CARDIA Y30 FINAL ECHO SOW.pdf

ATTACHMENT #3

STATEMENT OF WORK – CARDIA ECHOCARDIOGRAPHY READING CENTER

STATEMENT OF WORK – CARDIA ECHOCARDIAGRAPHY READING 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 disease.

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.

C. Examination Components

Data to be collected are approximated by the following list of components, which may be modified during protocol development. Unless there is a strong rationale, procedures should be similar to those used for previous data collections in CARDIA. The final protocol as approved by the NHLBI in consultation with the OSMB shall constitute the final content and schedule of the data to be collected.

• Consent

Table 1. List of Year 30 Exam components

• Demographic information

• Anthropometry

• Blood pressure

• Smoking history

• Medical history, including medications

• A limited number of questionnaires, including but not limited to perimenopause, behavioral factors related to weight gain and weight loss, and physical activity

• Fasting phlebotomy for whole blood, serum, plasma, and DNA collection

• Spot urine collection for albumin and creatinine

• M-mode and 2-D echocardiography with tissue doppler and speckle tracking

D. Laboratory Measures

The following specific types or classes of measurements will be made. The final protocol for lab measurements will be determined by the Steering Committee.

1. Established clinical measures of metabolism, renal function, and lipid metabolism.

2. Urine creatinine and albumin.

3. Collection and storage of DNA, serum, plasma, and urine.

E. 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 National 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).

F. 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.

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 four 12-month 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 July 1, 2017 – June 30, 2018

Table 3. 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

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

Close Out

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

Note: Throughout this statement of work, the terms “Contractor” and “Echocardiography Reading Center” are used interchangeably.

1. Participate in the CARDIA Steering Committee, the Imaging Committee, and Quality Control Committee, as appropriate.

Throughout the contract period, the Contractor shall:

2. Develop the protocol for the acquisition and reading/information abstraction of the echocardiograms to be performed as part of the CARDIA Year 30 Exam.

3. Determine comparability of the proposed CARDIA Year 30 echocardiographic measurement to that from the Year 5 and Year 25 Exams by performing repeat measures of about 200 digitized Year 5 echocardiographic studies and 200 Year 25 echocardiographic studies.

4. Propose a plan to evaluate myocardial function using novel techniques, particularly left ventricular function from the Year 30 echocardiographic studies. This plan should be based on sound scientific evidence and hypotheses.

5. Propose a plan to assess 25-year changes (from Year 5 to Year 30) in echocardiographic measurements utilizing the Year 5 and Year 25 results, particularly left ventricular structure and function, in the CARDIA cohort.

6. Train and certify Field Centers’ echocardiography technicians according to protocol.

7. Train and certify echocardiography readers at the Reading Center according to protocol, as well as orient professional staff from the Coordinating Center and NHLBI Project Office who have quality assurance responsibilities

8. Conduct a pretest of the Year 30 echocardiography protocol, including quality assurance activities, during the pilot testing phase of the Year 30 Exam, in collaboration with the CARDIA Coordinating Center and Field Centers.

9. Perform readings/information abstractions of echocardiograms in a timely manner during the pilot phase and throughout the Year 30 Exam period.

10. In collaboration with the Steering Committee, provide advice on the development of clinical alert values for reporting results to participants.

11. In collaboration with the Coordinating Center and Field Centers, provide timely reporting of clinically significant results to participants. Reviews for clinical alerts and referrals should be performed within 14 days.

12. Track the receipt, reading, and storage of echocardiograms

13. Develop and implement short-term archiving during the Year 30 Exam at the Field Centers, long-term archiving and storage of echocardiograms, and timely creation of backup copies.

14. Visit CARDIA Field Centers during the early phase of the Year 30 Exam and as needed, in support of quality assurance efforts of the study.

15. Participate actively in data analysis, presentation, and publication using the echocardiographic data.

16. Prepare and submit technical and financial reports as specified herein.

II. SPECIFIC REQUIREMENTS AND TASKS

A. Base, and Options 1-4 as per Table 3, Throughout the contract period, the Contractor shall:

1. Designate key personnel* to lead and manage the study who have the appropriate qualifications. (*Note: The NHLBI Project Office must approve key personnel.)

a. A principal investigator with:

i. Training and experience in echocardiography and cardiovascular epidemiology

ii. Demonstrated excellence as a manager and collaborator

b. Co-investigator(s)** knowledgeable in scientific areas relevant to the study and skilled in echocardiography protocol 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.)

2. Provide other staff, which may include the following:

a. Investigator(s)

b. Project manager

c. Echocardiography readers

d. Data management staff

3. Participate in and designate staff to participate in the Steering Committee, Imaging Committee, and Quality Control Committee, as appropriate. Establish and provide scientific and organizational leadership for an Echocardiography Subcommittee.

4. Participate in various administrative activities to include, but not be limited to:

visiting field centers as needed in support of quality assurance activities; preparing reports for the Steering Committee, Imaging Committee, Quality Control Committee, and Observational Study Monitoring Board.

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

a. Semi-annual progress reports that describe main operational activities during the period, general progress in each activity, problems encountered and how they were resolved, an accounting of personnel (include levels of effort and changes during the period), and scientific productivity.

b. Quarterly Staffing Report: Table containing a list of all current staff (name, position, administrative group, level of effort, and change in effort) and an explanation of any staffing changes.

c. Periodic financial reports, as required by NIH, specific to your institution.

B. Base and Option 1 as per Table 3, the Contractor shall:

1. Develop, at the direction of the Steering Committee and in collaboration with the

Imaging Committee, the Year 30 Exam protocol for performing the echocardiography examination at each Field Center, as well as the reading and information abstraction of the echocardiographic images at the Echocardiography Reading Center. The protocol will specify the techniques to measure the following measurements* and should aim to not exceed 30-40 minutes of participants' time during the examination (*Note: The list of measurements is subject to modification after the Echocardiography Reading Center contract is awarded, as a result of protocol development in collaboration with the Imaging Committee, Steering Committee, and NHLBI Project Office. The list of measurements should be based upon those performed at Year 5 and 25):

a. Left ventricular structure and function (systolic and diastolic),

b. Left atrial and aortic root dimensions,

c. Right atrial and ventricular structure and function,

d. Trans-mitral and aortic flow velocities,

e. Pulmonary artery systolic pressure, and

f. Echocardiography-based clinical diagnosis (e.g. aortic stenosis, chamber enlargement, wall motion abnormalities, left ventricular hypertrophy, mitral and tricuspid regurgitation, etc.).

2. Advise and assist the Field Centers in assuring the functionality of the Toshiba Artida echocardiography machines utilized during the CARDIA Year 25 Exam for the Year 30 Exam. If necessary, establish a service agreement with Toshiba.

3. Propose a plan to evaluate myocardial function using novel techniques, particularly left ventricular function from the Year 30 echocardiographic studies. This plan should be based on sound scientific evidence and hypotheses.

4. Propose a plan to assess 25-year changes (from Year 5 to Year 30) in echocardiographic measurements utilizing the Year 5 and Year 25 results, particularly left ventricular structure and function, in the CARDIA cohort.

5. Provide advice on language pertaining to the Year 30 echocardiography examination to be included in the informed consent document.

6. In collaboration with the Steering Committee, provide advice on the development of a graded alert system that identifies which abnormalities seen on the echocardiograms will be reported to the study participants, and in what form.

7. In collaboration with the Quality Control Committee, design quality control measures for performing the echocardiographic examinations at the Field Centers and reading of echocardiograms at the Echocardiography Reading Center. The goals should be to ensure reproducibility both for a given technician (i.e. limit intra-individual variability) and between technicians (i.e. limit inter-individual variability) at various Field Centers, as well as to ensure reproducibility both within and between readers at the Echocardiography Reading Center.

a. Develop quality assurance procedures and performance standards to ensure that studies from each echocardiography technician at each Field Center and the readings of the study echocardiograms at the Echocardiography Reading Center conform to protocol requirements. Include in the plan procedures for assessment and control of inter- and intra-technician variability, as well as inter- and intra-reader variability.

b. Develop protocol for performing a subset of blind duplicate echocardiographic studies at each Field Center, to be read as blind duplicates at the Echocardiography Reading Center. Compare results of blind duplicates to original studies in a timely manner as specified in the study protocol, and provide feedback to technicians on a regular basis.

c. Develop protocol for performing the re-reads of a subset of blind duplicate echocardiographic studies at the Echocardiography Reading Center. Compare results of blind duplicates to original studies in a timely manner as specified in the study protocol, and provide feedback to readers on a regular basis.

8. Prepare and present to the Steering Committee two Echocardiography Manuals of Operation: one for measurement (reading) of echocardiography data for the Echocardiography Reading Center and one for performing the echocardiography examination for the Field Centers. Both the draft and final forms of these Manuals of Operations shall be submitted to the Steering Committee for approval prior to training clinic staff. These Manuals of Operations shall be web-friendly for posting on the CARDIA internal website for use by the Field Centers, the Coordinating Center, and the Project Office.

9. Assist the Field Centers in the selection of appropriately trained and experienced echocardiography technicians. Train and certify technicians according to protocol.

This will include the initial training, certification, and orientation in the pilot testing phase, any necessary recertification, and the training, certification, and orientation of new technicians and quality assurance due to staff turnover.

10. Train and certify echocardiography readers at the Echocardiography Reading Center according to protocol. This will include the initial training, certification, and orientation in the pilot testing phase, any necessary recertification, and the training, certification, and orientation of new readers and quality assurance staff due to turnover.

11. Orient, as necessary, professional staff from the Coordinating Center with quality assurance responsibilities and the NHLBI Project Office according to the reading and information abstraction protocol.

12. Participate in the pilot testing for the Year 30 Exam. The pilot test will occur after training is complete, consisting of performing all of the components of the Year 30 Exam according to the draft Manual of Operations, in at least 9 volunteers per Field Center who are not study participants. The pilot tests also are to include transmission of echocardiographic images to the contractor, who shall read the images according to protocol. The contractor shall also participate in transmitting the abstracted echocardiographic data to the Coordinating Center. Results will be reviewed by the Steering Committee.

13. Redesign and implement changes in protocol, as recommended by the Imaging Committee and approved by the Steering Committee, based on pilot testing results.

14. Assist the Coordinating Center in making final modifications to the Manual of Operations based on the pilot test results at the direction of the Steering Committee.

15. Deliver the following to the Coordinating Center:

a. The Field Center and Reading Center Protocols and Manual of Operations:

draft at least 8 weeks prior to start of Year 30 pilot examination and final at least 4 weeks prior to start of Year 30 examinations.

b. Training materials for echocardiography technicians and the Coordinating Center at least 6 weeks prior to the technicians’ training session.

c. Pilot test results (raw data) and written evaluation and recommendations, within 14 days of receipt of Field Center images.

d. Reading Center clinical alert review and referral within 14 days after receipt of images from the Field Centers.

e. Reading Center results data transmitted electronically within 28-30 days after receipt of images from the Field Centers.

f. Quality control data, monthly and ending 1 month after end of exam.

g. Reading Center Status Reports for distribution to the SC, monthly

1. Prior to exam: Describe status of protocol, Manual of Operations, training materials, training plans

2. During pilot and exam: Describe number of images received from Field Centers, number read (monthly and cumulative), quality assessment of the echocardiography technicians, summary of feedback to technicians if applicable, number of scans reread for quality control, any problems identified and proposed solutions

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

I. GENERAL REQUIREMENTS AND TASKS

Throughout the contract period, the Contractor shall:

2. Develop the protocol for the acquisition and reading/information abstraction of the echocardiograms to be performed as part of the CARDIA Year 30 Exam.

3. Determine comparability of the proposed CARDIA Year 30 echocardiographic measurement to that from the Year 5 and Year 25 Exams by performing repeat measures of about 200 digitized Year 5 echocardiographic studies and 200 Year 25 echocardiographic studies.

4. Propose a plan to evaluate myocardial function using novel techniques, particularly left ventricular function from the Year 30 echocardiographic studies. This plan should be based on sound scientific evidence and hypotheses.

5. Propose a plan to assess 25-year changes (from Year 5 to Year 30) in echocardiographic measurements utilizing the Year 5 and Year 25 results, particularly left ventricular structure and function, in the CARDIA cohort.

6. Train and certify Field Centers’ echocardiography technicians according to protocol.

7. Train and certify echocardiography readers at the Reading Center according to protocol, as well as orient professional staff from the Coordinating Center and NHLBI Project Office who have quality assurance responsibilities

8. Conduct a pretest of the Year 30 echocardiography protocol, including quality assurance activities, during the pilot testing phase of the Year 30 Exam, in collaboration with the CARDIA Coordinating Center and Field Centers.

9. Perform readings/information abstractions of echocardiograms in a timely manner during the pilot phase and throughout the Year 30 Exam period.

10. In collaboration with the Steering Committee, provide advice on the development of clinical alert values for reporting results to participants.

11. In collaboration with the Coordinating Center and Field Centers, provide timely reporting of clinically significant results to participants. Reviews for clinical alerts and referrals should be performed within 14 days.

12. Track the receipt, reading, and storage of echocardiograms

13. Develop and implement short-term archiving during the Year 30 Exam at the Field Centers, long-term archiving and storage of echocardiograms, and timely creation of in support of quality assurance efforts of the study.

15. Participate actively in data analysis, presentation, and publication using the

a. A principal investigator with:

i. Training and experience in echocardiography and cardiovascular epidemiology

ii. Demonstrated excellence as a manager and collaborator

b. Co-investigator(s)** knowledgeable in scientific areas relevant to the study and skilled in echocardiography protocol design and data analysis

b. Project manager scientific and organizational leadership for an Echocardiography Subcommittee.

4. Participate in various administrative activities to include, but not be limited to:

visiting field centers as needed in support of quality assurance activities; preparing

a. Semi-annual progress reports that describe main operational activities during the period, general progress in each activity, problems encountered and how they were resolved, an accounting of personnel (include levels of effort and changes during the period), and scientific productivity.

b. Quarterly Staffing Report: Table containing a list of all current staff (name, B. Base and Option 1 as per Table 3, the Contractor shall:

1. Develop, at the direction of the Steering Committee and in collaboration with the Imaging Committee, the Year 30 Exam protocol for performing the echocardiography examination at each Field Center, as well as the reading and information abstraction of the echocardiographic images at the Echocardiography Reading Center. The protocol will specify the techniques to measure the following measurements* and should aim to not exceed 30-40 minutes of participants' time during the examination (*Note: The list of measurements is subject to modification after the Echocardiography Reading Center contract is awarded, as a result of protocol development in collaboration with the Imaging Committee, Steering Committee, and NHLBI Project Office. The list of measurements should be based upon those performed at Year 5 and 25):

a. Left ventricular structure and function (systolic and diastolic),

b. Left atrial and aortic root dimensions,

c. Right atrial and ventricular structure and function,

d. Trans-mitral and aortic flow velocities,

e. Pulmonary artery systolic pressure, and

f. Echocardiography-based clinical diagnosis (e.g. aortic stenosis, chamber enlargement, wall motion abnormalities, left ventricular hypertrophy, mitral and tricuspid regurgitation, etc.).

2. Advise and assist the Field Centers in assuring the functionality of the Toshiba Artida echocardiography machines utilized during the CARDIA Year 25 Exam for the Year 30 Exam. If necessary, establish a service agreement with Toshiba.

3. Propose a plan to evaluate myocardial function using novel techniques, particularly left ventricular function from the Year 30 echocardiographic studies. This plan should be based on sound scientific evidence and hypotheses.

4. Propose a plan to assess 25-year changes (from Year 5 to Year 30) in echocardiographic measurements utilizing the Year 5 and Year 25 results, particularly left ventricular structure and function, in the CARDIA cohort.

5. Provide advice on language pertaining to the Year 30 echocardiography examination to be included in the informed consent document.

6. In collaboration with the Steering Committee, provide advice on the development of a graded alert system that identifies which abnormalities seen on the echocardiograms will be reported to the study participants, and in what form.

7. In collaboration with the Quality Control Committee, design quality control measures for performing the echocardiographic examinations at the Field Centers and reading of echocardiograms at the Echocardiography Reading Center. The goals should be to ensure reproducibility both for a given technician (i.e. limit intra-individual variability) and between technicians (i.e. limit inter-individual variability) at various Field Centers, as well as to ensure reproducibility both within and between readers at the Echocardiography Reading Center.

a. Develop quality assurance procedures and performance standards to ensure that studies from each echocardiography technician at each Field Center and the readings of the study echocardiograms at the Echocardiography Reading Center conform to protocol requirements. Include in the plan procedures for assessment and control of inter- and intra-technician variability, as well as inter- and intra-reader variability.

b. Develop protocol for performing a subset of blind duplicate echocardiographic studies at each Field Center, to be read as blind duplicates at the Echocardiography Reading Center. Compare results of blind duplicates to original studies in a timely manner as specified in the study protocol, and provide feedback to technicians on a regular basis.

c. Develop protocol for performing the re-reads of a subset of blind duplicate echocardiographic studies at the Echocardiography Reading Center. Compare results of blind duplicates to original studies in a timely manner as specified in the study protocol, and provide feedback to readers on a regular basis.

8. Prepare and present to the Steering Committee two Echocardiography Manuals of Operation: one for measurement (reading) of echocardiography data for the Echocardiography Reading Center and one for performing the echocardiography examination for the Field Centers. Both the draft and final forms of these Manuals of Operations shall be submitted to the Steering Committee for approval prior to training clinic staff. These Manuals of Operations shall be web-friendly for posting on the CARDIA internal website for use by the Field Centers, the Coordinating Center, and the Project Office.

9. Assist the Field Centers in the selection of appropriately trained and experienced echocardiography technicians. Train and certify technicians according to protocol.

This will include the initial training, certification, and orientation in the pilot testing phase, any necessary recertification, and the training, certification, and orientation of new technicians and quality assurance due to staff turnover.

10. Train and certify echocardiography readers at the Echocardiography Reading Center according to protocol. This will include the initial training, certification, and orientation in the pilot testing phase, any necessary recertification, and the training, certification, and orientation of new readers and quality assurance staff due to turnover.

11. Orient, as necessary, professional staff from the Coordinating Center with quality assurance responsibilities and the NHLBI Project Office according to the reading and information abstraction protocol.

12. Participate in the pilot testing for the Year 30 Exam. The pilot test will occur after training is complete, consisting of performing all of the components of the Year 30 Exam according to the draft Manual of Operations, in at least 9 volunteers per Field Center who are not study participants. The pilot tests also are to include transmission of echocardiographic images to the contractor, who shall read the images according to protocol. The contractor shall also participate in transmitting the abstracted echocardiographic data to the Coordinating Center. Results will be reviewed by the Steering Committee.

13. Redesign and implement changes in protocol, as recommended by the Imaging Committee and approved by the Steering Committee, based on pilot testing results.

14. Assist the Coordinating Center in making final modifications to the Manual of Operations based on the pilot test results at the direction of the Steering Committee.

15. Deliver the following to the Coordinating Center:

a. The Field Center and Reading Center Protocols and Manual of Operations:

draft at least 8 weeks prior to start of Year 30 pilot examination and final at least 4 weeks prior to start of Year 30 examinations.

b. Training materials for echocardiography technicians and the Coordinating Center at least 6 weeks prior to the technicians’ training session.

c. Pilot test results (raw data) and written evaluation and recommendations, within 14 days of receipt of Field Center images.

d. Reading Center clinical alert review and referral within 14 days after receipt of images from the Field Centers.

e. Reading Center results data transmitted electronically within 28-30 days after receipt of images from the Field Centers.

f. Quality control data, monthly beginning on July 1, 2015 and ending 1 month after end of exam.

g. Reading Center Status Reports for distribution to the SC, monthly

3. Prior to exam: Describe status of protocol, Manual of Operations, training materials, training plans

4. During pilot and exam: Describe number of images received from Field Centers, number read (monthly and cumulative), quality assessment of the echocardiography technicians, summary of feedback to technicians if applicable, number of scans reread for quality control, any problems identified and proposed solutions

C. Options 1 and 2 as per Table 3, the Contractor shall:

1. Work cooperatively with other study centers, including Field Centers, Coordinating Center, Reading Centers, Laboratories, and the NHLBI Project Office staff in all relevant aspects of study development and execution.

2. Perform readings/information abstractions of echocardiographic measurements throughout the CARDIA Year 30 exam period. Enter and transmit abstracted information from the study’s echocardiograms into a computer, using software designed in cooperation with the Coordinating Center, and transmit the data to the Coordinating Center within 28-30 days of receipt of the echocardiographic images.

Echocardiograms should be read for any clinical alerts and referrals within 14 days of receipt. The Reading Center must notify the Coordinating Center in advance of, and the Coordinating Center must agree to, any proposed changes in the data transfer format during the exam cycle.

3. Assist in the analysis and interpretation of the echocardiographic data, the report of the results to the Steering Committee, and the design and implementation of any necessary corrective actions.

4. In collaboration with the Quality Control Committee, the Field Centers, and the

Coordinating Center, implement quality control measures for the acquisition of echocardiograms at the Field Centers and reading of echocardiograms at the Echocardiography Reading Center. Ensure both within- and between-technician reproducibility at various Field Centers. Ensure both within- and between-reader reproducibility at the Echocardiography Reading Center. Monitor performance to ensure uniformity of data collection among all Field Centers throughout the data collection period and report results of this monitoring to the Steering Committee:

a. Implement quality assurance procedures and performance standards to ensure that echocardiogram technicians at each Field Center and echocardiogram readers at the Echocardiography Reading Center conform to protocol requirements. This includes assessing and control of inter- and intra-technician variability, as well as inter- and intra-reader variability.

b. Implement the protocol for performing a subset of blind duplicate echocardiographic studies at each Field Center, to be read as blind duplicates at the Echocardiography Reading Center. Compare results of blind duplicates to original studies in a timely manner as specified in the study protocol, and provide feedback to technicians on a regular basis.

c. Implement the protocol for performing the re-reads of a subset of blind duplicate echocardiographic studies at the Echocardiography Reading Center. Compare results of blind duplicates to original studies in a timely manner as specified in the study protocol, and provide feedback to readers on a regular basis.

d. Transmit quality control data to the Coordinating Center according to specifications of the study protocol.

e. Participate in the analysis and interpretation of the quality control data.

f. Perform site visits of the four Field Centers during the first 4-6 weeks of the Year 30 exam and later as needed in support of quality control monitoring by the Coordinating Center. Prepare site visit reports within 21 days of site visit; the reports shall be delivered to the Field Center, the Project Office, and all other members of the site visit team.

g. Orient, as necessary, professional staff from the Coordinating Center with quality assurance responsibilities and the NHLBI Project Office according to the reading and information abstraction protocol.

h. Perform any necessary recertification and the training, certification, and orientation of new echocardiography technicians and readers due to staff turnover

5. Assist the Field Centers and Coordinating Center in generating clinical reports provided to the Field Centers for prompt reporting to participants, along with appropriate clinical recommendations (such as for clinical follow-up) within 14 days of receipt.

6. Track the receipt, reading, and storage of echocardiograms.

a. Develop and implement methods to assure complete and accurate transfer of echocardiograms between the Field Center and the Echocardiography Reading Center, including receiving the echocardiograms from the Field Centers, verifying that the number of echocardiograms received matches the number sent according to logs from the Field Centers, and resolving discrepancies with the Field Centers.

To ensure that scans were received for each participant who had an echocardiogram, transmit weekly to the Coordinating Center an electronic list of IDs for participants for whom echocardiograms were received that week. Work collaboratively with the Field Centers and Coordinating Center to resolve discrepancies.

b. Develop and implement methods to assure complete and accurate transfer of all data to the Coordinating Center. Data transmission will occur on a regular basis, approximately weekly or as agreed upon in protocol development (not to exceed 14 days for clinical alert and referrals and 30 days for full data transfer). The content and format of data transmitted will be developed in collaboration with the Coordinating Center.

c. To ensure that all activities have been performed for each participant’s data, maintain an electronic tracking database to include: date scan received from the Field Centers; date read and reader ID; scan quality assessment; reread dates and reader ID if appropriate; date of transmission to Coordinating Center; and location of original and backup copy if appropriate. Share database with Coordinating Center upon request.

d. Develop and implement short-term archiving during the Year 30 Exam at the Field Centers, long-term archiving and storage of echocardiograms, and timely creation of backup copies.

7. Determine comparability of the Year 30 echocardiographic measurement to that from the Year 5 and Year 25 Exams. This includes performing repeat measures of about 200 echocardiograms and 10% blind duplicates of studies from each Exam. Tasks related to this comparability study include, but are not limited to, the following:

a. Perform the measurements according to protocol and transmit all data to the Coordinating Center by December 1, 2015.

b. Assist in analysis of comparability study and provide summary of findings and recommendations for any further re-readings or analyses to the Steering Committee by December 30, 2015.

c. Assess and control intra- and inter-individual variability in reading protocol during the comparability study, and propose modification of this protocol as needed.

[Note: The Year 5 and 25 protocol and manual of operations can be found at http://www.cardia.dopm.uab.edu/]

8. Provide raw data to NHLBI Project Office, upon request

Option 2 Period (July 1, 2015 – June 30, 2016)

I. GENERAL REQUIREMENTS AND TASKS

Throughout the contract period, the Contractor shall:

2. Develop the protocol for the acquisition and reading/information abstraction of the echocardiograms to be performed as part of the CARDIA Year 30 Exam.

3. Determine comparability of the proposed CARDIA Year 30 echocardiographic measurement to that from the Year 5 and Year 25 Exams by performing repeat measures of about 200 digitized Year 5 echocardiographic studies and 200 Year 25 echocardiographic studies.

4. Propose a plan to evaluate myocardial function using novel techniques, particularly left ventricular function from the Year 30 echocardiographic studies. This plan should be based on sound scientific evidence and hypotheses.

5. Propose a plan to assess 25-year changes (from Year 5 to Year 30) in echocardiographic measurements utilizing the Year 5 and Year 25 results, particularly left ventricular structure and function, in the CARDIA cohort.

6. Train and certify Field Centers’ echocardiography technicians according to protocol.

7. Train and certify echocardiography readers at the Reading Center according to protocol, as well as orient professional staff from the Coordinating Center and NHLBI Project Office who have quality assurance responsibilities

8. Conduct a pretest of the Year 30 echocardiography protocol, including quality assurance activities, during the pilot testing phase of the Year 30 Exam, in collaboration with the CARDIA Coordinating Center and Field Centers.

9. Perform readings/information abstractions of echocardiograms in a timely manner during the pilot phase and throughout the Year 30 Exam period.

10. In collaboration with the Steering Committee, provide advice on the development of clinical alert values for reporting results to participants.

11. In collaboration with the Coordinating Center and Field Centers, provide timely reporting of clinically significant results to participants. Reviews for clinical alerts and referrals should be performed within 14 days.

12. Track the receipt, reading, and storage of echocardiograms

13. Develop and implement short-term archiving during the Year 30 Exam at the Field Centers, long-term archiving and storage of echocardiograms, and timely creation of in support of quality assurance efforts of the study.

15. Participate actively in data analysis, presentation, and publication using the

A. Base, and Options 1-4 as per Table 3, Throughout the contract period, the Contractor shall:

a. A principal investigator with:

i. Training and experience in echocardiography and cardiovascular epidemiology

ii. Demonstrated excellence as a manager and collaborator

b. Co-investigator(s)** knowledgeable in scientific areas relevant to the study and skilled in echocardiography protocol design and data analysis

b. Project manager scientific and organizational leadership for an Echocardiography Subcommittee.

4. Participate in various administrative activities to include, but not be limited to:

visiting field centers as needed in support of quality assurance activities; preparing

a. Semi-annual progress reports that describe main operational activities during the period, general progress in each activity, problems encountered and how they were resolved, an accounting of personnel (include levels of effort and changes during the period), and scientific productivity.

b. Quarterly Staffing Report: Table containing a list of all current staff (name, B. Option 1 and 2 as per Table 3, the Contractor shall:

1. Work cooperatively with other study centers, including Field Centers, Coordinating Center, Reading Centers, Laboratories, and the NHLBI Project Office staff in all relevant aspects of study development and execution.

2. Perform readings/information abstractions of echocardiographic measurements throughout the CARDIA Year 30 exam period. Enter and transmit abstracted information from the study’s echocardiograms into a computer, using software designed in cooperation with the Coordinating Center, and transmit the data to the Coordinating Center within 28-30 days of receipt of the echocardiographic images.

Echocardiograms should be read for any clinical alerts and referrals within 14 days of receipt. The Reading Center must notify the Coordinating Center in advance of, and the Coordinating Center must agree to, any proposed changes in the data transfer format during the exam cycle.

3. Assist in the analysis and interpretation of the echocardiographic data, the report of the results to the Steering Committee, and the design and implementation of any necessary corrective actions.

4. In collaboration with the Quality Control Committee, the Field Centers, and the Coordinating Center, implement quality control measures for the acquisition of echocardiograms at the Field Centers and reading of echocardiograms at the Echocardiography Reading Center. Ensure both within- and between-technician reproducibility at various Field Centers. Ensure both within- and between-reader reproducibility at the Echocardiography Reading Center. Monitor performance to ensure uniformity of data collection among all Field Centers throughout the data collection period and report results of this monitoring to the Steering Committee:

a. Implement quality assurance procedures and performance standards to ensure that echocardiogram technicians at each Field Center and echocardiogram readers at the Echocardiography Reading Center conform to protocol requirements. This includes assessing and control of inter- and intra-technician variability, as well as inter- and intra-reader variability.

b. Implement the protocol for performing a subset of blind duplicate echocardiographic studies at each Field Center, to be read as blind duplicates at the Echocardiography Reading Center. Compare results of blind duplicates to original studies in a timely manner as specified in the study protocol, and provide feedback to technicians on a regular basis.

c. Implement the protocol for performing the re-reads of a subset of blind duplicate echocardiographic studies at the Echocardiography Reading Center. Compare results of blind duplicates to original studies in a timely manner as specified in the study protocol, and provide feedback to readers on a regular basis.

d. Transmit quality control data to the Coordinating Center according to specifications of the study protocol.

e. Participate in the analysis and interpretation of the quality control data.

f. Perform site visits of the four Field Centers during the first 4-6 weeks of the Year 30 exam and later as needed in support of quality control monitoring by the Coordinating Center. Prepare site visit reports within 21 days of site visit; the reports shall be delivered to the Field Center, the Project Office, and all other members of the site visit team.

g. Orient, as necessary, professional staff from the Coordinating Center with quality assurance responsibilities and the NHLBI Project Office according to the reading and information abstraction protocol.

h. Perform any necessary recertification and the training, certification, and orientation of new echocardiography technicians and readers due to staff turnover

5. Assist the Field Centers and Coordinating Center in generating clinical reports provided to the Field Centers for prompt reporting to participants, along with appropriate clinical recommendations (such as for clinical follow-up) within 14 days of receipt.

6. Track the receipt, reading, and storage of echocardiograms.

a. Develop and implement methods to assure complete and accurate transfer of echocardiograms between the Field Center and the Echocardiography Reading Center, including receiving the echocardiograms from the Field Centers, verifying that the number of echocardiograms received matches the number sent according to logs from the Field Centers, and resolving discrepancies with the Field Centers. To ensure that scans were received for each participant who had an echocardiogram, transmit weekly to the Coordinating Center an electronic list of IDs for participants for whom echocardiograms were received that week.