Att_3_Statement_of_Work_(8-18-26).pdf

Attachment 3 – Statement of Work

STATEMENT OF WORK

Risk Underlying Rural Areas Longitudinal (RURAL) Heart and Lung Study Expansion Cohort

I. Background

The Risk Underlying Rural Areas Longitudinal (RURAL) Heart and Lung Study was initially funded as a Cooperative Agreement (U01HL146382) with the first Notice of Award being issued on May 2, 2019. The RURAL grant application was funded in response to NHLBI PAR-18-577, “New Epidemiology Cohort Studies in Heart, Lung, Blood, and Sleep Diseases and Disorders”. PAR-18- 577 solicited grant applications directly from the investigator community to establish a new longitudinal cohort study using a competitive, peer-reviewed process. The RURAL grant application had two specific aims:

Aim 1. Characterize a broad range of exposures across multiple domains both at the individual and at the community-level in RURAL participants. We will assess cross-sectionally how these exposures conjointly influence biological function and the prevalence of Heart, Lung, Blood, and Sleep (HLBS) risk factors, subclinical and clinical disease, and how these associations may be modified by age, sex, race/ethnicity, and residence in high vs. low-risk Appalachia, and Mississippi Delta (AMD) counties.

Aim 2. Relate the exposures (at the individual and group-level) to the incidence of overt HLBS disease and mortality prospectively, and evaluate both potential mediation by the presence of subclinical disease and effect modification by age, sex, race/ethnicity, and residence in high vs.

low-risk AMD counties. As an ancillary aim, compare the associations of various exposures with HLBS risk in RURAL counties with corresponding associations in existing urban cohorts in the South using harmonized data.

The initial recruitment goal of the RURAL Heart and Lung Study (https://theruralstudy.org) was to enroll a cohort of 4,600 participants, ages 25-64, in the rural Southeastern US to better understand the health of those living in rural, underserved communities. The design of RURAL utilizes a mobile exam unit (MEU) to enroll and examine participants in 6 high risk, and 4 low risk, rural Southeastern counties in Alabama, Mississippi, Louisiana, and Kentucky. Enrollment in MS (2 counties), LA (2 counties), and KY (4 counties), have an ecological paired design in that rural counties at high risk for cardiopulmonary outcomes are paired with counties at lower risk based on county level demographic profiles. In AL, both counties are at high risk as demographically similar lower risk counties were not found. Key components of the baseline exam include: anthropometry, biospecimen collection, behavioral/medical/demographic assessments, gated cardiac CT, inspiratory and expiratory chest CT, pulmonary function testing, Echocardiography, and an mHealth component that includes a smartphone with an embedded RURAL app, a Fitbit, and suite of questionnaires to comprehensively characterize Social Determinants of Health (SDoH).

The RURAL Heart and Lung Study was renewed in 2026 with a 5-year contract (HHS 75N98026D00018) to conduct a second comprehensive examination in previously enrolled participants, as well as prospectively follow participants through annual follow-up contacts and ascertainment of heart and lung events of clinical significance.

The objectives of this solicitation are to: (1) perform the necessary steps to design a longitudinal cohort study within the Southern Plains region of the US to serve as an expansion of the existing https://grants.nih.gov/grants/guide/pa-files/PAR-18-577.html https://theruralstudy.org/

RURAL Heart and Lung study cohort. The NHLBI intends to expand the footprint of RURAL to increase representation of the US rural population within the study. This expansion cohort will identify up to 4 rural counties in the Southern Plains region using rurality criteria comparable to the original cohort in the RURAL Heart and Lung study. The selected counties should be demographically representative of the targeted area of the rural Southern Plains region, with enrollment targets that will enable valid inferences across key continuous and dichotomous factors of risk and resilience with respect to key population subgroups. Where feasible, counties should be selected to mirror and enhance the ecological design of RURAL higher risk and lower risk counties with respect to cardiopulmonary outcomes; (2) secure suitable mobile examination unit(s) (semi-trailer, customized RV, etc.) to conduct a clinical examination of participants that is comparable in scope to the baseline clinical examination conducted in the RURAL Original cohort; (3) conduct cohort follow-up to ascertain health status, and accrue cardiovascular and pulmonary events for the purpose of assessing progression from subclinical disease to clinical disease in a manner identical to the RURAL Original cohort; (4) Establish and maintain data and biospecimen repositories, enabling their use to test new ancillary study hypotheses (adding new ancillary study data and biospecimens as they become available); and (5) engage the communities within the selected RURAL Expansion counties to facilitate recruitment and retention of study participants and to understand and work to improve the overall health of the communities.

II. Study Objectives

The goal of this acquisition is to provide a study coordinating center to provide the necessary expertise, solicit appropriate sub-awards, and manage relevant activities to carry out the necessary functions to achieve the overall objectives of the solicitation. The scientific objectives are to: (1) recruit and examine participants in rural, underserved areas in the US Southern Plains region to further enhance understanding of risk factor progression or identify potential factors of resilience with respect to cardiopulmonary health; (2) provide sufficient statistical power to perform analyses of biological, social, and behavioral predictors of subclinical disease or risk factors within relevant population groups defined by sex and race and ethnicity; (4) study the progression of subclinical to clinical CVD and pulmonary complications; and (5) identify new risk factors or interactions among factors that inform disease pathophysiology. The operational goals are to: (1) support the key study infrastructure including community level engagement to optimize recruitment and retention for participant clinical examinations, a data management center, support for cohort follow-up and data collection on clinical events; (2) provide to the RURAL Expansion communities lay reports based on data collected during the expansion cohort baseline examination that summarize key findings to enhance awareness of health conditions, inform participants and communities of the relationship of risk factors to disease, and promote healthy behaviors; (3) provide for maintenance of a data repository (adding new ancillary study data as they become available) and biospecimen repositories and integration of data resources with the RURAL Original cohort baseline materials to facilitate their use to test new hypotheses; and (4) foster scientific collaborations in particular among early career investigators.

All scientific data collected through core RURAL Expansion activities as well as ancillary studies will be prepared in a manner consistent with NIH and NHLBI data management and sharing policies and will be provided to qualified investigators through a defined process that encourages maximum data utilization and protects participant confidentiality and informed consent preferences.

III. Task Areas, Timeline, and Technical Requirements

A. Task Areas and Technical Requirements/Activities

Task Area A shall encompass conduct of and support for core study operations, community engagement activities, data analysis, manuscript preparation, morbidity and mortality ascertainment, and associated areas of management of data and biospecimen repositories, and related work. Task A specifically includes implementation of a protocol and process to define the key characteristics for the selection of counties to be included in the expansion cohort that is consistent with the approach utilized for the RURAL Original cohort, securing mobile examination facilities capable of implementing a clinical exam of participants that is of comparable scope to the RURAL Original cohort baseline exam, community-level engagement activities as needed to enhance participant recruitment and retention, establishment and maintenance data and biospecimen repositories, contact of all surviving and willing members of the RURAL Expansion cohort via periodic follow-up, ascertainment of hospitalizations and other changes in health status throughout the contract period, including changes in medications. The study coordinating center shall lead the classification of new clinical events. Task Area B will further involve: identification of sampling frames within the counties selected for the RURAL Expansion cohort, development and implementation for the recruitment and initial enrollment of expansion cohort participants, protocol development, pilot testing, and implementation of a clinical examination of enrolled participants of a comparable scope to the baseline exam in the RURAL Original cohort. Task Area C includes applicable study closeout activities. (See Table 1 below for a summary of the technical requirements and activities within each Task Area and Table 2 for a project timeline).

The task areas and timeline of the study activities are illustrated in Tables 1 and 2.

Task Area A - Core Study Operations, Community Engagement in Expansion Cohort Counties

Task Area B – RURAL Expansion Cohort Participant Clinical Examination

Task Area C – Study Closeout/Transfer

Table 1. Task Areas by Study Activities:

Tasks Activities

Task Area A

Core Study Operations

Estimated Period of Performance is June 1, 2027 – August 31, 2031

One task order with a total potential duration of 51 months (consisting of a 12-month base period, with three (3), 12-month option periods and one (1), 3-month option period)

• Solicit proposals for a suitable mobile examination unit or units to carry out a clinical examination of RURAL Expansion cohort participants

• Implement a plan to identify up to 4 counties for participant recruitment, enrollment, and examination of up to 2,000 rural participants in the US Southern Plains region

• Support for participant follow-up

• Support for clinical events investigation and review

• Clinical events classification

• Community engagement activities

• Core study operations

• Data analysis, manuscript writing Task Area B

RURAL Expansion Cohort Participant Clinical Examination: Plan and Complete Baseline Examination and Perform Exam Close-Out

Estimated Period of Performance is June 1, 2027 – August 31, 2031

Five (5) non-severable task orders (consisting of four (4) task orders, each with a 12-month period of performance and one (1), 3-month task order funded on an annual basis, for a total potential duration of 51 months under Task Area B)

• Protocol development, pilot testing, implementation of a baseline examination within the identified RURAL Expansion cohort counties

• Staff hiring, training, certification

• Conduct exam closeout and complete data cleaning

• Integrate final data into main RURAL databases

• Prepare and make available to designated repositories and qualifying researchers a research data set and applicable study documentation

Task Area C

Study Closeout/Transfer

Estimated Period of Performance is June 1, 2031 – August 31, 2031

One (1) non-severable task order for a 3-month period of performance

• Study transfer to a new entity

The scientific aims of the RURAL Expansion Study cohort are to: (1) investigate the relationship between baseline health profile and future fatal and non-fatal Cardiovascular and Pulmonary events in a Southern Plains rural population singularly and in conjunction with the RURAL Original cohort, and by High Risk/Low Risk County designation. Explore factors between and within rural population groups, and with non-rural population groups; (2) identify how trajectories of risk factors are mediated by social and environmental factors, factors that are associated with declines in pulmonary function and pulmonary disease (e.g., COPD); and (3) assess the impact of changes in socioeconomic factors, access to medical care and utilization of health services on the health of the cohort.

Table 2. Study Timeline by Task Area

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

1. Develop and maintain a web-based data collection system and provide other services as necessary to enable regular follow-up contacts of participants through geocoded updates of addresses. (Task Area A)

2. Conduct regular follow-up contacts with participants. (Task Area A)

3. Develop and maintain a web-based data collection system and provide other services as necessary to investigate participant's self-report of clinical events by collecting supporting medical records, death certificates, and other relevant materials; perform abstraction of data from such records required for events ascertainment; and conduct expert review and classification thereof. (Task Area A)

4. In collaboration with the program office, identify a minimum of 2 and maximum of 4 rural counties within the US Southern Plains region using criteria comparable to the identification of the rural counties in the RURAL Original cohort study design. Population sampling within the identified counties should be broadly representative of the population groups of the targeted region. Recruitment targets should permit comparisons of key cardiopulmonary risk or resilience factors by key demographic groups. (Task A)

5. Coordinate Community Engagement within selected recruitment counties. This shall include, but is not limited to, establishing community advisory boards (CABs) to solicit community level input regarding local area concerns and research needs, promotion of the study throughout the county, and engaging in opportunities to maximize retention of study participants. (Task A)

6. Procure appropriate mobile examination unit(s) for a clinical examination of enrolled participants. Solicit proposals from potential vendors, establish criteria for evaluation of

Activity Planned Start

Planned Completion

6/1/2027 to

5/31/2028

6/1/2028 to

5/31/2029

6/1/2029 to

5/31/2030

6/1/2030 to

5/31/2031

6/1/2031 to

5/31/2032 Task Area A 6/1/2027 8/31/2031 Task Area B 6/1/2027 8/31/2031 Task Area C 6/1/2031 8/31/2031 proposals and oversee the procurement process. Secure insurance to provide reasonable coverage protecting from losses due to theft, weather related damage, and damage from unforeseen acts. Ensure appropriate and reasonable liability insurance. Establish a maintenance program utilizing spare parts and local contractors to minimize any loss of time for participant examinations. (Task Areas A, B)

7. Design and implement appropriate quality assurance and quality control programs with particular attention to minimize manual entry of participant data. (Task Areas A, B)

8. Perform administrative, operational, and technical duties to support productive collaboration among the study personnel at all supported Institutions, outside researchers, and collaborations with RURAL Original cohort investigators, and the NHLBI Project Office. (Task Area A)

9. Establish and maintain study databases. This shall include database activities as needed for recruitment and enrollment of expansion cohort participants, participant tracking and audit logs, recording and tracking participant informed consent, recording measures from participant survey responses, procedural tests performed on the mobile exam unit, and newly ascertained events, mHealth components, and ancillary studies both for internal use and for posting on BioData Catalyst (BDC) (https://biodatacatalyst.nhlbi.nih.gov/ ) and other NIH databases, such as dbGaP (http://www.ncbi.nlm.nih.gov/gap ), as appropriate and according to NIH/NHLBI applicable Data Sharing Policies (see https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/nhlbi-policy-for-data-sharing ). (Task Areas A, B, C)

10. Maintain and support a biological specimen repository. (Task Area A, B)

11. Coordinate and participate collaboratively in study committees to provide a transparent committee process, open access to study documents, clear policies for access to data and materials, and an approval process for proposed manuscripts and ancillary studies that is fair and balanced. (See Appendix 2 below for details of the various study committees.) (Task Areas A, B)

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

13. Conduct statistical analyses and prepare scientific publications and presentations. (Task Areas A, B)

14. Provide statistical oversight and programming, and conduct analysis and data verification for collaborative publications with the RURAL Expansion investigators and the NHLBI Project Office. (Task Areas A)

15. Prepare and submit technical and financial reports. (Task Area A)

16. Perform activities related to study closeout as directed by the NHLBI Project Office. (Task Area C) [If deemed necessary by NHLBI, the Task Area will be issued as a Task Order]

17. Work cooperatively with all study investigators and staff, the NHLBI Project Office, and any subcontractors and consultants in all relevant aspects of the study. (Task Areas A, B, C)

18. Mentor early-stage investigators by providing formal and/or informal training opportunities for junior or less experienced investigators (assistant professors, fellows, and doctoral/medical students). (Task Area A) https://biodatacatalyst.nhlbi.nih.gov/ http://www.ncbi.nlm.nih.gov/gap https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/nhlbi-policy-for-data-sharing https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/nhlbi-policy-for-data-sharing

Note to Offerors:

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

Task Area A – Core Study Operations June 1, 2027 – August 31, 2031

Task Area A: The Task Area will be for 51 months (4 years and 3 months) and will include a twelve

(12) month severable base period and four (4) severable option periods. Estimated period of performance is June 1, 2027 to August 31, 2031. Each option will involve support for participant follow-up, support for clinical events investigation and review, clinical events classification, community engagement activities, core study operations, data analysis, and manuscript writing.

Task Area A will include Task Order 001, which will be awarded concurrently with the parent IDIQ contract. During the Task 001 period and if the Government chooses to exercise each subsequent Option period, the Contractor shall perform the following tasks:

A. Perform administrative, operational, and technical duties to support study implementation and productive collaboration among all RURAL Expansion study personnel, outside researchers, the RURAL Original cohort investigators, and the NHLBI.

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

a) Coordinate activities of Steering Committee and all subcommittees. (See Appendix B below for details of RURAL Expansion study committees.) to provide a transparent committee process, open access to study documents, clear policies for access to data and materials, and an approval process for proposed manuscripts and ancillary studies that is fair and balanced.

b) 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.

c) Make arrangements for and convene an annual Steering Committee meeting and monthly conference calls.

1. Prepare and distribute annual Steering Committee meeting materials, including but not limited to an annual study progress report, and the agenda one (1) week prior to the meeting. Include both operational and scientific topics in the agenda.

2. Record and distribute minutes from Steering Committee meetings to the Committee and the Project Office within ten (10) working days.

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

d) Maintain, support, and update as necessary the structure and functions of the RURAL Expansion Steering Committee and subcommittees to:

1. Optimize study oversight and operations

2. Ensure the safety and privacy of the RURAL Expansion cohort participants

3. Oversee use of RURAL Expansion cohort data and biological specimens to ensure compliance with participant consents.

e) Maintain Publication & Presentation (P&P) and Ancillary Study policies that ensure:

1. Clear information about access to RURAL Expansion data and specimens by interested investigators

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

3. Central monitoring for appropriate use of RURAL Expansion data and samples and avoidance of overlap among proposed ancillary studies and manuscripts.

f) Assist the P&P Committee in its review of new paper proposals and penultimate drafts, and the creation and monitoring of study policies.

1. Maintain databases of paper proposals and manuscripts in progress, and of published manuscripts and presentations.

2. Create reports for P&P Committee calls monthly or more often as needed.

g) Contribute to study management through service on the Steering Committee and subcommittees. Coordinating center PI, subcontract PIs, and ancillary study PIs must have representation on the Steering Committee and relevant subcommittees.

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

i) Establish a framework to ensure engagement and collaboration with the RURAL Original cohort investigators on collaborative science topics.

2. Utilizing state-of-the-art web design and content by employing appropriate expertise in this field, maintain and keep up-to-date, a high-quality RURAL Expansion web site including the following sections: an external section for participants and researchers including information about each study core, an internal section for participants to provide return of results, and an internal section for study investigators and others, as necessary.

a) The external section for participants shall include but not be limited to:

1. General information about the study

2. Up-to-date, frequently refreshed newsworthy articles / media

3. Helpful contact information, include social media handles

4. RURAL Expansion cohort participant newsletters

b) The internal section for participants shall include but not be limited to:

1. Return of relevant study results

c) The external section for researchers shall include but not be limited to:

1. Study description, timeline, and past and present participating sites including Study Coordinating Center, study cores, biorepository, and the

NHLBI

2. Study components by exam, including completed ancillary study components incorporated into the main RURAL Expansion data base

3. Directory of investigators

4. Brief descriptions of subcommittees and working groups

5. Manuals of Operations

6. Descriptions of available data and specimens

7. Description and guidance for ancillary studies

8. Description and guidance for publications

9. Data use agreement forms

10. Acknowledgments for manuscripts

11. List of published papers with links to PubMed citations

12. Information on how to request data

d) The internal section for study investigators and others as necessary shall include but not be limited to:

1. Manuscript proposals and manuscripts in progress

2. Ancillary studies proposed and in progress

3. Other materials related to study operations, coordination, or administration

e) For all web-based systems designed under this contract, comply with the requirements found in Section 508 of the Rehabilitation Act. More information is available on the Web at: https://www.section508.gov/manage/laws-and-policies/#508-policy

f) All derived documents must be accessible and 508 compliant

3. If appropriate to the study design, translate all necessary materials for participants into Spanish, including but not limited to the following:

https://www.section508.gov/manage/laws-and-policies/#508-policy https://www.section508.gov/manage/laws-and-policies/#508-policy

a) Questionnaires

b) Instructions for other aspects of study/community engagement

c) Newsletters

B. Maintain IRB approval to conduct the study according to NIH/NHLBI policy, including RURAL Expansion cohort follow-up and event investigation.

1. Maintain documentation of IRB approval.

2. Establish a mechanism for communication between the IRB and all participating RURAL sites.

C. Arrange for and manage annual meetings of the RURAL Expansion cohort Observational Studies Monitoring Board (OSMB) as directed by the NHLBI Project Office. For planning purposes, assume meetings will be convened via videoconference.

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

2. Provide honoraria to OSMB members. [Note: Assume five (5) members of the OSMB.]

3. Arrange video conferencing set-up.

D. Stimulate new scientific developments within the study and monitor scientific output.

1. Within the Study Coordinating Center and in collaboration with the other centers and consortia including the RURAL Original cohort investigative team, propose new, innovative research, methodological questions, and scientific directions; analyze data, interpret findings, and prepare manuscripts for publication.

2. Pursue and facilitate new collaborations to achieve the goal of advancing new scientific objectives.

3. Develop and implement strategies to encourage investigators new to RURAL or the RURAL Expansion cohort to collaborate by joining working groups and proposing manuscripts and/or ancillary studies.

a) Provide basic genetic, statistical, epidemiological, logistical, and computer expertise, and advice for investigators interested in applying to the study to use its data or samples.

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

4. Mentoring of early career investigators.

a) Activities may include but are not limited to: hosting early career learning events focused on scientific opportunities and/or funding opportunities through NIH or other sources; integration of early career stage investigators within relevant scientific or operational committees; encouragement of participation in publications and presentations at national or international scientific meetings.

5. Monitor scientific output:

a) Maintain a list and insofar as possible, repository of public presentations made using RURAL Expansion cohort data by investigators.

b) Generate annual reports on the status of publications and presentations for the Steering Committee and OSMB reports.

c) Maintain a database on manuscript proposals and manuscripts in progress.

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

E. Prepare and submit technical and financial reports.

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

a) Main operational activities

b) Problems encountered and how they were resolved

c) An accounting of personnel, including proposed and actual levels of effort and changes during the period

d) Modifications to any subcontracts or consulting agreements

e) Scientific productivity including but not limited to the following metrics for the previous six months:

1. Numbered list of RURAL Expansion cohort publications, highlighting those in high-profile journals

2. Number of early career investigator first authors

3. Number of collaborative papers published

4. Number of different first authors on manuscripts and authors from non- RURAL institutions

5. List and describe currently active ancillary studies

6. Number and type (data collection or variable clarification, request for additional data, analysis help, etc.) of queries from non-RURAL Expansion cohort investigators related to data obtained from publicly available databases (e.g., dbGaP, Biodata Catalyst)

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

f) Staffing, including for each staff member:

1. Area of responsibility

2. Committee participation

3. Study-related activities since the previous reporting period

4. Negotiated and actual levels of effort (include levels of effort, changes during the period, and compliance with the FTE requirements of the contract

5. Explanations of any changes during the period

g) Subcontractor performance, including for subcontract:

1. Area of responsibility

2. Number of staff, levels of effort, and study roles

3. Committee participation

4. Study-related activities since the previous reporting period

5. Explanations of any performance issues during the period

2. Submit semi-annual cumulative reports on Data and Materials Distribution Agreements (DMDAs) that contain at minimum the following:

a) Date of execution

b) Title of project

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

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

e) Date of Steering Committee approval (for materials) or Publication committee approval (for data)

f) Anticipated or actual date of expiration

3. Submit 508 Annual Reports in accordance with contract requirements. A VPAT/ACR should be provided for each web-based system. See https://www.section508.gov/sell/how-to-create-acr-with-vpat/ for additional information.

4. Submit monthly financial invoices and Contract Burn-rate tracking sheet as required by

NIH.

5. Submit a Final Progress Report and Final Financial Report on or before the completion date of the contract.

a) Summarize the work performed over the entire contract period of performance

b) Include salient results, recommendations, and conclusions.

F. Facilitate, coordinate, and conduct periodic follow-up contacts of participants, using data collection procedures compatible with those presently used in the RURAL Original cohort study.

Follow-up entails periodic contact with participants to ascertain vital status, update contact and proxy information, identify interim hospitalizations and outpatient visits, conveying information about the RURAL Expansion cohort, and serving as a vehicle to recruit for ancillary studies.

https://www.section508.gov/sell/how-to-create-acr-with-vpat/

1. Develop forms for periodic follow-up; update as needed.

2. Implement the study protocol and procedures for periodic follow-up, including interviews with proxies and next of kin when necessary.

3. Maintain a tracking system summarizing periodic follow up progress and completion rates.

4. Monitor data collection, including timelines of collection and receipt.

5. Search national databases (e.g., National Death Index, LexisNexis) to locate matches for RURAL Expansion participants with whom the study has lost touch.

6. Perform geocoding methodologies on all addresses provided by participants.

G. Facilitate, coordinate, and perform tasks as necessary to classify clinical endpoints.

1. Process to adopt the RURAL Original cohort Events protocol and Manual of Operations.

a) Adoption of the set of RURAL Original cohort clinical endpoints. At minimum, the following cardiovascular and pulmonary endpoints should be included:

myocardial infarction, angina, stroke, TIA, heart failure (with subtype, if available), peripheral arterial disease, atrial fibrillation, cardiovascular interventions, COPD exacerbations, and all mortality events.

b) Refine as needed, maintain, and oversee implementation of the protocol and manual of operations for 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, maintain comparability to the RURAL Original cohort study.

2. Collect medical records, death certificates, and other event-related materials needed to classify clinical endpoints and investigate self-reported potential clinical events.

a) Identify, collect, and review records from hospitalizations; physician visits;

death certificates; interviews with family, friends or nursing homes; and any other information used to ascertain clinical endpoints.

b) Provide a centralized abstraction of event data from such records; and coordinate expert review and classification thereof.

c) Update as needed and implement the protocol and procedures for participant events investigations and reporting.

d) Maintain data collection and management procedures, and update as needed.

Revise data collection forms for outcomes ascertainment as necessary.

e) Monitor data collection including timelines of collection and receipts of all reports, including final completed investigations.

3. Maintain and implement standardized procedures to identify and classify endpoints, and coordinate expert review and classification thereof.

a) Identify and convene a RURAL Expansion committee dedicated to the surveillance and adjudication of endpoints, which will be comprised of representatives knowledgeable about nosology and clinical assessment of cardiovascular, pulmonary, and related diseases.

b) Prepare case packets that include abstracted data and source documents from field centers; coordinate reviews of case packets by members of committee for endpoint classification on an ongoing basis.

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

d) Create and submit regular reports on the status of events investigations and the outcomes of final adjudicated endpoints that have accrued in the study.

H. Provide qualified staff to support and coordinate community engagement activities in each Expansion county targeted for participant recruitment, enrollment, and baseline examination.

Community engagement is expected to be coordinated by state-specific investigators and their staff, with heavy involvement from locally-based community engagement coordinators, community engagement consultants, and Community Advisory Boards (CABs). Staffing should provide the capability to meet the following strategic objectives:

1. Engage appropriate consultative services to strengthen aspects of community engagement as needed during the course of the study to achieve study objectives of representativeness of the recruited sample to the targeted population across sex, race, ethnicity, and age groups and maximal retention of recruited participants as required by the study design. Any consultative service can be assessed such as the Community Engagement Alliance Consultative Resource (CEACR) (https://nihceal.org/programs/community-engagement-alliance-consultative-resource-ceacr ). For planning purposes, budget for 1-2 consultations per year.

2. Organize informational and promotional events aligned with the goals of the RURAL Expansion study to specifically engage potential study participants and/or generally promote health and well-being in county residents.

3. When the MEU is in county, organize efforts to retain RURAL participants and encourage MEU exams.

4. Engage local community leaders through Community Advisory Boards and community engagement consultants to solicit feedback and assistance on recruitment and retention strategies, media and other outreach outlets, assistance with planning engagement events, and other community support as needed.

a) Community Advisory Board members should be paid a set stipend for their participation, and community engagement consultants paid a fee commensurate with their level of involvement.

5. Provide regular communications on RURAL Expansion study news and research findings with the study participants, and other community members as appropriate.

a) Produce a periodic newsletter for study participants, disseminated in print and digital form.

https://nihceal.org/programs/community-engagement-alliance-consultative-resource-ceacr https://nihceal.org/programs/community-engagement-alliance-consultative-resource-ceacr

1. Solicit contributions from collaborating investigators on items for the newsletter, including articles on study findings, community activities, and other appropriate items of interest to participants.

2. Include lay summaries of relevant published manuscripts.

6. Work closely and collaboratively with ancillary study investigators to coordinate and recruit participants for ancillary studies even when the MEU is not present in the county.

I. Coordinate the planning and initial development of a comprehensive data book focused on lay summaries of data collected in the RURAL Expansion cohort counties.

1. In collaboration with the NHLBI project office, RURAL Expansion cohort Steering Committee, and relevant study cores, lead the planning of a comprehensive RURAL study report based on data collected during baseline exam.

a) A writing team should be proposed composed of the Coordinating Center, NHLBI project office, and relevant study cores to determine the content of the report to the communities.

b) A timeline should be proposed that encompasses key milestones, including initiation, content decision making, writing, penultimate draft, Steering Committee approval, and production of electronic and printed copies.

c) Include dissemination plans including potential for mail, email, social media, and media conference release.

2. The intent of the report is community dissemination, and thus should use plain language and visual information such that those unfamiliar with medical literature can easily understand key health-related messages.

J. Implement and maintain a web-based data collection system and provide other services as necessary to enable efficient digital data entry and transfer to the Data Center.

1. Provide all study centers written documentation of the system, training in its use, and user service when questions/problems arise.

2. Provide, distribute, and coordinate utilization of appropriate common devices to the MEU and Recruitment and Retention Center for collecting and communicating data to the Data Center.

3. Maintain security and confidentiality of the data, including personal identifiers and personal health information (PHI).

4. Maintain and update as necessary participant consent status and medical authorization forms.

5. The Contractor shall establish and maintain an information security environment compliant with HHS and NIH requirements (currently NIST 800-53) within a timeline that should not exceed 12 months from the contract start date. Following the initial authorization, the Contractor shall implement Continuous Monitoring (ConMon) in accordance with NIST SP 800-137. This includes, but is not limited to, performing regular vulnerability scans, maintaining a Plan of Action and Milestones (POA&M), and providing monthly security status reports to the NHLBI Information System Security Officer (ISSO) to ensure the ongoing integrity of the system throughout the contract lifecycle.

6. Perform upgrades as necessary.

K. Provide infrastructure for the study to deploy questionaries via the RURAL Expansion mHealth app for exam components, periodic follow-up, and ancillary study implementation

1. Retain appropriate personnel with expertise in mHealth.

2. Furnish all necessary services, qualified personnel, materials, and infrastructure needed to maintain the mHealth app.

3. Consult with RURAL Expansion, RURAL Original cohort, and non-RURAL investigators to develop new studies that utilize appropriate mHealth apps for questionnaire deployment.

4. Conduct quality management studies and assessments of the response rates and data quality collected via the mHealth app.

L. Design and implement quality control and quality assurance programs in conjunction with the QA/QC Committee.

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

2. Monitor the quality of all data on an ongoing basis and in a timely manner.

3. Verify completeness, timeliness, reliability, and accuracy of collection.

4. Include development and modification of standards to identify outlying values and initiate and coordinate separate review of these observations for accuracy with the appropriate cores.

5. Include all questionnaires, interview, morbidity and mortality follow-up, and measurement data.

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

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

8. Coordinate initial certification and maintain ongoing retraining and recertification of performance capabilities of MEU staff through localized training.

9. Include quality control and quality assurance information in annual reports to the Steering Committee and the OSMB.

M. Establish and maintain study databases, including images.

1. Maintain and update as needed an appropriate RURAL web-based data entry and management system (as described above).

2. Use common data elements (CDEs) where possible to facilitate data sharing and standardization, improve data quality, and enable data integration from multiple studies and sources, including electronic health records. NIH has established a “CDE Resource Portal” (http://cde.nih.gov ) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms and other instruments for data collection.

CDEs are data elements that have been identified and defined for use in multiple datasets across different studies.

3. Include data from MEU visit examinations and interviews, follow-up data and interviews, imaging measurements and results, and laboratory measurements, morbidity, and mortality data, and from all sub-studies and ancillary studies. Incorporate ancillary study data into the contract study data set upon finalization of ancillary study data suitable for peer-reviewed publications.

4. Update follow-up and morbidity and mortality events and endpoints data.

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

6. Maintain a database on informed consent versions and participant responses covering the baseline exam and other participant contact interactions as appropriate. Assure that samples and databases are distributed in accordance with the expressed desires of participants in their signed informed consents.

7. Prepare documentation for data distributed internally to RURAL Expansion or RURAL Original cohort investigators or their collaborators, and for NIH repository databases per NIH data sharing policies (https://sharing.nih.gov/data-management-and-sharing-policy/about-data-management-and-sharing-policies/data-management-and-sharing-policy-overview ).

8. Provide data documentation to data users.

9. Maintain data on quality control measurements.

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

a) Include computed tomography, ultrasound, and other imaging studies.

b) Provide necessary archiving equipment and storage for digital archives.

c) Maintain a system for sharing and tracking use of imaging studies. Prepare imaging data for sharing and tracking through cloud-based databases such as BioData Catalyst ( https://biodatacatalyst.nhlbi.nih.gov/ ), dbGaP (https://www.ncbi.nlm.nih.gov/gap/ ), or other designated database as appropriate and directed by NHLBI.

11. Prepare datasets of genetic and associated phenotype data and necessary documentation for release through dbGaP (http://www.ncbi.nlm.nih.gov/gap ) or other NCBI database as appropriate.

http://cde.nih.gov/ https://sharing.nih.gov/data-management-and-sharing-policy/about-data-management-and-sharing-policies/data-management-and-sharing-policy-overview https://sharing.nih.gov/data-management-and-sharing-policy/about-data-management-and-sharing-policies/data-management-and-sharing-policy-overview https://sharing.nih.gov/data-management-and-sharing-policy/about-data-management-and-sharing-policies/data-management-and-sharing-policy-overview https://biodatacatalyst.nhlbi.nih.gov/ https://www.ncbi.nlm.nih.gov/gap/ http://www.ncbi.nlm.nih.gov/gap

a) Obtain and incorporate ancillary study data into the contract study dataset for release through repositories.

b) Update the study information in the database as needed.

12. Prepare NHLBI Data Repository data sets and associated documentation for submission to the BioData Catalyst (BDC) (https://biodatacatalyst.nhlbi.nih.gov/ ) or other NHLBI designated data repository in accordance with the NHLBI Guidelines for Preparing Clinical Study Data Sets for Submission to the NHLBI Data Repository.

a) See https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/guidelines-for-preparing-clinical-study-data-sets-for-submission-to-the-nhlbi-data-repository .

b) Include ancillary study data in datasets prepared for the NHLBI Data Repository.

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

a) The NIH Public Access Policy (https://publicaccess.nih.gov ), which requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central (http://www.ncbi.nlm.nih.gov/pmc/ ) immediately upon acceptance for publication.

b) The NHLBI Adverse Event (AE) and Unanticipated Problem (UP) Reporting Policy, which describes the procedures for identifying, monitoring, and reporting adverse events and unanticipated problems encountered by research participants. (http://www.nhlbi.nih.gov/funding/policies/adverse.htm ).

14. Annually review and update as needed the NHLBI listing in ClinicalTrials.gov (https://clinicaltrials.gov ).

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

16. Manage execution of and maintain Data Distribution Agreements for Affiliated Investigators and Data and Materials Distribution Agreements for Collaboration Investigators.

N. Conduct statistical analyses, develop statistical methodologies as needed, and advise on appropriate study designs for scientific manuscripts and presentations.

1. Perform data analyses in a timely fashion and support study investigators, via consultation, on appropriate analytic methods.

2. Review analyses performed outside of the Data 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.

O. Maintain the biospecimen repository in accordance with the RURAL Expansion cohort protocol.

https://biodatacatalyst.nhlbi.nih.gov/ https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/guidelines-for-preparing-clinical-study-data-sets-for-submission-to-the-nhlbi-data-repository https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/guidelines-for-preparing-clinical-study-data-sets-for-submission-to-the-nhlbi-data-repository https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/guidelines-for-preparing-clinical-study-data-sets-for-submission-to-the-nhlbi-data-repository https://publicaccess.nih.gov/ http://www.ncbi.nlm.nih.gov/pmc/ http://www.nhlbi.nih.gov/funding/policies/adverse.htm https://clinicaltrials.gov/ https://ocio.nih.gov/aboutus/publicinfosecurity/acquisition/Pages/table3.aspx

1. Retain appropriate personnel with expertise in laboratory medicine, laboratory measurements, molecular and genetic epidemiology, and appropriate uses of biospecimens.

2. Furnish all necessary services, qualified personnel, material, equipment, and facilities needed to ensure proper storage and maintenance of previously collected and any future samples in a repository for storage of aliquots, following best practices such as described at https://isber.org/BPR .

a) Property standards as required during the grant period in accordance with regulatory requirements in 2 CFR Parts 200.310 through 200.316 must be met or exceeded, particularly regarding ensuring safeguards for preventing property loss, damage, or theft, and regular maintenance procedures for biospecimen storage equipment.

3. Track inventory of available specimens and provide annual updates of the inventory status to the Steering Committee.

4. Provide specimens to designated laboratories for approved ancillary and sub-studies in accordance…