Questions and Answers for RFA-AI-17-044, Revision Applications for International Centers of Excellence for Malaria Research (U19, Clinical Trial Optional)

NIH published this funding opportunity announcement (FOA) in a December 22, 2017 Guide announcement.

Table of Contents

Questions Published on January 18, 2018

Questions Published on January 18, 2018

Purpose, Eligibility

  1. What is the goal of the program?

    This request for applications (RFA) solicits revision applications to existing International Centers of Excellence for Malaria Research (ICEMR) grants awarded in fiscal year (FY) 2017. These revision awards will support the conduct and oversight of observational studies or implementation studies to evaluate the impact of in-country, approved vector control and malaria prevention interventions on the incidence, prevalence, and transmission of malaria.

    The studies outlined in the funding opportunity announcement (FOA) will leverage the baseline data, infrastructure, and capacity established by the ICEMRs and will augment and use the established ICEMR malaria surveillance systems to study the impact of the vector control and malaria prevention interventions on human health outcomes.

  2. Who may apply?

    Only current ICEMR awardees funded under RFA-AI-15-056 may submit an application. The parent grant must be active when they submit the revision application.

  3. If I am a current Scientific Advisory Group (SAG) member, can I participate in an ICEMR application?

    Yes, but first you will need to recuse yourself from all future ICEMR SAGs.

  4. What studies does this FOA support?

    This FOA solicits three distinct types of studies. Applications may propose only one project for each Study Type.

    • Study Type 1 is a Controlled Environment study.
    • Study Type 2 is an Observational study.
    • Study Type 3 is an Implementation study. For this Study, the FOA supports a Go/No-Go approach to funding, which is significantly different from most U19 projects. Continued funding for the full award duration is dependent upon achieving negotiated Go/No-Go criteria by the end of the revision award’s second year.
       
  5. What about Cores?

    The projects will fold into the existing core structure of the ICEMR; therefore, cores are not allowed for this competitive revision FOA.

  6. Must the current ICEMR PD/PI also be the PD/PI of this application?

    The project director/principal investigator (PD/PI)—or contact PD/PI for multiple PI awards—on the parent award must remain the same on the revision application. However, you can list different or new PIs as project leads for a given study.

  7. Can the studies take place in a country that the ICEMR does not currently support?

    No. Research projects must be conducted only in the countries listed in the original ICEMR application. However, new field sites within the countries where the ICEMR is currently supported may be included.

  8. Where can I find out more about NIH’s definition of a clinical trial?

    NIH is launching a series of initiatives that are rolling out through 2018 to enhance the accountability and transparency of clinical research. These initiatives target key points along the whole clinical trial lifecycle from concept to results reporting. To learn more about these changes and how they will affect your research, see the links below:

Study Types

  1. What will Study Type 1 (Controlled Environment study) involve?

    This study will involve outdoor contained/controlled environments, such as studies in contained biospheres within the ICEMR endemic sites. Studies may include evaluation of novel EPA-approved or non-EPA-approved chemicals or insecticides, new vector control products, genetically modified mosquitoes, or microbial symbiont-infected mosquitoes.

    These studies will not involve human subjects as research participants, and all products must be approved for testing or further evaluation by appropriate in-country government or regulatory authorities.

    Controlled Environment studies may include, but are not limited to the following:

    • Collecting data necessary for preparing and implementing environmental interventions, which will inform future field studies
    • Evaluating novel chemical attractants or repellents in a controlled setting

    Note: For Study Type 1, all applicants will be required to serve as the regulatory sponsor in-country (if required by the local authorities).

    Additional guidance for Study Type 1: Applicants should address a translational research question. The study will be considered nonresponsive if it can be feasibly conducted in the natural habitat or an uncontrolled environment. For studies that do not propose evaluating a product, a strong justification describing the need for a controlled, outdoor environment is required.

  2. What will Study Type 2 (Observational study) involve?

    This study involves collecting preliminary background data from the community and stakeholders to inform the design of future, larger implementation studies. Examples of observational studies include:

    • Small, socio-behavioral studies that will assess community acceptability, concerns, and factors that influence conducting future large-scale implementation studies. These socio-behavioral studies can include surveys, questionnaires, focus group discussions, and interviews, but may not include collection of biological specimens or samples.
    • Community-based, socio-behavioral surveys to inform and plan future clinical trials or implementation studies that introduce interventions such as:
      • Drug prophylaxis or treatment approaches
      • Diverse vaccination strategies, including novel routes of delivery
      • Strategies to target special populations for treatment or prevention
      • Field release of new mosquito strains (e.g., strains with reduced transmission competence)
      • Field release of genetically modified mosquitoes

    Additional guidance for Study Type 2: Study Type 2 requires a component of community engagement beyond stakeholders. Engagement of stakeholders only or pure data analyses will be nonresponsive.

  3. What will Study Type 3 (Implementation study) involve?

    This study will assess the impact or effectiveness of country-approved public health interventions on malaria incidence or transmission in an endemic setting. Such studies must include in country-approved products or control strategies provided by the domestic Ministry of Health (MOH). However, in-country approved products that are not used as a part of current routine public health practice in the country due to cost or supply considerations may be included.

    Implementation studies

    • May include controlled, cluster-randomized studies in which participants are given combinations of interventions (such as bed nets, larvicides, indoor residual spraying, prevention, and treatment), each of which is approved by in-country MOHs
    • Should be designed to determine the most cost-effective treatment combinations and strategy that will reduce the burden of disease due to malaria. The Center will design the study in cooperation with the relevant government agencies or MOH to determine where, when, and how to administer the available intervention(s).

    The government agency, MOH, or organizations working with the MOH routinely implementing malaria control activities will fund, manage, and administer all aspects of the actual intervention. Participants may also purchase interventions or personal protectants.

    The ICEMR may provide advice and direction to the MOH but should not be involved in the actual field operations related to administering or implementing control activities. The Center will be engaged in overseeing the study, collecting data, and measuring the outcome of the intervention.

    Note that routine monitoring and evaluation studies designed as a part of implementing public health interventions do not qualify for Study Type 3. The studies should implement trial designs with a comparison group designed to minimize bias and address the limitations of interpreting routine monitoring and evaluation indicators.

    Implementation studies may include, but are not limited to the following:

    • Acceptability, compatibility, and effectiveness of in-country approved outdoor personal protection measures against mosquitoes, e.g., topical repellents containing DEET, topical creams with citronella, bracelets with repellents, insecticide impregnated fabric
    • Integrated vector management with different combinations of existing vector control tools and assessment of their combined impact on risk, disease transmission, and clinical outcomes
    • Studies to evaluate effectiveness of in-country approved insecticides and products, such as traps, attractants, repellents and larvicides, and their impact on risk, disease transmission, and clinical outcomes
    • Studies evaluating impact of different drug treatment strategies, such as mass drug administration, focal treatment strategies, school-based prevention and treatment interventions, or seasonal malaria prophylaxis, in conjunction with other routine malaria control activities
    • Studies evaluating in-country approved drugs targeting gametocytes
    • Studies evaluating the effectiveness of the RTS,S (Mosquirix®) vaccine in conjunction with other malaria control strategies

    Additional guidance for Study Type 3: NIAID recommends that this project include a cost-effectiveness or cost-benefit analysis and that studies imbed secondary endpoints related to risk and transmission beyond the impact assessment on disease and vectors. Examples include cluster sampling of sub-populations to evaluate of changes in the following:

    • Parasite diversity
    • Immune status of the population
    • Drug and insecticide resistance in the parasite and vectors
    • Asymptomatic prevalence in rats
       
  4. How does the Go/No-Go Criteria work for Study Type 3 (Implementation study)?

    For Study Type 3 only, this FOA requires projects to include Go/No-Go criteria to be met by the end of the second year of the award. Initially, support will be provided for up to two years. Upon successful completion of the stated goals in the first two years, funding may be continued for an additional three years (for a total of five years of support), depending on the availability of funding and the relative merit of the study. The stated Go/No-Go criteria will be included in the Notice of Award.

    Although applicants will submit an application including five years of research, at the end of year two, NIH program staff will evaluate the progress of research towards the stated Go/No-Go criteria. Contingent upon the availability of funds, three additional years of funding may be available for those who successfully meet their criteria and are set up to most effectively scale up the study.

    For applicants not meeting their Go/No-Go criteria, the revision award will close out at the end of year two. Also see question #13. In addition, the recommended endpoints referenced in question #11 (under Additional guidance for Study Type 3) should be measured in the first two years, as well as in the scale-up years three to five. Results for these endpoints for the first two years will factor into the selection of the ICEMRs that proceed to years three to five.

  5. Where do I specify the Go/No-Go criteria for Study Type 3 and what must I include?

    In a clearly labeled section under the Research Strategy section for this project, state the Go/No-Go criteria for completion of the first 2 years of research. Include a description of the population that will be enrolled in the first two years of study, which must be at least 2,000 individuals, divided into two or more clusters.

    Describe the surveillance that will be set up to track the 2,000 individuals and additional surveillance sites for the subsequent years. Include a discussion of the 1) suitability of the proposed milestones for assessing success of the first two years of research and 2) implications of successful completion of these milestones for the proposed final three years of work.

    Include milestones related to the recommended primary and secondary endpoints referred to in question #11 (Additional guidance for Study Type 3). Include a discussion of the field readiness to scale up during years three to five, the status of the data management system level of conformance to Clinical Data Interchange Standards Consortium (CDISC) standards, and sharing of data from years one and two.

  6. Is CDISC compliance necessary for Study Type 3 (Implementation study)?

    Yes. It is recommended that the data systems in the field for the ICEMR projects be CDISC compliant. For Study Type 3, a description of the state of the data system, along with the level of conformance to CDISC standards, should be provided in the application.

Award Information

  1. How much money is NIAID committing to the program and how should applicants budget for the different studies?

    NIAID intends to commit $4 million in FY 2019 to fund up to 12 awards/projects as follows:

    • Application budgets for Study Types 1 and 2 should not exceed $200,000 annually in direct costs for years one and two.
    • Application budgets for Study Type 3 should not exceed $400,000 annually in direct costs for years one and two and $900,000 annually in direct costs for years three to five.
    • At least 80 percent of the annual direct costs must be committed for field work and related research activities at the endemic sites.
    • ICEMR funds may not be used to procure the malaria control interventions or to fund the logistics and staff associated with implementing the malaria control activities.
       
  2. How many years can I request?

    You should request the amount of time you need to complete the funded activities, per the following:

    • You may request support for up to two years for Study Types 1 and 2.
    • For Study Type 3, you must submit a five-year project period and are required to identify Go/No-Go decision criteria to be achieved for the year two progress report to allow continued funding for years three to five. Achieving the stated goal(s) (Go) will render your application eligible for continuing the U19 for years three to five. Failure to achieve the stated goal(s) (No-Go) will result in award closeout.
    • Requests for support must not exceed the remaining number of years on the parent grant. The parent grant must be active when the application is submitted.
       
  3. The revision RFA states that at least 80 percent of the annual direct costs must be committed for field work and related research activities at the endemic sites. What if 20 percent of annual direct cost does not cover all non-endemic countries’ salaries?

    If necessary, you can show a time commitment in the budget without associated cost to meet the direct cost percent requirements.

  4. Are there recommendations on the time commitment of the Project Lead (PL)?

    Yes. As stated in the parent ICEMR announcement, PLs are expected to commit at least 90 days of their annual effort to conduct field site activities at the endemic sites where the ICEMR is being implemented. This could be through multiple trips to the field sites spread out over the year. PLs should visit each field site at least once each year.

  5. If I cannot commit 90 days of my annual effort, can I still participate in the grant application?

    Yes, as a participating investigator but not as a PL. As with the parent ICEMR, it is expected that a PL should commit 90 days of his or her annual effort at field sites.

  6. If I reside near the endemic site, am I still expected to commit to 90 days a year at the field site(s)?

    Yes, all PDs/PIs/PLs are expected to spend at least 90 days each year onsite at the malaria endemic sites where the ICEMR is being implemented. You are expected to commit 90 days at the site even if you live in-country but not near the field site.

Application Information

  1. How many applications can each ICEMR institution submit?

    Only one application per institution/ICEMR (normally identified by having a unique DUNS number or NIH Institutional Profile File (IPF) number) is allowed.

  2. Do all field sites or participating institutions need an eRA Commons account?

    No. Only the primary institution that submits the application needs an eRA Commons account.

  3. In what format should the application be submitted?

    The application should be submitted in the U19 application format with an Overall section, up to three projects, and no cores. The forms are provided in the FOA.

  4. Must each application include all three studies/projects?

    Applications may propose one, two, or all three of the studies listed. Each Study Type should be a distinct project in the U19 application. Applicants can propose only one project on each Study Type.

  5. Is there a limit to the number of collaborations or subcontractors I can propose?

    No.

  6. What is a letter of intent and is one required?

    Although you are not required to submit a letter of intent, NIAID strongly encourages you to do so since it helps us estimate the workload for peer review and plan accordingly.

    In your letter of intent, include the following:

    • Descriptive title of the proposed research
    • General information about the PI such as name, address, and telephone number
    • Names of key personnel
    • General information about the participating institution such as name, address, and telephone number
    • Number and title of the FOA, i.e., Limited Competition: Revision Applications for International Centers of Excellence for Malaria Research (RFA-A1-17-044)
    • The number and types of studies you plan to submit

    The letter of intent is due by April 30, 2018 (at least 30 days before the application due date). Email it to Ann-Marie Cruz. Find detailed application and submission information in Section IV of the FOA, including instructions for submitting a letter of intent.

  7. What additional letters of support are required?

    Applicants must provide letters of support from each applicable site director, local government/responsible government or MOH collaborator, and/or significant research contributor indicating agreement for continued use of collaborative resources (e.g., a Network, Clinical and Translational Science Award (CTSA), or Consortium).

    For the Controlled Environment study (Study Type 1): Include letters of support from the concerned in-country regulatory authorities or MOH permitting the use of in-country approved experimental products to be studied in a contained controlled environment. The letter should specify the exact site/location(s) where the evaluation will be permitted.

    For the Observational study (Study Type 2): Include letters of support from the concerned in-country regulatory authorities or MOH that endorses conducting the survey. The letter should state that the types of interventions contained in the survey are of relevance to the treatment and/or prevention of malarial disease within that country.

    For the Implementation study (Study Type 3): For situations in which a government agency or MOH is the sole implementer of malaria control activities, provide a letter(s) of agreement from the government agency to fund and administer all aspects of the actual intervention.

    In countries where other agencies also support and implement malaria control activities, include letters of support from these other agencies expressing willingness to work with the ICEMR and the responsible government agency or MOH to adopt and adhere to the study design outlined in the application. The letter should state that the agency will be responsible for all costs associated with procuring and implementing the interventions.

  8. When should I submit the application?

    Applications are due by May 30, 2018. It is strongly recommended to submit well in advance of the deadline.

  9. How is an application organized?

    In general, the U19 application is a multi-project application with many parts. For the revision application, note that no cores will be proposed (see question #4). The following components are required:

    Part 1: Overview—describes overall research goals of the main ICEMR, how individual projects relate to each other and to the main ICEMR award, and other details (see FOA Section IV, Part 6. Other Submission Requirements and Information: Overall Research Plan).

    Part 2: Individual Project Descriptions—a separate, detailed description of each proposed research project (up to the three distinct projects previously referenced)

    • Project 1
    • Project 2
    • Project 3
       
  10. Do foreign institutions need to have FWA and IACUC numbers?

    Yes. All institutions must have an active Federalwide Assurance (FWA) number if conducting human subjects research and, if necessary, an institutional animal care and use committee (IACUC) number. However, the in-country agencies implementing the routine public health interventions do not need an FWA number or IACUC number. See the following links for additional details:

Application Forms

  1. What do I need to know about the new Forms-E used for this application?

    A new Human Subjects and Clinical Trial Information form is required for all human subjects and/or clinical trial research beginning with January 25, 2018 due dates. To learn more about this new form and what it means for your grant application or contract proposal, go to New Human Subjects and Clinical Trial Information Form.

    Also see the following links for detailed information:

Application Submission

  1. Should I submit the application electronically?

    Yes. Applications to this FOA must be submitted electronically using Application Submission System & Interface for Submission Tracking (ASSIST) or an institutional system-to-system solution; paper applications will not be accepted.

    ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including pre-populating organization and PD/PI data, pre-submission validating of many agency business rules, and generating data summaries in the application image used for review.

    Follow the Multi-Project (M) Instructions in the SF 424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide to Grants and Contracts).

  2. Where can I find out more about applying electronically through ASSIST?

    See the following links to find instructions to apply using ASSIST:

  3. How are Grants.gov and eRA Commons related?

    Your grant application starts in Grants.gov and is routed to eRA Commons for agency processing. Post-submission, you will be interacting with NIAID through eRA Commons. See more under Systems and Roles.

  4. Whom do I contact if I need technical assistance submitting my application or if I have questions about the general application content?

    For technical assistance with ASSIST, contact the eRA Service Desk. Direct questions about application content to Grants.gov at support@grants.gov.

  5. Where can I find additional help on applying and submitting?

    Detailed instructions are provided on the NIH website; see the links below:

  6. Where can I find post-submission information about my application?

    For details about tracking your application, viewing summary statements and scores, sending just-in-time information, and more, see the following pages on the NIAID website.

  7. Whom do I contact for more information on this FOA?

    NIAID’s scientific/research contact for this opportunity is Malla R. Rao.

Content last reviewed on January 19, 2018