Attachment_1 _TTIMS_DDCC_SOW.docx

Donation Database Coordinating Center (DDCC)

Draft Statement of Work (SOW) June 18, 2015

1.0 Introduction

1.1 Background

The U.S. Food and Drug Administration (FDA) is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, tobacco products, our nation’s food supply, cosmetics and products that emit radiation. The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines, devices, products, and foods more effective, safer, and more affordable; and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health.

During its July 2, 2013 meeting, the Department of Health and Human Services (DHHS) Blood, Organ, and Tissue Senior Executive Council (BOTSEC), which includes representation from Department of Health and Human Services, Office of the Assistant Secretary of Health (DHHS/OASH), Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), Centers for Medicare & Medicaid Services (CMS), Health Resources Services Administration (HRSA), Food and Drug Administration (FDA), HHS-Assistant Secretary for Planning and Evaluation (ASPE), HHS-Assistant Secretary for Preparedness and Response (ASPR), and Agency for Healthcare Research and Quality (AHRQ), unanimously voted to enhance monitoring of Transfusion-Transmissible Infections (TTIs) in the US. The TTIMS will build on the NIH National Heart Lung Blood Institute’s REDS-II Transfusion-Transmitted Retrovirus Study (REDS) procedures established for centralization of proprietary blood center operational data, successful coordination of standardized data definitions, collection, analysis, and reporting of baseline epidemiologic and risk factor data for 50 % or more of the United States (US) donor base. At present, no single comprehensive blood donor or recipient surveillance system exists in the United States to monitor TTIs, such as Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), and Hepatitis C (HCV) in such a large donor population. Subsequently, the external Federal DHHS Advisory Committee on Blood and Tissue Safety and Availability (ACBTSA) met in December 2013 and concurred with the BOTSEC and recommended that DHHS establish “an ongoing, integrated, coordinated, and nationally representative U.S. transfusion transmissible infections monitoring system.”

The FDA requires the establishment of a Transfusion-Transmissible Infections Monitoring System (TTIMS) through two separate complimentary contracts consisting of an integrated, comprehensive Donor Donation Coordinating Center (DDCC) system, the subject of this statement of work, and a Laboratory and Risk Factor Coordinating Center (LRCC) to provide in-depth laboratory assessment of donors who have confirmed markers for TTIs of interest.

The TTIMS program will build on the infrastructure and initial consensus infectious disease testing classification algorithms that were developed for the REDS-II Transfusion Transmitted Viral Infection (TTVI) Marker Prevalence and Risk Factor Study. The program will support the collection of integrated risk factor data and disease marker surveillance information across different blood collection organizations. Furthermore, systematically collected and combined data are critical for this national surveillance effort.

This effort requires close coordination between the DDCC and LRCC to ensure timely confidential data transfers between the organizations, and ensure integration of activities to achieve the aims of the TTIMS project. Blood collection organizations interested in participating in TTIMS shall agree to participate in both the LRCC and DDCC data collection efforts. In particular blood collection organizations must share relevant donor data compiled by their organization as well as blood specimens with both Contractors for compilation and evaluation of TTI risks and identify, survey, characterize, and provide risk factor and other data on HIV and incident HCV and HBV blood donors.

1.2 TTIMS DDCC Governance Framework

Oversight and governance of TTIMS will be provided by the US FDA Contracting Officer’s Representative (COR) within the CBER Office of Biostatistics and Epidemiology. The Contractor shall establish the TTIMS Steering/Monitoring Committee (Committee) within 30 calendar days of contract award, to work with FDA and CDC representatives (including statisticians) to study historical trends. Data analyses and reports provided by the Contractor will be reviewed by the COR and Committee members comprised of the Principal Investigators (PI), and Co-PI representing participating blood center organizations, DDCC and LRCC personnel, and experts from stakeholder Department of Health and Human Services (DHHS) Agencies, including, FDA, NIH, and CDC.

The Committee shall meet no less than every month by teleconference and in person at least twice a year. Unforeseen circumstances may arise requiring additional communication which would likely be by teleconference.

If necessary, the COR will form smaller subcommittees and executive subcommittees to address issue specific priorities. The Contractor shall report back with findings and recommendations for discussion and any necessary action by the Committee/subcommittees. The Government Officials on the Committee (NHLBI, FDA and CDC) will provide necessary information to the appropriate internal Federal Agencies. The Contractor shall receive feedback on the reports they generate, as well as any weaknesses and make recommended changes.

2.0 Objectives

The TTIMS project purpose is to establish an integrated, comprehensive US Blood Donor surveillance system to monitor TTIs such as HIV, HBV, and HCV including characterization of TTI marker risks in the US blood supply with monitoring of temporal, geographic, and demographic trends to and provide a framework for evaluating the effect of a new intervention (such as implementation of a new deferral policy) on TTI risks and blood donor risk factors. TTIMs is expected to fill a significant gap in current public health blood donor surveillance efforts and to serve as a resource for additional investigations. Specifically the primary objective of this Contract is to:

· Establish a Diagnostic Donor Coordinating Center (DDCC) in the United States to monitor HIV, HBV, and HCV that will function to:

a. Monitor and characterize infections (HIV, HBV, and HCV) identified at participating blood collection organizations and assess prevalence and incidence rates, overall and by demographic and geographic subgroups.

b. Evaluate temporal, demographic, and geographic trends in incidence and prevalence rates for these viruses over the period of the project.

c. Evaluate and monitor risk factor characteristics of donors whose donations are confirmed positive for HIV or recently acquired HBV or HCV.

d. Integrate risk factor data and disease marker surveillance information across different blood collection organizations

e. Collect and compile bio-specimens and donation datasets from TTI-positive donors in repositories to enable additional researchers to compile donation datasets

f. Serve as a resource to the scientific community by enabling collaborations and investigations into additional research questions The contractor shall be required to interface with FDA staff in multiple locations throughout the Washington, DC metropolitan area. All CBER business staff are located at FDA’s White Oak campus in Silver Spring, MD. Travel outside the DC area may be needed for the 2 site visits

3.0 Task Description(s)

The following tasks constitute the performance work expectations for DDCC support.

Establish a Diagnostic Donor Coordinating Center (DDCC) The Contractor shall identify, recruit, and manage TTIMS blood center participants in sufficient volume to establish an allogeneic blood donation test result and demographic database representing 50% or more of the U.S mainland allogeneic volunteer blood collections within 30 calendar days of contract award. The Contractor shall provide a Blood Donor Center Enrollee Report and de-identified data to the FDA COR. Furthermore, the Contractor shall lead the donation database effort including the identification and evaluation of HIV and incident hepatitis-infected blood donor efforts.

a. The Contractor shall collect blood donor datasets and corresponding donor demographic data including age, gender, and race as required to achieve overall program objectives (i.e. 50% or more of US blood donors). Additionally, the Contractor shall provide screening and supplemental/confirmatory test results for all allogeneic blood donations collected.

b. The Contractor shall work collaboratively with the Committee to develop and finalize both the overall TTIMS project protocol within two months of contract award and a Manual of Operations (MOP) within three months of contract award by providing technical expertise in the areas of blood banking and transfusion medicine, infectious disease, databases/datasets management, study design and analytical/bio-statistical approaches including incidence and prevalence estimation.

i. The MOP shall describe in detail procedures, timeframes, and frequencies of performance for the TTIMS project and shall be approved by the COR prior to implementation. At a minimum, the overall MOP shall address governance; coordination; communication; identification of TTI-positive donors and recall procedures; survey development and administration; all laboratory procedures; bio-specimen collection, shipping, and storage; data collection, management/tracking, consensus definitions, security, transfer and sharing considerations; TTI risk and risk factor monitoring and associated trigger thresholds and resulting investigation procedures; training and site visit procedures; statistical and analytical plans for all data reports, and analyses; presentations, reports, and publications policy; human subject considerations; and processes to obtain all necessary administrative/regulatory clearances including applicable Institutional Review Boards (IRBs), and Office of Management and Budget (OMB).

c. The Contractor shall assign a unique Identification (ID) number to accompany the data files transmitted to the LRCC, and other stakeholders for each test positive donor, allowing the donor to be longitudinally followed and individual donations and components identified in the databases to be maintained by both the DDCC and LRCC.

i. The Contractor shall securely handle, store and maintain the link between the unique study donor ID and the donor identification information to allow the LRCC to contact the donor for appropriate follow-up.

Table 1 Task 3.1 Deliverables

Perform Data Collection and Data Management The Contractor shall develop and implement secure and robust data collection, tracking, management, and storage for TTI test results, demographic, first-time/repeat status, and other blood donor/donation data from participating blood collection centers.

The Contractor shall provide evidence of availability of electronic medical record data capture system(s) that can be accessed for study purposes. Additionally, the Contractor shall provide all necessary and relevant data management, tracking procedures, and tools to the participating blood collection organizations.

The Contractor shall provide datasets (in formats and according to timeframes delineated in the MOP) and bio-specimens to the LRCC that include at a minimum:

a. Screening and supplemental/confirmatory test results for all allogeneic blood donations collected, as well as corresponding donor demographic data that includes age, gender, and race. Donor/donation data shall be as comprehensive as possible to achieve overall program objectives;

b. Managing data relevant to evaluation of risk factors in TTI-positive donors per specified format, as coordinating follow-up evaluations;

c. Assigning and securely storing and handling a unique Identification (ID) number to accompany data files transmitted to the LRCC, the COR, and Committee members, for each test positive donor, allowing donors to be longitudinally followed and individual donations and components identified in the databases maintained by the DDCC and LRCC;

d. Collaborate/coordinate with the LRCC to ensure appropriate data transfers and cross-talk between datasets.

e. Collect and ship bio-specimens to the LRCC and coordinate with the LRCC to manage all data relevant to the evaluation of risk factors in TTI-positive donors as well as follow-up evaluations.

Table 2 Task 3.2 Deliverables Perform Data Analysis and Reporting The Contractor shall complete all TTI relevant analyses, to include:

a. Calculate blood donor marker prevalence and incidence with 95% Confidence Interval (CI) for HIV, HBV, and HCV for TTIMS sites. HIV incidence estimates shall be determined based on both a window period (inter-donation interval model for seroconverting repeat donors, on validated HIV Nucleic Acid Test (NAT) only observations and upon validation for HIV "recency" testing (provided by the LRCC) as appropriate.

b. Provide TTI prevalence and incidence estimates (when available) with 95% CI; stratified by demographic, first-time/repeat status, geographic, and temporal variables.

c. Provide estimates of residual risk (and 95% CI) for HIV, HBV, and HCV for the US blood supply on an annual basis.

d. Provide well-characterized TTI donor/donation data to the LRCC to permit analysis of TTI donor data stratified by donor risk factors.

e. Contribute independent hypotheses for analysis of study data.

f. Provide a monthly list of all HIV, HBV, and HCV marker positive donations, together with information on the date of the donation (day/month/year), the type of donation (if other than allogeneic), the procedure (apheresis platelet, whole blood, Double Red Blood Cell (RBC) apheresis, etc.), screening and supplemental/confirmatory tests results (including follow-up testing and HIV recency testing), final TTI confirmatory status interpretation, incidence vs. prevalence status, age, gender, race, and geographic indicator.

g. Provide corresponding donation denominator data including total number of donations collected per month by each blood collection organization broken down by the type of donation (if other than allogeneic donation data are collected), the procedure (apheresis platelet, whole blood, RBC apheresis, etc.), age, gender, race and geographic indicator.

i. Number of incident HIV infections per month

ii. Number of incident HCV infections per month

iii. Number of incident HBV infections per month

iv. Number of prevalent HIV infections per month

v. Number of prevalent HCV infections per month

vi. Number of prevalent HBV infections per month

vii. Incidence rates and 95% CI for HIV-1/HIV-2, HCV, HBV

viii. Per month, overall and stratified by gender

ix. Per year, overall and stratified by type of donation (if other than allogeneic donation data are collected), the procedure (apheresis platelet, whole blood, 2RBC apheresis, etc.), age, gender, race, and geographic indicator.

a) Prepare and submit recurring technical progress reports containing descriptive information about the activities undertaken during the reporting period and will require information about planned activities for future reporting periods. The submission frequency is expected to be on a quarterly basis, but is subject to change as trends develop.

b) Prepare and submit semiannual (every six (6) months) Progress Reports summarizing all work results for the period covered in sufficient detail to comprehensively explain the results achieved. The report shall be in letter form (minimum 2-3 pages) and include progress for the six month period, problems encountered during the six month period, goals met or missed, a summary of activities planned for the next six months, and reports / abstracts / presentations / manuscripts in progress, submitted or published.

c) Prepare an Annual Technical Report summarizing all work results performed. Specifically, the report shall include:

i. Face page to include contract number, title, period of performance being reported, Contractor's name and address, telephone and facsimile numbers, and date of submission.

ii. An executive summary, to include:

· A statement of intended work for the reporting period

· A brief overview of the work that was completed for the reporting period; any problems (technical or financial) that occurred and their resolution or status;

· Advancements made in relation to any of the technical tasks set forth in the Statement of Work

· A full description of data pertaining to, work performed during the reporting period, materials and methods pertaining to the work, relationship between the accomplishments made relative to goals and tasks of the Statement of Work, problems encountered and resolution. If applicable, full disclosure of any efforts to transfer the technology or receipt of support from outside entities interested in future access, partnering, or license to the developing technologies.

d) Prepare a Final Technical Report consisting of a description of work performed and results obtained for the entire contract period of performance in sufficient detail to describe comprehensively the results achieved.

e) Prepare published or unpublished abstracts, presentations, reports, and manuscripts derived from analyses under the contract.

(Please reference the next page)

Table 3 Task 3.3 Deliverables

Communication and Outreach

3.4.1. Participate in TTIMs Committees and Subcommittees

The Contractor shall act as a member of the TTIMS Committee and any assigned subcommittees. Moreover, the contractor shall provide regular updates on the work being accomplished to the Committee and other identified stakeholders. The Contractor shall establish and serve on a TTIMS Steering/Monitoring Committee (Committee) within 30 calendar days of contract award. The Contractor shall meet with FDA, NIH, and CDC representatives (including statisticians), donor organizations and the LRCC Principal Investigator (PI) monthly. The Contractor shall be responsible for leading discussions, participating in discussions, contributing questions and answers; raising and addressing issues, risks and concerns; developing and giving presentations, and other active oral and written communications. The Contractor shall prepare meeting agendas, minutes, and action items and circulate to the Committee in a timely manner.

The Contractor’s Principal Investigator (PI) shall attend face-to-face semi-annual Committee meetings located at Silver Spring, Maryland (1-day duration each) with the first meeting conducted within two months of contract award. Moreover, the Contractor’s Principal Investigator (PI) shall attend all Committee and subcommittee conference calls, at least once per month for the duration of the contract period of performance. The Contractor shall coordinate, schedule, and provide logistical support for Committee/Subcommittee meetings / conference calls.

3.4.2. Quality Control and Site Visits

The Contractor shall work collaboratively with the COR to assess, recommend, and document the practices, training needs, provide training as applicable, and conduct a minimum of two (2) site visits to address and remedy issues encountered with each participating blood collection organizations relevant to the database component of the TTIMS project. The Contractor shall develop a donor site visit schedule and training materials that will ensure quality and consistency of the collective data and reports.

3.4.3. External Collaborations

The Contractor shall collaborate with other Government Agencies and/or other individual blood organizations. All external collaborations and investigations will be approved by the CBER COR and/or Committee. The purpose of these collaborations will be to use existing TTIMS data or resources to address additional research questions.

Table 4 Task 3.4 Meetings

(Please reference the next page)

Table 5 Task 3.4 Deliverables

Project/Contract Management

3.5.1. Facilities

The Contractor shall provide facilities and equipment necessary to work with infectious materials, in order to accomplish the requirements as specified in the task areas 3.1-3.4. Specifically, the Contractor shall provide facilities and equipment (i.e. BSL-3 facility) to complete biohazard containment procedures, which is required when working with infectious materials. Additionally the Contractor shall provide the capacities to store biological/infectious materials and specimens at -70 C. Lastly, the Contractor shall ensure that electronic data is captured, retained and protected for future study purposes.

3.5.2. Project Meetings and Status Reporting

The Contractor shall provide project/contract management to ensure that contracted tasks stay on track and milestones, performance measures, deliverables and work products are met.

The Contractor shall participate in a kickoff meeting within 10 calendar days of contract award. The purpose of the kickoff meeting is to introduce the contractor staff to the Government and discuss the contractor’s approach to meeting the requirements of the PWS.

The Contractor shall deliver a Monthly Status Report (MSR) to the COR on the 10th business day of each month following the end of the previous calendar month. At a minimum the MSR shall contain the following information:

a. An overview of work completed, in progress, and planned for each task.

b. Identification of problem areas with recommended remedial actions.

c. Challenges, issues, and risks

3.5.3. Quality Control

The Contractor shall deliver high quality data and information and obtained following FDA Statute, Guidance and Good Manufacturing Processes (GMP’s), required of all licensed blood collection organizations operating within the United States and high quality written materials (technical documents, analyses, reports, etc.). See Appendix A, Quality Assurance Surveillance Plan (QASP) for performance standard matrix.

Comprehensive, clear analysis of trends and their effects in order to provide strategic profiles and advice to senior management on suitable policies and the effects of policy decisions and new regulations.

a. Information shall reflect state-of-the-industry practices and current applicable regulatory requirements.

b. The Contractor shall take the lead in developing documents and shall incorporate a high level of quality assurance and responsiveness.

c. The Contractor shall not receive more than two customer complaints regarding documents prepared within any twelve-month period of performance.

d. Reports and technical documents shall be delivered within the time frame specified with minimal errors and need for corrections.

e. The Contract shall ensure the following:

· That its staff have the requisite subject matter expertise and skill sets 100% of Key Personnel shall be on boarded within 30-calendar days of award

In addition, the Contractor shall be proactive in informing the designated CBER COR of any issues, problems and recommendations that shall be addressed in order for the overall effective accomplishment of contract goals and deliverables. Recommendations for actions that need to be taken by FDA staff, or other Contractors shall be clearly defined and communicated to the responsible party and the FDA, and have identified dates for completion.

3.5.4. Transition Out

A smooth and orderly transition-out between the incumbent Contractor and the successor Contractor or Government is necessary to ensure minimum disruption to vital FDA business. The Contractor shall submit and execute a Transition-Out plan to ensure business continuity for the FDA in the event that a new Contractor is chosen. At a minimum, this Transition-out plan will include the following:

a. Transition-Out Plan and Schedule

b. Inventory of documentation to be turned over

c. Submission of knowledge transfer documentation to include current and up-to-date Standard Operating Procedures

d. Participate in all transition-in activities with successor Contractor

e. Provide “shadowing” and participate in knowledge transfer meetings and opportunities to facilitate the transfer of information, processes, and data needed to continue the services being performed by the Contractor

f. Identify, track and discuss with the Government any known problems, risks or issues associated with the transition – Deliverables, Inspection and Acceptance

Table 6 Task 3.5 Meetings

Table 7 Task 3.5 Deliverables

4.0 Contract Constraints

The following constraints are applicable to this contract

a. The Contractor shall ensure that all appropriate administrative and regulatory approvals are obtained as described in the MOP by any participating blood collection organizations before TTIMS data collection begins. These include but are not limited to those that address human subject considerations; and clearances including applicable Institutional Review Boards (IRBs), and Office of Management and Budget (OMB).

b. The identity of the blood donor shall not be provided to the Committee.

c. Interim data used in technical progress reports and other reports developed for the purpose of study monitoring and shall not be released publicly. Premature release of such data could result in interpretations that prove to be unreliable or invalid once the study is completed and the full context for the data is known and lead the public and medical practitioners to pursue inappropriate measures.

d. Legend for Technical Progress Reports Containing Interim Study Data

· The Contractor shall incorporate the following legend on the cover of technical progress reports and reports containing interim study data that are prepared for internal and confidential use by the Committee or other Committees such as the Blood Product Advisory Committee or the Advisory Committee on Blood & Tissue Safety & Availability:

· "The data, if any, contained in this report/deliverable are preliminary and may contain un-validated findings. These data are not intended for public use. Public use of these data could create erroneous conclusions which, if acted upon, could threaten public health or safety."

e. Manuscripts/reports in progress and proposed for publication shall be provided to the COR for review and comment at least 30 calendar days prior to submission for publication.

f. Abstracts and presentations shall be provided to the FDA COR for review and comment at least 5 calendar days before submission or presentation, respectively.

g. The computer programs, data management systems, databases, and other resources developed through this contract shall comply with data standards and procedures established by DHHS and FDA (per http://www.fda.gov/ForIndustry/DataStandards/default.htm).

h. The Contractor shall coordinate with the LRCC, as tasked in section 3.0.

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