CARDIA Y30 FINAL CC SOW.pdf

ATTACHMENT #3

STATEMENT OF WORK – CARDIA COORDINATING CENTER

BACKGROUND

The Coronary Artery Risk Development in Young Adults (CARDIA) study was established in 1985 by the National Heart, Lung, and Blood Institute (NHLBI) to study the distribution and evolution of cardiovascular disease risk beginning in young adulthood in four U.S. communities (Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA) (http://www.cardia.dopm.uab.edu/). The original cohort (n=5,115) was selected to have approximately the same number of participants in subgroups of age (18-24 and 25-30), sex, race (black and white), and education (high school or less and more than high school) within each community. Participants were sampled from the total population, selected census tracts or, in the case of one Center, the membership of a large health plan. The baseline examination (Year 0) was conducted over a 14-month period during 1985-86. The examination consisted of questionnaires on sociodemographic characteristics, health behaviors, and psychological factors;

an exercise treadmill test; resting electrocardiography; a diet history assessment; anthropometry;

pulmonary function testing; and resting blood pressure. Fasting blood measurements included total cholesterol and its subfractions, insulin, glucose, liver enzymes and other serum chemistry measurements, and hematology.

Seven additional examinations have been completed every 2-5 years, including a Year 25 examination completed in 2011. Repeat measurements on traditional risk factors, including plasma lipids, blood pressure, anthropometry, smoking behavior, and physical activity have used the same methods at each examination to assess age and secular trends in these factors during young adulthood to middle-age. In selected years, additional measurements have been made, including a treadmill exercise test at baseline and Year 7; diet history at baseline, Year 7, and Year 20; cardiovascular reactivity measurements in Year 2; ambulatory blood pressure monitoring (in a subset) at Year 5; skin reflectance and assessment of the experience of discrimination and other psychosocial measures and urine sodium and creatinine (in a subset) in Year 7; glucose tolerance testing in Year 10, Year 20, and Year 25; microalbuminuria at Year 10, Year 15, Year 20, and Year 25; echocardiography at Year 5, Year 10 (in a subset), and Year 25; cardiac CT scan in Year 15 and Year 20; carotid ultrasound in Year 20; abdominal CT scan in Year 25; and brain MRI at Year 25 (in a subset). Investigator initiated ancillary studies have also contributed significantly to the CARDIA program of research.

Retention of the surviving cohort was 90, 86, 81, 79, 74, 72, and 72 percent at each of the respective seven follow-up examinations. Cohort members are contacted every six months to obtain information on vital status and current residence. Every other six-month contact also includes speaking with the participant to ascertain information on major illness or injury, and hospitalizations occurring between contacts.

At Year 30, the eighth examination, participants will be 48-60 years old, a time when risk factors and subclinical abnormalities are prevalent and clinical events continue to emerge. CARDIA offers the opportunity to address aspects of the development and progression of subclinical and clinical disease that cannot be addressed in older cohorts. Specifically, CARDIA offers the http://www.cardia.dopm.uab.edu/� opportunity to phenotype early cardiovascular disease, including heart failure in a large cohort of white and black adults. In addition, risk factors for cardiovascular disease can be updated. With risk factor data from previous examinations, CARDIA has the ability to study how the entire trajectory of early adulthood to mid-to-late middle-age risk factors and their control affects development and progression of cardiac dysfunction.

A. Scientific Objectives

This renewal will fund continued follow-up and a limited clinical examination of the CARDIA cohort to address the following objectives:

1. To determine abnormalities in cardiac structure and function that exist in a community-based sample of mid-to-late middle-aged adults; to utilize novel measures to better understand myocardial dysfunction; to examine 25-year trajectories in cardiac structure and function; and to assess whether these abnormalities and trajectories differ between white and black adults.

2. To assess the impact of timing and varying levels of risk factors acquired throughout young adulthood and middle-age on the occurrence and progression of myocardial dysfunction and early clinical events.

3. To utilize a comprehensive approach to elucidate the basis for racial disparities in the development of cardiovascular disease risk factors, subclinical cardiac abnormalities, and potentially early clinical events.

4. To continue cohort follow-up for cardiovascular events, including heart failure, coronary heart disease, stroke, and atrial fibrillation.

5. To provide a platform for ancillary studies particularly to the cohort examination, a training ground for new investigators, and data sharing.

The final protocol (including any additional scientific objectives and measurements) will be developed in collaboration with the NHLBI Project Office, and will be reviewed and approved by NHLBI in consultation with the existing CARDIA Observational Studies Monitoring Board

(OSMB).

The study will support in-depth ancillary studies that are funded outside of the current contract.

These studies will be operationally integrated into the main study, and the data will be shared across both types of studies, per current CARDIA and NIH data-sharing policies. The study’s data will be provided to interested investigators through a defined process that encourages maximum data utilization but that protects participant confidentiality. See the Appendix for more information regarding ancillary studies.

The study will also continue to serve as a training ground for early stage investigators, who will work with senior investigators and be provided with guidance on conducting research.

B. Study Operations

All surviving and willing members of the CARDIA cohort will be followed up and included in the Year 30 exam during 2015-2016 (approximately 12 months in duration). It is estimated that approximately 3500 participants will be examined. Participants will be contacted every 6 months to ascertain vital status and change in address; every other 6-month contact includes contacting the participant to characterize new clinical events and other changes in health status.

A timeline for the study is provided in Table 1. A list of exam components is provided under Option 1 and 2 Period.

Collaborating centers will include four Field Centers, a Coordinating Center, and an Echocardiography Reading Center. The Coordinating Center will establish other Reading Center(s) and laboratories as necessary. Principal Investigators from each of the 6 collaborating centers plus any relevant large subcontracts as determined by the NHLBI Project Office, and the NHLBI Project Officer form the CARDIA Steering Committee. The chairperson of the Steering Committee serves through a subcontract with the Coordinating Center.

Data analysis, publications, and cohort follow-up for morbidity and mortality will occur throughout the Base and five Option periods. If all periods are exercised the contract will be a 5 year requirement.

Base July 1, 2013 – June 30, 2014 Option 1 July 1, 2014 – June 30, 2015 Option 2 July 1, 2015 – June 30, 2016 Option 3 July 1, 2016 – June 30, 2017 Option 4 March 1, 2017 – June 30, 2018 Option 5 July 1, 2017 – June 30, 2018

Table 1. Timeline according to Base Period and Options Funding Schedule

July '13- June '14

July '14- June '15

July ’15 – June ‘16

July '16- June '17

Mar '17- June '18

July ’17- June‘18

BASE

Protocol Development

Follow-up and Retention

Analysis and Publications

OPTION 1

OMB Preparation

OMB Submission, clearance

Protocol Review NHLBI and OSMB

Staff Training and Certification

Pilot Testing

Exam

OPTION 2

Exam

OPTION 3

OPTION 4

Delivery of Final Datasets

Delivery of Biospecimens

OPTION 5

Note: It is possible that the OMB Clinical Exemption under which the study currently operates will remain in effect during the renewal but this is not guaranteed.

Base Period (July 1, 2013 – June 30, 2014)

I. GENERAL REQUIREMENTS AND TASKS

The Contractor shall provide appropriate senior personnel with expertise in cardiovascular epidemiology, clinical and subclinical cardiovascular disease, longitudinal studies, laboratory measurements, statistics, bioinformatics, statistical methods development, statistical genetics, and administrative management to:

A. Establish and manage laboratories, and other consultants and subcontracts, as necessary.

B. Manage the subcontract for the Steering Committee chairperson.

C. Coordinate in collaboration with Project Office staff the establishment of a limited number of consultant agreements for experts in imaging, laboratory medicine, women’s health, lipid metabolism, genetics, and other disciplines as appropriate. These consultants will participate in protocol development and in analysis, interpretation, and publication of study data. These consultants shall participate in Steering Committee meetings and conference calls on a regular basis and otherwise be incorporated into study operations.

D. Participate actively in the study as members of the Steering Committee and other study committees.

E. Coordinate development of the study protocol/manual of operations by the Steering Committee.

F. Facilitate and coordinate the tracking of regular follow-up contact of participants.

G. Facilitate and coordinate the collection of data on clinical events and classification thereof.

Provide a centralized abstractor to abstract event data from medical records, death certificates, and other relevant materials received from the Field Centers.

H. Perform administrative duties to support productive collaboration among the study centers and the NHLBI Project Office.

I. Provide relevant desktop computers, tablet computers, scanners, and other standardized equipment to the Field Centers for performing examinations, collecting data, and communicating data to the Coordinating Center and Reading Centers.

J. Maintain study databases.

K. Direct quality assurance and quality control programs.

L. Conduct statistical analyses for quality assurance, and scientific publications and presentations.

M. Create databases for investigators and the scientific community and support data sharing.

N. Contribute to new scientific developments within the study and work collaboratively with all centers to support early stage investigators in training.

O. Encourage investigators from outside the existing CARDIA sites to participate in data analysis and publication of the “public use” data from the NHLBI Data Repository. Also seek outside investigators to work with CARDIA investigators in analyzing the data not yet available through the NHLBI Data Repository. Formalize and expand existing plans to facilitate this to include (but not be limited to) publicizing the availability of data from Data Repository, the publication policy, and the ancillary study mechanisms on the CARDIA public website, at scientific meetings, or by letters to investigators. Provide data user support and designated staff to respond to inquiries about data or ancillary studies.

P. Prepare and submit technical and financial reports.

Q. Event Ascertainment: Follow-up shall be performed for morbidity (acute myocardial infarction, angina, stroke, heart failure, atrial fibrillation; peripheral vascular disease; chronic obstructive pulmonary disease; obstructive sleep apnea); mortality; and any cardiovascular disease interventions received. In addition, all hospitalizations will be identified and data collected on discharge diagnoses. All participants, including those who have refused participation and unequivocally expressed the desire not to be re-contacted, will be followed through the Social Security Death Index and other commercial databases as appropriate.

Table 2. Types of data to be collected for event ascertainment

1. Dates of deaths and hospitalizations

2. Interview data from participants or proxy

3. Hospital discharge diagnosis and ICD codes

4. Data collected from hospital inpatient and outpatient records

Events shall be classified in a standard manner and consistent with current CARDIA practice, as developed by the Endpoints Surveillance and Adjudication Subcommittee. Refinements to the protocol and Manual of Operations for event ascertainment should to the extent possible be comparable to other NHLBI-sponsored large cohort studies such as the Atherosclerosis Risk in Communities (ARIC) Study and the Multi-Ethnic Study of Atherosclerosis (MESA).

R. Mentoring Early Stage Investigators: Each Center shall provide formal and/or informal training opportunities for early stage investigators (assistant professors, fellows, and students). This includes but is not limited to early stage investigator working on data analyses and publications and serving on study subcommittees. Sites are encouraged to apply for supplements from existing NIH programs or include CARDIA experiences in existing training programs.

II. SPECIFIC REQUIREMENTS AND TASKS

A. Designate key personnel to lead and manage the study who have the appropriate qualifications and provide other staff to support the function of the study.

1. Designate a principal investigator with the following:

a. Training and experience in cardiovascular epidemiology

b. Demonstrated excellence as a manager and collaborator

c. Experience successfully managing the coordination of multi-center cohort studies.

2. Designate co-investigator(s)* knowledgeable in scientific areas relevant to the study and skilled in study design and data analysis

(* Include the designation of one co-investigator who is qualified to temporarily serve in the place of the principal investigator as needed.)

Note: The NHLBI Project Office must approve key personnel.

3. Designate other staff, including but not limited to:

a. Investigators

b. Project manager

c. Analysts

d. Operations staff

e. Events ascertainment coordinator

f. Events abstractor

g. Computer specialists

h. Publications and Presentation Committee coordinator

i. Ancillary studies manager/coordinator

j. Website manager

k. Administrative staff

B. Establish and manage laboratories, and other consultants and subcontracts, as necessary.

1. Identify qualified sources or justify providing a contract to a previously-used source;

provide Statement of Work and Deliverables; negotiate and award contracts, taking into account technical capabilities and cost; and manage contract. Coordinate with the NHLBI Project Office, as appropriate, for all phases of this work.

2. Identify and manage the Central Blood and Urine Repository, the DNA Laboratory, and all other laboratories for laboratory measures and specimens to be collected in the CARDIA Year 30 Exam (See Section I.D. for list of laboratory measurements). The tasks shall include, but are not limited to:

a. The laboratories shall develop and perform laboratory analyses of blood, urine, and DNA samples collected.

i. In collaboration with the Steering Committee, Laboratory Committee, and NHLBI Project Office develop protocols/manuals of operations for the Year 30 Exam laboratory components.

ii. For all laboratory measures that have been previously collected in CARDIA, use comparable methods unless otherwise justified.

iii. Include quality control measures to assure accuracy of measurements over time. Monitor and report quality control measurements at least biannually. Investigate and act to correct apparent errors in measurements.

iv. For planning purposes, estimate 5% repeat measurements and samples for quality control of assays.

v. Participate in comparability studies as deemed appropriate and necessary by the Steering Committee.

vi. As requested by the Coordinating Center, contribute to the training and certification of Field Center laboratory technicians.

vii. Assist Field Centers in establishing alert values as appropriate.

viii. Contribute to scientific aspects of the study, including data analysis and manuscript preparation.

b. The DNA Laboratory shall maintain a repository of extracted DNA and blood cells from which DNA may be extracted; create standard dilutions of DNA;

and retrieve, aliquot, and distribute selected DNA specimens to qualified investigators, under the direction of the Coordinating Center.

c. The Central Blood and Urine Repository shall maintain a repository of blood and urine specimens; and retrieve, aliquot, and distribute selected specimens to qualified investigators, under the direction of the Coordinating Center.

3. Identify and manage any reading centers that may be required as potential exam components are added to the study at a later date after further consideration by the Project Office.

4. As necessary and as directed by the Project Office, provide consultant agreements for analyses using previously-collected data and any data collected subsequently, and other areas where specific expertise is needed.

C. Coordinate development of the study protocol by the Steering Committee.

1. Facilitate and coordinate development of the study protocols and Manuals of

Operation for the following:

a. Field Centers operations

i. Assure that guidelines and protocols are in place to promptly identify and refer clinically significant findings from the examinations for routine reports and recommendations to participants.

ii. See Table 3 for list of examination components.

b. Laboratory Centers

c. Quality Control

d. Events

e. Data Analysis

i. Develop data documentation and manuals.

ii. Provide guidance for data analysis, including handling unusual features of the dataset and recommending analysis methods.

D. Facilitate and coordinate periodic follow-up contact of participants per protocol developed by the Steering Committee. Manage the data collected on clinical events and the classification of these events.

1. Coordinate Field Center follow-up contact of participants according to protocol.

2. Monitor data collection including timelines of collection and receipt of all reports, including final completed investigations. Notify Field Centers when reports are overdue.

3. Coordinate the activities of the Endpoints Surveillance and Adjudication Subcommittee, which will be comprised of representatives from the Coordinating Center and Field Centers knowledgeable about nosology and clinical assessment of cardiovascular and related diseases.

4. In conjunction with the Endpoints Surveillance and Adjudication Subcommittee, maintain standardized procedures to identify and classify morbid cardiovascular events (including myocardial infarction and other forms of coronary heart disease, stroke, heart failure, and atrial fibrillation), cardiovascular interventions, and all mortal events. Assure standardization of methodology and consistency of procedures over time with appropriate quality assurance activities.

5. Refine as needed, maintain, and oversee implementation of the protocol and Manual of Operations for Morbidity and Mortality Follow-up and Events investigations and reporting. The refinement shall include the addition of standardized procedures and forms for data abstraction by a centralized abstractor. Refinements should to the extent possible be comparable to other NHLBI-sponsored large cohort studies such as the Atherosclerosis Risk in Communities (ARIC) Study and the Multi-Ethnic Study of Atherosclerosis (MESA).

6. Provide Coordinating Center staff to serve as centralized data abstractor(s) of medical records, death certificates, and other relevant materials received from the Field Centers.

7. Create and post on the CARDIA internal web site regular reports on the status of events investigations and the outcomes of final adjudicated events that have accrued in the study.

E. Perform administrative duties to support productive collaboration among the study centers and the NHLBI Project Office.

1. Facilitate meetings and communications among all Centers, subcontractors, and the

NHLBI Project Office as necessary throughout the contract period.

2. Contribute leadership and membership as needed, as well as coordinate activities of the Steering Committee, Executive Committee, Endpoints Surveillance and Adjudication Subcommittee, Laboratory Committee, Imaging Committee, Quality Control Committee, Publications and Presentations Committee, Clinic Coordination and Retention Committee, Genetics Committee, and other subcommittees, as appropriate.

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

4. Update Ancillary Studies procedures to be consistent with NIH data sharing policies, including the Limited Access Data Set policy (http://www.nhlbi.nih.gov/funding/datasharing.htm) and other data sharing policies, such as for genome-wide association studies (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-06-094.html)

5. 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.

6. For conference calls, distribute meeting materials and the agenda at least three working days prior to meetings, and record and distribute minutes within 5 working days.

7. Make arrangements for and convene regular (biannual) in-person meetings for the Steering Committee. Distribute meeting materials and the agenda two weeks prior to in-person meetings. Record and distribute minutes from in-person meetings to the Project Office within 10 working days.

8. Make arrangements for and convene regular in-person meetings (generally at the time and location of the Steering Committee meetings) and conference calls for the subcommittees, as necessary and proposed by the subcommittee chairs.

9. Arrange for and manage annual meetings of the CARDIA Observational Studies Monitoring Board (OSMB) as directed by the NHLBI Project Office; distribute meeting materials at least three weeks prior to meetings; make travel and meeting arrangements for OSMB members; and provide expense reimbursement to OSMB members.

10. Coordinate the Executive Committee review and approval process of ancillary study proposals. Specific tasks include, but are not limited to:

a. Submit proposals approved by the Executive Committee to the OSMB Executive Secretary for OSMB review

b. Generate Executive Committee approval letters for ancillary studies (within 1 week of approval)

c. Maintain a log of all ancillary studies proposed, approved, or funded.

http://www.nhlbi.nih.gov/funding/datasharing.htm� http://grants.nih.gov/grants/guide/notice-files/NOT-OD-06-094.html�

11. Utilizing state-of-the-art web design and content by employing appropriate expertise in this field, modify and maintain CARDIA web sites, including an external site for the public and an internal site for study investigators and others, as necessary. The sites should contain, but not be limited to, the following:

a. Study description and timeline

b. Directory of investigators

c. Description of subcommittees

d. Manuals of Operations

e. Study Protocol and forms

f. Description and guidance for preparation and review of ancillary study proposals

g. Log of ancillary studies proposed, approved, ongoing, and completed

h. Newsworthy articles

i. Publications materials, including Abstracts and Published papers (or PubMed link to the paper), and papers in progress.

j. Guidance for preparation, submission, and review of paper proposals

k. Lists of Reading and Laboratory Centers and the NHLBI Project Office

l. Lists of examination components

12. Provide continuously updated status of blood, urine, and DNA specimen repositories, as well as provide a summary report table annually for inclusion in the OSMB report.

13. Oversee development and implementation of standardized informed consents.

a. In conjunction with the Steering Committee, coordinate development of standardized informed consent among the Field Centers.

b. Assure inclusion of all required elements.

c. Maintain a database on informed consent versions and participant responses, covering Exams from Years 0 to 30.

d. Assure that samples and data bases are distributed in accordance with the expressed desires of participants in their signed informed consents.

e. Post results of informed consent responses such that interested investigators may determine the availability of samples with appropriate consent.

Note: CARDIA has a Certificate of Confidentiality for DHHS Funded Studies that should be noted in the informed consent forms.

F. Provide relevant computers, tablets, scanners, and other standardized equipment to the Field Centers for performing examinations, collecting data, and communicating data to the Coordinating Center and Reading Centers.

1. Investigate, purchase, distribute, and coordinate utilization of appropriate common computer and other equipment among all centers, as relevant.

2. Coordinate utilization and upgrades, as necessary.

G. Maintain study databases.

1. Prepare data sets of examination results within 4 months of the end of Year 30 exam.

2. Maintain updated Morbidity and Mortality events data on a monthly basis.

3. Prepare documentation for distribution to investigators and the NHLBI Project Office and outside collaborations, per NIH data sharing policies and with appropriate protections for participant privacy and assuring that only qualified investigators have access. (Procedures for gaining access to the data by investigators will generally be through the manuscript proposal procedures or through an NHLBI-administered program.)

4. Provide data documentation to eligible users upon request

5. Provide updates with corrections to or clarifications of the database as necessary and maintain a record of these corrections or clarifications for future use.

6. Include data from examinations, interviews, follow-up data, imaging measurements and results, and laboratory measurements, morbidity and mortality data, and from all substudies and ancillary studies. (Note: Ancillary studies should provide data within 12 months of completion of data collection and editing.)

7. Maintain data on quality control measurements.

8. Provide to NHLBI Project Office raw data without individual identifiers whenever difficulties arise with the database, or on request.

H. Direct quality control and quality assurance programs.

1. Designate a Quality Control Committee to be chaired or co-chaired by a staff member from the Coordinating Center.

2. In conjunction with the Quality Control Committee and relevant subject matter experts within CARDIA:

a. Prepare a plan to monitor the quality of all data in a timely manner.

b. Include all questionnaire, interview, morbidity and mortality follow-up, laboratory, and imaging measures.

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

d. Where warranted, provide for approximately 5% blind duplicate measurements within an examination cycle (e.g., certain biochemical laboratory-based and imaging measures).

e. Include assessment and control of measurement temporal drift within and between examination cycles for each laboratory and reading center measurement, as feasible and necessary.

f. Include assessment of stability of stored laboratory specimens.

g. Assess on an ongoing basis and provide annual reports to the Steering Committee and to the OSMB including a review of collected data. Verify completeness, timeliness, reliability, and accuracy of collection and coding.

Include comparisons of measures of distribution of values between the Field Centers and/or technicians/instruments as appropriate to the measurement method. Include development and modification of standards to identify outlying values, and initiate and coordinate separate review of these observations for accuracy with the appropriate Field, Reading, and Laboratory Center.

h. When necessary, appropriate, and feasible, develop and implement plans for comparability studies when technologies or assays have changed over time or differ across centers.

i. Maintain logs of data received, edit checks conducted, and identified errors;

pursue missing data and correctable errors by communication with Field, Reading, and Laboratory Centers within three weeks of receipt and review of data; and develop, maintain, and modify an audit trail for all data entry and data correction activities, including electronically transferred data.

j. Monitor scheduled maintenance of equipment at Field Centers in collaboration with appropriate Reading Centers and Central Laboratory.

k. Establish QC activities for scanned data.

l. Coordinate initial certification and maintain ongoing retraining and recertification of performance capabilities of Field Center staff and Reading Center staff through centralized and localized training appropriate to the Center.

m. Coordinate and participate in periodic site visits to the collaborating centers as needed.

I. Conduct statistical analyses for quality assurance and scientific publications and presentations.

1. Perform centralized data analyses.

2. Support, via consultation, collaborating Centers in local analyses.

3. Develop statistical methods, as needed, to analyze new types of data.

4. Review analyses performed outside of the Coordinating Center for appropriateness.

This level of review should include only those manuscripts deemed necessary by the Publications and Presentations Committee, the Steering Committee, or NHLBI

Project Office.

5. Maintain a list and insofar as possible, repository of public presentations made using CARDIA data by the investigators.

6. Generate periodic reports on the status of publications and presentations, at least biannually for the Steering Committee and OSMB.

7. Maintain a database on paper proposals and manuscripts in progress.

8. Analyze data in a timely fashion for the presentation and publication of study results.

9. Provide statistical support for development and analysis of all quality assurance activities.

10. Provide timely responses to specific requests from the Project Office, Steering Committee, and OSMB.

J. Create databases for investigators and the scientific community and support data sharing, consistent with NIH policy, which may be found at http://www.nhlbi.nih.gov/funding/datasharing.htm. (For policies on sharing genome-wide association data see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-06-094.html)

1. Provide limited access data. Limited access data refers to study data, with certain deletions and recoding that are released to requesting institutions and investigators for specific purposes and with certain restrictions and conditions. Limited access data will be made available to the public in accordance with the NHLBI Policy for Distribution of Data (http://www.nhlbi.nih.gov/funding/datasharing.htm). All changes to the policy are hereby incorporated by reference without further amendment to the contract.

a. For the Year 20 Exam: Limited access data sets were released on September 1, 2011. Annual updates containing additional data such as genotyping, morbidity, and mortality should be provided (each September 1).

b. For the Year 25 Exam: Limited access data sets should be provided on September 1, 2014 and annually with updated events data, create limited access data sets with documentation.

c. For the Year 30 Exam: Consistent with NIH policy or three years after the completion of the Year 30 Exam (whichever comes first) and annually, with updated events data, create limited access data sets with documentation.

d. Include all ancillary study data in the limited access data sets.

Note: The limited access data sets will contain all the data deriving from an examination cycle or data collection activity, but may exclude raw data that is used solely for the purpose of creating summary or derived variables. It should exclude individual identifiers but include detailed documentation appropriate for independent use by an investigator external to the study and unfamiliar with details of the data. Participant privacy must also be assured by removing or modifying http://www.nhlbi.nih.gov/funding/datasharing.htm� variables that could lead to individual identification.

Data will not be released if believed to be unreliable or invalid by the NHLBI Project Office. Delays in data release must be approved by the NHLBI Project Office.

2. Working with the NHLBI Project Office, publicize the existence of CARDIA data sets for use by qualified scientists outside of the CARDIA investigators.

K. In conjunction with the Publications and Presentations Committee.

1. Coordinate the proposal, development, and prioritization of study manuscripts, and monitor progress in completing manuscripts,

2. Maintain an archive of proposed manuscripts (with search capabilities by CARDIA investigators), manuscript drafts, completed manuscripts and abstracts in print, in press, and in preparation, and

3. Supply reprints of published manuscripts upon request.

4. Oversee investigator utilization of Data Distribution Agreements, and track and manage files thereof.

5. Revise the CARDIA publication policy as needed in accordance with new NHLBI and NIH policies (e.g. NIH Public Access Policy:

http://publicaccess.nih.gov/index.htm)

L. Contribute to new scientific developments within the study and work collaboratively with all centers to support early stage investigators.

1. In collaboration with the other centers, or within the Coordinating Center, propose new ideas for analyses, testing, and scientific directions.

2. Propose new collaborations to achieve the goal of advancing new scientific objectives.

3. Support training of and providing experience for early stage investigators.

a. Both at the Coordinating Center and at collaboration centers, provide assistance to develop new research projects

b. Encourage early stage investigators to apply for programs to bring support for training

c. Provide guidance in accessing the data set, proposing manuscripts, analyzing data, interpreting findings, preparing manuscripts, identifying next steps for research, and proposing ancillary studies

M. Prepare and submit technical and financial reports, including the following:

1. Provide quarterly progress reports that include descriptive information about the activities undertaken during the reporting period and those planned for future http://publicaccess.nih.gov/index.htm� reporting periods. The Contractor shall report on:

a. Main operational activities

b. Problems encountered and how they were resolved

c. An accounting of personnel, including levels of effort and changes during the period

d. Progress report on the support of early stage investigators

e. Modifications to any subcontracts

f. Scientific productivity

2. Provide semi-annual status reports on Data and Materials Distribution Agreements that contain at minimum the following:

a. Date of request

b. Title of project

c. Names of investigator and Institution

d. For materials, the amount requested, including type and number of samples

e. Date of Executive Committee approval (for materials) or Publication Committee approval (for data)

f. Date materials are delivered to investigator(s), including amount of material and number of samples delivered and a return date of DNA/specimen if applicable.

4. Provide quarterly financial reports, as required by NIH.

N. Additional specific tasks for all Offerors:

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

The Offeror shall include the following documentation in the proposal. These plans are to be implemented by the Contractor during the period between July 1, 2013 and December 31, 2013.

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.

Option 1 Period (July 1, 2014 – June 30, 2015)

I. GENERAL REQUIREMENTS AND TASKS

The Contractor shall provide appropriate senior personnel with expertise in cardiovascular epidemiology, clinical and subclinical cardiovascular disease, longitudinal studies, laboratory

B. Manage the subcontract for the Steering Committee chairman.

C. Coordinate in collaboration with Project Office staff the establishment of a limited number of consultant agreements for experts in imaging, laboratory medicine, women’s health, lipid metabolism, genetics, and other disciplines as appropriate. These consultants will participate in protocol development and in analysis, interpretation, and publication of study data. These consultants shall participate in Steering Committee meetings and conference calls on a regular basis and otherwise be incorporated into study operations.

D. Participate actively in the study as members of the Steering Committee and other study committees.

E. Oversee development of and coordinate Field Center staff training and certification and pilot testing.

F. Oversee central administrative aspects of participant recruitment/retention and participant satisfaction assurance.

G. Monitor implementation of the study protocol by the Field Centers, Reading Centers, and laboratories, in accordance with the study timelines (Table 1 above).

H. Facilitate and coordinate the tracking of regular follow-up contact of participants.

I. Facilitate and coordinate the collection of data on clinical events and classification thereof.

Provide a centralized abstractor to abstract event data from medical records, death certificates, and other relevant materials received from the Field Centers.

J. Perform administrative duties to support productive collaboration among the study centers and the NHLBI Project Office.

K. Provide relevant desktop computers, tablet computers, scanners, and other standardized equipment to the Field Centers for performing examinations, collecting data, and communicating data to the Coordinating Center and Reading Centers.

L. Maintain study databases.

M. Direct quality assurance and quality control programs.

N. Conduct statistical analyses for quality assurance, and scientific publications and presentations.

O. Create databases for investigators and the scientific community and support data sharing.

P. Contribute to new scientific developments within the study and work collaboratively with all centers to support early stage investigators in training.

Q. Encourage investigators from outside the existing CARDIA sites to participate in data analysis and publication of the “public use” data from the NHLBI Data Repository. Also seek outside investigators to work with CARDIA investigators in analyzing the data not yet available through the NHLBI Data Repository. Formalize and expand existing plans to facilitate this to include (but not be limited to) publicizing the availability of data from Data Repository, the publication policy, and the ancillary study mechanisms on the CARDIA public website, at scientific meetings, or by letters to investigators. Provide data user support and designated staff to respond to inquiries about data or ancillary studies.

R. Prepare and submit technical and financial reports.

S. Event Ascertainment: Follow-up shall be performed for morbidity (acute myocardial infarction, angina, stroke, heart failure, atrial fibrillation; peripheral vascular disease; chronic obstructive pulmonary disease; obstructive sleep apnea); mortality; and any cardiovascular disease interventions received. In addition, all hospitalizations will be identified and data collected on discharge diagnoses. All participants, including those who have refused participation and unequivocally expressed the desire not to be re-contacted, will be followed through the Social Security Death Index and other commercial databases as appropriate.

Table 2. Types of data to be collected for event ascertainment

1. Dates of deaths and hospitalizations

2. Interview data from participants or proxy

Events shall be classified in a standard manner and consistent with current CARDIA practice, as developed by the Endpoints Surveillance and Adjudication Subcommittee. Refinements to the protocol and Manual of Operations for event ascertainment should to the extent possible be comparable to other NHLBI-sponsored large cohort studies such as the Atherosclerosis Risk in Communities (ARIC) Study and the Multi-Ethnic Study of Atherosclerosis (MESA).

T. Mentoring Early Stage Investigators: Each Center shall provide formal and/or informal training opportunities for early stage investigators (assistant professors, fellows, and students). This includes but is not limited to early stage investigator working on data analyses and publications and serving on study subcommittees. Sites are encouraged to apply for supplements from existing NIH programs or include CARDIA experiences in existing training programs.

II. SPECIFIC REQUIREMENTS AND TASKS

A. Designate key personnel to lead and manage the study who have the appropriate qualifications and provide other staff to support the function of the study.

1. Designate a principal investigator with the following:

b. Demonstrated excellence as a manager and collaborator

c. Experience successfully managing the coordination of multi-center cohort studies.

2. Designate co-investigator(s)* knowledgeable in scientific areas relevant to the study and skilled in study design and data analysis

(* Include the designation of one co-investigator who is qualified to temporarily serve in the place of the principal investigator as needed.)

Note: The NHLBI Project Office must approve key personnel.

3. Designate other staff, including but not limited to:

a. Investigators

b. Project manager

c. Analysts

d. Operations staff

e. Events ascertainment coordinator

f. Events abstractor

g. Computer specialists

h. Publications and Presentation Committee coordinator

i. Ancillary studies manager/coordinator provide Statement of Work and Deliverables; negotiate and award contracts, taking into account technical capabilities and cost; and manage contract. Coordinate with the NHLBI Project Office, as appropriate, for all phases of this work.

2. Identify and manage the Central Blood and Urine Repository, the DNA Laboratory, and all other laboratories for laboratory measures and specimens to be collected in the CARDIA Year 30 Exam (See Section I.D. for list of laboratory measurements). The tasks shall include, but are not limited to:

a. The laboratories shall develop and perform laboratory analyses of blood, urine, and DNA samples collected.

i. In collaboration with the Steering Committee, Laboratory Committee, and NHLBI Project Office develop protocols for the Year 30 Exam laboratory components.

ii. For all laboratory measures that have been previously collected in CARDIA, use comparable methods unless otherwise justified.

iii. Include quality control measures to assure accuracy of measurements over time. Monitor and report quality control measurements at least biannually. Investigate and act to correct apparent errors in measurements.

iv. For planning purposes, estimate 5% repeat measurements and samples for quality control of assays.

v. Participate in comparability studies as deemed appropriate and necessary by the Steering Committee.

vi. As requested by the Coordinating Center, contribute to the training and certification of Field Center laboratory technicians.

vii. Participate in a pilot study that will include receipt of a specified number of specimens from the Field Centers to test the Year 30 exam protocol for collecting and shipping samples. The samples must be analyzed and the results sent to the Coordinating Center no later than 14 days after receipt of Field Center’s specimens.

viii. Assist Field Centers in establishing alert values as appropriate.

ix. Assist Field Centers in reporting clinical values to participants in a timely manner.

x. Contribute to scientific aspects of the study, including data analysis and manuscript preparation.

b. The DNA Laboratory shall maintain a repository of extracted DNA and blood cells from which DNA may be extracted; create standard dilutions of DNA;

and retrieve, aliquot, and distribute selected DNA specimens to qualified investigators, under the direction of the Coordinating Center.

c. The Central Blood and Urine Repository shall maintain a repository of blood and urine specimens; and retrieve, aliquot, and distribute selected specimens to qualified investigators, under the direction of the Coordinating Center.

3. Identify and manage any reading centers that may be required as potential exam components are added to the study at a later date after further consideration by the Project Office.

4. As necessary and as directed by the Project Office, provide consultant agreements for analyses using previously-collected data and any data collected subsequently, and other areas where specific expertise is needed.

C. Finalize protocols and support OMB Forms Clearance Process.

1. Develop and finalize protocols.

a. Circulate protocols to Steering Committee and NHLBI Project Office for review and develop Manuals of Operations.

b. Finalize protocols and Manuals and post to web site.

c. Periodically update protocols and Manuals as needed.

2. Support the OMB Forms Clearance Process by preparing all materials required for the Year 30 exam and ongoing follow-up contacts as described in the OMB public access webpage http://www.hhs.gov/ocio/policy/collection/ (Section II, References), under the direction of the NHLBI Project Office. The renewal OMB clearance package shall be submitted by October 31, 2014. Note: It is possible that the OMB Clinical Exemption under which the study currently operates will remain in effect during the renewal but this is not guaranteed

D. Oversee development of and coordinate Field Center staff training and certification and pilot testing.

1. Make arrangements for central training of staff from all Field Centers approximately six weeks prior to the start of the Year 30 Exam. Plan for staff persons to attend from each Field Center, plus trainers and experts in the various components.

2. Develop a program to certify technicians and maintain certification to assure high quality and standardized measurements across the Field Centers.

3. Oversee pilot testing, analysis and review of the pilot results with the Steering Committee. Pilot testing is to be conducted after training is complete, and is to consist of performing the examination, according to the draft Manual of Operations, in at least 9 volunteers per Field Center, who are not study participants. The pilot tests are to include shipping blood samples to the appropriate laboratories and transmission of images and other data from the appropriate reading centers.

4. Oversee implementation of improvements in protocols and manuals based on the pilot study results.

5. Update staff on protocol changes.

E. Monitor implementation of the study protocol by the Field Centers, Reading Centers, and Laboratories, in accordance with the study timelines.

1. Support the functions of the Steering Committee in all aspects of protocol implementation and scientific and operational management of the study.

2. In conjunction with the Steering Committee and Field Centers, develop and, to the extent possible, standardize methods of participant recruitment and retention across Field Centers.

3. Develop, implement, and maintain a web-based tracking system for use by the Field Centers, to collect and monitor follow-up contacts and events.

4. Develop, implement, and maintain a web-based system for use by the Field Centers, to track and electronically provide participants with their clinical results and other communications (e.g., birthday cards, scheduled exam date).

5. Update the data collection and entry systems to allow Field Center staff to perform http://www.hhs.gov/ocio/policy/collection/� computer-assisted data entry and initial verification and correction of the entered data.

a. Collection of data for the Year 30 Exam and follow-up activities should be performed using electronic means (i.e., computer entry or tablet) to the extent possible. Use of paper forms for data collection should be limited.

b. Provide software to the Field Centers for electronically entering medication data against a computerized database of medications.

6. Oversee data collection for the Year 30 Exam

a. Monitor timeliness, completeness, and quality of all data collected.

b. Report periodically to the NHLBI Project Office and Steering Committee and/or post results at least every two weeks on the web site.

c. Report at least every two weeks to sites and centers on overdue, missing, or out-of-range data or other data irregularities.

d. Provide weekly recruitment reports for the exam by center, race, and gender group, including number examined for each week, cumulative number examined, average number examined per week, number needed to reach target, and percent of target examined.

7. Prepare for use by the Field Centers reports on clinical information for participants and their physicians. Coordinate the efforts to ensure the reports are distributed in a timely matter (Note: Non-urgent findings from examinations should be reported within 4 weeks of examination. Urgent findings must be reported the same day or as clinically relevant and feasible.)

F. Examination Components

Data to be collected during the…