Pre-receipt Webinar for Chronic Kidney Diseases of UnceRtain Etiology (CKDu) in Agricultural Communities (CURE) Research Consortium FOAs

Event Details

Background

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Environmental Health Sciences (NIEHS) and the Fogarty International Center (FIC) issued the following three Funding Opportunity Announcements (FOAs) for the Chronic Kidney Diseases of UnceRtain Etiology (CKDu) in Agricultural Communities (CURE) Research Consortium, RFA-DK-20-017, RFA-DK-20-018 and RFA-DK-20-019.

This Notice is to inform potential applicants that NIDDK, NIEHS and FIC will host a pre-application webinar on August 17, 2020, from 3:00 p.m. to 5:00 p.m. (Eastern Daylight Time) for those interested in learning more about the FOAs.

Meeting Purpose

NIDDK, NIEHS and FIC staff will provide programmatic information about the FOAs and the application review process, as well as answer questions from prospective applicants. The webinar is open to all prospective applicants, although participation in the webinar is not required to submit an application to RFA-DK-20-017, RFA-DK-20-018 or RFA-DK-20-019.

Prospective applicants are highly encouraged to submit their questions regarding the FOA in advance of the webinar to ckduconsortiumfoa@niddk.nih.gov by COB August 14, 2020. Time permitting, participants also will be able to ask questions during the webinar.

Questions and Answers for CURE Research Consortium RFAs

This document provides responses to questions submitted prior to or during the August 17, 2020 pre-receipt webinar and/or via email to NIH contacts. Questions have been organized by general topic area. Questions not answered in this document can be submitted via email to the NIH contacts for the consortium:

Susan Mendley, NIDDK: susan.mendley@nih.gov
Bonnie Joubert, NIEHS: bonnie.joubert@nih.gov
Kathleen Michels, FIC: michelsk@ficod.fic.nih.gov

Abbreviations used in this document:

Scientific Data Coordinating Center (SDCC)
Field Epidemiology Sites (FES)
Renal Science Core (RSC)
Human Health Exposure Analysis Resource (HHEAR)
Steering Committee (SC)

Consortium structure and collaboration

Will the CURE investigators have to collaborate?

• Yes. All data, samples, protocols and publications will be shared with all the CURE investigators. All publications will be submitted on behalf of the CURE Consortium and authorship decisions will be made by the Publications sub-committee of the Steering Committee.

Study design

What study designs are planned?

• As noted in RFA-DK-20-017 and RFA-DK-20-019, “The SDCC and each of the FES applicants will propose study designs to be implemented at the FES that will elucidate the cause or causes of CKDu, the exacerbating and protective factors, sex differences, as well as the long-term course of CKDu. The designs should include both baseline assessments of cases and controls (which might include, but are not limited to, occupational, biological family, household family, local environment) and longitudinal assessments, that can define progressive loss of kidney function, episodes of acute kidney injury and periods of disease stabilization [emphasis added].”

• No. The CURE investigators will collaboratively devise the study protocol that will be reviewed by the Observational Study Monitoring Board (OSMB) and approved by NIDDK, NIEHS and FIC. Thus, all studies proposed in the applications will be a starting point for discussions regarding the research to be undertaken.
• There will be one common protocol for the consortium carried out at each FES:
  “The Consortium will work together to finalize ethical epidemiology research designs, execute common strategies for biological sampling and environmental assessment…The final design of the study, as determined by the Steering Committee, may significantly vary from individual applications. It is required that all funded sites fully abide with the final harmonized design set by the Consortium Steering Committee.”

Can I propose a clinical trial?

• “This FOA will not support clinical trials or intervention trials.” Improved understanding of the cause or causes of CKDu will permit trials of or recommendations for treatments or public health interventions. But that is not planned during this funding period.

I know the cause of CKDu. Can I apply for a FES or the RSC to study my idea?

• The studies proposed and conducted will be broad-based to encompass a range of relevant hypotheses. Avoid study designs that test only a single hypothesis. Per RFA-DK-20-017: “Propose approaches to understand the cause or causes of CKDu…provide grounded biological plausibility”
  
  “Studies designed to look at a single hypothesis are discouraged.”
  
  Review criteria: “How well do the proposed study designs address the potential causes of CKDu, avoiding a narrow focus or single hypothesis?”

Should the FES application propose hypothesis-driven aims or should it be directed towards recruitment?

• Both would be appropriate.

Is genetic testing expected?

• The consortium, through its Steering Committee, will determine the final protocol. It is highly likely that genetic studies will be part of the strategy. Other ‘omics strategies may also be appropriate and will be discussed.

What is the anticipated sample size for the total of all the field studies?

• “Each FES will enroll at least 400 participants who are affected by CKDu (cases, as defined in the RFA-DK-20-017 Background section) and 400 or more control participants, depending upon study design which will be finalized by the Consortium Steering Committee.”

Should applicants to the FES already have cohorts from which they have collected data?

• Pre-existing cohorts are not required. However, feasibility of recruitment and retention strategies will be reviewed.

Is there a preferred methodology for study designs? Should a case/control approach be used or a longitudinal cohort?

• Per the RFAs, “Study design: Describe proposed epidemiology study designs to be implemented at FES that will elucidate the cause or causes of CKDu, the exacerbating and protective factors, the sex differences in incidence and outcome, as well as the long-term course of CKDu. The application should describe baseline assessments of cases and controls and longitudinal assessments that can define progressive loss of kidney function, episodes of acute kidney injury and periods of disease stabilization.”
• In the RFA we have been careful to use straightforward language, avoiding terms more common in specific fields (e.g., that epidemiologists or kidney researchers might use). So, we would consider baseline assessments to occur at enrollment of the study participants and longitudinal assessments occur at multiple follow-up time points.

Location of FES

Are the high CKDu prevalence areas restricted to agricultural communities only or is any affected region eligible for a field study if it has high prevalence of CKDu? What is the scope of considering the CKDu study in construction workers?

• FES are not restricted to agricultural communities only or specific occupations. The FES RFA-DK-20-017 states “The FES will identify, recruit, enroll, and follow study participants in CKDu-endemic regions, including individuals with evidence of CKDu and appropriate controls.” An applicant must convincingly demonstrate that (s)he can recruit participants in a CKDu-endemic area.

What about areas with high prevalence of CKD but not CKDu?

• FES must propose activities in locations with evidence of CKDu endemicity, not just CKD.

Case definition of CKDu

• Please note that notices to the RFA have been published to correct an error in the urinalysis description: NOT-DK-20-041, NOT-DK-20-042 and NOT-DK-20-043

Is the CURE Consortium targeting severe cases of CKDu? Can you explain the case definition further in the context of the overall objectives?

• The case definition in the RFA is intended to ensure that enrolled participants are affected by CKDu. It does not include individuals considered ‘at risk’ based upon their locale or occupation.
• The inclusion or exclusion of patients with diabetes and hypertension will be determined by the Steering Committee.

If the steering committee thinks the definition for CKDu should be different from what you’ve put in RFA, is that going to be acceptable?

• Yes. “The final definition and selection of cases and controls will be based on deliberations by the full CURE Consortium, once it is formed.” However, the case definition in the RFA must be used in the application to describe the FES plan to “identify, recruit, enroll, and follow study participants in CKDu-endemic regions.”

When screening for CKD in the field epidemiology sites, will point of care analysis be an option and will this be under the FES budget or the Renal Science Core budget?

• Point-of-care testing would be an option for screening. Screening activities are the responsibility of the FES. The RSC will only analyze specimens sent to them.

Biorepository

For SDCC applications (RFA-DK-20-019), can you please clarify the requirements for the interim biorepository?

• The SDCC will include, or will contract with, a biorepository. Each FES will transfer samples to the SDCC-designated biorepository for analysis by the RSC or by HHEAR. FES sites are responsible for working with local health ministries and local privacy boards to address regulatory requirements to permit data and sample transfer. The SDCC is expected to have expertise in this area as well.
• At the end of the study, long-term data and biological sample storage will be in the NIDDK Central Repository.

Budget

What is the budget?

• NIH intends to commit $4,000,000 in Fiscal Year 2021 and anticipates awarding 1 Scientific Data Coordinating Center, 1 Renal Science Core and 3-4 Field Epidemiology Sites. The exact allocation of funds will be determined by the NIDDK and NIEHS based on scientific merit (as recommended by peer-review) and programmatic priority (in consultation with the National Advisory Councils).

Can I request a larger budget than specified in the RFA?

• You can request with justification, but we cannot guarantee funding.

What is the opportunity pool?

• It is a pool of funds – administered by the SDCC – to form new partnerships with investigators from both inside and outside of the CURE Consortium to serve the needs of the Consortium. The Steering Committee and NIH will be decision-makers in the Opportunity Pool Program. This pool of funds will be used for grants to enable relevant infrastructure, resources and ancillary studies. The organization of these funds should be flexible, as the size and use of the pool may change.

Is the Opportunity Pool expected to be included in each year’s budget or only in Year 1?

• Applicants may request an Opportunity Pool in subsequent years, but its availability will depend upon availability of funds.

Can the FES budget for freezers and other equipment?

• Yes, freezers and equipment to support initial temporary storage of collected biological samples at FES prior to shipping to the SDCC is appropriate.

Will the FES budget include the costs for shipping or analysis of biosamples and environmental samples?

• The cost of shipping sample collection kits to the FES and samples to the biorepository will be budgeted by the SDCC. The RSC will provide sample collection kits based upon the sampling strategy agreed upon by the consortium. Analysis of biologic and environmental samples will be conducted by the RSC and HHEAR.

What is the budget for the SDCC each year (years 2-5)? Is this the same as years 1 and 2?

• The budget for the SDCC is anticipated to be no more than $600,000 per year for all five years.

If the FES proposes genetics, does it need to budget for the genetic data generation?

• No, genetic data generation will be covered by the RSC.

Application content and structure

Can I apply to more than one FOA?

• Yes, if you bring appropriate expertise to both and avoid budgetary overlap.

Why does the SDCC application have a 30-page limit?

• The research strategy including study design, data analysis and project management merited more room. However, you should consider reviewers’ attention span when writing the application.

Will the renal science core conduct the data analysis for the analyses it runs, e.g., genomics, or is everything done at SDCC?

• If the RSC proposes ‘omics, it should include expertise and describe plans for the data analysis. Per RFA-DK-20-018, “If omics-based technologies are proposed, describe the available expertise to perform data analysis and interpret findings. Document the collaborative research experience of the team.”

What is meant by “provide statistical analytic support and implement analyses”? Will the SDCC be leading ALL statistical analyses for publications?

• The SDCC will be leading all statistical analyses, with the exception of omics data, if proposed by the RSC.

Are newer etiologies appropriate to consider in applications?

• Yes, proposals to evaluate etiologies not yet explored in the literature are encouraged. However, “Studies designed to look at a single hypothesis are discouraged.”

Reporting of results

Is return of results to local communities/partners planned?

• The Consortium Steering Committee will make this decision. It is possible that renal histopathology can be returned to clinicians at FES, but that will depend on the capabilities of the RSC. The return of clinically informative laboratory results to study participants will be discussed and the final details will be determined by the Consortium Steering Committee.

Data/sample sharing and ancillary studies

Will an ancillary project process be put in place to use biologic samples in CURE?

• Yes, an ancillary studies process will be set up by the consortium once the study protocol and study questions have been formalized. Ancillary studies will not be permitted to interfere with the primary objectives of the consortium and utilize samples that might be needed for consortium analyses.

After the consortium has finished, will there be a mechanism for anonymized data to be made available to other researchers?

• Yes. Data and biologic samples will be stored by NIDDK and at the completion of the funding period, they will be made publicly available.

COVID-19

How will COVID-19 affect the consortium?

• OER has advised maximum flexibility in confronting this pandemic.
  https://grants.nih.gov/policy-and-compliance/policy-topics/natural-disasters/corona-virus
  The RFA does not mention COVID-19. If NIH revises the RFA, a Notice will be published
  In planning for your role in the CURE Consortium, consider the impact of COVID-19 on operations of study and on analytic strategy

Other questions and comments

Before making awards, will NIH make sure that the countries of foreign field sites will allow data and samples to be transferred to the US?

• Yes. NIH expects that foreign field sites will ensure that data and samples can be transferred to the US for analysis. Further, there are specific review criteria in the RFAs: “How clearly do the letters of support from health ministries and local governments demonstrate evidence of strong commitment to cooperate with the research endeavor proposed?”

Agenda

There is no formal agenda for this meeting. Attendees are highly encouraged to email their questions regarding the FOA by August 14, 2020 to ckduconsortiumfoa@niddk.nih.gov. Time permitting, participants also will be able to ask questions during the webinar.