dd15-1507 amendment 05.14.15.pdf

Part I. Overview Information Applicants must go to the synopsis page of this announcement at www.grants.gov and click on the "Send Me Change Notifications Emails" link to ensure they receive notifications of any changes to CDC-RFA-DD15-1507. Applicants also must provide an e-mail address to www.grants.gov to receive notifications of changes.

A. Federal Agency Name:

Centers for Disease Control and Prevention (CDC) B. Funding Opportunity Title:

Public Health Surveillance for the Prevention of Complications of Bleeding Disorders C. Announcement Type: New - Type 1 This announcement is only for non-research domestic activities supported by CDC. If research is proposed, the application will not be considered Research for this purpose is defined at http://www.cdc. gov/od/ science / integrity/ docs/cdc- policy- distinguishing- public- health- research- nonresearch. pdf.

D. Agency Funding Opportunity Number:

CDC-RFA-DD15-1507

E. Catalog of Federal Domestic Assistance (CFDA) Number:

93.080 F. Dates:

1. Due Date for Letter of Intent (LOI): 05/01/2015

2. Due Date for Applications: 05/20/2015, 11:59 p.m. U.S. Eastern

Standard Time, at www.grants.gov.

3. Date for Informational Conference Call: 04/13/2015 April 13, 2015 3pm-4pm Eastern Time; (855) 644-0229, Conference ID: 2963605

G. Executive Summary:

1. Summary Paragraph:

Hemophilia, von Willebrand disease and other congenital bleeding disorders that decrease normal blood clotting cause significant disease burden and reduced quality of life. The purpose of this FOA is to build upon the work currently ongoing in the United States Hemophilia Treatment Center Network (USHTCN) under DD11-1103/DD14-1409 to prevent and reduce the complications of bleeding disorders by supporting the collection, aggregation and use of nationally representative data and specimens for surveillance for inhibitors and other complications of bleeding disorders. The awardee or awardees are required to collaborate with hemophilia treatment centers that are part of the USHTCN and are expected to build or model upon the structures, processes and instruments implemented under DD11-1103/DD14-1409. The awardee or awardees (should USHTCN regions choose to collaborate with different applicants) are expected to implement these five strategies and their corresponding activities: 1) establish collaborations with HTCs;

2) data collection and transfer; 3) specimen collection and transfer; 4) data evaluation; and 5) disseminate information (see Part 11.A.2.a.iii. Strategies and Activities), in order to achieve the following project outcomes: data collection legally and financially enabled; HTCs provide administrative input on existing capacity and barriers for project implementation; HTCs provide multidisciplinary input on project content based on professional practice and research expertise; HTCs contribute uniform data on bleeding disorders complications to a pooled national dataset; HTCs provide data for refinement of project processes and content; researchers and other stakeholders have access to more comprehensive evidence base for inhibitors and other complications; researchers, providers and other stakeholders: a) monitor trends in, b) identify potential disparities between subpopulations in the rates of, c) identify high risk populations for interventions https://foa.grantsolutions.gov/announcementmodule/www.grants.gov https://foa.grantsolutions.gov/announcementmodule/www.grants.gov http://www.cdc.gov/od/science/integrity/docs/cdc-policy-distinguishing-public-health-research-nonresearch.pdf http://www.cdc.gov/od/science/integrity/docs/cdc-policy-distinguishing-public-health-research-nonresearch.pdf http://www.grants.gov potential disparities between subpopulations in the rates of, c) identify high risk populations for interventions to reduce or prevent, and d) assess gaps in data collection on inhibitors and other complications of bleeding disorders. Applicants are encouraged to propose methods for maximizing national inhibitor surveillance.

a. Eligible Applicants: Open Competition

b. FOA Type: Cooperative Agreement

c. Approximate Number of Awards: 1

d. Total Project Period Funding: $21,500,000

e. Average One Year Award Amount: $4,300,000

f. Number of Years of Award: 5

g. Estimated Award Date: 08/31/2015

h. Cost Sharing and / or Matching Requirements: N Cost sharing or matching funds are not required for this program. Although no statutory matching requirement for this FOA exists, leveraging other resources and related ongoing efforts to promote sustainability is strongly encouraged.

Part II. Full Text A. Funding Opportunity Description

1. Background

a. Overview

Hemophilia, von Willebrand disease (VWD) and other congenital bleeding disorders that decrease normal blood clotting cause significant disease burden and reduced quality of life. About 20,000 people in the United States (US) (mostly males) have hemophilia, with healthcare costs approaching $3 billion annually.

People with hemophilia have spontaneous internal bleeding and prolonged bleeding after injury or surgery that can lead to long-term damage and chronic conditions such as disabling joint disease. VWD occurs in about 1% of the population. Severe VWD causes symptoms like those of hemophilia in men and women.

With other forms, women are more likely to have symptoms because VWD increases bleeding during menstrual periods and after childbirth. VWD increases risk for miscarriage, bleeding during pregnancy and maternal death. Historically, persons with bleeding disorders have also suffered infection with blood-borne viruses due to contaminated treatment products.

Patients with bleeding disorders are largely treated at specialized hemophilia treatment centers (HTCs) which provide comprehensive care. The federal HTC system (the US Hemophilia Treatment Center Network or USHTCN) includes 132 centers throughout the US and its territories. From January 2012 through December 2014, the USHTCN provided care to more than 16,200 patients with hemophilia, 11,000 with VWD and 5,700 with other bleeding disorder diagnoses.

Since the 1980s, CDC has collaborated with the USHTCN to reduce the complications of bleeding disorders and their treatment. This began with programs to reduce the secondary spread of HIV to partners of infected patients. In 1991, in response to requests from constituents, Congress authorized CDC to expand its activities to the prevention of other complications. CDC collaborated with the USHTCN to design and implement the Universal Data Collection (UDC) project (1998-2011). The UDC was designed to monitor the complications of bleeding disorders over time, especially joint disease and blood-borne infections. UDC demonstrated that some complications related to joint disease had decreased over time. The proportion of patients on treatment to prevent bleeding episodes (prophylaxis) increased. Overweight and obesity were shown to increase and accelerate the loss of joint range of motion, leading to programs to help patients maintain or achieve healthy weight. No new hepatitis or HIV infections from contaminated treatment products were found. The percentage of youth with severe hemophilia using prophylaxis varied widely across HTCs and evidence suggested other viruses may still be transmitted in plasma-derived treatment products.

In 2010 CDC hosted a stakeholder meeting to identify ongoing and new areas of concern to the bleeding disorders community. Stakeholders individually identified numerous health indicators that should be monitored in order to protect the health of persons with bleeding disorders, including inhibitors. An inhibitor is an antibody created by the patient’s immune system that inactivates clotting factor concentrate, making treatments ineffective and increasing complications and hospitalization rates. A single patient with complications and an inhibitor can have over $1 million in treatment costs annually. Widely cited as the most serious complication of hemophilia treatment, approximately 15-20% of hemophilia patients develop an inhibitor. Numerous risk factors for inhibitor development have been identified yet the causes are not completely understood, including whether specific treatment products play a role. Nationally representative data on inhibitor development in the US bleeding disorders population are not available. Determining the incidence and prevalence of inhibitors in this group and better understanding the risk factors associated with their development and their consequences is a priority for the Division of Blood Disorders, as are joint disease, intracranial hemorrhage and complications of treatment product use. In 2011, under cooperative agreement DD11-1103/DD14-1409, CDC and the USHTCN substantially revised data collection to reflect revised priorities. Data collection under the revised project, Community Counts, began in 2012.

b. Statutory Authorities

Sections 301(a) [42 USC 241(a)] and 317 (C) of the Public Health Service Act [42 U.S.C. Section 247b-4] as amended.

c. Healthy People 2020

This program addresses the “Healthy People 2020” focus area(s) of Blood Disorders and Blood Safety.

BDBS-11(Developmental) Increase the proportion of persons with bleeding disorders who receive recommended vaccinations.

BDBS-15 Increase the proportion of females with von Willebrand disease (VWD) who are timely and accurately diagnosed.

BDBS-16 Reduce the proportion of persons with hemophilia who develop reduced joint mobility due to bleeding into joints.

http://www.healthypeople.gov/2020/topics-objectives/topic/blood-disorders-and-blood-safety

d. Other National Public Health Priorities and Strategies

N/A

e. Relevant Work

This FOA builds on previous projects for the surveillance of complications of bleeding disorders, Prevention of the Complications of Bleeding Disorders through Hemophilia Treatment Centers (DD06-005, Universal Data Collection) and Public Health Surveillance for the Prevention of Complications of Bleeding and Clotting Disorders (DD11-1113/DD14-1409, Community Counts). Awardees are expected to build or model upon the structures, processes and instruments implemented under DD11-1103/DD14-1409.

2. CDC Project Description

a. Approach http://www.healthypeople.gov/2020/topics-objectives/topic/blood-disorders-and-blood-safety http://www.cdc.gov/ncbddd/blooddisorders/udc/ http://www.cdc.gov/ncbddd/blooddisorders/udc/

The logic model below describes the expected approach to and outcomes of this program. Awardees will be responsible for accomplishing the outcomes marked with an asterisk (*).

Strategies and Activities

Short-term Outcomes Intermediate Outcomes Long-term Outcomes

Strategy 1:

Establish collaborations with HTCs

1. Data collection legally and financially enabled*

2. HTCs provide administrative input on existing capacity and barriers for project implementation*

3. HTCs provide multi-disciplinary input on project content based on professional practice and research expertise*

4. HTCs invested in implementation and success of project

Researchers, providers and other stakeholders:

• have increased awareness of inhibitors and other complications, treatment practices and patterns

• monitor trends*

• identify potential disparities*

• identify high risk populations for interventions*

• assess gaps in data collection*

• generate hypotheses for research

Reduce and prevent inhibitors and other complications of bleeding disorders

Strategy 2: Data collection and transfer

1. HTCs contribute uniform data on bleeding disorders complications to a pooled national dataset*

2. Patients receive regular inhibitor screening

3. Patients receive regular screening for HCV and HIV

Strategy 3:

Specimen collection and transfer

Strategy 4: Data evaluation

1. Researchers and other stakeholders have confidence in the quality of data

2. HTCs provide data for refinement of project processes and content*

3. HTCs committed to implementation and success of project

Strategy 5:

Disseminate information

1. HTCs monitor progress towards participation and data quality expectations

2. Researchers and other stakeholders have access to more comprehensive evidence base for inhibitors and other complications*

CDC-RFA-DD15-1507 Logic Model: Public Health Surveillance for the Prevention of Complications of Bleeding Disorders

i. Purpose

The purpose of this FOA is to build upon the work currently ongoing in the USHTCN under DD11-1103/DD14-1409 to prevent and reduce the complications of bleeding disorders by supporting the collection, aggregation and use of nationally representative data and specimens for surveillance for inhibitors and other complications of bleeding disorders. These data will be used to increase awareness of inhibitors and other complications among stakeholders; monitor trends in complications; identify disparities among subpopulations of bleeding disorder patients; identify high risk populations for interventions; assess gaps in data collection; generate hypotheses for research; and, ultimately, prevent the complications of bleeding disorders.

ii. Outcomes

Awardees are expected to achieve the following outcomes during the 5-year FOA project period:

1. Data collection legally and financially enabled (maintain or put in place)

2. HTCs provide administrative input on existing capacity and barriers for project implementation (maintain or put in place)

3. HTCs provide multidisciplinary input on project content based on professional practice and research expertise (maintain or put in place)

4. HTCs contribute uniform data on bleeding disorders complications to a pooled national dataset (increase)

5. HTCs provide data for refinement of project processes and content (maintain or put in place)

6. Researchers and other stakeholders have access to more comprehensive evidence base for inhibitors and other complications (increase)

7. Researchers, providers and other stakeholders:

i. monitor trends in;

ii. identify potential disparities between subpopulations in the rates of;

iii. identify high risk populations for interventions to reduce or prevent; and

iv. assess gaps in data collection on inhibitors and other complications of bleeding disorders (increase)

iii. Strategies and Activities

Awardees are expected to implement the following strategies and activities in order to achieve the project outcomes:

Strategy 1: Establish collaborations with HTCs

• Activity 1: Identify and execute needed business agreements with HTCs

• Activity 2: Establish process for regular input from HTCs on implementation of project

Strategy 2: Data collection and transfer Awardees must coordinate and facilitate data collection and transfer from HTCs to CDC for inclusion in a pooled national data set such that the number of patients represented in the data set at Activity 2 is maintained or increased and the number at Activity 3 increases relative to the number enrolled at the close of DD11-1103/DD14-1409 in September 2015. Additional information regarding the acceptance testing and data elements referred to in activities 1-4 below can be found in CDC-RFA-DD15-1507 Supporting Information.

• Activity 1: Choose data collection and transfer methods and processes CDC has developed a web-based data entry application (DBD Gateway) for use by sites collecting data for DBD surveillance projects. Applicants must indicate whether HTCs will use DBD Gateway for data submission or whether the applicant will provide another method of transferring data from the HTCs to CDC electronically. Awardees that choose not to use DBD Gateway will be required to participate in acceptance testing of data files, including submission of associated documentation.

• Activity 2: Coordinate collection and transmission of annual minimal patient-level data on all patients with agreed-upon bleeding disorder diagnoses at HTCs

• Activity 3: Coordinate enrollment of patients and collection and transmission of longitudinal,

• Activity 3: Coordinate enrollment of patients and collection and transmission of longitudinal, patient-level data on health indicators, including seroconversion follow-up, at the HTCs

• Activity 4: Coordinate collection and transmission of patient-level data on deaths of bleeding disorder patients at the HTCs

Strategy 3: Specimen collection and transfer from participants of Strategy 2, Activity 3 (longitudinal patient-level health indicator data)

• Activity 1: Coordinate at HTCs the collection and transfer of plasma specimens from participants enrolled in Activity 3 of Strategy 2 for inhibitor testing and seroconversion follow-up

• Activity 2: Coordinate at HTCs the collection and transfer of serum specimens from participants enrolled in Activity 3 of Strategy 2 for evaluation of treatment product safety and seroconversion follow-up

Strategy 4: Data evaluation Awardees must maintain, or put in place, a process for gathering and analyzing data from the HTCs for the purpose of assessing and refining project processes and content.

• Activity 1: Develop and implement process to ensure collection of accurate data

• Activity 2: Evaluate feasibility of data collection at HTCs

Strategy 5: Disseminate information

• Activity 1: Collaborate with CDC to develop and provide internal reports to HTCs

• Activity 2: Collaborate with CDC to develop public information reports/materials (for example, key findings)

• Activity 3: Collaborate with CDC to plan, develop and produce peer-reviewed publications

• Activity 4: Collaborate with CDC and the USHTCN to use the data collected to:

i. monitor trends in;

ii. identify potential disparities between subpopulations in the rates of;

iii. identify high risk populations for interventions to reduce or prevent; and

iv. assess gaps in data collection on inhibitors and other complications of bleeding disorders

Applicants may propose additional strategies and activities.

1.Collaborations

Please see below for expected collaborations for this FOA.

a. With CDC-funded programs:

Awardees are required to collaborate with CDC Division of Blood Disorders. In the event that more than one award is made under this cooperative agreement, awardees will be required to collaborate with each other to produce and disseminate public information reports and materials and peer-reviewed manuscripts using the nationally pooled data. Awardees are not expected at this time to collaborate with CDC-funded programs other than those funded by this cooperative agreement to achieve these outcomes.

b. With organizations external to CDC:

Awardees are required to collaborate with HTCs that are part of the USHTCN for data and specimen collection. The USHTCN is regionally organized (see CDC-RFA-DD15-1507 Supporting Information) and receives funds through Special Projects of Regional and National Significance (SPRANS) administered by the Health Resources and Services Administration (HRSA). The hemophilia regional core centers, the grantees for HRSA SPRANS funds, determine which treatment centers within their geographic region are included in the USHTCN. This determination includes an assessment of whether each center meets the criteria set for HTCs by the Medical and Scientific Advisory Committee of the (US) National Hemophilia Foundation (MASAC). These criteria are stated in MASAC Recommendation # 132- Standards and Criteria for the Care of Persons with Congenital Bleeding Disorders (Revised April 2002), which may be found at:

http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=57&;contentid=220.

http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=57&contentid=220

In the event that different regions of the USHTCN agree to collaborate with different applicants, CDC will consider making up to three awards under this cooperative agreement to preserve geographic and demographic representativeness. The HTCs of any single region may not be funded by more than one award under this cooperative agreement. Applicants must specify whether they are collaborating with all of the regions of the USHTCN, or a subset of the regions. If collaborating with a subset of the regions, applicants must specify which regions those are.

Awardees may also collaborate with treatment centers that are not currently part of the USHTCN supported by HRSA SPRANS funds if:

• The non-USHTCN center meets the criteria stated in MASAC Recommendation # 132- Standards and Criteria for the Care of Persons with Congenital Bleeding Disorders (Revised April 2002), which may be found at: http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=57&;contentid=220; and

• Participation of the non-USHTCN center will not reduce the funds that would otherwise be directed to USHTCN centers for use on project activities; and

• The core center for the region in which the non-USHTCN center is located agrees that the non-USHTCN center may participate.

Applicants must document that each non-USHTCN center meets all three criteria for participation.

Applicants may provide evidence of fulfillment of each of the criteria set out in MASAC Recommendation # 132, or provide a written statement from the regional core center confirming that the non-USHTCN center meets the criteria. Documentation indicating that the core center for the region in which the non-USHTCN center is located agrees that the non-USHTCN center may participate must be signed by the Regional Coordinator and Regional Director.

Applicants must provide documentation that HTCs have agreed to collaborate with the awardee and CDC to carry out the strategies and activities relevant to the HTCs that are proposed for this project. This documentation may be in the form of letters of support, letters of agreement, memoranda of understanding, memoranda of agreement, or contracts from or with collaborating HTCs (hereafter referred to collectively as “letters of support”). Documentation from the regional core center on behalf of the participating HTCs within its region may be provided in place of individual documentation from each HTC. Documentation that any non-USHTCN centers fulfill the criteria for participation may be provided in the same attachment as the letters of support from USHTCN HTCs.

2. Target Populations

The target populations are people of all ages with congenital bleeding disorders, primarily those due to factor deficiencies such as hemophilia A and B, von Willebrand disease and other clotting factor deficiencies.

However, since inhibitor surveillance is a CDC priority, those patients at risk for development of an inhibitor to factor VIII or factor IX (patients with a diagnosis of hemophilia A, hemophilia B or type 3 VWD, especially racial and ethnic minorities) are considered to be of highest priority for enrollment in Strategy 2, Activity 3 (longitudinal patient-level health indicator data). Applicants should describe the geographic catchment area and demographic make-up (number and diagnoses, gender, race, ethnicity, age:

0-10 years; 11-19 years; 20 years and older) of the patient population of the HTCs with which it proposes to collaborate, as well as the percentage of all USHTCN bleeding disorder patients represented at its collaborating HTCs.

a. Inclusion

Applicants should strive to include people with disabilities; non-English speaking populations; lesbian, gay, bisexual, and transgender (LGBT) populations; people with limited health literacy; and/or populations that may otherwise be overlooked by the program.

iv. Funding Strategy (for multi-component FOAs only)

N/A

b. Evaluation and Performance Measurement

i. CDC Evaluation and Performance Measurement Strategy

Evaluation and performance measures are directly linked to the program outcomes and strategies. Evaluation findings will be used to refine and improve program activities. Process evaluation methods will be used to assess the extent to which planned program activities have been implemented and have led to desired programmatic outcomes. Short and intermediate-term outcome evaluation will assess whether the project activities are leading to the intended long-term outcomes. All evaluation activities will support the logic model and approach presented earlier. Audiences for performance measures and evaluation findings include CDC, HTC leadership and staff and the public. Results are expected to be disseminated as technical notes and findings in public presentations and as reports to HTC leadership and staff.

Process Measures Strategy 1- Establish collaborations with HTCs Activity 1- Identify and execute needed business agreements with HTCs

• # of HTCs with business and financial agreements in place within 3 months of beginning of project period (reported to CDC quarterly until completion)

Activity 2- Establish process for regular input from HTCs on implementation of project

• Documented process for gathering input on administrative/business issues (reported to CDC once, upon completion)

• Documented process for gathering multidisciplinary input on professional practice and scientific issues (reported to CDC once, upon completion)

• Written agreement between the awardee, CDC and the HTCs on data use by the parties and sharing or release for public use, and implementation thereof (reported to CDC once, upon completion)

Strategy 2- Data collection and transfer Activity 1- Choose data collection and transfer methods and processes

• Timely receipt of correct data files at CDC*

- Timely: Percent of data files received at CDC within the agreed-upon timeframe

- Correct: Percent of data files conforming to the file structure and data field content specified by

CDC

Activities 2-4- Coordinate collection and transmission of minimal, longitudinal and mortality data

• # of HTCs obtaining institutional approval within 6 months of beginning of project period (reported to CDC quarterly until completion)

• Written regional plans to assess HTC participation and address barriers on an on-going basis within 6 months of beginning of project period (reported to CDC semiannually)

• # of HTCs submitting timely and complete longitudinal patient level health indicator data*

- Timely: Percent of initial submissions made within the agreed-upon timeframe; percent of data queries resolved within the agreed-upon timeframe

- Complete: Percent of non-missing responses

Strategy 3- Specimen collection and transfer On a per HTC basis:

Activity 1- Coordinate collection and transfer of plasma specimens

• Percent of expected specimens submitted for inhibitor screening (# of specimens appropriately submitted for inhibitor screening ÷ # of participants eligible for inhibitor screening)*

Activity 2- Coordinate collection and transfer of serum specimens

• Percent of expected specimens submitted for infectious disease and/or biomarker screening (# of specimens appropriately submitted for infectious disease and/or biomarker screening ÷ # of participants eligible for infectious disease and/or biomarker screening)*

Activities 1 & 2- Coordinate collection and transfer of plasma and serum specimens

• Percent of specimens prepared and shipped according to agreed-upon protocols. Includes collecting correct specimen, appropriate processing, notification to serum bank, completed specimen form (see CDC-RFA-DD15-1507 Supporting Information) and proper shipping*

Strategy 4- Data evaluation Activity 1- Develop and implement process to ensure collection of accurate data

• Written plan for periodic evaluation and documentation of the accuracy of data collected and any indicated refinements (reported to CDC once, upon completion)

Activity 2- Evaluate feasibility of data collection at HTCs

• Written plan for periodic evaluation of the process and ease of data collection at HTCs (reported to CDC once, upon completion)

Strategy 5- Disseminate information Activity 1- Collaborate with CDC to develop and provide internal reports to HTCs

• Provision of HTC-level quarterly progress reports on participation to HTCs (reported to CDC annually)

• Provision of recurrent HTC-level reports of clinically relevant measures to HTCs (reported to CDC annually)

• Provision of reports to HTCs on findings from periodic evaluations of data accuracy and the data collection process, as completed (reported to CDC annually)

• Notification to HTCs about materials under production for public and scientific community, at least semiannually (reported to CDC annually)

Activity 2- Collaborate with CDC to develop public information reports/materials

• Process measures to be developed in collaboration with CDC

Activity 3- Collaborate with CDC to plan, develop and produce peer-reviewed publications

• Process measures to be developed in collaboration with CDC

Activity 4- Collaborate with CDC and the USHTCN to use the data collected to monitor trends in; identify potential disparities between subpopulations in the rates of; identify high risk populations for interventions to reduce or prevent; and assess gaps in data collection on inhibitors and other complications of bleeding disorders

• Process measures to be developed in collaboration with CDC

Outcome Measures Outcome 1: Data collection legally and financially enabled

• # of HTCs with completed business and financial agreements in place (reported to CDC annually)

Outcome 2: HTCs provide administrative input on existing capacity and barriers for project implementation

• Evidence of implementation of process such as call schedules, agendas, minutes, communications, etc. (reported to CDC annually)

Outcome 3: HTCs provide multidisciplinary input on project content based on professional practice and research expertise

• Evidence of implementation of process such as call schedules, agendas, minutes, communications, etc. (reported to CDC annually)

Outcome 4: HTCs contribute uniform data on bleeding disorders complications to a pooled national dataset

• # of HTCs submitting annual minimal patient-level data, on an annual basis*

• # of HTCs submitting longitudinal health indicator data, on a quarterly basis*

• # of HTCs submitting mortality data, on an annual basis*

Outcome 5: HTCs provide data for refinement of project processes and content

• Written findings from evaluation(s) of data accuracy, including # and representativeness of HTCs participating in data quality assessment (reported to CDC upon completion)

- Representativeness includes USHTCN region; characteristics of patient population (number, pediatric vs. adult, diagnoses); resources available for data collection/project activities

• Written findings from evaluation(s) of data collection process, including # and representativeness of HTCs participating in evaluation of project processes (reported to CDC upon completion)

- Representativeness includes USHTCN region; characteristics of patient population (number, pediatric vs. adult, diagnoses); resources available for data collection/project activities

Outcome 6: Researchers and other stakeholders have access to more comprehensive evidence base for inhibitors and other complications

• Dissemination of at least one public information product per year targeting participants and other consumers (reported to CDC annually)

• Dissemination of at least one public information product per year targeting researchers, providers or policy-makers (reported to CDC annually)

• Production of at least one peer-reviewed manuscript explaining methods and data results (reported to CDC annually)

Outcome 7: Researchers, providers and other stakeholders:

i. monitor trends in;

ii. identify potential disparities between subpopulations in the rates of;

iii. identify high risk populations for interventions to reduce or prevent; and

iv. assess gaps in data collection on inhibitors and other complications of bleeding disorders.

• Documentation of discussion and review with CDC, the USHTCN and other partners (if applicable) of trends, disparities, high risk populations, potential interventions and gaps in data collection on inhibitors and other complications of bleeding disorders (reported to CDC annually beginning with project year 4)

Measures marked with an asterisk (*) can be evaluated directly by CDC and do not require additional reporting by the awardee. The data collected relative to performance measures are limited to that which will be analyzed and used for this purpose.

ii. Applicant Evaluation and Performance Measurement Plan

Applicants must provide an evaluation and performance measurement plan that is consistent with the CDC evaluation and performance measurement strategy. In this plan, applicants must:

1. Affirm their ability to collect the data for the performance measures

2. Describe how the applicant’s key project staff, USHTCN regional core center staff, HTC staff and other key partners if applicable (for example, other federal agencies, consumer-based organizations, professional organizations, etc.) will be engaged in the evaluation and performance measurement process

3. Describe key evaluation questions to be answered, ensuring that the relevant outcomes, as displayed in the logic model, are included

4. Describe strategies for appropriate collection of performance evaluation data

5. Describe how evaluation findings will be used for quality improvement

c. Organizational Capacity of Awardees to Execute the Approach

Applicants must have the organizational structure and capacity to execute the CDC strategies and activities and meet project period outcomes. Applicants should address their collaboration with USHTCN regional core center staff, HTC staff and other key partners if applicable (for example, federal agencies other than CDC, consumer-based organizations, professional organizations, etc.); their ability to carry out evaluation, performance monitoring, financial reporting, subcontracting, budget management and administration; and their expertise and experience related to the surveillance of conditions among persons with congenital bleeding disorders. For those capacities that involve collaboration with other organizations (including the USHTCN regional core centers, HTCs and other key partners), existing capacity may be documented within letters of support.

Key capacity considerations to address in the application:

• Applicants must describe their experience related to the surveillance of conditions among persons with congenital bleeding disorders.

• Applicants must specify which HTCs are anticipated to participate in the project.

• Applicants must describe the roles and expertise of their key project staff, USHTCN regional core center staff, HTC staff and other key partners if applicable (for example, other federal agencies, consumer-based organizations, professional organizations, etc.), and their ability to collaboratively implement the FOA.

• Applicants must provide a staffing plan, describing in detail their own resources and staffing levels for this project, including an organizational chart and resumes/CVs.

• Applicants must describe, generally, the resources and staffing levels of the participating HTCs.

• If proposed collaboration with non-USHTCN or non-HTC partners (for example, federal agencies other than CDC, consumer-based organizations, professional organizations, etc.) is key to the success of this project, applicants must include each non-USHTCN or non-HTC partner’s organizational chart and resumes/CVs of the partner’s key project staff.

• Applicants must provide regional data collection projections for the first year of the project for Strategy 2, Activity 3 (Data collection and transfer, longitudinal patient level health indicator data), accounting for both expected initial enrollments and subsequent episodes of participation by patients enrolled previously. These projections should be based on the expectation that any HTC funded under this cooperative agreement will also participate in Activities 2 and 4 of Strategy 2, as well as Activities 1 and 2 of Strategy 3 (Specimen collection and transfer). Projections should be commensurate with available resources and the cost of carrying out the project at each HTC. CDC is interested in maximizing national surveillance for inhibitor development, characterizing its risk factors and monitoring the outcomes of patients at risk of inhibitor development. To that end, applicants may propose reductions to the set of elements collected for Strategy 2, Activity 3 under DD11-1103/DD14-1409 (see CDC-RFA-DD15-1507 Supporting Information) that would reduce the amount of data collected on each participant, freeing resources for the enrollment of additional participants at risk for inhibitor development. Proposed reductions to the set of elements should preserve elements describing inhibitor-related risk factors (patient characteristics, treatment products, treatment regimen) and outcomes (bleeds, joint disease, ability to control bleeding episodes with routine doses and frequency of factor). Applicants must specify the elements they propose to remove from the set by item number and text of item and provide the rationale for removal; this information may be provided in the budget narrative under contractual costs. Applicants proposing a reduction to the set of elements must provide data collection projections based on both the complete set of elements and the proposed reduced set. Applicants are welcome to submit multiple scenarios. If the applicant wishes to provide data collection projections based on a reduced set of elements but is unable to provide such projections at the time of application, it must provide a plan for developing such projections and a timeline for accomplishing this before the beginning of the project period. Applicants that do not propose reductions to the set of elements should justify why no change is needed. Final decisions on whether and how to alter the set of elements will be made jointly by CDC, the awardee and the

USHTCN.

• Applicants must demonstrate that they have adequate technical resources to meet the project’s goals, including informational technology (IT) infrastructure. Applicants must describe how data will be collected and submitted to CDC. If the applicant chooses to provide a method of submitting data from the HTCs to CDC electronically other than DBD Gateway, it must describe the current status of the application and the estimated amount of time before the application can be used for this project.

d. Work Plan

A work plan aids in monitoring progress towards expected project outcomes. Applicants must provide a high-level work plan that covers the duration of the project, with more detail for the first year of the project period. The first year details should include program strategies, activities, performance measures, person(s) responsible, timeframe and activity completion date. The high-level work plan should include a description of intended strategies, activities, outputs, and outcomes for the entire five-year project period.

A work plan template using Outcome 5 as an example is shown below; such a table should be completed for each project period outcome.

Outcome 5:

HTCs provide data for refinement of project processes and content

Outcome Measure(s):

1. Written findings from evaluation(s) of data accuracy, including # and representativeness of HTCs participating in data quality assessment

2. Written findings from evaluation(s) of data collection process, including # and representativeness of HTCs participating in evaluation of project processes

Strategies/Activities Process Measure Person(s) Responsible

Time-frame Activity Completion

Date

Strategy 4- Data Evaluation

Activity 1- Develop and implement process for collection of accurate data

Written plan for periodic evaluation and documentation of the accuracy of data collected and any indicated refinements

Strategy 4- Data Evaluation

Activity 2- Evaluate feasibility of data collection at HTCs

Written plan for periodic evaluation of the process and ease of data collection at HTCs

e. CDC Monitoring and Accountability Approach Monitoring activities include routine and ongoing communication between CDC and awardees, site visits, and awardee reporting (including work plans, performance, and financial reporting). Consistent with applicable grants regulations and policies, CDC expects the following to be included in post-award monitoring for grants and cooperative agreements:

Tracking awardee progress in achieving the desired outcomes.

Ensuring the adequacy of awardee systems that underlie and generate data reports.

Creating an environment that fosters integrity in program performance and results.

Monitoring may also include the following activities:

Ensuring that work plans are feasible based on the budget and consistent with the intent of the award.

Ensuring that awardees are performing at a sufficient level to achieve outcomes within stated timeframes.

Working with awardees on adjusting the work plan based on achievement of outcomes, evaluation results and changing budgets.

Monitoring performance measures (both programmatic and financial) to assure satisfactory performance levels.

Other activities deemed necessary to monitor the award, if applicable.

These activities may include monitoring and reporting activities that assist grants management staff (e.g., grants management officers and specialists, and project officers) in the identification, notification, and management of high-risk grantees.

f. CDC Program Support to Awardees (THIS SECTION APPLIES ONLY TO COOPERATIVE

AGREEMENTS)

In a cooperative agreement, CDC and awardees share responsibility for successfully implementing the award and meeting identified outcomes. CDC will:

1. Collaborate with awardee(s) and the USHTCN to balance priorities, and provide technical assistance, in finalization of data collection instruments;

2. Provide technical support for collection of data including data collection instruments, data cleaning and a secure interface for data submission;

3. Work with awardee(s) to assess training needs;

4. Obtain Office of Management and Budget (OMB) Paperwork Reduction Act (PRA) Information Collection Clearance if necessary;

5. Serve as host and steward of data aggregated from HTCs;

6. Prepare surveillance reports and other public health practice reports of data aggregated from HTCs;

7. Provide technical assistance to awardee(s) and USHTCN for analysis of their data as requested;

8. Participate in project site visits and scheduled conference calls as appropriate;

9. Work with awardee(s) to disseminate findings;

10. Coordinate information sharing between awardees (if applicable);

11. Provide guidance for ethical conduct of non-research data collection and patient authorization;

12. Provide guidance on appropriate collection, processing and shipping of blood specimens;

13. Perform, or arrange for, laboratory tests called for by the project;

14. Report test results to the contributing HTC; and

15. Serve as host and steward of specimen repository for future use.

B. Award Information

1. Funding Instrument Type: Cooperative Agreement CDC's substantial involvement in this program appears in the

CDC Program Support to Awardees Section.

2. Award Mechanism: U27

Surveillance of Complications of Hemophilia Cooperative Agreements

3. Fiscal Year: 2015 Estimated Total Funding: $4,300,000

4. Approximate Total Fiscal Year Funding: $4,300,000

5. Approximate Project Period Funding: $21,500,000

6. Total Project Period Length: 5 year(s)

7. Expected Number of Awards: 1

8. Approximate Average Award: $4,300,000 Per Budget Period

9. Award Ceiling: $4,300,000 Per Budget Period

10. Award Floor: $100,000 Per Budget Period

11. Estimated Award Date: 08/31/2015 Throughout the project period, CDC will continue the award based on the availability of funds, the evidence of satisfactory progress by the awardee (as documented in required reports), and the determination that continued funding is in the best interest of the federal government. The total number of years for which federal support has been approved (project period) will be shown in the “Notice of Award.” This information does not constitute a commitment by the federal government to fund the entire period. The total project period comprises the initial competitive segment and any subsequent non-competitive continuation award(s).

12. Budget Period Length: 12 month(s)

13. Direct Assistance Direct Assistance (DA) is not available through this FOA.

C. Eligibility Information

1. Eligible Applicants Eligibility Category: Unrestricted (i.e., open to any type of entity above), subject to any clarification in text field entitled "Additional Information on Eligibility"

2. Additional Information on Eligibility Applicants must provide documentation that HTCs have agreed to collaborate with the awardee and CDC

Applicants must provide documentation that HTCs have agreed to collaborate with the awardee and CDC to carry out the strategies and activities relevant to the HTCs that are proposed for this project. This documentation may be in the form of letters of support, letters of agreement, memoranda of understanding, memoranda of agreement, or contracts from or with collaborating HTCs (hereafter referred to collectively as “letters of support”). Documentation from the regional core center on behalf of the participating HTCs within its region may be provided in place of individual documentation from each HTC. If letters of support are not provided, the applicant will be considered non-responsive.

The award ceiling for this FOA is $4,300,000. CDC will consider any application requesting an award higher than this amount as non- responsive and it will receive no further review. If a pre-application is required, then specify here and include it in the special eligibility requirements section. (http:// www.hhs.gov/ asfr/ ogapa/ aboutog/ hhsgps107.pdf)

3. Justification for Less than Maximum Competition

N/A

4. Cost Sharing or Matching Cost Sharing / Matching Requirement:

No

Cost sharing or matching funds are not required for this program. Although no statutory matching requirement for this FOA exists, leveraging other resources and related ongoing efforts to promote sustainability is strongly encouraged.

5. Maintenance of Effort

Maintenance of effort is not required for this program.

D.1. Required Registrations

Additional materials that may be helpful to applicants: http://www.cdc.gov/od/pgo/funding/docs/Financial ReferenceGuide.pdf.

1. Required Registrations An organization must be registered at the three following locations before it can submit an application for funding at www.grants.gov.

a. Data Universal Numbering System: All applicant organizations must obtain a Data Universal Numbering System (DUNS) number. A DUNS number is a unique nine-digit identification number provided by Dun & Bradstreet (D&B). It will be used as the Universal Identifier when applying for federal awards or cooperative agreements.

The applicant organization may request a DUNS number by telephone at 1-866-705-5711 (toll free) or Internet at http:// fedgov.dnb.com/webform/displayHomePage.do. The DUNS number will be provided at no charge.If funds are awarded to an applicant organization that includes sub-awardees, those sub-awardees must provide their DUNS numbers before accepting any funds.

b. System for Award Management (SAM): The SAM is the primary registrant database for the federal government and the repository into which an entity must submit information required to conduct business as an awardee. All applicant organizations must register with SAM, and will be assigned a SAM number. All information relevant to the SAM number must be current at all times during which the applicant has an application under consideration for funding by CDC. If an award is made, the SAM information must be maintained until a final financial report is submitted or the final payment is received, whichever is later. The SAM registration process usually requires not more than five business days, and registration must be renewed annually. Additional information about registration procedures http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf http://www.cdc.gov/od/pgo/funding/docs/FinancialReferenceGuide.pdf http://www.cdc.gov/od/pgo/funding/docs/FinancialReferenceGuide.pdf http://fedgov.dnb.com/webform/displayHomePage.do days, and registration must be renewed annually. Additional information about registration procedures may be found at www.SAM.gov.

c. Grants.gov: The first step in submitting an application online is registering your organization through www.grants.gov, the official HHS E-grant website. Registration information is located at the "Get Registered" option at www.grants.gov.

All applicant organizations must register with www.grants.gov. The one-time registration process usually takes not more than five days to complete. Applicants must start the registration process as early as possible.

2. Request Application Package Applicants may access the application package at www.grants.gov.

3. Application Package Applicants must download the SF-424, Application for Federal Assistance, package associated with this funding opportunity at www.grants.gov. If Internet access is not available, or if the online forms cannot be accessed, applicants may call the CDC PGO staff at 770-488-2700 or e-mail PGO PGOTIM@cdc.gov for assistance. Persons with hearing loss may access CDC telecommunications at TTY 1-888-232-6348.

4. Submission Dates and Times If the application is not submitted by the deadline published in the FOA, it will not be processed. PGO personnel will notify the applicant that their application did not meet the deadline. The applicant must receive pre-approval to submit a paper application (see Other Submission Requirements section for additional details). If the applicant is authorized to submit a paper application, it must be received by the deadline provided by PGO.

a. Letter of Intent Deadline (must be emailed or postmarked by) Due Date for Letter of Intent: 05/01/2015

b. Application Deadline Due Date for Applications: 05/20/2015, 11:59 p.m. U.S. Eastern Standard Time, at www.grants.gov. If Grants.gov is inoperable and cannot receive applications, and circumstances preclude advance notification of an extension, then applications must be submitted by the first business day on which grants.gov operations resume.

Date for Informational Conference Call: 04/13/2015

April 13, 2015 3pm-4pm Eastern…