NHLBI-ECB-HV-2017-02-TK_Amend_2_11.16.15.pdf

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E. IMPORTANT: Contractor is not, is required to sign this document and return copies to the issuing office.

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT 1. CONTRACT ID CODE

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Previous edition unusable

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT CONTINUATION PAGE Page 2 of 2

Note to Offerors: For clarification purposes, the term “Cohort Visit 6” refers to the contract supported exam intended to occur during these revised dates: 1/01/2018 – 9/30/2019.

Item 1. Questions received on or before October 28, 2015.

1. For the past renewal, we were allowed to put appendices on a CD. Can we do the same this time?

Response:

No, the technical proposal and appendices should be on 1 cd per the instructions provided and within the page limitations outlined in the RFP.

2. Can some of the substantial funds available to the Coordinating Center be used as subcontracts to the Field Centers to offset some of these needs?

Some of the Coordinating Center (CC) funds can be used as subcontracts to the field centers to offset some needs, but this would be at the discretion of the CC.

3. More broadly, can a substantial amount of the Coordinating Center funds be used propose sub-contracts to the field centers for components of the EHR feasibility and calibration study?

Some of the Coordinating Center (CC) funds can be used to propose subcontracts to the field centers for certain components of the study, but this would be at the discretion of the CC.

4. On page 107 of the field center RFP, the due date is Nov 13, 2015, but on page 1 is Dec 18, 2015. I believe the coordinating center RFP has a similar inconsistency. Is Dec 18, 2015 the correct due date?

Please see the October 1, 2015 solicitation Amendment. The due dates on both pages were corrected to December 18, 2015. (The date change also applies to the CC. See pages 1 and 105 of the CC RFP.)

Item 2. Section J, Revisions to Attachment #3, “Statement of Work and Deliverables.” See highlighted text.

ATTACHMENT #3

Attachment #3 - SOW and Deliverables

STATEMENT OF WORK

Coordinating Center - The Atherosclerosis Risk in Communities (ARIC) Study

I. Background The Atherosclerosis Risk in Communities (ARIC) Study was initiated in 1985 with two components: community-based surveillance and a prospective cohort study. The community surveillance aimed to monitor trends in hospitalized myocardial infarction (MI) and fatal coronary heart disease (CHD) in four U.S. communities: Forsyth County, NC; Jackson, MS; suburbs of Minneapolis, MN; and Washington County, MD. Surveillance for hospitalized heart failure (HF) events was added in 2005. The communities were selected to provide data across 4 geographic locations with a range of mortality rates, in urban, suburban, and rural settings. The cohort study aimed to investigate the risk factors for and natural history of atherosclerosis and development of clinical atherosclerosis in middle-aged white or African American adults from the same communities. The study recruited in 15,792 white or African American participants initially aged 45-64 years and selected participants received triennial clinical exams over the first ten years of the study (1987-1989, 1990-1992, 1993-1995, and 1996-1998), with a fifth clinical exam in 2011-2013, providing a rich set of data on physical, behavioral, genetic, and psychosocial factors. Since 1988, the cohort has been contacted annually in 2011 semiannual follow-up was initiated. Findings have been presented in over 1,400 publications as of 2014.

Participants were examined for evidence of subclinical atherosclerosis using B-mode ultrasound in carotid and popliteal arteries, ankle-brachial index measurement, and retinal photography and, in subsets, abdominal aortic computed tomography (CT) scan, hemostatic factors;

established and putative laboratory risk markers; socioeconomic, psychological, behavioral, and environmental characteristics; and genetic factors. Examinations included a variety of components, with a grant-funded detailed cognitive function testing component added in the most recent exam during 2011-2013. Blood samples have been assayed for putative biochemical risk factors and stored for case-control studies. DNA has been extracted and lymphocytes cryopreserved (for possible immortalization) for study of candidate genes, genome-wide scanning, expression, and other –omics investigations. Participation of the surviving cohort was 91, 82, 74, and 65% at each of the respective follow-up examinations.

Since baseline, cohort members have also been contacted every 12 months to obtain information on vital status, current residence, major illness or injury, and hospitalizations occurring between contacts to identify clinical cardiovascular disease (CVD) events. Cohort contact was 84% at the last completed follow-up ending on December 31, 2013.

The ARIC community surveillance enumerates and validates MI, CHD death, and HF events through annual surveillance and produces age-specific and age-adjusted event rates among black and white residents of the four ARIC Study communities. In 2011, the combined study population included over 400,000 adults 35-84 years old. Since it began in 1987, the study has surveyed hospitalized MI and CHD deaths in residents’ ages 35-74 years, expanded in 2005 to ages 35-84 years. Also, in 2005, the scope of events was expanded to include hospitalized HF for persons ages 55 years and older, with sub-classification by chronic stable versus acute decompensated HF. The sampling sources include all acute care hospitals located in the study communities.

The ARIC Study has supported a large number and variety of independently funded ancillary studies that have contributed to the data repository a unique set of data, including major ancillary studies on venous thrombosis, aortic aneurysm, cognitive impairment, and genetics. A wealth of data and biological samples has been collected since the study’s inception. Data from the cohort’s fifth clinical exam conducted in 2011-2013 provide a new baseline for further scientific discoveries. For a list of all phenotypic data documentation and protocols, refer to the ARIC website: https://www2.cscc.unc.edu/aric/ . The ARIC data are available to qualifying investigators directly from the study and also through dbGaP (http://www.ncbi.nlm.nih.gov/gap) and BioLINCC (https://biolincc.nhlbi.nih.gov). A variety of stored biospecimens, including DNA, serum, plasma, and urine are also available to qualifying researchers.

The incumbent contractors for ARIC are presented in Table 1.

Table 1. ARIC Incumbent Contractors for the period 11/15/2010-11/14/2016

Institution Role Contract Number

University of North Carolina at Chapel Hill Coordinating Center HHSN268201100005C

University of North Carolina at Chapel Hill Field Center HHSN268201100007C

University of Mississippi Medical Center Field Center HHSN268201100010C

University of Minnesota Field Center HHSN268201100008C Johns Hopkins University Field Center HHSN268201100009C Baylor College of Medicine Central Laboratory HHSN268201100006C Brigham and Women’s

Hospital Echocardiography Reading Center HHSN268201100011C

University of North Carolina at Chapel Hill

Cardiovascular Outcomes Research Center HHSN268201100012C

This acquisition is for one contract for an ARIC coordinating center with subcontracts or other mechanisms to accomplish all necessary work, including maintenance of existing biological samples. A parallel acquisition is being released for up to four (4) ARIC field centers.

II. Study Objectives

The goal of this acquisition is to provide a coordinating center to maximize use of data and samples amassed in ARIC over 29 years to address new questions about the development and progression of clinical CVD and related conditions. The scientific objectives are to (1) enhance statistical power to perform analyses of predictors of clinical events, particularly in informative subgroups; (2) study the progression of subclinical to clinical CVD; (3) identify new risk factors or interactions among factors that inform disease pathophysiology; and (4) evaluate the feasibility and validity of surveillance for myocardial infarction (MI) and HF using Electronic Health Record (EHR) technology. The operational goals are to (1) support the field centers to continue cohort follow-up and data collection on clinical events; (2) continue to foster scientific collaborations; and (3) support the field centers to conduct of a limited clinical examination of the ARIC participants as a platform for ancillary study examination components.

ARIC will continue to serve as a platform for in-depth ancillary studies that are funded outside of the ARIC contract. These ancillary studies will be operationally integrated into the main study, and the data will be shared per ARIC and NIH data sharing policies. The studies’ data will be provided to qualified investigators through a defined process that encourages maximum data utilization but that protects participant confidentiality.

https://www2.cscc.unc.edu/aric/ http://www.ncbi.nlm.nih.gov/gap https://biolincc.nhlbi.nih.gov/

III. Task Areas, Timeline, and Technical Requirements

A. Task Areas and Technical Requirements/Activities

Task Area 1 shall encompass conduct of and support for core study operations, data analysis, manuscript preparation, and morbidity and mortality ascertainment. [Note to Offerors: For planning purposes, assume approximately 8,150 surviving participants in 2016.] The field centers will contact all surviving and willing members of the ARIC cohort approximately every 6 months throughout the contract period to ascertain hospitalizations and other changes in health status, including changes in medications. The field centers will obtain hospitalization records to investigate and provide expert review of new clinical events and other changes in health status.

The coordinating center shall lead the classification of new clinical events. Task Area 2, if funded, will involve a limited examination of the ARIC cohort during 2017-2019. It is estimated that up to approximately 5,300 participants will be examined. Task Area 3 will involve a feasibility and calibration study of the use of EHR data for community surveillance. Study closeout activities will comprise Task Area 4. Task Area 5 will include mentoring early stage investigators through diversity supplements. See Table 2 below for a summary of the technical requirements and activities within each Task Area and Figure 1 for a project timeline.

Table 2. Task Areas

Tasks Activities Task Area 1 November 15, 2016 – November 14, 2021 (60 months)

• Support for field centers’ participant follow-up

• Support for field centers’ clinical events investigation and review

• Clinical events classification

• Core study operations

• Data analysis, manuscript writing

Task Area 2 August 15, 2017 – September 30, 2019 (25.5 months)

Cohort Visit 6 (contract-supported visit)

Task Area 2.A August 15, 2017 – December 31, 2017 (4.5 months)

Visit 6 preparation:

• Protocol development and review

• Staff training and certification

• Pilot testing

Task Area 2.B January 1, 2018 – September 30, 2019 (21 months)

• Support for field centers’ examination of up to approximately 5,300 ARIC participants

• Visit 6 closeout

Task Area 3 November 15, 2016 – November 14, 2019 (36 months)

Community surveillance feasibility and calibration study

Task Area 3.A.

November 15, 2016 – May 31, 2017 (6.5 months)

Quality control activities for 2014 community surveillance Preparation of analytic data files and report of surveillance trends through 2014 for MI, CHD death, and HF hospitalization

Task Area 3.B November 15, 2016 – November 14, 2019 (36 months)

Feasibility and Calibration study Final report

Task Area 4 November 15, 2020 – November 14, 2021 (12 months)

Study closeout

Task Area 5 November 15, 2016 – November 14, 2021 (60 months)

Mentoring through diversity supplements

Figure 1. Project Timeline (See changes in timeline in Task Areas 2.A and 2.B.)

11/15/2016 to 11/14/2017

11/15/2017 to 11/14/2018

11/15/2018 to 11/14/2019

11/15/2019 to 11/14/2020

11/15/2020 to 11/14/2021

Task Area 1 Task Area 2 Task Area 2.A Exam protocol development Training, certification Pilot testing Task Area 2.B Visit 6 Exam closeout Task Area 3 Task Area 3.A Complete 2014 surveillance Task Area 3.B Feasibility and Calibration study

Task Area 4 Task Area 5

B. General Description of the Overall Technical Requirements: Throughout the period of performance, the Contractor shall provide appropriate senior personnel with expertise in cardiovascular disease epidemiology, clinical cardiovascular disease, longitudinal studies management, biostatistics, bioinformatics, medical informatics, human genetics and genomics, administrative and biorepository management. The Contractor shall:

1. Develop and maintain a web-based data collection system for and provide other services as necessary to enable regular follow-up contacts of participants by field centers. (Task Area 1)

2. Develop and maintain a web-based data collection system for and provide other services as necessary to enable abstraction of data from medical records, death certificates, other relevant materials, and expert review of clinical events by field centers; and conduct classification thereof. (Task Area 1)

3. Support a re-examination of ARIC participants, including developing and maintaining a data collection system for Visit 6. (Task Area 2) [Note to Offerors: The NHLBI will determine later whether to award this Task Area.]

4. Design and implement appropriate quality assurance and quality control programs.

(Task Areas 1, 2, and 3)

5. Work cooperatively with the Jackson Heart Study investigators in all relevant aspects of study development and execution to maximize the cost-effectiveness of the study operations and to minimize the burden to the Jackson participants who enrolled in both ARIC and the Jackson Heart Study. (Task Areas 1 and 2)

6. Conduct a feasibility and calibration study of community surveillance for MI and HF using digitally transmitted data from Electronic Health Record (EHR) systems of the hospitals in the ARIC study catchment areas. The study will assess the feasibility of obtaining the EHR data from community hospitals and determine how to access the numeric and text digital data and will compare incidence estimates from data collected by the traditional ARIC procedures for MI and HF and with estimates from data obtained via digital transmission of EHR for MI and HF and develop calibration factors. (Task Area 3)

7. Perform administrative, operational, and technical duties to support productive collaboration among the study personnel at all ARIC centers, outside researchers collaborating with ARIC, and the NHLBI Project Office. (Task Area 1)

8. Establish and maintain study databases, including updating the databases with data from newly ascertained events and ancillary studies both for internal use and for posting on BioLINCC (https://biolincc.nhlbi.nih.gov) and other NIH databases, such as dbGaP (http://www.ncbi.nlm.nih.gov/gap), as appropriate. (Task Area 1)

9. Establish and manage a biological specimen repository. (Task Area 1)

10. Coordinate and participate collaboratively in study committees to provide a transparent committee process, open access to study documents, clear policies for access to data and materials, and an approval process for proposed manuscripts and ancillary studies that is fair and balanced. (Task Area 1)

11. Arrange for and manage annual meetings of an NHLBI-appointed Observational Studies Monitoring Board (OSMB) as directed by the NHLBI Project Office. (Task Area 1)

12. Conduct statistical analyses and prepare scientific publications and presentations. (Task Areas 1 and 3)

13. Provide statistical oversight and programming, and conduct analysis and data verification for collaborative publications with the field center investigators and NHLBI Project Office.

14. Prepare and submit technical and financial reports. (Task Areas 1 and 4)

15. Perform activities related to study closeout as directed by the NHLBI Project Office.

(Task Area 4)

16. Work cooperatively with all study investigators and staff, the NHLBI Project Office, and any subcontractors and consultants in all relevant aspects of the study. (Task Areas 1, 2, 3, and 4)

17. Mentor early stage investigators from underrepresented racial and ethnic groups, individuals with disabilities, and individuals from disadvantaged backgrounds by providing formal and/or informal training opportunities for junior or inexperienced investigators (assistant professors, fellows, and students). (Task Area 5)

Note to Offerors:

For all years, costs incurred to prepare and distribute analytic data sets and/or biological samples to approved outside investigators must be covered by the investigators and not the contract. Furthermore, when new exam procedures, assays or genotyping in ancillary studies reveal potentially clinically actionable conditions, the costs associated with participant notifications must come from the ancillary studies and not the contract.

https://biolincc.nhlbi.nih.gov/ http://www.ncbi.nlm.nih.gov/gap

C. Detailed Description of Technical Requirements in Each Task Area

1. Task Area 1: During the period November 15, 2016 – November 14, 2021

During this period, the Contractor shall:

A. Develop and maintain a web-based data collection system for and provide other services as necessary to enable regular follow-up contact of participants by ARIC field centers. To that end:

1. Update as needed the protocol and procedures for participant follow-up. (See the ARIC Participant Follow-Up Manual of Operations at https://www2.cscc.unc.edu/aric/annual-follow-up-manuals .)

2. Work cooperatively with the Jackson Heart Study investigators to minimize the follow-up contact burden to the Jackson participants who enrolled in both ARIC and the Jackson Heart Study and maximize study cost-effectiveness.

3. Provide participants with the following:

a. A high quality website with participant-oriented information

b. An annual newsletter to disseminate study-related information and to foster enthusiasm and continued participation in the study

4. All web-based systems designed under this contract shall meet the requirements of

Section 508 of the Rehabilitation Act. More information is available on the Web at:

http://www.access-board.gov/508.htm.

The Section 508 Applicable Electronic and Information Technology (EIT) Accessibility Standards are as follows:

Subpart B - Technical Standards

• Software Applications and Operating Systems (1194.21)

• Web-based Intranet and Internet Information and Applications (1194.22)

• Video and Multimedia Products (1194.24)

Subpart C - Functional Performance Criteria

• Functional Performance Criteria (1194.31)

Subpart D - Information, Documentation, and Support

• Information, Documentation, and Support (1194.41)

B. Develop and maintain a web-based data collection system for and provide other services as necessary to enable abstraction of data from medical records, death certificates, and other relevant materials for investigation of potential study endpoints; and conduct expert review and event classification thereof.

1. Update as needed the protocol and procedures for participant follow-up and events investigations and reporting. (See the ARIC Participant Follow-Up Manual of Operations at https://www2.cscc.unc.edu/aric/annual-follow-up-manuals and the Surveillance Procedures Coronary Heart Disease Manual and the Surveillance Events Heart Failure Manual at https://www2.cscc.unc.edu/aric/surveillance-manuals .)

a. Develop data collection and management procedures.

b. Revise as necessary current data collection forms for outcomes ascertainment and selected exposures.

c. Search national databases (e.g., National Death Index, Lexis-Nexis) to locate matches for ARIC participants. Obtain death certificates as appropriate.

2. Maintain and implement standardized procedures to identify and classify morbid cardiovascular events (including myocardial infarction, angina, stroke, transient https://www2.cscc.unc.edu/aric/annual-follow-up-manuals http://www.access-board.gov/508.htm http://www.access-board.gov/sec508/guide/1194.21.htm http://www.access-board.gov/sec508/guide/1194.22.htm http://www.access-board.gov/sec508/guide/1194.24.htm https://www2.cscc.unc.edu/aric/annual-follow-up-manuals https://www2.cscc.unc.edu/aric/surveillance-manuals https://www2.cscc.unc.edu/aric/surveillance-manuals ischemic attack (TIA), heart failure, peripheral arterial disease, and atrial fibrillation), cardiovascular interventions, and all mortal events.

a. Provide appropriate personnel with knowledge of the ARIC events protocol, nosology, and clinical assessment of cardiovascular and related diseases;

prepare case packets for event classification on an ongoing basis; organize and support the activities of the CHD and HF Morbidity and Mortality Committees (MMCC); coordinate and monitor timely expert review of events by MMCC members.

b. Perform classification of MI and HF using computer algorithms and expert review following standardized methodology of the ARIC Study,

c. Assure standardization of methodology and consistency of procedures over time with appropriate quality assurance activities.

d. Produce regular reports on the status of events investigations and final adjudicated events that have accrued in the study and present at regular surveillance committee calls.

3. Perform linkage of study data with Medicare claims data approximately annually to:

a. Identify major clinical events for participants lost to follow-up

b. For selected cardiovascular outcomes to be mutually agreed upon with the

Project Office, compare estimates identified using Medicare claims data with estimates using participant-reported hospitalization data.

c. Enable analyses to address questions related to resource utilization among ARIC participants.

[Note to Offerors: The NHLBI currently has an Intra-Agency Agreement in place with CMS that allows ARIC to obtain Medicare claims data for cohort members on an annual basis at no cost. The current IAA is scheduled to end on September 30, 2016. For planning purposes, assume the IAA will be renewed.]

4. Work cooperatively with the Jackson Heart Study investigators to maximize the cost-effectiveness and minimize participant burden of investigation of potential study endpoints for the Jackson participants who enrolled in both ARIC and the Jackson Heart Study.

C. Perform administrative, operational, and technical duties to support productive collaboration among the study personnel at all ARIC field centers, outside researchers collaborating with ARIC, and the NHLBI Project Office.

1. Facilitate meetings and communications among ARIC and collaborating investigators and staff, subcontractors, consultants, and the NHLBI Project Office as necessary throughout the contract period.

a. Coordinate activities of Steering Committee and all subcommittees.

b. Update and document policies and procedures for all committees, as necessary.

c. Facilitate communications among the subcommittees and the Steering

Committee by organizing regular conference calls, maintaining web site communications, and otherwise facilitating dissemination of material and information among committee members. Incorporate subcommittee recommendations approved by the Steering Committee into study policies and Manuals of Operations.

d. Contribute to study management through service on the Steering Committee and subcommittees.

2. Make arrangements for and convene semiannual in-person Steering Committee meetings and monthly conference calls.

a. Prepare and distribute Steering Committee meeting materials, including but not limited to an annual study progress report, and the agenda two weeks prior to the meetings.

b. Record and distribute minutes from Steering Committee meetings to the Committee and the Project Office within 3 weeks.

c. Distribute conference call meeting materials and the agenda at least two working days prior to meetings, and record and distribute minutes within 5 working days.

3. Make arrangements for and convene regular conference calls (generally, monthly) for other study committees, as necessary and proposed by the committee chairs.

4. Arrange for and manage annual meetings of the NHLBI ARIC Observational Studies Monitoring Board (OSMB) as directed by the NHLBI Project Office, to be held in conjunction with annual Steering Committee meetings.

a. Distribute meeting materials at least two weeks prior to meetings.

b. Make travel and meeting arrangements for OSMB members, and provide expense reimbursement to OSMB members. [Note to Offerors: Assume eight members of the OSMB.]

5. Utilizing state-of-the-art web design and content by employing appropriate expertise in this field, maintain and keep current ARIC web sites, including an external site for participants, an external site for researchers, and an internal site for study investigators and others, as necessary. The internal and external websites shall be Section 508 compliant.

a. The external site for participants shall include:

i. General information about the study

ii. Newsworthy articles

iii. Helpful contact information

iv. Other items of potential interest to ARIC participants, including most recent newsletter

b. The external site for researchers shall include:

i. Study description, timeline, and participating sites including coordinating center, field centers, reading centers and laboratories, and the NHLBI

ii. Study components by exam, including completed ancillary study components incorporated into the main ARIC data base

iii. Directory of investigators

iv. Description of subcommittees and working groups

v. Protocols and manuals of operations

vi. Descriptions of available data and specimens

vii. Description and guidance for ancillary study proposals, including templates

viii. Description and guidance for manuscript proposals, including templates and Acknowledgment Statements for manuscripts

ix. Data use agreement templates

x. Listing of published papers

xi. Information on access to the main data base

xii. Any other data base of mutual benefit as determined jointly by the

Steering Committee and/or the NHLBI Project Office

b. The internal site for study investigators and others as necessary shall include:

i. Approved manuscript proposals and published article citations

ii. Approved ancillary study proposals, including funding status

iii. Study committee, subcommittee, and working group meeting agendas, minutes, and other materials

iv. Other materials related to study operations, coordination, or administration, including IRB approvals from all centers, and informed consent templates for clinical examinations

6. Develop and implement strategies to encourage investigators new to ARIC to collaborate by proposing analyses and/or ancillary studies.

7. Provide basic statistical, epidemiological, logistical, and computer expertise, advice, and support for investigators interested in applying to the study to use its data and/or biological specimens [Note to Offerors: the costs required to obtain analytic data sets and biological specimens for approved applications from outside investigators must be covered by the applicant.]

8. Maintain IRB approvals and record of IRB approvals from each site.

9. Manage execution of and maintain Data Distribution Agreements for Affiliated

Investigators and Data and Materials Distribution Agreements for Collaboration Investigators.

10. Cooperate with and assist the NHLBI Project Office with development of an Office of Management and Budget (OMB) submission for review by the OMB. [Note to Offerors: The OMB renewed approval for the ARIC Study in April 2014 (OMB # 0925-0281, exp. 05/31/2017), but any new protocols in this project will require review.]

D. Establish and manage the biological specimen repository. [Note to Offerors: The biorepository currently houses more than 1.2 million vials of blood-based and urine samples which are stored in 67 dedicated freezers (-70°C to -80°C) and genetic specimens comprising more than 350,000 vials of buffy coats, DNA, RNA, peripheral blood mononuclear cells (PBMCs) and red blood cells (RBCs) which are stored in 15 dedicated freezers, including 12 ultra-low (-80°C) and three liquid nitrogen (-145°C), occupying approximately 6,400 square feet.]

1. Maintain the ARIC biologic specimen repository in accordance with the ARIC protocol and established operating procedures.

2. Track inventory of available specimens.

3. Provide specimens to approved investigators in accordance with study policies and procedures for access to specimens. Ensure delivery of approved specimens within 30 days of request by the investigator with any exceptions approved by the NHLBI Project Office. [Note to Offerors: Investigators requesting specimens must provide funding necessary for this service.]

4. Conduct quality management studies as needed.

E. Establish and maintain study databases, including images.

1. Maintain and update as needed a Section 508 ARIC web-based data entry and management system.

2. Maintain security and confidentiality of the data.

3. Include data from clinical visit examinations and interviews, follow-up phone interviews, imaging measurements and results, laboratory measurements, morbidity and mortality data, and from all sub-studies and ancillary studies. [Note to Offerors: Per the Guidelines for Data Sharing from Clinical Trials and Epidemiology Studies at http://www.nhlbi.nih.gov/research/funding/human-subjects/set-preparation-guidelines, ancillary studies must provide data within 12 months of completion of data collection.]

4. Annually update follow-up and morbidity and mortality events data.

5. Provide updates with corrections to or clarifications of the data base as necessary.

6. Maintain a data base on informed consent versions and participant responses covering Exams 1-5 and, if conducted, Visit 6. Assure that samples and data bases are distributed in accordance with the expressed desires of participants in their signed informed consents.

7. Prepare documentation for data distribution to or downloading from the ARIC website and use by approved investigators, per NIH data sharing guidelines and with appropriate protections for participant privacy and assuring that only qualified investigators have access. (Approval for gaining access to the data by investigators will generally be through the ancillary study or manuscript proposal process or through an NIH-administered program.)

8. Provide data documentation to users upon request.

9. Maintain data on quality control measurements.

10. Maintain a repository for previously collected and any future images (collected by the contract, under subcontract or by ancillary study).

a. Maintain a system for sharing and tracking use of images.

b. Include data derived from all readings performed on images.

11. In collaboration with NHLBI and the National Center for Biotechnology Information (NCBI), prepare genetic and phenotypic data sets and necessary documentation for release through dbGaP (http://www.ncbi.nlm.nih.gov/gap) or other NCBI database as per either the NIH Genomic Data Sharing Policy or the NIH GWAS Policy, whichever is in effect during the contract award period (http://gds.nih.gov/03policy2.html )..

a. Incorporate ancillary study data into the contract study data set for release through NCBI dbGaP (or other appropriate NCBI database) after an appropriate period of time as per the NIH Genomic Data Sharing Policy or the NIH GWAS Policy, whichever is in effect during the contract award period (http://gds.nih.gov/03policy2.html). Update the study information in the database as needed.

12. Prepare NHLBI Data Repository data sets (formerly called “limited access data sets”) and associated documentation for submission to the Biological Specimen and Data Repository Information coordinating center (BioLINCC) in accordance with the NHLBI Policy on Data Sharing from Clinical Trials and Epidemiological Studies (http://www.nhlbi.nih.gov/funding/datasharing.htm).

a. Incorporate ancillary study data into the contract study data set after an appropriate period of time (generally 12 months after completion of data collection). Include such ancillary study data in data sets prepared for the NHLBI Data Repository in accordance with NHLBI Policy on Data Sharing from Clinical Trials and Epidemiological Studies (http://www.nhlbi.nih.gov/funding/datasharing.htm) [Note to Offerors: further details can be found on the BioLINCC FAQ page:

https://biolincc.nhlbi.nih.gov/faqs/#toc4.]

13. Comply with other NHLBI and NIH policies, which include but are not limited to the following:

a. The NIH Public Access Policy requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central (http://www.ncbi.nlm.nih.gov/pmc/) immediately upon acceptance for publication. To that end, the Contractor shall do so for any manuscript that arises from any direct funding from the contract. For more information, see NOT-OD-08-033 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08- 033.html) and the Public Access website (https://publicaccess.nih.gov/ ).

http://www.ncbi.nlm.nih.gov/gap http://gds.nih.gov/03policy2.html http://gds.nih.gov/03policy2.html http://www.nhlbi.nih.gov/funding/datasharing.htm http://www.nhlbi.nih.gov/funding/datasharing.htm https://biolincc.nhlbi.nih.gov/faqs/%23toc4 http://www.ncbi.nlm.nih.gov/pmc/ http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html https://publicaccess.nih.gov/

b. The NHLBI Adverse Event (AE) and Unanticipated Problem (UP) Reporting Policy describes the procedures for identifying, monitoring, and reporting Adverse Events and Unanticipated Problems (http://www.nhlbi.nih.gov/funding/policies/adverse.htm).

14. Annually review and update as needed the ARIC listing in www.ClinicalTrials.gov.

15. Develop, update, and implement an information systems security plan in accordance with Table 3 of the Federal Information Security Safeguard Requirements Summary at https://ocio.nih.gov/aboutus/publicinfosecurity/acquisition/Pages/table3.aspx .

F. Coordinate and participate collaboratively in study committees to provide a transparent committee process, open access to study documents, clear policies for access to data and materials, and an approval process for proposed manuscripts and ancillary studies that is fair and balanced.

1. Maintain, support, and update as necessary the structure and functions of the ARIC Steering Committee and subcommittees to:

a. Optimize study oversight and operations

b. Ensure the safety and privacy of the ARIC participants

c. Oversee use of ARIC data and biological specimens to ensure compliance with participant consents.

2. Maintain Publication and Ancillary Study policies that ensure:

a. Clear policies for access to ARIC data and specimens by interested investigators

b. Fair, balanced, and timely review processes for proposed manuscripts and ancillary studies

c. Central monitoring for quality and avoidance of overlap among proposed ancillary studies and manuscripts.

3. Assist the Publications Committee in its review of new manuscript proposals and penultimate drafts, and the creation and monitoring of study policies.

a. Maintain data bases of manuscript proposals and of published manuscripts.

b. Create proposal review reports for the monthly Publications Committee calls.

G. Design and implement quality control and quality assurance programs in conjunction with appropriate committees, including but not limited to: the Quality Control Committee, the Surveillance Committee, the Retention and Follow-up Committee.

1. Prepare and implement a plan to monitor the quality of all data on an ongoing basis.

2. Develop and oversee implementation of recommendations to correct errors in a timely manner.

3. Include assessment of stability of stored laboratory specimens.

4. Include a review of collected data in annual reports provided to the Steering

Committee and the OSMB. Verify completeness, timeliness, reliability, and accuracy of collection and coding.

5. Coordinate initial certification and maintain ongoing retraining and recertification of performance capabilities of relevant staff.

H. Conduct statistical analyses for scientific publications and presentations

1. Perform data analyses and support study investigators, via consultation, on analyses.

I. Prepare and submit technical and financial reports.

http://www.nhlbi.nih.gov/funding/policies/adverse.htm http://www.clinicaltrials.gov/ https://ocio.nih.gov/aboutus/publicinfosecurity/acquisition/Pages/table3.aspx

1. Submit annual progress reports that include descriptive information about the activities undertaken during the reporting period. Report on:

a. Main operational activities

b. Problems encountered and how they were resolved

c. Modifications to any subcontracts or consulting agreements

d. Scientific productivity, including but not limited to the following metrics:

i. Number of publications

ii. Number of publications in high-profile journals

iii. Number of citations garnered by publications

iv. Number of different first authors on manuscripts and authors from non-ARIC institutions

v. Number of funded ancillary studies

vi. Number of collaborative papers published

vii. Number of requests of data from BioLINCC and dbGaP

viii. Use of data in clinical guidelines or other clinical applications, or to stimulate or guide clinical trials or basic investigations

2. Submit semi-annual cumulative reports on Data and Materials Distribution

Agreements (DMDAs) that contain at minimum the following:

a. Date of execution

b. Title of project

c. Names of principal investigator(s) and institution(s)

d. Anticipated or actual date of expiration

3. Submit quarterly staffing reports that include for each staff member:

a. Area of responsibility

b. Study-related activities in the previous quarter

c. Proposed and actual levels of effort

d. Explanations of any changes during the period

4. Submit 508 Annual Reports in accordance with contract instructions in Article H.

Electronic Information Technology Accessibility, HHSAR 352-73(b) (January 2010).

5. Submit monthly financial invoices, as required by NIH.

J. Work cooperatively with all study investigators and staff, the NHLBI Project Office, and any subcontractors and consultants in all relevant aspects of the tasks listed above. Provide timely responses to specific requests from the NHLBI, Steering Committee, and OSMB.

K. Additional specific tasks for all Offerors other than the incumbent:

The Offeror shall include the following documentation in the proposal. These plans are to be implemented by the Contractor during the period between November 15, 2016 and May 16, 2017.

1. A detailed plan for a smooth and seamless transition of coordinating center’s responsibilities from the existing coordinating center Contractor.

2. A detailed plan for obtaining IRB approval with appropriate consideration for conditions that have been established and existing in the previous contract. This should include informed consent conditions agreed to by the participants, and existing IRB approved conditions at the original field centers.

3. A detailed plan for transition of all data and biospecimens from the existing Contractor, including plans for confidentiality and security of all data as necessary.

4. A detailed plan for transition of all existing protocols, documents, minutes, and reports from the current Contractor as necessary.

5. A detailed plan for transition of the internal and public use web sites.

2. Task Area 2: On or about August 15, 2017 – September 30, 2019

During this period, the Contractor shall provide support to the field centers for a limited re-examination of all surviving and willing ARIC participants for Visit 6. The targeted recruitment is up to approximately 5,300 participants. This Task Area will be broken down into two smaller Task Areas (Task Areas 2.A and 2.B; see Table 2 and Figure 1): the first will be for exam preparation activities and the second to conduct the exam and exam closeout. The Contractor shall work collaboratively throughout the period with ancillary study investigators and staff to coordinate exam components from multiple funding sources with those of the contract-funded Visit 6. The Visit 6 components and approximate times are listed in Table 3.

Note to Offerors: The NHLBI will determine later whether to fund this specific Task Area. The exact dates are also subject to change as determined by NHLBI.

Table 3. Cohort Visit 6 components and approximate times

Component Time

Reception, Consent 20 minutes Demographic information 10 minutes Anthropometry 10 minutes Blood pressure 15 minutes Smoking history 5 minutes Medical history, including medications 25 minutes Phlebotomy 15 minutes

A. Task Area 2.A. On or about August 15, 2017 – December 31, 2017, the Contractor shall:

1. Provide qualified staff to support and coordinate the planning activities and preparations for Visit 6.

2. In collaboration with the ARIC Steering Committee and field centers, develop a protocol for re-examination of the ARIC cohort. The protocol will be reviewed by the ARIC Observational Study Monitoring Board. (The protocol for ARIC Visit 5 can be found on the ARIC website at https://www2.cscc.unc.edu/aric/cohort-manuals.)

3. In collaboration with the ARIC Steering Committee and field centers, develop a Visit 6 manual of operations based on the protocol.

a. Unless a strong rationale exists to do otherwise, data collection procedures shall be consistent with those used previously in ARIC.

b. Comparability of measures with those from previous examinations must be assured wherever possible.

4. Develop and maintain web-based data entry system for use by field centers to collect new and repeat measures from Visit 6.

5. In collaboration with the ARIC Steering Committee or designated sub-committee, and field centers, develop a standardized informed consent form. Assure inclusion of all required elements.

https://www2.cscc.unc.edu/aric/cohort-manuals

a. ARIC has a Certificate of Confidentiality for DHHS Funded Studies, which shall be noted in the standardized informed consent form.

6. Based on the protocol and manual of operations and in collaboration with field centers, plan and conduct central training for clinic staff. Coordinate the completion of initial certification of performance capabilities of relevant staff.

7. Plan and coordinate pilot testing for the examination, including receipt of blood samples at the biospecimen repository. The results shall be reviewed by the Operations Committee and Steering Committee.

8. Redesign and implement changes in the protocol and manual of operations, as recommended by the Operations Committee and approved by the Steering Committee, based on pilot testing results

9. Obtain IRB approval to conduct the study and maintain documentation of IRB approvals for each field center.

B. Task Area 2.B. On or about January 1, 2018 – September 30, 2019, the Contractor shall:

1. Maintain the web-based data entry system developed in Task Area 2A for use by field centers to conduct Visit 6.

2. Plan and conduct quality assurance and quality control activities according to established study procedures and as recommended by the Quality Control Committee to assure high quality data collection.

3. Plan and conduct the receipt and processing of collected blood samples by the biospecimen repository for long-term storage. The final blood volume to be collected per participant will be determined by the Steering Committee and the NHLBI Project Office. [Note to Offerors: For planning purposes, assume a blood draw volume of approximately 40 cc.]

4. Support the timely (within 4 weeks of examination) preparation of exam reports for participants and, with consent, for their health care providers, to include of clinically relevant results and indications of any abnormalities of clinical significance. The field centers will provide the individualized reports to each participant.

5. Monitor ongoing retraining and recertification of performance capabilities of relevant staff at all field centers through centralized and/or localized training as needed.

6. Conduct exam closeout and complete data cleaning.

7. Prepare and make available to qualifying researchers a Visit 6 research data set.

3. Task Area 3: On or about November 15, 2016 – December 31, 2019

The goal of Task Area 3 is to perform community surveillance for MI and HF using the digital content contained in a hospital’s Electronic Health Record (EHR). This task has a first phase (Task Area 3A) to complete community surveillance for 2014 using the current methods of event identification and validation and prepare a trend report for surveillance for MI, CHD deaths, and HF events from 1987 through 2014. The second phase is (Task Area 3B) to conduct a feasibility and calibration study of the use of digitally transmitted EHR data for use in surveillance of MI incidence and HF hospitalization events. The study aims will be 1) to assess the feasibility of obtaining the EHR data from community hospitals; 2) to determine the optimal method to access the numeric and text digital data; 3) to compare incidence estimates from data collected by the traditional ARIC methods for MI and HF with estimates from data obtained via digital transmission of EHR for MI and HF and develop calibration factors for these estimates; 4) to conduct an analysis of bias using existing data and 5) to prepare a final report encompassing results of the feasibility and calibration studies and the analysis of bias.

The studies shall be carried out in the four ARIC Study communities. – (1) Forsyth County, North Carolina (including the city of Winston-Salem) (2) the city of Jackson, Mississippi (3) eight northern suburbs of Minneapolis, Minnesota and (4) Washington County, Maryland (including the city of Hagerstown). The study community boundaries are defined by county lines for Forsyth and Washington Counties, and by metropolitan boundaries in Jackson and Minneapolis suburbs.

A. Task Area 3.A. On or about November 15, 2016 – May 31, 2017, the Contractor shall:

1. Complete quality control activities for the sample of 2014 community surveillance data related to ascertainment of CV events, including, but not limited to, any abstraction, classification, or related activities to finalize data files for 2014. Follow the surveillance procedures developed in the earlier contract period to assure comparability of these data.

2. Prepare and submit to the Project Office a report on residents aged 55 years and older on trends in incidence and mortality of hospitalized MI and CHD deaths for the period 1987-2014, and incidence of HF hospitalization for the period 2005-2014.

3. Prepare data files for community surveillance data through 2014 and distribute to

ARIC centers and Project Office.

a. Prepare a NHLBI Data Repository data set (formerly called “limited access data sets”) and associated documentation for submission to the Biological Specimen and Data Repository Information coordinating center (BioLINCC) in accordance with the NHLBI Policy on Data Sharing from Clinical Trials and Epidemiological Studies (http://www.nhlbi.nih.gov/funding/datasharing.htm).

B. Task Area 3.B. On or about November…