted and validated by Grants.gov no later than 5:00 p.m. Eastern Standard Time on the application submission receipt date (see “Key Dates” below.)

2) Applicants must complete a verification step in the Electronic Research Administration (eRA Commons) within two business days of notification. Note: Since email can be unreliable, it is the responsibility of the applicant to periodically check on their application status in the eRA Commons.

Funding Opportunity Announcement (FOA) Number: RFA-DD-11-002 Catalog of Federal Domestic Assistance Number(s): 93.073

Key Dates

Release/Posted Date:

Letter of Intent Receipt Date: December 20, 2010 NOTE: On-time submission requires that applications be successfully submitted to Grants.gov and validated no later than 5:00 p.m. eastern time on the deadline date. Please see Section IV, 3.C. “Application Processing.”

Application Submission Receipt Date(s): January 18, 2011 Peer Review Date(s): March 2011 Council Review Date(s): April 2011

Earliest Anticipated Start Date(s): June 30, 2011 Additional Information to Be Available Date: None Expiration Date: January 19, 2011 Due Date for E.O. 12372 Executive Order 12372 does not apply to this program.

Additional Overview Content

Executive Summary

· This funding opportunity announcement has two components (A and B). CDC solicits U01 grant applications to support Component A - continuation of the epidemiological research capability of the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE), and implementation of the Study to Explore Early Development (SEED) Phase II. All eligible applicants for component A may also apply for Component B – an award for the continuation of the SEED Phase I Central Laboratory and Biosample Repository and implementation of the SEED Phase II Central Laboratory and Biosample Repository. However, only one CADDRE awardee from Component A will be funded for Component B, and will serve all awardees as the central laboratory and biosample repository.

· The participating organizations intend to commit a total of $5,250,000 in FY 2011 to this FOA for payment of applications responsive to this announcement.

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

· The anticipated number of awards to be issued under this FOA: up to 5 awards for Component A; with 1 CADDRE site receiving an award to implement Component B.

· Budget Period, Project Period, and Award Amounts: Component A awards for the first 12-month budget period will be approximately $900,000 (reflecting delay in active implementation of SEED Phase II until all study approvals are in place); budget periods 2-5 funding will be approximately $1,200,000 per year (reflecting full scale SEED Phase II implementation). The Component B award for the first 12-month budget period will be approximately $750,000 (reflecting delay in active implementation of SEED Phase II until all study approvals are in place) and will be available for one CADDRE site selected to serve as the consolidated SEED Central Laboratory and Biosample Repository; funding for budget periods 2-5 will be approximately $1,000,000 per year (reflecting full scale SEED Phase II implementation).

· Research Plan Component Length. The research plan may not exceed 25 pages.

· Eligible Organizations: Public nonprofit organizations; private nonprofit organizations; for profit organizations; small, minority, and women-owned businesses; universities; colleges; research institutions; hospitals; community-based organizations; faith-based organizations; federally recognized or state-recognized American Indian/Alaska Native tribal governments; American Indian/Alaska Native tribally designated organizations; Alaska Native health corporations; urban Indian health organizations; tribal epidemiology centers; state and local governments or their Bona Fide Agents (this includes the District of Columbia, the Commonwealth of Puerto Rico, the Virgin Islands, the Commonwealth of the Northern Marianna Islands, American Samoa, Guam, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau); and political subdivisions of states (in consultation with states.) 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 you are applying as a bona fide agent of a state or local government, you must provide required documentation from the state or local government as documentation of your status. Attach this documentation behind the first page of your application form or for electronic applications, use a PDF file and attach as “Other Documents” and label as appropriate.

· See Section IV.1 for application materials. The SF424 (R&R) Application Guide for this FOA is located at these Web sites: http://grants1.nih.gov/grants/funding/424/SF424_RR_Guide_General.doc (MS Word); http://grants1.nih.gov/grants/funding/424/SF424_RR_Guide_General.pdf (PDF)

· For general information on SF424 (R&R) Application and Electronic Submission, see these the following Web sites: SF424 (R&R) Application and Electronic Submission Information: http://grants.nih.gov/grants/funding/424/index.htm; General information on Electronic Submission of Grant Applications: http://era.nih.gov/ElectronicReceipt/

· HHS/CDC Telecommunications for the hearing impaired is available at the following number: TTY 770-488-2783.

Funding Opportunity Announcement Glossary: FOA Glossary Terminology Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Section II. Award Information

1. Mechanism(s) of Support

2. Funds Available

Section III. Eligibility Information

1. Eligible Applicants A. Eligible Institutions

2.Cost Sharing or Matching 3.Other - Special Eligibility Criteria

Section IV. Application and Submission Information

1. Request Application Information

2. Content and Form of Application Submission

3. Submission Dates and Times A. Receipt and Review and Anticipated Start Dates

1. Letter of Intent B. Submitting an Application to CDC C. Application Processing

4. Intergovernmental Review

5. Funding Restrictions

6. Other Submission Requirements

Section V. Application Review Information

1. Criteria

2. Review and Selection Process A. Additional Review Criteria B. Additional Review Considerations C. Sharing Research Data D. Sharing Research Resources

3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information

1. Award Notices

2. Administrative and National Policy Requirements A. Cooperative Agreement

1. Recipient Rights and Responsibilities

2. HHS/CDC Responsibilities

3. Collaborative Responsibilities

3. Reporting

Section VII. Agency Contact(s)

1. Scientific/Research Contact(s)

2. Peer Review Contact(s)

3. Financial/ Grants Management Contact(s)

4. General Questions Contact(s)

Section VIII. Other Information - Required Federal Citations

Section IX. Appendix

1. SEED Phase II Protocol (Please contact the program official [Michael A. Brown] at mab5@cdc.gov and he will provide you a copy.)

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

The National Center on Birth Defects and Developmental Disabilities (NCBDDD) of CDC within HHS is committed to achieving the proposed health promotion and disease prevention objectives of "Healthy People 2020" and to measuring program performance as stipulated by the Government Performance and Review Act (GPRA). This RFA addresses “Healthy People 2020” priority area(s) of Maternal, Infant, and Child Health and is in alignment with NCBDDD performance goal(s) to prevent birth defects and developmental disabilities. For more information, http://www.healthypeople.gov/document/, and http://www.whitehouse.gov/omb/mgmt-gpra/.

Nature of the Research Opportunity

The purpose of this program is to support: 1) continuation of the epidemiological research capability of the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE); with implementation of the Study to Explore Early Development (SEED) Phase II; and 2) continuation of the SEED Central Laboratory and Biosample Repository with implementation of reporting for SEED Phase II. CADDRE is a collaborative effort between NCBDDD and the funded sites. The primary CADDRE collaborative activity is SEED, a case-control study of genetic and environmental risk factors for autism with multiple-source, population-based ascertainment of case and control groups.

Background

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by qualitative impairments in social interaction and communication and stereotyped behaviors and interests. Since the 1990s, a number of systematic population surveys and routine monitoring systems in the US and other countries indicate the prevalence to be 70 to 100 affected persons per 10,000 children. Based on recent data from CDC’s Autism and Developmental Disabilities Monitoring Network, it has been estimated that 730,000 children in the United States have an ASD. Economic studies estimate the lifetime cost to care for an individual with an ASD is $3.2 million. Accompanying advances in population-based monitoring of autism prevalence have been changes in diagnostic criteria and development of improved clinical methods, including growth in the number of standardized behavioral assessment tools for autism screening and diagnosis. Yet, apart from the identification of some rare genetic conditions that are commonly associated with autism, causal mechanisms for the disorder largely remain unknown. Our lack of understanding of the causes off ASD fuels concern as the number of children identified with autism continues to increase.

The Children’s Health Act of 2000 mandated CDC to establish autism surveillance and research programs to address the number, incidence, and causes of autism and related developmental disabilities. Under the provisions of this act, NCBDDD funded five Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) through program announcements in FY2001 and FY2002 (California, Colorado, Maryland, North Carolina and Pennsylvania). CDC’s NCBDDD served as the sixth CADDRE site.

For the first funding cycle (2001-2006), each CADDRE grantee had three core objectives: 1) to establish a multi-site collaborative epidemiologic study focused on autism; 2) to conduct surveillance of autism and other developmental disabilities; and 3) to conduct site-specific investigator-initiated studies on autism. Although protocol development for the multi-site collaborative epidemiologic study (named SEED) took place during this time, due to funding shortfalls SEED was not initiated in the first funding cycle.

In FY 2006, a limited competition was held for the next five year funding cycle of the CADDRE. The original five CADDRE grantees were funded for a new five year award. The CADDRE activities for this second funding cycle project period ending June 29, 2011 were targeted to the implementation of SEED. CDC’s NCBDDD served as the sixth CADDRE SEED site during this period.

SEED’s original primary scientific aims were to: 1) characterize the autism behavioral phenotype and associated developmental, medical and behavioral conditions of autism, with a special focus on identifying homogeneous autism subgroups for etiologic analysis, and 2) understand the genetic and environmental risk factors for autism with a special focus on immunological, hormonal, gastrointestinal, and sociodemographic features. Secondary areas of scientific interest included investigation of the association of autism and maternal lifestyle factors in pregnancy (tobacco, alcohol, and recreational drug use), parental occupational exposures around pregnancy, select maternal and child mercury exposures, and assessment of postnatal health and sleep characteristics.

SEED used a case-control design with multiple-source, population-based ascertainment of case and comparison groups. Cases (CASE) comprised children meeting study definitions for Autistic Disorder, Pervasive Developmental Disorder-Not Otherwise Specified, or Asperger Syndrome. Two different control groups were defined: 1) a group of children sampled from the General Population (POP), and 2) a Neurodevelopmentally Impaired Comparison (NIC) group of children with developmental problems other than ASD. Comparisons between CASE and POP were designed to identify risk factors for ASD relative to children in the general population. Comparisons between CASE and NIC may provide the opportunity to distinguish risk factors for ASD independent of factors common to other developmental problems. The NIC group also provides a means of controlling for recall bias that may be associated with having a child with developmental problems.

Originally, children were potentially eligible for SEED if: 1) they were born in a study catchment area between September 1, 2003 and August 31, 2006, and still resided there during study implementation, and 2) lived with a knowledgeable caregiver (family member/caregiver of legal age who resided with and consistently cared for the child since s/he was aged 6 months or younger) who was competent to communicate orally in English (or at two sites, in English or Spanish) and give consent. To remain eligible, enrolled children must also have been aged 30 to 68 months at the completion of the clinical developmental assessment to maintain the appropriate age range for validated study instruments.

Both potential CASE and NIC children to be invited into the study were ascertained through multiple sources serving or evaluating children with developmental problems, including early intervention, special education and related service programs for toddlers and young children, hospitals, clinics, and individual providers. Potential participants met specific criteria for ASD or a related condition from early intervention/special education services (e.g., intellectually disabled, severe emotional disorder), or had received an ASD or related diagnosis of one or more select conditions associated with ASD (e.g., conduct disorder, intellectual disability, significant developmental delay) from a clinical provider. This broad diagnostic net for ascertainment of potential CASEs ensured that both previously diagnosed and undiagnosed cases were identified. Parents who had a child with a documented ASD or ASD-related diagnosis/condition could also contact the study directly and be considered for inclusion. Population control children to be invited into the study were identified by randomly sampling state birth certificates of children born in the specified birth date range to mothers resident in a study catchment area at delivery.

Recruitment was initiated by mailing an invitation packet, written in English (and Spanish at two sites), to the primary caregiver of all potentially eligible participants. Non-responders received a second invitation letter or a telephone call (up to 9 attempts), depending on the site. During the study introductory telephone call, SEED staff members screened for study eligibility. The Social Communication Questionnaire (SCQ), a 5-10 minute interview, was also administered to the primary caregiver of eligible participants to identify children who require clinical diagnostic evaluation to determine final CASE status. Enrolled children with positive SCQ screens or a previous ASD diagnosis/special education designation (regardless of SCQ score) were assigned to the CASE workflow. Enrolled NIC or POP children with negative SCQ screens were assigned to the NIC or POP workflow, respectively.

Final participant classifications were dependent on the child’s ascertainment source (i.e., via the broad diagnostic net or birth certificate), workflow classification and, for children in the CASE workflow, the results from both the Autism Diagnostic Observation Schedules (ADOS) and the Autism Diagnostic Interview–Revised (ADI-R) administered during the SEED clinical diagnostic evaluation. SEED final participant classifications included: 1) Final CASE, 2) Possible CASE, 3) Final NIC, and 4) Final POP.

Extensive data were collected via multiple modalities to address the SEED primary and secondary scientific aims: telephone interviews, self administered instruments, clinic visits for developmental and physical (brief exam for minor dysmorphic features) evaluation, biosampling (buccal samples, blood and hair), and medical record abstraction. Data collection was organized into multiple stages to more evenly distribute study burden on participants over time, as well as enhance the completion of data collection at one stage before proceeding to the next. Scheduling of the stages was determined with input from participants to accommodate their schedule and enhance compliance. Support in completing self-administered forms was provided as needed to overcome literacy barriers. Periodic contacts by phone, email, or biannual newsletter served as reminders for data item completion or scheduled data events.

Data collection was uniform across all participants, except that those in the CASE workflow completed additional instruments to assess specific ASD features (ADOS, ADI-R, Vineland Adaptive Behavioral Scales, Early Development Questionnaire, Services & Treatments questionnaire).

For most SEED components, Quality Control (QC) procedures and standards for field staff were established a priori, including a variety of training exercises, initial “ready-for-the-field” standards, and thereafter ongoing standards to maintain “field-worthiness”.

A Central Laboratory and Biologic Repository was established for SEED for initial processing and archiving of SEED biosamples (funded as a supplemental activity of one CADDRE site), as well as a Data Coordinating Center (DCC) (funded under a separate cooperative agreement DD09-002) to develop, host and support the CADDRE Information System (CIS), a web-based application developed exclusively for CADDRE. The CIS provides the mechanisms for managing workflow and data processing through the course of the study. All participant data were entered into CIS by SEED staff and securely stored in a HIPAA-class facility. The DCC also performs medical coding of SEED data and manages data cleaning functions. Once data are cleaned, authorized users download datasets through CIS for review and analysis.

Major SEED strengths include:

1) Multiple US sites located in diverse communities that improves study generalizability;

2) Population-based, multi-source ascertainment of potential CASE/NIC participants that improves sample representativeness in each study community;

3) Ascertainment of both diagnosed and undiagnosed CASE participants that ensures preschool children who meet SEED CASE criteria but lack a community diagnosis are represented in the sample;

4) Two comparison groups designed to detect potential recall bias in CASE parents and to more accurately distinguish features of autism from both typical development and other developmental problems;

5) Uniform eligibility criteria and data collection protocols, including final participant classification procedures, and robust quality control measures that insures high intra- and inter-site data collection and developmental assessment reliability, enhances quality and precision of the multi-site pooled data, and enhances size of the multi-site pooled analytic sample;

6) Data collection under different modalities (e.g., self report and medical record abstraction) better insures certain classes of risk factor information are not missed and permits assessment of data retrieval and quality across different data collection modalities;

7) Where feasible, actively recruiting Spanish-only speaking families that will greatly inform the future development of appropriate autism study methods and improvement of autism instruments for Spanish-only speakers; and

8) Use of both existing and novel CADDRE-derived instruments will permit assessment of feasibility and performance in large, population-based research settings of both existing standardized instruments (performance of many instruments has not been assessed outside smaller clinical research applications), and CADDRE-derived novel instruments and approaches for special data types (e.g., stool, diet, and dysmorphology).

As of May 2010, a total 2,647 families were enrolled in SEED; 2,011 caregiver interviews had been completed; 1,843 buccal samples had been collected; 1,639 clinical developmental assessments had been completed; and 1,408 families had provided blood samples. Recruitment for the first round of SEED is expected to continue through 2010 and data collection is expected to be completed in 2011.

Scientific Knowledge to be Achieved through this Funding Opportunity

The original SEED target sample size (in part, guided by resource expectations) was deemed good for many principal analyses but was not ideal for many genetic analyses. It was also not optimal for many autism subgroup or stratified analyses. This FOA will enhance our understanding of the genetic and environmental risk and protective factors for autism by building on the established SEED data resource. Specifically, a key goal is to implement a second round of SEED data collection to increase the total SEED pooled sample size for investigation of high priority hypotheses thereby enhancing SEED’s analytic potential. Maintaining the same basic study design and general protocol integrity will ensure that data pooling can be achieved across all sites and across all SEED phases for this purpose. Modifications that will be implemented in the second round of data collection will include: 1) recruitment from a more recent cohort of children (since the original SEED cohort has aged out of the target enrollment age), 2) more focused data collection, and 3) strategies to improve recruitment and completion rates.

Research Objectives and Approach

This funding announcement will have two Funding Components;

1) Component A - “Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE): Study to Explore Early Development (SEED) Phase II;” and

2) Component B is a single award to a Component A awardee for - “CADDRE/SEED Phase II – Central Laboratory and Biosample Repository”.

Component A: Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE): Study to Explore Early Development (SEED) Phase II The objectives of Component A of this FOA are to identify potential risk and protective factors for autism by expanding on previous years’ CADDRE efforts specifically related to SEED. Applicants under this FOA should describe how they will carry out the SEED Phase II protocol (same basic study design and implementation approach as SEED). Former SEED sites should also describe the types of analyses they propose to perform for publication of a minimum of 5 manuscripts using the SEED Phase I multi-site pooled data set. The SEED Phase II protocol can be found in Appendix 1 (Seed Phase II Protocol) (Please contact the program official [Michael A. Brown] at mab5@cdc.gov and he will provide you a copy.), but important distinctions from the original SEED protocol as described above are outlined here:

1) High priority scientific areas of interest for SEED Phase II will include:

a) Characterize the autism behavioral phenotype and associated developmental, medical and psychiatric conditions of autism, with a special focus on identifying more homogeneous autism subgroups for etiologic analysis, and

b) Understand the genetic and environmental risk factors for autism with a special focus on immunological, hormonal, perinatal, and sociodemographic features.

Secondary areas of scientific interest will include investigation of autism and maternal lifestyle factors in pregnancy (tobacco, alcohol, and recreational drug use) and maternal occupational history around pregnancy, and assessment of child postnatal health characteristics. These primary and secondary scientific interests for SEED Phase II are the same as the original SEED aims, but with a narrower focus. Specifically, emphasis on the following original SEED primary and secondary areas of interest will be dropped or significantly reduced: gastrointestinal features, phenotypic assessment of minor dysmorphic features, paternal occupational exposures, select maternal and child mercury exposures, and sleep patterns. On the other hand, although perinatal factors (such as obstetric complications, maternal medications, neonatal complications) were not originally singled out as one of SEED’s primary scientific areas of interest, they have been a critical focus in SEED data collection and will remain as important areas of interest in SEED Phase II.

2) The SEED criteria will be retained that each site’s study catchment area should be a contiguous geographic sector with a minimum population size of 30,000 births.

3) The SEED case-control design, including an ASD CASE group and NIC and POP comparison groups at a 1-1 case-control ratio, will be retained.

4) SEED’s original multi-source, population-based ascertainment approach for potential CASE and NIC participants will be retained, including use of the broad diagnostic net to ensure both previously diagnosed and undiagnosed cases are identified, as well as random sampling of birth certificates for ascertaining potential POP participants. Applicants are expected to demonstrate effective partnership with multiple data sources for potential CASE/NIC participants and ability to sample from birth certificates to ensure a robust ascertainment pool for all three participant groups.

5) SEED’s original overall recruitment approach will be retained with enhancements. Applicants are expected to demonstrate their ability to implement robust SEED recruitment approaches to ensure enhanced recruitment rates including:

a) Community outreach, including social networking, to boost awareness and interest among invitees;

b) Strategies to facilitate invitee response to the study invitation letter by expanding the number of response mode options (e.g., text messaging, logging into a web site, mail-in response card, directly calling a dedicated study telephone number)

c) Strategies to boost self-referral by potential CASE families (e.g., directly work with key providers of children with disabilities, work with local parent advocacy organizations, develop opportunities for public visibility of project);

d) Ability of data sources to generate repeated lists over the course of the study of potential new CASE/NIC participants for recruitment purposes;

e) Robust tracing of contact information using multiple people search data bases and social networking sites;

f) Strategies to avoid child aging-out before invitation contact can be made;

g) Post-first invitation follow-up procedures (i.e., procedures for contacting invitee if written invitation does not prompt a response), especially active follow-up via telephone when possible, or strategies for repeat invitations; and

h) Dedicated staff supported by the project to implement such recruitment strategies, including persons to work closely with data sources in order to optimize response to invitations and possibly provide active post-invitation follow-up. Applicants should provide evidence of negotiation with each data source concerning the possibility for active follow-up of non-responders to the study invitation.

6) All original SEED eligibility criteria will be retained, however with the following cohort update and eligible caregiver refinement:

a) Eligible cohort dates for SEED Phase II will be within the following date range: July 1, 2007 to June 30, 2011 (actual cohort dates within the range to be determined close to study start depending on practical implementation considerations); and

b) Eligible children must currently be living with the biologic mother (as child’s legal guardian) who resided with and consistently cared for the child since the child was 6 months of age or younger.

7) The original SEED data collection will be more focused for SEED Phase II (e.g., fewer data collection elements) primarily to reduce participant burden. Reduced participant burden may make participation in the study more appealing and improve enrollment rates as well as improve data collection completeness (i.e., less likelihood that participants will drop out before data collection is complete). The core SEED Phase II data collection items will include: (see Appendix 1 for details regarding each item):

a) Initial telephone screen for study eligibility and for autism

i) Autism screen: Social Communication Questionnaire (SCQ)

b) Maternal telephone-assisted interview:

i) Assess maternal reproductive history,

ii) Index pregnancy health and occupational history,

iii) Family demographics, and

iv) Early childhood health and conditions

c) Self-administered forms (compiled into a single packet of forms mailed to the family):

i) Maternal medical history,

ii) Paternal medical history,

iii) Family autoimmune worksheet (index child, biologic parents, biologic siblings),

iv) Services and treatment questionnaire (CASE only),

v) Social Responsiveness Scale (index child only), and

vi) Child Behavior Check List

d) Buccal and blood biosampling, retaining the same collection protocols (child, biological mother, biological father)

e) Clinical evaluation to assess developmental status and confirm CASE classification:

i) CASE children and parents:

(a) Autism Diagnostic Observation Schedule (ADOS),

(b) Autism Diagnostic Interview – Revised (ADI-R),

(c) Vineland Adaptive Behavioral Scales (VABS), and

(d) Mullen Scales of Early Learning

ii) NIC/POP children:

(a) Mullen Scales of Early Learning.

f) Anthropometry of child (head circumference, height, weight) and biologic parents (height, head circumference)

g) Abstraction of prenatal, labor and delivery, neonatal and pediatric medical records

8) The SEED Phase II recruitment target over the entire project period will be, at a minimum, approximately 540 participants (approximately 180 per participant group) per site in order to achieve complete data collection on a minimum of 125 participants in each of the three study groups per site.

Established CADDRE SEED collaborative processes will be retained in SEED Phase II. Specifically, a number of workgroups with representatives from each site and CDC will be charged to provide guidance and oversight over all aspects of SEED Phase II implementation, such as the Study Methods Workgroup, Developmental Clinicians Workgroup, Data Collections Workgroup, Project Coordinators Workgroup, Laboratory Methods Workgroup, and Data Coordinating Center Workgroup. In addition, the Coordinating Committee (CC), formerly called the PI Workgroup (including all grantee and CDC PIs, and the CDC Scientific Collaborator [SC]) and Data Sharing Committee will be responsible for making collaborative key decisions regarding SEED scientific and analytic issues, and SEED publications or other external communication. In particular, SEED analytic and publication priorities will be set collaboratively by the CC based on both scientific importance and public health relevance. The existing detailed CADDRE Data Analysis and Publications Guidelines will also continue to be used in order to:

1) Assure and expedite orderly and timely presentation to the scientific community of all pertinent data resulting from CADDRE SEED;

2) Promote accurate and scientifically sound presentations and papers from CADDRE and its collaborating investigators;

3) Promote collaboration among CADDRE sites and to assure that all participating investigators have the opportunity to be involved in data analysis and the preparation of CADDRE papers and presentations;

4) Assure that press releases, presentations, and publications related to SEED are accurate and objective, and do not compromise the collaborative study and the acceptance of its results;

5) Establish guidelines for authorship, acknowledgments, and funding citations for any presentations and publications of CADDRE.

Component B: CADDRE/SEED II - Central Laboratory and Biosample Repository The objectives of Component B of this FOA are to support the maintenance and storage of the SEED Phase I biosample repository and support the collection and storage of the SEED Phase II biosamples. It is CDC’s goal that all SEED biosamples (from Phases I and II) will be stored in one repository. Applicants under this FOA should describe how they will support the SEED Phase I biosample maintenance and the Phase II biosample protocol (same sampling and implementation approach as SEED Phase I except that hair collection is dropped). Specifically, the Central Laboratory and Biosample Repository (CLBR) will be responsible for developing, implementing and coordinating protocols for local site collection and shipping of blood and buccal specimens to the CLBR (SEED Phase II specimens); CLBR intake and processing of received specimens (SEED Phase II specimens); long term storage of specimens (SEED Phases I and II); and subsequent shipping of specimen samples to other laboratories for analyses as needed.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity will use the U01 activity code.

The HHS/CDC U01 is a cooperative agreement assistance instrument. Under the U01 assistance instrument, the Recipient Organization retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, and with HHS/CDC staff is substantially involved as a partner with the Recipient Organization, as described in Section VI.2.A., "Cooperative Agreement”.

2. Funds Available The participating Centers, Institutes and Offices (CIO)(s) NCBDDD intends to commit approximately $5,250,000 (direct and indirect) dollars in FY2011 to fund for:

1) Component A up to 5 awards for CADDRE/SEED II. The average award amount for the first year of CADDRE/SEED Phase II will be $900,000 (reflecting delay in active implementation of SEED Phase II until all study approvals in place). Budget years 2-5 funding will be approximately $1,200,000 per year (reflecting full SEED II implementation). An applicant may request a project period of up to a five year Project Period. An applicant may request up to $900,000 Ceiling of Award Amount for the first 12 month budget period,

2) Component B is one award for approximately $750,000 for the first year to serve as the CADDRE/SEED Phase II - Central Laboratory and Biosample Repository (reflecting delay in active implementation of SEED Phase II until all study approvals in place). Budget years 2-5 funding will be approximately $1,000,000 per year (reflecting full SEED II implementation). An applicant may request a project period of up to a five year Project Period. An applicant may request up to $750,000 Ceiling of Award Amount for the first 12 month budget period.

The approximate total project period funded amount is $33,250,000. The anticipated start date for new awards is June 30, 2011.

All estimated funding amounts are subject to availability of funds.

CDC will accept and review applications with budgets greater than the ceiling amount.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit an application(s) if your organization has any of the following characteristics:

· Public nonprofit organizations

· Private nonprofit organizations

· For profit organizations

· Small, minority, and women-owned businesses

· Universities

· Colleges

· Research institutions

· Hospitals

· Community-based organizations

· Faith-based organizations

· Federally recognized or state-recognized American Indian/Alaska Native tribal governments

· American Indian/Alaska Native tribally designated organizations

· Alaska Native health corporations

· Urban Indian health organizations

· Tribal epidemiology centers

· State and local governments or their Bona Fide Agents (this includes the District of Columbia, the Commonwealth of Puerto Rico, the Virgin Islands, the Commonwealth of the Northern Marianna Islands, American Samoa, Guam, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau)

· Political subdivisions of States (in consultation with States)

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 you are applying as a bona fide agent of a state or local government, you must provide a letter from the state or local government as documentation of your status. Attach this documentation behind the first page of your application form or for electronic applications, use a PDF file and attach as “Other Documents” and label as appropriate.

2. Cost Sharing or Matching

Sharing, matching, or cost-participation are not required under this program.

The most current HHS Grants Policy Statement is available at: http://www.hhs.gov/grantsnet/docs/HHSGPS_107.doc

3. Other-Special Eligibility Criteria

Component A: Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE): Study to Explore Early Development (SEED) Phase II

1) The proposed CADDRE/SEED Phase II study catchment area had at least 30,000 births in 2009 and is in a contiguous geographic sector defined by clear territory, state(s) or county(ies) boundaries.

a) The proposed SEED Phase II study catchment area for a former CADDRE SEED (Phase I) grantee that is applying under this FOA must include, but may not be limited to, their entire original SEED (Phase I) study catchment area.

b) Evidence in the form of vital records- or census-based data (e.g., from official reports, documents, websites) should be provided and should include data to describe the racial/ethnic/socioeconomic characteristics of the proposed study catchment area and study population.

2) Access to birth certificate files for: selecting and contacting potential POP participants; linking birth certificate data to CASE and NIC participants ascertained from education and clinic sources to confirm study birth residence eligibility requirements; collect birth certificate data on all participants for SEED analyses; and use birth certificate data to characterize the broader study population.

a) Evidence of negotiation (e.g., letter or other official documentation) with the state vital records holder should be provided concerning the applicant’s terms of access to birth certificate data for these purposes.

3) Partnership with multiple CASE/NIC ascertainment sources that serve or include children who are 24-68 months of age, including children who would fall within the SEED Phase II birth cohort: July 1, 2007- June 30, 2011.

a) Evidence may include letters of support or other materials that document partnership with each CASE/NIC ascertainment source and verify that the source serves or includes children in the SEED Phase II cohort.

Applicants should provide their response to these eligibility criteria as part of their response to the Other Submission Requirements described below (Section IV.6.).

If your application is incomplete or non-responsive to the special requirements listed in this section, it will not enter into the review process.

Note: Title 2 of the United States Code Section 1611 states that an organization described in Section 501(c)(4) of the Internal Revenue Code that engages in lobbying activities is not eligible to receive Federal funds constituting an award, grant, or loan.

Section IV. Application Review Information

To download a SF424 (R&R) Application Package and SF424 (R&R) Application Instructions for completing the SF424 (R&R) forms for this FOA, link to Grants.gov/Apply and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at the following:

· Grants.gov Get Registered: http://www.grants.gov/applicants/get_registered.jsp

· eRA Commons Prepare to Apply: http://era.nih.gov/ElectronicReceipt/preparing.htm Note: Both the applicant organization, as well as, the PD/PI must register in eRA Commons for an application to be accepted electronically. The Credentials Log-In, referenced in Section IV. 2. Content and Form of Application Submission, is obtained through Step #3 in the required actions below.

PD/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.

The following three steps are required before an applicant institution/organization can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov Get Registered, http://www.grants.gov/applicants/get_registered.jsp

· Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants.gov registration process.

· If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration.

· The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days.

· Direct questions regarding Grants.gov registration to:

Grants.gov Customer Support Contact Center Phone: 1-800-518-4726 Business Hours: 24 hours/day, seven days/week Email support@grants.gov

2) Organizational/Institutional Registration in the eRA Commons Prepare to Apply, http://era.nih.gov/ElectronicReceipt/preparing.htm

· To find out if an organization is already eRA Commons-registered, see the "List of Grantee Organizations Registered in eRA Commons.”

· Direct questions regarding the eRA Commons registration to:

eRA Commons Help Desk Phone: 301-402-7469 or 866-504-9552 (Toll Free)

TTY: 301-451-5939

Business hours M-F 7:00 a.m. – 8:00 p.m. Eastern Time Email commons@od.nih.gov

3) Project Director/Principal Investigator (PD/PI) Registration in the eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

· The individual designated as the PD/PI on the application must also be registered in the eRA Commons. It is not necessary for PDs/PIs to register with Grants.gov.

· The PD/PI must hold a PD/PI account in the eRA Commons and must be affiliated with the applicant organization. This account cannot have any other role attached to it other than the PD/PI.

· This registration/affiliation must be done by the Authorized Organization Representative/Signing Official (AOR/SO) or their designee who is already registered in the eRA Commons.

· Both the PD/PI and AOR/SO need separate accounts in the eRA Commons since both hold different roles for authorization and to view the application process.

Note that if a PD/PI is also an HHS peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the eRA Commons. The HHS/CDC strongly encourages applicants to use the Grants.gov electronic applications process and have organizations and PD/PIs complete all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g. sample forms, forms from another FOA); although some of the "Attachment" files may be useable for more than one FOA.

If you do not have access to the Internet, or if you have difficulty accessing the forms online, you may contact the CDC Procurement and Grants Office Technical Information Management Section (PGOTIMS) staff. For this, or further assistance, contact PGO TIMS: Telephone (770) 488-2700, Email: PGOTIM@cdc.gov.

HHS/CDC Telecommunications for the hearing impaired: TTY 770-488-2783.

If the applicant encounters technical difficulties with Grants.gov, the applicant should contact Grants.gov Customer Service. The Grants.gov Contact Center is available 24 hours a day, 7 days a week. The Contact Center provides customer service to the applicant community. The extended hours will provide applicants support around the clock, ensuring the best possible customer service is received any time it’s needed. You can reach the Grants.gov Support Center at 1-800-518-4726 or by email at support@grants.gov. Submissions sent by e-mail, fax, CD’s or thumb drives of applications will not be accepted.

Organizations that encounter technical difficulties in using www.Grants.gov to submit their application must attempt to overcome those difficulties by contacting the Grants.gov Support Center (1-800-518-4726, support@grants.gov). After consulting with the Grants.gov Support Center, if the technical difficulties remain unresolved and electronic submission is not possible to meet the established deadline, organizations may submit a request prior to the application deadline by email to PGO TIMS for permission to submit a paper application. An organization's request for permission must: (a) include the Grants.gov case number assigned to the inquiry, (b) describe the difficulties that prevent electronic submission and the efforts taken with the Grants.gov Support Center (c) be submitted to PGO TIMS at least 3 calendar days prior to the application deadline. Paper applications submitted without prior approval will not be considered.

If a paper application is authorized, the applicant will receive instructions from PGO TIMS to submit the original and two hard copies of the application by mail or express delivery service.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide (MS Word or PDF).

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to HHS/CDC. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by HHS/CDC (e.g., the “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component must contain the PD/PI assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see “Tips and Tools for Navigating Electronic Submission” on the front page of “Electronic Submission of Grant Applications.”

The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/Apply will include all applicable components, mandatory and optional. A completed application in response to this FOA will include the following components:

Required Components:

SF424 (R&R) (Cover component)

Research & Related Project/Performance Site Locations Research & Related Other Project Information Research & Related Senior/Key Person Profile

PHS398 Research & Related BudgetPHS398 Cover Page Supplement PHS398 Research Plan PHS398 Checklist For K awards include: PHS398 Career Development Award Supplement Form PHS398 Cover Letter File Research & Related Sub award Budget Attachment(s) Form

Note: While both budget components are included in the SF424 (R&R) forms package, the CDC U01 (activity…