Where can I get answers to specific questions?
You can e-mail the NIH Human Microbiome Project Working Group at the following address: hmprfaInformation@mail.nih.gov.
Which RFAs are limited competition and what does that mean?
The competition for all of the RFAs that have been released under the NIH Human Microbiome Project, except one, is open to all applicants. Only RFA RM-08-001 entitled "Construction of a Reference Sequence Data Set for the Human Microbiome Project (U54)"; is a limited competition (see RFA RM-08-001 for more information), meaning that only those investigators who are invited to may submit an application.
However, some of the RFAs do have specific eligibility requirements. For example, some RFAs are open to U.S. institutions only. Interested investigators should review all applicable RFAs to determine their eligibility. Contact the relevant NIH program officers if there are questions.
RFA RM-08-001: Construction of a Reference Sequence Data Set for the Human Microbiome Project (U54)
Will there be any mechanism for linking the full genome sequence of the microbes with full genome sequence to donors and, if so, what will the implications be for informed consent?
We are not anticipating that there will be a link between donors and microbial isolates for which the full genome sequence is determined. If that link were necessary for a project, it would raise issues for informed consent and data release. If you are planning to submit a strain for sequencing and would like to maintain a link to the donor, please contact Jean McEwen to discuss pertinent consent issues.
What does it mean that this RFA is limited competition?
This is a limited competition RFA, meaning that only certain investigators, who have been invited to do so, are eligible to submit an application. The eligible principal investigators who have been invited to apply include the principal investigator and/or any other designate/approved individual of the NHGRI and NIAID awardees of the large scale sequencing centers.
RFA RM-08-012: Human Microbiome Demonstration Projects (UH2/UH3)
Who at NIH will assess the consent forms for the demonstration projects?
Consent forms will be evaluated by Dr. Jean McEwen (firstname.lastname@example.org), an ELSI expert on the NHGRI staff, in consultation with an HMP consent working group and by other NIH staff who are familiar with research and clinical trials that study the relevant body sites. The purpose of the assessment is to determine whether the discussion of data release in the consent form is adequate for the investigators to comply with the data release standards that will be applied to these awards and to make sure that any other unique ELSI issues raised by the design of the particular project are adequately addressed in the consent form. This NIH assessment does not take the place of appropriate IRB review, which will continue to be required for all proposals involving human subjects.
We have already collected samples under an IRB-approved protocol. Will this pose a problem in our application and can we submit this protocol now for NIH approval?
It does not present a problem for the submission of your application, but it may or may not propose a problem for any grant application that NIH will fund. Additional documentation may be required prior to the award. It depends on whether the consent form signed by the sample donors will allow release of the collected data according to the data release policy for the HMP and whether any other unique ELSI issues raised by the design of the particular project are adequately addressed in the consent form. NIH staff will be happy to advise you during the preparation of your application; you may submit your protocols at any point. We encourage you to contact Dr. Jean McEwen as early as possible to discuss your existing protocols and consent forms.
For the demonstration projects, will NIH consider projects involving the elderly or children or other potentially vulnerable populations?
There are no limits on the age of donors who may be recruited and sampled as part of the demonstration projects, as long as proper consents are in place. We strongly suggest that any groups considering sampling of children or other potentially vulnerable populations contact Dr. Jean McEwen to discuss development of a robust consent process.
How will the UH2/UH3 transition work? What will be the timeframe for making this transition?
The UH2 award provides for one year of funding, starting April 2009, to support awardees to carry out a demonstration of the strength of their approach and its potential to show a correlation between an important human health phenomenon and the composition of the relevant microbiome. NIH wishes to fund as many of these initial studies as possible, but expects only a fraction of them to develop enough data to suggest that a correlation will be found. To determine which of the initial studies warrant continuation, an administrative review will be held toward the end of the first year. On the basis of the results of this review, NIH staff will make the determination of which of the UH2 awards should be continued by funding a UH3 award. The UH3 phase will be funded for three additional years, beginning April 2010. Awardees who do not receive a UH3 will not continue to receive NIH Roadmap funds for this RFA
Will there be a funding gap during the UH2/UH3 transition?
We anticipate that the projects that successfully make the transition from the UH2 to the UH3 mechanism will not experience a funding gap. The transition decisions will be made on the basis of an administrative scientific review in order to achieve a rapid turnaround.
What criteria will be used to determine the UH2/UH3 transition?
In the application, the Principal Investigator is required to propose a set of quantitative goals and milestones to be achieved by 6 months and 1 year of the UH2 phase. The RFA states: "Beyond attaining or exceeding the stated milestones, the successful projects will be those that are judged to have the most significant impact on understanding the relationship between the human microbiome and human health. Other factors that will be considered include significance of the health problem being addressed and program balance. Thus, along with milestones, applicants should propose, where possible, other approaches to determining progress and significance.";
Elsewhere in the RFA it is stated: "The criteria that will be used to determine which of the UH2 projects will make the transition to the UH3 phase will include:
- Progress toward meeting the defined milestones for the first year of the project.
- Potential for meeting the goals of the initiative to demonstrate whether there is or is not a definable relationship between the microbiome at a specific body site and the chosen phenotype.
- Significance of the health problem being studied.
- Program balance.";
The RFA states that no more than five of the demonstration projects will transition to funding at the UH3 level. If more than five of the projects demonstrate solid science and progress, will additional funds be available through funding by an NIH Institute to support the remainder?
This is a trans-NIH initiative, so individual Institutes/Centers may consider funding an outstanding UH2 demonstration project that is not selected for the transition to the UH3 if it fits within their mission and funds are available. It is not possible at present to predict the likelihood of alternative sources of funding because it will depend on whether funds are available and the Institutes' interests at the time.
What progress specifically will be evaluated during the UH2/UH3 transition? Will research done prior to the initiation of the UH2 grant be factored into the decision of whether to transition a given project?
The decision on transitioning projects will depend on which ones have the most potential to be able to achieve the goals of the RFA and demonstrate a correlation between the composition of the human microbiome and the health/disease under study. If results from research performed with funds other than those provided through the Roadmap program support the argument made in the proposed system, these can be presented in the application to support the proposal.
Since data from the sequencing centers that are generating a sequence-based data resource for the project under RFA RM-08-001 may be relevant to the proposal for a demonstration project, will there be an opportunity for demonstration project applicants to obtain updates on the progress of those sequencing projects before the application submission date?
All of the data generated by the NIH-supported sequencing centers are released immediately to the NIH/NLM/NCBI trace archive, where it is publicly accessible. Additionally, the HMP website will post data and point to websites at each center from which the data can be obtained.
Best practices for sample collection and preparation do not yet exist. Could a major portion of the first phase be devoted to the development of sample collection and preparation protocols?
Since these are such important questions, they are reasonable goals to be included in the first phase. However, a successful demonstration project will need to be able to demonstrate by the end of the UH2 phase not only that samples can be collected and processed, but that information can be obtained that will be useful for demonstrating the correlation between the composition of the relevant microbiome and the health/disease under study.
Will metagenomic sequencing and data analysis be required for these grants?
These awards are aimed at analysis of the human microbiome, and there is limited experience in these metagenomic approaches to limit applicants to a single technology platform. However, NIH is encouraging projects that take advantage of available technologies, resources and strategies to produce the most comprehensive possible picture of the relevant microbiome being studied. At this point, we anticipate that projects that include sequencing components will be well situated to meet these criteria. Researchers seeking high-throughput sequencing without access to such facilities should consider establishing collaborations with experienced sequencing groups. Proposals to generate data other than sequence data will be considered; however, in such a case, the applicant must justify the proposed approach in terms of its ability to generate data useful to establish whether there is a correlation between the composition of the relevant microbiome and the health/disease under study.
Will this set of RFAs be open to analysis of proteomic techniques aimed at characterizing community functionality?
At this stage in the research, the objective of the NIH Roadmap Human Microbiome Project is to fund studies that can demonstrate whether there is a correlation between the composition of the microbiome at a particular body site and a human phenotype. To the extent that proteomic data are useful in addressing this question, inclusion of such techniques would be acceptable. However, projects that are designed to investigate questions of functionality only and do not explore the correlation between the microbiome and the human phenotype, would not be considered responsive to this RFA.
Has the UH2/UH3 mechanism been used previously?
This is a new mechanism that was created for this project. It is modeled very closely after the existing R21/R33 paired mechanisms, with the difference being that the UH2/UH3 awards will be cooperative agreements grants.