CDC-RFA-DD20-2004.pdf

Centers for Disease Control and Prevention

National Center on Birth Defects and Developmental Disabilities

Public Health Surveillance for the Prevention of Complications of Bleeding Disorders

CDC-RFA-DD20-2004

Application Due Date: 05/11/2020

Public Health Surveillance for the Prevention of Complications of Bleeding Disorders

CDC-RFA-DD20-2004

TABLE OF CONTENTS

Part I. Overview Information A. Federal Agency Name B. Funding Opportunity Title C. Announcement Type D. Agency Funding Opportunity Number E. Assistance Listings (CFDA) Number F. Dates G. Executive Summary

Part II. Full Text A. Funding Opportunity Description B. Award Information C. Eligibility Information D. Application and Submission Information E. Review and Selection Process F. Award Administration Information G. Agency Contacts H. Other Information I. Glossary

Part I. Overview Information Applicants must go to the synopsis page of this announcement at www.grants.gov and click on the "Subscribe" button link to ensure they receive notifications of any changes to CDC-RFA- DD20-2004. 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) / Agency for Toxic Substances and Disease Registry (ATSDR) B. Notice of Funding Opportunity (NOFO) 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 activities supported by CDC. If research is proposed, the application will not be considered. For this purpose, research is defined at https ://www.gpo.gov/fdsys/pkg/CFR-2007-title42-vol1/pdf/CFR-2007-title42-vol1-sec52-2.pdf.

Guidance on how CDC interprets the definition of research in the context of public health can be found at https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html (See section 45 CFR 46.102(d)).

D. Agency Notice of Funding Opportunity Number:

CDC-RFA-DD20-2004

E. Assistance Listings (CFDA) Number:

93.080 F. Dates:

1. Due Date for Letter of Intent (LOI): 03/16/2020

2. Due Date for Applications: 05/11/2020, 11:59 p.m. U.S. Eastern

Standard Time, at www.grants.gov.

3. Date for Informational Conference Call:

3/09/2020 Scheduled for 3:00 pm - 4:00 pm, Eastern Standard Time.

Phone Number: (855) 644-0229 Conference ID Number: 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 NOFO is to build upon the work currently ongoing in the U.S. Hemophilia Treatment Center Network (USHTCN) under DD15-1507 to prevent and reduce the complications of bleeding disorders by supporting the collection, aggregation and use of data and specimens that https://www.grants.gov https://www.grants.gov https://www.gpo.gov/fdsys/pkg/CFR-2007-title42-vol1/pdf/CFR-2007-title42-vol1-sec52-2.pdf https://www.gpo.gov/fdsys/pkg/CFR-2007-title42-vol1/pdf/CFR-2007-title42-vol1-sec52-2.pdf https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html https://www.grants.gov are representative of the USHTCN for surveillance for inhibitors and other complications of bleeding disorders, including emerging issues. The recipient or recipients are required to collaborate with HTCs and are expected to build upon the structures, processes and instruments implemented under DD15-1507. The recipient or recipients 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 quality evaluation and improvement; and 5) disseminate information. The 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.

a. Eligible Applicants: Open Competition

b. NOFO Type: Cooperative Agreement

c. Approximate Number of Awards: 1 CDC will consider making up to three awards under this cooperative agreement to preserve geographic and demographic representativeness.

d. Total Period of Performance Funding: $21,500,000

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

f. Total Period of Performance Length: 5

g. Estimated Award Date: 08/31/2020

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 NOFO exists, leveraging other resources and related ongoing efforts to promote sustainability is strongly encouraged.

Part II. Full Text A. Funding Opportunity Description

Part II. Full Text

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. These bleeding disorders cause spontaneous or prolonged bleeding, leading to disabling joint disease, intracranial bleeding, miscarriage, bleeding during pregnancy and death. Historically, persons with bleeding disorders have also suffered infection with blood-borne viruses due to contaminated treatment products. About 20,000 people in the United States (US) (mostly males) have hemophilia, with healthcare costs approaching $3 billion annually. VWD occurs in about 1% of the population.

Patients with bleeding disorders are largely treated at specialized hemophilia treatment centers (HTCs) which provide comprehensive care. Since 1975, Congress has provided support for these centers through the Maternal and Child Health Bureau, Health Resources and Service Administration (HRSA) and the CDC. Currently, the federally funded HTC system comprises a network of 141 centers throughout the US and its territories (hereafter, "the US Hemophilia Treatment Center Network" or "USHTCN"). From January 2012 through September 2018, the USHTCN provided care to more than 24,000 patients with hemophilia, 20,000 with VWD and 12,000 with other bleeding disorder diagnoses.

Since the 1980s, CDC has collaborated with the HTCs of the USHTCN to reduce the complications of bleeding disorders and their treatment. Work from prior cooperative agreements has demonstrated that some complications related to joint disease have decreased over time. The proportion of patients on treatment to prevent bleeding episodes (prophylaxis) has increased. No new hepatitis or HIV infections from contaminated treatment products have been found.

However, the percentage of youth with severe hemophilia using prophylaxis varies widely across HTCs and evidence suggested other viruses may still be transmitted in plasma-derived treatment products. Bleeding disorder stakeholders have identified additional health indicators that should be monitored over time in order to protect the health of persons with bleeding disorders, including conditions associated with aging in the general population and inhibitors to clotting factor concentrates. An inhibitor is an antibody to factor which inhibits the action of the factor and decreases its treatment efficacy. Decreased treatment efficacy leads to increased hospitalizations for bleeding and higher healthcare costs. As many as one-third of patients with severe hemophilia A will develop an inhibitor. Additionally, hemophilia treatment is changing.

Non-clotting factor products, gene therapy and other new treatment products are changing the frequency and mode of hemophilia treatment. The effects of these new treatments on the hemophilia population need to be monitored to ensure continued progress towards eliminating complications of both the bleeding disorders themselves and their treatment.

This NOFO continues the work ongoing through DD15-1507 to reduce and prevent the complications of bleeding disorders by monitoring treatment and outcomes in order to a) increase knowledge and awareness of inhibitors and other complications, treatment practices and patterns;

b) monitor trends in these issues; c) identify potential disparities; d) identify high risk populations for interventions; e) assess gaps in data collection; and f) generate hypotheses for research on inhibitors and other complications. Additionally, this NOFO increases the priority placed on data quality and dissemination.

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

c. Healthy People 2030

BDBS-2030-1 (Proposed) Reduce the proportion of persons with severe hemophilia who have more than four joint bleeds per year.

BDBS-2030-D2 (Proposed, Developmental) Increase the proportion of persons with von Willebrand disease (VWD) seen in speciality care centers who were diagnosed by 21 years of age.

https://www.healthypeople.gov/

d. Other National Public Health Priorities and Strategies N/A

e. Relevant Work This NOFO 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 (DD11-1103/DD14- 1409/DD15-1507, Community Counts). Recipients are expected to build or model upon the structures, processes and instruments implemented under DD11-1103/DD14-1409/DD15-1507.

2. CDC Project Description

a. Approach

Bold indicates period of performance outcome.

CDC-RFA-DD20-2004 Logic Model: Public Health Surveillance for the Prevention of Complications of Bleeding Disorders Bold indicates period of performance outcome

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 multidisciplinary input on project content based on clinical practice and research expertise

4. Timely review of data proposals and analysis products to facilitate timely analysis and dissemination

Strategy 2: Data 1. HTCs contribute uniform

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

Reduce and prevent inhibitors and other complications of bleeding disorders https://www.cdc.gov/ncbddd/blooddisorders/udc/ https://www.cdc.gov/ncbddd/hemophilia/communitycounts/index.html collection and transfer

Strategy 3:

Specimen collection and transfer data on bleeding disorders complications to a pooled national dataset

2. At-risk patients receive regular inhibitor screening

3. At-risk patients receive regular screening for HCV and HIV

Strategy 4: Data quality evaluation and improvement

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

2. HTCs provide consistently accurate and appropriate data

Strategy 5:

Disseminate information

1. HTCs provided with data for continuous improvement of participation and data quality

2. Researchers and other stakeholders have access to a more comprehensive evidence base for the occurrence of inhibitors and other complications data collection

· generate hypotheses for research

i. Purpose This NOFO builds upon ongoing work to prevent and reduce complications of bleeding disorders through the collection, aggregation and use of data and specimens representative of USHTCN bleeding disorder patients for surveillance on inhibitors and other complications of bleeding disorders, including emerging issues. These data will be used to increase awareness of inhibitors and other complications; monitor trends; identify disparities and high-risk populations for interventions; assess gaps in data collection; generate hypotheses for research; and prevent complications of bleeding disorders.

ii. Outcomes Recipients are expected to achieve the following outcomes during the 5-year NOFO period of performance:

1. Data collection legally and financially enabled

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

3. HTCs provide multidisciplinary input on project content based on clinical practice and research expertise

4. Timely review of data proposals and analysis products to facilitate timely analysis and dissemination

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

6. At-risk patients receive regular inhibitor screening through submission of specimens to

CDC

7. At-risk patients receive regular screening for Hepatitis C Virus (HCV) and Human

Immunodeficiency Virus (HIV) through submission of specimens to CDC

8. HTCs provide consistently accurate and appropriate data

9. HTCs provided with data for continuous improvement of participation and data quality

10. Researchers and other stakeholders have access to a more comprehensive evidence base for the occurance of inhibitors and other complications

11. Researchers and other stakeholders monitor trends, identify potential disparities, identify high risk populations for interventions, and assess gaps in data collection

iii. Strategies and Activities Recipients 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 the USHTCN, including regional core centers and HTCs, as appropriate

Activity 2: Establish or maintain process for regular input from the USHTCN, including regional core centers and HTCs on implementation of project o Input on administrative, business, and implementation issues across regions o Input on clinical practice and scientific issues across regions

Strategy 2: Data collection and transfer Recipients must coordinate and facilitate data collection and transfer from HTCs to align with CDC data system and requirements for inclusion in a pooled national data set such that the number of patients represented in the HTC Population Profile data set (Activity 5) is maintained or increased and the number in the Registry (Activity 6) increases relative to the number enrolled at the close of September 2020. Additional information regarding the acceptance testing and data elements referred to in activities 1-4 below can be found in CDC-RFA-DD20-2004 Supporting Information.

Activity 1: Document secure, electronic data collection and transfer mechanism Activity 2: Submit sample data files to CDC for acceptance testing.

Activity 3: Develop data management plan

Activity 4: Submit timely and correct data files to CDC.

Activity 5: Coordinate timely collection and transmission of annual minimal patient-level data (HTC Population Profile) on all patients with eligible bleeding disorder diagnoses at HTCs

Activity 6: Coordinate enrollment of patients and timely collection and transmission of longitudinal, patient-level data (Registry), including seroconversion follow-up, at the HTCs

Activity 7: Coordinate timely collection and transmission of patient-level data on deaths of bleeding disorder patients at the HTCs (Mortality Reporting)

Strategy 3: Specimen collection and transfer from participants of Strategy 2, Activity 6 (longitudinal patient-level health indicator data/Registry)

Activity 1: Coordinate at HTCs the collection and transfer of plasma specimens from participants enrolled in Activity 6 of Strategy 2 to CDC for inhibitor testing and seroconversion follow-up

Activity 2: Coordinate at HTCs the collection and transfer of serum specimens from participants enrolled in Activity 6 of Strategy 2 to CDC for evaluation of treatment product complications and safety issues and seroconversion follow-up

Strategy 4: Data quality evaluation and improvement

Activity 1: Implement data quality checks to identify and correct data inaccuracies Activity 2: Develop and implement process to ensure collection of accurate data Activity 3: Develop and implement processes to ensure training of HTC staff on project processes and procedures Activity 4: Evaluate feasibility of implement point-of-data entry/submission logical validations within data collection system(s)

Strategy 5: Disseminate Information

Activity 1: Report on project progress and data quality activities to HTCs Activity 2: Facilitate development of web reports, abstracts, posters, surveillance reports, presentations, peer-reviewed manuscripts, and other materials Activity 3: Ensure that web reports, abstracts, posters, surveillance reports, presentations, peer-reviewed manuscripts, and other materials are disseminated to researchers, providers and other stakeholders

Activity 4: Develop a strategy to promote project findings and products to HTC staff and project participants

1. Collaborations

a. With other CDC programs and CDC-funded organizations:

Recipients 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. Recipients 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 not funded by CDC:

Recipients 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-DD20-2004 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).

CDC will consider making up to three awards under this cooperative agreement to preserve geographic and demographic representativeness. 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. Recipients must collaborate with USHTCN HTCs within the recipient's proposed geographic area of surveillance.

Applicants must provide documentation that HTCs have agreed to collaborate with the recipient 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.

Applicants must file the letters of support, name the file ?Letters of Support?, and upload it as a PDF file at www.grants.gov.

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. Inhibitor surveillance is a CDC priority; patients at risk for development of an inhibitor to factor VIII or factor IX are those with a diagnosis of hemophilia A, hemophilia B or type 3 VWD, therefore, these are considered high priority diagnoses for enrollment in the Registry [Strategy 2, Activity 6 (longitudinal patient-level health indicator data)]. Racial and ethnic minorities and persons initiating treatment with clotting factor concentrates, especially young children, are at a higher risk for inhibitor development and should be considered high priority for enrollment. Additionally, patients with any bleeding disorder diagnosis using new non-factor products and other novel treatments (including gene therapy) should be enrolled.

Applicants should describe the geographic catchment area and demographic make-up (diagnoses, gender, race, ethnicity, age: <2 years; 2-10 years; 11-19 years; 20-44 years; 45-64 years; 65+ years and older) of the patient population of the HTCs (in aggregate) with which it proposes to collaborate, as well as the percentage of all USHTCN bleeding disorder patients represented at its collaborating HTCs.

https://www.hemophilia.org/Researchers-Healthcare-Providers/Medical-and-Scientific-Advisory-Council-MASAC/MASAC-Recommendations/Standards-and-Criteria-for-the-Care-of-Persons-with-Congenital-Bleeding-Disorders https://www.hemophilia.org/Researchers-Healthcare-Providers/Medical-and-Scientific-Advisory-Council-MASAC/MASAC-Recommendations/Standards-and-Criteria-for-the-Care-of-Persons-with-Congenital-Bleeding-Disorders https://www.grants.gov/

a. Health Disparities Where such patients are represented in the patient population, applicants are encouraged to include people with disabilities; non-English speaking populations; lesbian, gay, bisexual, transgender, and questioning (LGBTQ) populations; people with limited health literacy; people from geographically underserved communities; or populations that may otherwise be overlooked by the program. Racial and ethnic minorities with a diagnosis of hemophilia A or B or type 3 VWD are a priority for enrollment in the Registry component; however, enrollment of these populations is encouraged for other diagnoses as well.

iv. Funding Strategy N/A

b. Evaluation and Performance Measurement

i. CDC Evaluation and Performance Measurement Strategy Evaluation and Performance Measurement help demonstrate program accomplishments and determine whether the NOFO strategies and activities were implemented as expected. Evaluation and Performance Measurement also tracks if the intended outcomes were achieved during the period of performance. This information is integral to help CDC keep NOFO recipients on track with implementation, to demonstrate the effectiveness of the NOFO on reaching outcomes, and to suggest ways to improve the program.

Evaluation and Performance Measurement will be approached through assessing process and outcome measures. Throughout the period of performance, CDC will work individually and collectively with recipients to track the implementation of recipient strategies and activities and assess progress in achieving NOFO outcomes. Process measures will inform CDC to what extent the recipient has implemented the activities as intended. Outcome measures will inform CDC if the recipient achieved the period of performance outcomes.

Process Measures

Strategy Activity Measure

Maintain a documented process for gathering input on administrative, business, and implementation issues across regions.

Codify, with key program partners, the purpose, process, and activities for gathering input on administrative, business, and implementation issues.

1) Establish collaborations with HTCs

Maintain a documented process for gathering input on clinical practice and scientific issues across regions.

Codify, with key program partners, the purpose, process, and activities for gathering input on clinical practice and scientific issues across regions.

Document secure, electronic data collection and transfer mechanism.

Submission of documentation. 2) Data collection and transfer

Submit sample data files to CDC for CDC receives data files with agreed-acceptance testing. upon content and format.

Develop data management plan. Submission of data management plan within first 6 months.

Submit timely and correct data files to

CDC.

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 agreed-upon by CDC and recipient

Coordinate timely collection and transmission of annual minimal patient-level data (HTC Population Profile) on all patients with eligible bleeding disorder diagnoses at HTCs.

Coordinate enrollment of patients and timely collection and transmission of longitudinal, patient-level data (Registry), including seroconversion follow-up, at the HTCs.

Coordinate timely collection and transmission of patient-level data on deaths of bleeding disorder patients at the HTCs (Mortality Reporting)

Percentage of HTCs submitting timely data from Activities 5-7

Timely: Percent of initial submissions made within the agreed-upon timeframe

Percent increase in timely submission of all indicated items (as compared to historical/ baseline).

3) Specimen collection and transfer

Coordinate at HTCs the collection and transfer of plasma specimens from participants enrolled in Activity 6 of Strategy 2 to CDC for inhibitor testing and seroconversion follow-up Coordinate at HTCs the collection and transfer of serum specimens from participants enrolled in Activity 6 of Strategy 2 to CDC for evaluation of treatment product complications and safety issues and seroconversion follow-up

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-DD20- 2004 Supporting Information) and proper shipping

4) Data quality Implement data quality checks to identify Percent of data validation queries and correct data inaccuracies resolved in a timely manner.

Percent of HTCs submitting data validation responses that lead to resolution within the agreed-upon timeframe.

Develop and implement process to ensure collection of accurate data

Percent decrease in errors among identified problem elements upon initial data quality check (as compared to historical/baseline error rate).

Evaluate feasibility of implementing point-of-data entry/submission [logical] validations within data collection system(s)

Submission of documentation of existing logical validations and what changes to the system would be required, if any, in order to implement cross item and cross form checks, and other potential validations.

evaluation and improvement

Develop and implement process to ensure training of HTC staff on project processes and procedures

Submission of training plan including identification of new HTC project staff, onboarding of new HTC project staff, regular refresher training for all relevant HTC project staff, and regular review of expectations and documented project procedures with HTC project staff

Report on project progress and data quality activities to HTCs

Evidence of at least semi-annual reports to the HTCs regarding results of data quality activities and project progress

Facilitate development of web reports, abstracts, posters, surveillance reports, presentations, peer-reviewed manuscripts, and other materials

Number of web reports, abstracts, posters, surveillance reports, presentations, peer-reviewed manuscripts, and other materials produced or under development each budget year

Ensure that web reports, abstracts, posters, surveillance reports, presentations, peer-reviewed manuscripts, and other materials are disseminated to researchers, providers and other stakeholders

Number of web reports, abstracts, posters, surveillance reports, presentations, peer-reviewed manuscripts, and other materials posted, published, or presented each budget year

5) Disseminate information

Develop a strategy to promote project findings and products to HTC staff and

Targeted promotion plan for each of the products project participants

Outcome Evaluation Measures

Outcomes Measures

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.

HTCs provide multidisciplinary input on project content based on clinical practice and research expertise

Evidence of implementation of process such as call schedules, agendas, minutes, communications, etc.

Timely review of data proposals and analysis products to facilitate timely analysis and dissemination

Completion of proposal review process within the agreed upon timeframe

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

Number of HTCs submitting timely annual minimal patient-level data of good quality Number of HTCs submitting timely longitudinal health indicator data of good quality Number of HTCs submitting timely mortality data of good quality

At-risk patients receive regular inhibitor screening Number of participants that qualify for inhibitor screening for whom an appropriate specimen is submitted when indicated

At-risk patients receive regular screening for HCV and HIV

Number of participants that qualify for viral screening for whom an appropriate specimen is submitted when indicated

HTCs provide consistently accurate and appropriate data

Decrease in the number of validation queries from baseline across all form types and all HTCs

Researchers and other stakeholders have access to a more comprehensive evidence base for the occurrence of inhibitors and other complications

Dissemination of at least one public information product per year targeting participants and other consumers or consumer-based organizations Dissemination of at least one public information product per year targeting researchers, providers or policy makers

Researchers, providers and other stakeholders:

monitor trends

Documentation of discussion and review with CDC, the USHTCN and other partners (if applicable) of trends, disparities, high risk identify potential disparities identify high risk populations for interventions assess gaps in data collection populations, potential interventions and gaps in data collection on inhibitors and other complications of bleeding disorders

Since this NOFO involves the generation or collection of public health data, a Data Management Plan is required for this NOFO. At a minimum, the Data Management Plan (DMP) must include:

A description of the data to be collected or generated in the proposed project;

The standards to be used for the collected or generated data;

Mechanisms for, or limitations to, providing access to the data, including a description for the provisions for the protection of privacy, confidentiality, security, and intellectual property, or other rights;

Statement of the use of data standards that ensure all documentation that describes the method of collection, what the data represent, and

Because the data are being submitted to CDC, CDC will take responsibility for plans for archiving and long-term preservation of the data in compliance with federal law and CDC policies, or explaining why long-term preservation and access are not justified. If all of this information is not available when applying, applicants should include a DMP that is as complete as possible. The DMP may be submitted as a checklist, paragraph, or other format. Currently, HHS/CDC does not have a standardized DMP template or checklist. However, below are DMP examples to help guide applicants as they develop their DMP:

Stanford University DMPTool National Network of Libraries of Medicine Data Management Planning Tool

CDC will work with recipients on operationalizing and further defining each performance measure, and guidance will be provided prior to the first report. Reports will be provided to CDC, and CDC will use the reports to assess recipient program improvements and respond to broader technical assistance needs. All evaluation findings produced by the recipients will contribute to:

(1) continuous improvement of quality and effectiveness of the program, (2) the evidence base of bleeding disorder surveillance, and (3) future funding opportunities supported by CDC.

CDC will review the work plan and evaluation and performance measurement plan and meet with the recipient to finalize them. Key program partners may include applicant's key program staff, USHTCN regional core center staff, HTC staff and other key partners (for example, federal agencies other than CDC, consumer-based organizations, professional organizations, etc.), as applicable.

ii. Applicant Evaluation and Performance Measurement Plan Applicants must provide an evaluation and performance measurement plan that demonstrates how the recipient will fulfill the requirements described in the CDC Evaluation and Performance Measurement and Project Description sections of this NOFO. At a minimum, the plan must https://library.stanford.edu/research/data-management-services/data-management-plans/dmptool https://nnlm.gov/data/thesaurus/data-management-planning-tool-dmptool describe:

How applicant will collect the performance measures, respond to the evaluation questions, and use evaluation findings for continuous program quality improvement.

How key program partners will participate in the evaluation and performance measurement planning processes.

Available data sources, feasibility of collecting appropriate evaluation and performance data, and other relevant data information (e.g., performance measures proposed by the applicant)

Plans for updating the Data Management Plan (DMP), if applicable, for accuracy throughout the lifecycle of the project. The DMP should provide a description of the data that will be produced using these NOFO funds; access to data; data standards ensuring released data have documentation describing methods of collection, what the data represent, and data limitations; and archival and long-term data preservation plans. For more information about CDC’s policy on the DMP, see https://www.cdc.gov/grants/additionalrequirements/ar-25.html.

Where the applicant chooses to, or is expected to, take on specific evaluation studies, they should be directed to:

Describe the type of evaluations (i.e., process, outcome, or both).

Describe key evaluation questions to be addressed by these evaluations.

Describe other information (e.g., measures, data sources).

Recipients will be required to submit a more detailed Evaluation and Performance Measurement plan, including a DMP, if applicable, within the first 6 months of award, as described in the Reporting Section of this NOFO.

c. Organizational Capacity of Recipients to Implement the Approach Applicants must have the organizational structure and capacity to execute the CDC strategies and activities and meet outcomes throughout the period of performance. 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.

https://www.cdc.gov/grants/additionalrequirements/ar-25.html

Applicants must specify which regions and 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 NOFO.

Applicants must provide a staffing plan, describing in detail their own resources and staffing levels for this project, as well as their project management structure, including an organizational chart and resumes/CVs of key project staff. Applicants must name this file "CVs/Resumes" or "Organizational Charts" and upload it at www.grants.gov.

Applicants must describe their ability to manage the required procurement efforts, including the ability to write and award contracts in accordance with applicable grants regulations.

Applicants must provide regional data collection projections for the first year of the project for Strategy 2, Activity 6 (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 5 and 7 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. Applicants should also figure in effort to be spent on ensuring quality data when making these projections.

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 via a secure, electronic mechanism, including how unique participant identifiers will be assigned and linked to current identifiers, how data will be collected at the HTCs (including how uniform data abstraction and adherence to skip patterns will be ensured), the file type to be used for each data form, and the method and frequency of transmission of data to CDC The applicant must describe the application that they intend to use for data submission and transfer and outline the estimated amount of time before the application and associated documentation can be used for this project.

Applicants must demonstrate that they have a financial management system that will allow proper funds management and segregation of funds by program, and meet the requirements as stated in the Uniform Administrative Requirements, Cost Principles, and Audit Requirements for HHS Awards: CFR 75.302. The financial system should permit the preparation of reports required by general and program-specific terms and conditions;

and the tracing of funds to a level of expenditure adequate to establish that such funds have been used according to the federal statutes, regulations, and terms and conditions of the federal award.

d. Work Plan Applicants must submit a detailed work plan for the first year of the project and a high-level work plan for subsequent years (years 2-5). The work plan should describe how the applicant plans to implement all of the required strategies and activities to achieve NOFO outcomes. A sample work https://www.ecfr.gov/cgi-bin/text-idx?node=pt45.1.75#se45.1.75_1302 https://www.ecfr.gov/cgi-bin/text-idx?node=pt45.1.75#se45.1.75_1302 plan format is presented below to show how a traditional work plan aligns with the logical model and narrative. A separate table should be included in the work plan for each of the outcomes that will be addressed during the first year period of performance. If a particular activity leads to multiple outcomes, it should be described under each outcome measure. No specific work plan format is required, as long as it is clear how the components in the work plan crosswalk to the strategies and activities, outcomes, and evaluation and performance measures presented in the logic model and the narrative sections of the NOFO; however, all work plans must contain all of the elements shown in the example (outcome(s), outcome measure(s), etc).

Example Work Plan Table

Period of Performance Outcome:

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

Outcome Measure(s):

Number of HTCs submitting timely annual minimal patient-level data of good quality Number of HTCs submitting timely longitudinal health indicator data of good quality Number of HTCs submitting timely mortality data of good quality

Strategies and Activities

Process Measure [from Evaluation and Performance Measurement section]

Responsible Position/Party Completion Date

1. Strategy: Data collection and transfer Activity:Document secure, electronic data collection and transfer mechanism.

Submission of documentation

(applicant to fill in appropriate personnel)

(applicant to fill in appropriate date)

2. Strategy: Data collection and transfer Activity:Submit sample data files to CDC for acceptance testing.

CDC receives data files with appropriate content and format

(applicant to fill in appropriate personnel)

(applicant to fill in appropriate date)

3. Strategy: Data collection and transfer Activity:Develop data management

Submission of data management plan within first 6 months

(applicant to fill in appropriate personnel)

(applicant to fill in appropriate date) plan.

4. Strategy: Data collection and transfer Activity:Submit timely and correct data files to CDC.

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

(applicant to fill in appropriate personnel)

(applicant to fill in appropriate date)

5. Strategy: Data collection and transfer Activity:

a.) Coordinate timely collection and transmission of annual minimal patient-level data (HTC Population Profile) on all patients with eligible bleeding disorder diagnoses at HTCs.

b.) Coordinate enrollment of patients and timely collection and transmission of longitudinal, patient-level data (Registry), including seroconversion follow-up, at the HTCs.

c.) Coordinate timely

Percentage of HTCs submitting timely data from Activities 5-7

- Timely: Percent of initial submissions made within the agreed-upon timeframe Percent increase in timely submission of all indicated items (as compared to historical/ baseline)

(applicant to fill in appropriate personnel)

(applicant to fill in appropriate date) collection and transmission of patient-level data on deaths of bleeding disorder patients at the HTCs (Mortality Reporting)

6. Strategy: Data quality evaluation and improvement Activity: Implement data quality checks to identify and correct data inaccuracies

Percent of data validation queries resolved in a timely manner.

Percent of HTCs submitting data validation responses that lead to resolution within the agreed-upon timeframe.

(applicant to fill in appropriate personnel)

(applicant to fill in appropriate date)

7. Strategy: Data quality evaluation and improvement Activity:Develop and implement process to ensure collection of accurate data

Percent decrease in errors among identified problem elements upon initial data quality check (as compared to historical/baseline error rate).

(applicant to fill in appropriate personnel)

(applicant to fill in appropriate date)

8. Strategy: Data quality evaluation

Submission of documentation of

(applicant to fill in appropriate (applicant to fill in and improvement Activity: Evaluate feasibility of implementing point-of-data entry/submission [logical] validations within data collection system(s) existing logical validations and what changes to the system would be required, if any, in order to implement cross item and cross form checks, and other potential validations.

personnel) appropriate date)

e. CDC Monitoring and Accountability Approach Monitoring activities include routine and ongoing communication between CDC and recipients, site visits, and recipient 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 recipient progress in achieving the desired outcomes.

Ensuring the adequacy of recipient 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 deemed necessary to monitor the award:

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

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

Working with recipients 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.

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 recipients.

CDC's priority performance measures to track recipient progress and determine whether the project is achieving NOFO outcomes are:

Strategy 1: Completion of proposal review process within the agreed upon timeframe.

Strategy 2: Timely receipt of correct data files at CDC; Percentage of HTCs submitting timely data from Activities 5-7 Strategy 3: Percent of specimens prepared and shipped according to agreed-upon protocols.

Strategy 4: Percent of HTCs submitting data validation responses that lead to resolution within the agreed-upon timeframe. Percent decrease in errors among identified problem elements upon initial data quality check (as compared to historical/baseline error rate). Submission of documentation of existing logical validations and what changes to the system would be required, if any, in order to implement cross item and cross form checks, and other potential validations.

(process) Strategy 5: Number of web reports, abstracts, posters, surveillance reports, presentations, peer-reviewed manuscripts, and other materials posted, published, or presented each budget year;

dissemination of at least one public information product per year targeting participants and other consumers or consumer based organizations; dissemination of at least one public information product per year targeting researchers, providers or policy-makers CDC will meet with recipient(s) to review progress and provide feedback quarterly or as mutually agreed with recipient(s).

CDC and the recipient(s) will have 6-months after award to finalize the performance monitoring and accountability approach.

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

COOPERATIVE AGREEMENTS)

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

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

2. Provide technical support for data cleaning;

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

4. Submit Office of Management and Budget (OMB) Paperwork Reduction Act (PRA)

Information Collection Clearance package 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 recipient(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 recipient(s) to disseminate findings;

10. Coordinate information sharing between recipients (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 Recipients Section.

2. Award Mechanism: U27 Surveillance of Complications of Hemophilia Cooperative Agreements

3. Fiscal Year: 2020

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

5. Approximate Period of Performance Funding: $21,500,000

This amount is subject to the availability of funds.

Estimated Total Funding: $21,500,000

6. Approximate Period of Performance Length: 5 year(s)

7. Expected Number of Awards: 1 CDC will consider making up to three awards under this cooperative agreement to preserve geographic and demographic representativeness.

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

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

This amount is subject to the availability of funds.

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

11. Estimated Award Date: 08/31/2020

12. Budget Period Length: 12 month(s)

Throughout the project period, CDC will continue the award based on the availability of funds, the evidence of satisfactory progress by the recipient (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.