New Epidemiology Cohort Studies in Heart, Lung, Blood, and Sleep Diseases and Disorders (U01 - Clinical Trials Not Allowed)

Q1:  What features is NHLBI looking for in a new epidemiology cohort study?

A1:  The six minimal requirements for a new cohort study are: enroll at least 2000 participants; predominantly focus on U.S. populations; address research gaps in heart, lung, blood, and/or sleep diseases, disorders, or phenotypes; innovate; investigate a broad array of putative exposures and risk factors; and support the study of research questions across heart, lung, blood, and/or sleep phenotypes.  In addition, applications that propose to preemptively address the challenges of analyzing data across multiple cohorts, such as by proposing to adopt or use data standards, common data elements, and/or standard ontologies that would facilitate harmonization and sharing/analysis of data across studies, are of high programmatic interest.  The NHLBI is also interested in how the proposed cohort study will permit research that will address multiple scientific hypotheses; align with the Institute’s Strategic Vision (https://www.nhlbi.nih.gov/sites/default/files/2017-11/NHLBI-Strategic-Vision-2016_FF.pdf); and has visions for the short, medium, and long term.

Q2:  What is the maximum number of participants a study may enroll?

A2:  There is no maximum cap on the number of participants that can be enrolled into the study.  Studies are permitted to enroll as many participants as needed to address the study’s scientific objectives.  The final cohort size should be sufficiently powered in both overall and key subgroup analyses to address the study’s scientific hypotheses.

Q3:  Do all 2000+ participants need to be enrolled at the same time?

A3:  No, the study does not need to enroll all 2000+ participants at the same time.  Participants may be recruited over several years within the proposed project period (which may not exceed six years) so that prior to the end of the project period there are at least 2000 participants enrolled in the cohort and that participant data have undergone data cleaning, quality control, and initial baseline analyses.

Q4:  If I have an existing cohort with less than 2000 participants, may I propose to enroll additional participants to increase the cohort size to 2000 participants in order to apply to this funding opportunity?

A4:  Yes, applicants are free to propose adding additional participants to an existing cohort to bring it up to the required minimum threshold of 2000 participants.  It is expected that existing participants and newly enrolled participants would both undergo the same detailed baseline assessment to ensure that both types of participants have the same level of deep phenotype data available for analyses.  When appropriate, applicants may want to consider how to harmonize existing data with newly collected data to ensure that cohort data collected prior to this award can be integrated with newly collected data.

Q5:  What is the difference between PAR-18-577 (New Epidemiology Cohort Studies in Heart, Lung, Blood, and Sleep Diseases and Disorders) and PAR-17-338 (Continuation of Existing Grant Based Epidemiology Cohort Studies in Heart, Lung, Blood, and Sleep Diseases and Disorders)?

A5:  PAR-18-577 (https://grants.nih.gov/grants/guide/pa-files/PAR-18-577.html) is designed to support deep baseline phenotyping of at least 2000 participants and is intended to establish new epidemiology cohort studies to address research gaps in heart, lung, blood, and/or sleep phenotypes.  In contrast, PAR-17-338 (https://grants.nih.gov/grants/guide/pa-files/PAR-17-338.html) is intended to sustain the study infrastructure of an existing cohort and to support only a minimal content data collection cycle that would serve as a platform for future ancillary study content; in other words, PAR-17-338 will only support minimal phenotyping of cohort participants.  Additionally, there are differences in the budget, project period, and number of anticipated awards for each of these funding opportunity announcements (FOAs).  Applicants may wish to contact program staff for assistance with determining which FOA would be most appropriate for their proposed study.

Q6:  If I have an existing cohort with more than 2000 participants, may I propose to continue following my cohort via this FOA?

A6:  These types of applications are best suited for NHLBI’s related FOA, PAR-17-338 (see Q5 above).  If applicants intend to apply to PAR-18-577, they must provide compelling justification for how the existing cohort will be made novel under this FOA (e.g., new clinical measurements, addition of novel scientific hypotheses).  Simply stating that a detailed assessment of cohort participants is needed will not be a compelling justification.

Q7:  The FOA mentions that NHLBI currently funds several large epidemiology cohort studies.  Where can I find a list of these cohort studies?

A7:  A partial list of NHLBI’s large epidemiology cohort studies can be found at: https://www.nhlbi.nih.gov/science/population-and-epidemiology-studies.

Q8:  Do heart, lung, blood, and sleep hypotheses need to be included in my application, or may I focus on only one phenotype or heart/lung/blood/sleep domain?

A8:  No, applicants do not need to study heart and lung and blood and sleep scientific hypotheses; studies may focus on heart or lung or blood or sleep hypotheses.  Applicants are free to study as few or as many phenotypes as they want; the only requirement is that the cohort study is designed to address multiple scientific hypotheses.  As an example, studies may propose to cover multiple phenotypes with only one or a few hypotheses per phenotype, or alternatively studies may propose to focus on one phenotype with multiple hypotheses for this single phenotype.

Q9:  Are registries eligible for this FOA?

A9:  Yes, registries are eligible for this FOA.  However, a key component to this FOA is to support a detailed baseline assessment on participants to address a wide array of research questions.  Therefore, the registry should have the ability to re-contact registry members to perform detailed assessments to gather suitable baseline data for longitudinal follow-up. 

Q10:  The application receipt dates for this FOA do not align with the standard timelines provided in the NHLBI’s policy for applications with direct costs that exceed the program project grant (PPG) cap of $1,515,000.  How will these applications be handled?

A10:  The NHLBI normally only considers applications that exceed the PPG cap twice per year.  However, for this FOA only, the NHLBI will conduct a single ad hoc consideration of these applications for each of the receipt dates.  To accommodate this ad hoc consideration, applicants MUST abide by the following deadlines for applications that exceed the PPG cap; these dates supersede the deadlines listed online in the NHLBI’s policy (https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/applications-with-direct-costs-of-500000-or-more-in-any-one-year).

Note that if NHLBI grants permission to submit an application for peer review, it does NOT guarantee that the NHLBI will fund the application or that it will fund the application at the requested levels, regardless of the outcome of peer review.

Q11:  What does the required staff consultation entail?

Applicants should direct all questions to the NewEpiCohorts@nhlbi.nih.govmailto: email address.  Several NHLBI program staff will be monitoring this email to ensure timely responses to applicant questions.  Questions sent to this email address may be posted on this FAQ page, and staff will remove any identifying details about the applicant or the proposed study before posting the question and its response.  This is being done to ensure that all applicants will have equal access to information related to this funding opportunity.  The staff consultation requirement will be satisfied by completing BOTH of the following:either attending viewing the applicant informational webinar (either live or the recording)on February 5, 2018 or viewing the webinar recording; AND reviewing this FAQ page; or sending questions to the email listed above.  In their Letter of Request, applicants should indicate the date(s) they viewed the webinar and, read this FAQ page, and/or emailed questions to program staff.

Q12:  What information needs to be included in the Letter of Request?

A12:  The information required in the Letter of Request can be found on the NHLBI’s webpage that describes our policy for applications with direct costs of $500,000 or more in any one year, including the five page limit (https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/applications-with-direct-costs-of-500000-or-more-in-any-one-year).  Use the budget template provided on that page (https://www.nhlbi.nih.gov/sites/default/files/media/docs/500K-Budget-Tables_2017-12-14.docx).  When describing the significance of the proposed cohort study, applicants should emphasize the heart, lung, blood, and/or sleep research gap(s) the study aims to address, as well as how the proposed cohort study is innovative.  When emailing the completed letter to the appropriate division director, please carbon copy (cc) the NewEpiCohorts@nhlbi.nih.gov email address. 

Budget

Q13:  What is the budget allocated for each award?

A13:  NHLBI expects to make one award per application due date (i.e., one award in FY19 and one award in FY21).  As shown in the table below, budgets should not exceed $1,948,000 in direct costs for the first year of each award’s project period (FY19 or FY21).  In all subsequent years of each award’s project period (FY20-24 or FY22-26), budgets should not exceed $3,896,000 in direct costs per year.  Thus, the entire direct cost budget for each award is $21,428,000.  Future year amounts may vary depending on annual appropriations.  Application budgets should reflect the actual needs of the proposed project.

1. Q: So there will be just one award per application cycle?

A: Yes, only 1 award each cycle is anticipated.

2. Q: Does the letter for pre-approval need to be sent through the official institutional submission route or be signed by an authorized institutional official? Or can the PI email this 5 page letter directly to NHLBI?

A: The PI should send the 5-page letter of request directly to NHLBI. The NHLBI $500K policy page lists the appropriate email addresses for sending the letter of request. Please CC the email address NewEpiCohorts@nhlbi.nih.gov when sending the letter.

3. Q: What is the date for submitting the $500K letter if budgets are between $500K and $1.515M?

A: Letters of request for permission to submit an application for the June 5, 2018 due date with direct costs greater than $500K in any given year but less than the PPG cap of $1.515M in each year are due no later than April 13, 2018. Due to intense interest in this funding opportunity, applicants proposing such applications are encouraged to submit letters prior to the deadline.

4. Q: So this FOA will not support existing cohorts, only NEW? Continuation of existing cohorts should be directed to the PAR-17-338?

A: A study proposing to enrich an existing cohort with new participants would be eligible to submit under this funding opportunity.  Both new participants and existing participants would need to have the same detailed assessment during the project period to establish the same baseline phenotyping. The funding opportunity PAR-17-338 specifically targets continuation of an existing cohort and thus would be more appropriate for applications that do not intend to recruit additional participants.

5. Q: Does NHLBI envision this FOA supporting the development of real-world cohorts (i.e. cohorts identified through EHR-based enrollment, phenotyping and follow-up in integrated health systems)?

A: Potentially yes. Applications proposing an EHR or registry based cohort, for example, are eligible.  Such applications would need to address consent/assent of participants such that a detailed baseline assessment could be established that would allow the study to address a wide array of research questions.

6. Q: Are there particular areas of knowledge gap that are of interest?

A: NHLBI does not have pre-specified research gaps of interest for this PAR.  Applicants may consult the NHLBI Strategic Vision for science in the heart, lung, blood, and sleep domains, which lists numerous compelling questions and critical challenges for research.  Note that not all phenotypes, diseases, and health concerns relevant to the NHLBI’s mission are named in the Strategic Vision; therefore, applicants are welcome to propose research aims that address other important research gaps within the NHLBI’s purview.   

7. Q: Is it desirable to cover as many NHLBI strategic vision elements as possible?

A: Not necessarily. The key elements to consider in a cohort study proposed in response to this funding opportunity include: addressing research gaps, innovation, and investigation of a broad array of exposures and research questions. The NHLBI is interested in high-quality science; therefore, if a study proposes to collect data across multiple strategic vision elements, it should have a scientific justification for doing so.

8. Q: Is there any age restriction on the structure of the cohort?

A: No, there are no age restrictions with respect to enrolled participants.

9. Q: Did the working group that recommended this PAR identify specific gaps that are of programmatic interest to NHLBI?

A: No, the working group did not identify specific scientific gaps. As emphasized in recommendation 7, the goal is to “implement a competitive peer review–based model for its portfolio of large epidemiologic and population studies”, thus this funding opportunity allows the investigator community to propose not only hypothesis driven research within a study design, but propose the study platform as well (see Roger VL, et al. Strategic transformation of population studies: recommendations of the working group on epidemiology and population sciences from the National Heart, Lung, and Blood Council and Board of External Experts. Am J Epidemiol. 2015. 181(6):363-8.)

10. Q: What is the difference between a new cohort and an established cohort? Can an existing cohort not followed for many years be considered a new cohort?

A: Potentially yes. Given the large expanse of time since the last assessment, it would be expected that the key objectives of the cohort will have transformed to new research questions. However, this cohort would also be eligible for support under PAR-17-338; therefore, investigators may wish to explore with NHLBI which funding opportunity would best fit their research agenda.

11. Q: Regarding data standards, how much of the collected data will be required to be publicly available, and at what resolution?

A: NHLBI anticipates that individual participant data will be shared according to NIH and NHLBI data sharing policies. Data sharing using both internal study based processes as well as the eventual sharing through established data repositories is anticipated.

12. Q: Are applications focused in one scientific domain (e.g., sleep) required to include outcomes/measures from other domains (i.e., non-sleep) in order to be considered responsive?

A: No. The application would need to include the scientific hypotheses driving the measures, and also be eligible in terms of addressing research gaps, innovation, and investigation of a broad array of exposures and research questions.

13. Q: Is this funding opportunity applicable for cohorts in other countries or developing countries, with US principal investigators?

A: To be eligible, the proposed cohort would need to be primarily based on a US population.

14. Q: Although you explained that baseline data is expected to be collected, may we include follow-up visits if contained within the approved budget?

A: Yes, follow-up visits would be a supported activity.

15. Q: How do you satisfy requirement for additional review if cost exceeds $1.5M total cost if need to?

A: To clarify, an NHLBI internal review panel will discuss proposed applications based on the letter of request if the direct costs exceed $1.515M in any given year. Submitting the letter of request by March 6 will satisfy this requirement. Information about the letter of request is available on the NHLBI web page, Applications with Direct Costs of $500,000 or More in Any One Year.  

16. Q: Does the application focus on U.S. populations refer to those who are U.S. citizens / permanent residents? Or can it explicitly focus on those who are undocumented?

A: Any population that resides within the US and/or its territories would be appropriate to enroll. A study proposing to recruit exclusively undocumented individuals living in the U.S. would be eligible, providing the other components of eligibility are met (e.g., addressing research gaps, innovation, and investigation of a broad array of exposures and research questions).

17. Q: Could you speak to the interest in generating cohorts to address disease-related hypotheses (e.g. a focus on disease X) as compared to the interest in more general population-based studies (e.g. a focus on population Y)?

A: NHLBI does not have a preference for a more general population study as compared to a more clinical disease/disorder phenotype.  Either design would need to establish how the study will address key research gaps.

18. Q: Is it required ALL 2,000 participants be NEW recruits? Is it eligible to re-phenotype an existing cohort as a subset of the 2,000?

A: Enrichment of an existing cohort with new participants is permissible. Please refer also to Q4.  A study proposing to enrich an existing cohort will need to establish how the enriched cohort study will address research gaps, be innovative, and investigate a broad array of exposures and research questions.

19. Q: If there are different institutions involved, each collecting different types of data  that require different IRB approvals from different institutions, would this type application be exempt from the NIH’s Single IRB (sIRB) policy?

A: According to the NIH’s Single IRB Policy for Multi-Site Research, applicants will be expected to include a plan for the use of a single IRB. Information about what types of applications may be exempt from this requirement is available on the Single IRB & Exceptions Process Webinar website.

20. Q: Is a follow-up visit with detailed phenotyping required in addition to the baseline assessment?

A: No, detailed phenotyping in a follow-up exam is not required. NHLBI does anticipate that regular follow-up for the purposes of ascertaining events, vital status, interim history, etc. may be appropriate.

21. Q: Just to confirm, the example timeline is an example and the actual timeline can vary from it?

A: Yes, the example timeline is meant to be illustrative and should be adjusted as needed for the proposed study. NHLBI recognizes that not all study designs will necessarily fit the specific example given in the timeline; further, not all study designs will require a six-year duration. The timeline proposed should be justified scientifically.

22. Q: Are cohorts focused on underrepresented minorities a priority?

A: While under-represented minorities are an area for which research gaps exist, NHLBI recognizes that research gaps are present for many population groups.

23. Q: Do the direct costs need to include things like genotyping and/or omics, or would that be done separately?

A: Genotyping or Omics can be supported under this FOA. Both collection and measurement costs would need to be accounted for in the direct costs If support for both activities is part of the application. 

24. Q: So no direct consultation with NHLBI staff for the LOR is requested?

A: For this specific FOA, an arranged staff consultation with a higher level of interaction with program staff is not required, but investigators are encouraged to reach out with any questions.

25. Q: In the 2013 working group report that called for the establishment of new cohorts, what kinds of gaps (or examples thereof) were identified that NHLBI now seeks to fill?

A: The 2015 published report from the working group did not identify specific gaps.  The intent was to have more investigator-initiated research help drive the agenda. Please refer to question 10 as well for additional detail on the working group recommendations.

26. Q: Will this be eligible to apply for a renewal application?

A: The NHLBI cannot guarantee continued funding of the project beyond the initial project period and we do not know at this time whether a FOA for renewal will be available.  The incumbent grantee may pursue funding for the renewal through standard NIH grant mechanisms.    

27. Q: Can the follow-up extend beyond 6 years?

A: For the purposes of applying to this specific FOA, follow-up activities beyond the maximum six-year project period cannot be supported with the awards made under this FOA.

28. Q: The focus of the PAR is on US populations. Can an international registry or cohort study qualify?

A: It depends; if the majority of the cohort is non-US population then it would not be eligible under this funding opportunity.

29. Q: Is an offspring study of an existing cohort supported under this FOA?

A: Potentially yes. In addition to enrolling a minimum of 2,000 primarily US participants, the proposed study would also need to establish how the study will address research gaps, be innovative, and investigate a broad array of exposures and research questions.

30. Q: May a study have two PI's (co-PI) or is a proposal limited to one PI?

A: Yes, multiple PIs, as described at https://grants.nih.gov/grants/multi_pi/, are allowed.

31. Q: When will the timeline for applications for the 2nd cycle be available?

A: The timeline is very similar and is described within the FOA as well as within the slides. In brief, staff consultation must be completed by February 28, 2020; Letter of Request must be received by March 8, 2020; applications must be submitted by June 5, 2020.

32. Q: How detailed does the budget need to be for the letter due by March 6th? Line-itemed per site/subcontract?

A: The 500K Budget Table template is available via a link on the NHLBI’s Applications with Direct Costs of $500,000 or More in Any One Year web page. The template indicates all budget information required for the letter.

33. Q: Can additional key personnel be added (or removed) after the pre-approval stage?

A: Yes, key personnel can be added or changed in the grant application from that described in the approved request letter. However, the proposed budget may not increase.

34. Q: If you get funded in the first cycle, and want to be considered for funding for a follow-up, will you be competing with 'new' cohorts' that submit for cycle 2?

A: No, since it will at that time be considered an existing cohort rather than a new cohort.  Please see question 26 concerning renewal applications.

35. Q: Where can I learn more about common data elements and other data standards?

A: Please visit the NIH’s CDE Repository and Resource Portal.

36. Q: What specifically is required for the staff consultation as well as the letter of request?

A: Due to the extremely high interest in this funding opportunity, the staff consultation requirements can be satisfied by viewing the webinar (either live on February 5th or the recorded webinar) AND by reviewing the FAQs for this FOA.   The NHLBI greater than $500K policy page (https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/nhlbi-policy-for-data-sharing-from-clinical-trials-and-epidemiological-studies) provides specific instructions for the information to include in the letter of request. When discussing the significance of the project, be sure to include the research gap(s) your study intends to address and how the study is innovative. 

37. Q: Is a formal letter of request required for these grants because it should be a given that each year's budget will exceed $500K direct costs?  If it is required, does the budget need to be detailed and final or can it be a preliminary budget?

A: This funding opportunity is a program announcement with review, therefore a letter of request is required.  The budget template (available on the NHLBI’s $500K policy page) asks for direct cost totals, so a detailed budget isn’t needed.  Please be aware that the budget requested in the application cannot exceed what was given in the Letter of Request either in total or by year.

38. Q: NHLBI currently supports several large ongoing cohorts. Why is a new cohort needed? What’s the gap these new cohort studies should fill that the current ones cannot?

A: In brief, a working group led the NHLBI Board of External Experts and Advisory Council published a report recommending to that the Institute seek out investigator-initiated proposals to address research gaps in the Institute’s epidemiology research portfolio. This funding opportunity provides a mechanism for the research community to inform the Institute on key research gaps that should be filled through a new epidemiological cohort study.  The minimum number of participants targeted for enrollment should equal or exceed 2,000 participants.

39. Q: We have a cohort that we have been following using questionnaires and have the ability to re-contact participants. Would this cohort be eligible for PAR-18-577 as a new cohort?

A: If the cohort will not be enriched through the enrollment of additional participants, then a more appropriate mechanism for the continued study of an established cohort may be PAR-17-338 (https://grants.nih.gov/grants/guide/pa-files/PAR-17-338.html).  Please contact NewEpiCohorts@nhlbi.nih.gov with any specific questions about your particular cohort.

40. Q: Are sites expected to generate omics data or focus exclusively on building a dataset for future generation of omics?

A: No, the FOA does not require the generation of omics data nor does it require building a dataset for future omics data generation.  However, studies are welcome to propose these activities if they align with the study’s scientific objectives.

41. Q: Where can we find the FORMS-E packet online?

A: The FORMS-E packet that should be used for this FOA can be accessed through the NIH ASSIST system or through Grants.gov.

42. Q: I have an existing cohort that I would like to expand and enrich by enrolling family members (e.g., siblings, offspring, parents).  Would this qualify as a new cohort study for PAR-18-577?

A: An existing cohort, with plans to enrich through the recruitment of new participants, would be eligible under PAR-18-577 as long as the cohort fulfills the six study eligibility requirements: (1) Enrolls at least 2000 participants by the end of the project period. (2) Predominantly focuses on U.S. populations. (3) Addresses research gaps in heart, lung, blood, and/or sleep diseases, disorders, or phenotypes. (4) Is innovative (e.g., creative study designs, novel populations or scientific hypotheses, use of new or emerging technologies). (5) Investigates a broad array of putative exposures and risk factors, such as the confluence of diet, exercise, therapies, environmental, behavioral, and biological or other molecular factors. (6) Supports the study of research questions across a range of heart, lung, blood, and/or sleep phenotypes.

43. Q: We have an international cohort.  Would it be eligible for this FOA?

A: No, PAR-18-577 requires the participant population to be primarily US-based.

44. Q: Is it possible to share an example of a Letter of Request?

A: Examples of Letters of Request are not available; however, the NHLBI greater than $500K policy page (https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/nhlbi-policy-for-data-sharing-from-clinical-trials-and-epidemiological-studies ) provides specific instructions for the information to include in the letter of request. When discussing the significance of the project, be sure to include the research gap(s) your study intends to address and how the study is innovative. 

45. Q: What qualifies as a new cohort?

A: Anything that meets the 6 eligibility criteria: (1) Enrolls at least 2000 participants by the end of the project period. (2) Predominantly focuses on U.S. populations. (3) Addresses research gaps in heart, lung, blood, and/or sleep diseases, disorders, or phenotypes. (4) Is innovative (e.g., creative study designs, novel populations or scientific hypotheses, use of new or emerging technologies). (5) Investigates a broad array of putative exposures and risk factors, such as the confluence of diet, exercise, therapies, environmental, behavioral, and biological or other molecular factors. (6) Supports the study of research questions across a range of heart, lung, blood, and/or sleep phenotypes.

46. Q: What will the budget cap be?

A: $21,428,000 (direct costs) across the 6 year budget period.  $1.948M (direct costs) in the first year, $3.896M (direct costs) in every subsequent year.

47. Q: Is there an expectation of molecular genetic work in the proposal?

A: No, molecular genetic work is not expected. However, genomic or other molecular data generation may be included in the proposal if desired and within budget. Genomic and other omic data generation may also be well-suited for an independently-funded ancillary study.

48. Q: Does this PAR support biomarker verification cohorts?

A: Any proposed study would need to meet the 6 elements of the eligibility criteria including the ability to address multiple scientific hypotheses.  Thus, biomarker verification cannot be the sole focus/aim of the study.

49. Q: Are HIV-infected cohorts, or combined HIV+ and HIV- cohorts, permitted or encouraged?

A: No, PAR-18-577 only allows non-AIDS applications.

Q1. When preparing my budget, should I use the direct costs as my budget cap or the total costs?

A1. Application budgets should not exceed the direct cost cap as indicated in the FOA ($1.948M in the first year of the project and $3.896M in subsequent years). Please be advised that the total costs ($3M in the first year and $6M in subsequent years) are the amount that NHLBI has budgeted for each award made under PAR-18-577. As stated in NHLBI’s policy regarding applications requesting more than $500k in any one year, even if NHLBI grants permission to submit an application for peer review, the Institute may not fund the application at the requested levels depending on reviewer comments, programmatic needs, and annual appropriations.

Q2. The budget template for the Letter of Request only lists five budget years, but I want to request a six year project period. How do I include the budget for the sixth year in the budget template?

A2. Add a row to the table for the sixth year of the project.