July 3, 2014
Opportunities and Resources
- Advancing the Efficacy of Topical HIV Microbicides
- For Your Consideration: Funding Opportunities on HIV Persistence
- Opportunities for Multidisciplinary Studies of HIV and Viral Hepatitis Coinfection
In The News
- News and Notes From NIAID's Advisory Council
- Your Insight Into NIAID's Funding Priorities: Council-Approved Concepts
- News Briefs
- Tips for Writing a Strong Multiple PI Leadership Plan
- Reader Questions
New Funding Opportunities
You're likely aware that several major journals, scientific organizations, foundations, and government agencies, including NIH, are working on new policies designed to improve data sharing. But you may be surprised to learn that in many cases NIAID already provides research data openly through several Web sites.
In Perspectives From NIAID's Experiences With Open Data Sharing, we shared our experience with two of those Web sites: ImmPort and TrialShare. Here, we talk about Web sites supported by NIAID's Bioinformatics Resource Centers (BRCs) for Infectious Diseases.
What Are BRCs?
BRCs are a consortium of NIAID-funded research centers collecting research data on a variety of pathogens and sharing that data through five Web sites:
- Eukaryotic Pathogens Database (EuPathDB)
- Vectors of Human Pathogens (VectorBase)
- Influenza Research Database (IRD)
- Virus Pathogen Resource (ViPR)
- Pathosystems Resource Integration Center (PATRIC)
These BRC Web sites integrate data and associated metadata, including data on genomics and a variety of other "omics," population genetics, protein 3D structures, worldwide animal surveillance, clinical phenotypes, metabolic pathways, host-pathogen interaction, and host response to infection.
Each Web site shares processed data and data from ongoing research, with links to the corresponding raw data in other public repositories.
You can download data sets without restriction. To upload data, you have to ask BRC staff to package your data according to BRC standards, which they will do upon request. Find a BRC contact for each sharing platform through its respective Web site.
To help you make use of large volumes of data, each Web site offers a suite of open-source annotation, classification, visualization, and analysis tools, as well as free bioinformatics training.
Addressing Data Sharing Challenges
As with all data sharing efforts, BRC Web sites confront challenges related to cost, utility, privacy, and quality of data. NIAID has taken the following steps to address those challenges, in hopes of lessening their impact:
- BRC contracts include funding for costs associated with data sharing (in addition to costs for the actual research).
- Staff in our Division of Microbiology and Infectious Diseases (DMID) review research progress and engage BRC investigators to ensure prompt sharing, according to data sharing plans that take into account unique aspects of an investigator's research and capacity to provide data.
- While BRCs collect very little identifiable private information, they must restrict that small portion of data due to concerns about the privacy of human subjects. NIAID has established a panel of experts to recommend solutions.
- To help with reproducibility and usability, BRCs share the same metadata format, which was developed in concert with BRC investigators.
- Each BRC Web site includes tools and filters to help researchers find and make the best use of data. For example:
- PATRIC features Rapid Annotation Using Subsystem Technology (RAST) and Metagenomics RAST (MG-RAST) for annotating bacterial genomes and microbiome.
- IRD has Highly Pathogentic H5N1 Clade Classification Tool, Metadata-Driven Comparative Analysis Tool, and an algorithm to Analyze Sequence Variation to help analyze the influenza virus.
Examples of Sharing Data Through the BRCs
To illustrate the results we've seen from open data sharing through the BRCs, consider our experience with EuPathDB.
EuPathDB provides genomic-scale data sets associated with eukaryotic pathogens in many genera. It has generated over 6,000 citations in Google Scholar since its creation in 2004, with over 1,000 citations in 2013 alone.
In 2013, EuPathDB saw more than 13,000 unique users monthly, with users logging in from more than 100 countries and visiting a total of 1.2 million pages. Total data sets and the number of downloads continue to grow steadily.
For more usage statistics, go to Statistics for: EuPathDB.org.
Our experience with EuPathDB is similar to that of other BRC sites, and we may cover some of those in a future issue of this newsletter.
Participation From Individual Labs
If you'd like to share your data, reach out to any BRC or BRC investigators. They'll work with you to get your data into a BRC database.
Also, feel free to adopt our NIAID/DMID Data Sharing and Release Guidelines and DMID Metadata Standards into your work. If you do, it'll be easier for you to share your data through one of the BRC sites.
To speak to an NIAID program official about participating in BRCs or any of the data sharing platforms mentioned above, contact DMID's Dr. Alison Yao.
- BRC Awards—list of PIs for BRC databases.
- Standardized Metadata for Human Pathogen/Vector Genomic Sequences—reports the development of a common format for sharing data developed by representatives from the BRCs, the Genome Sequencing Centers for Infectious Diseases (GSCIDs), and NIAID.
- NIH's Working Group on Data and Informatics—advisory committee on the management, integration, and analysis of large biomedical data sets.
- NIAID’s Division of Microbiology and Infectious Diseases (DMID)
Investigators who missed out on last year’s funding opportunity announcement (FOA) Integrated Preclinical/Clinical Program for HIV Topical Microbicides and Biomedical Prevention (IPCP-MBP) will be excited to learn that NIH has reissued the FOA. This U19 cooperative agreement FOA contains significant modifications to previous iterations, so pay close attention.
The goal of the IPCP-MBP is to support the development of microbicides, topical or systemic PreExposure Prophylaxis, or Multipurpose Prevention Technologies to prevent HIV acquisition and transmission in the male or female genital or gastrointestinal (GI) tracts. Our current emphasis is on sustained, rather than on-demand, protection, either in the form of noncoital products that provide a 7-day window of protection or sustained release products that provide a 30-day window.
Specific IPCP-MBP scientific and developmental objectives include:
- Developing novel single and combination products for sustained HIV prevention in the male and female genital and GI tracts.
- Translating innovative products from preclinical development to early clinical testing.
- Advancing new technologies that can identify safe and efficacious prevention products with high levels of adherence or acceptability.
Applications must include a minimum of two projects, an administrative core, and an industrial partner. Applicants can propose up to five years of funding if a clinical component is included or four years without a clinical component. The FOA allows investigators to choose their specific areas of research, such as clinical testing, investigational new drug (IND)-enabling critical path studies, or developing biomedical methods to measure adherence. Together, the projects and cores should establish an integrated and iterative effort that promotes advancement to IND filing, initial clinical testing, or both.
Read the June 4, 2014, Guide notice to ensure that your area of research fulfills the requirements of this opportunity. The notice provides examples of the project types that we are looking for, as well as lists of research areas considered responsive or nonresponsive.
Note that your application’s total direct costs must not exceed $2.6 million per year.
Optional letters of intent are due October 18, 2014, and the deadline to apply is November 18, 2014.
Two funding opportunity announcements (FOAs)—a companion R01 and R21—may be of interest if your research can help increase understanding of persistent HIV-1 infection in patients receiving highly active antiretroviral therapy (HAART).
You must be able to develop new ideas or approaches for studying or eliminating HIV-1 persistence. These can include model or assay development, as well as the design of therapeutic strategies to achieve either 1) long-term remission without treatment or 2) a complete eradication of viral reservoirs.
Research topics of interest include studies of:
- The relative contributions of latency and low-level ongoing active HIV infection to HIV persistence.
- Host factors and pathways that can be activated in the relevant cell type (not in cell lines) to overcome latency.
- The nature of the functional integrated latent proviruses that contribute to viral rebound in vivo.
- HIV reservoirs and persistence in children and adults who have been treated very early after infection.
- The effects of chemotherapy and transplantation on the persistent HIV reservoir.
We encourage collaborations with NIH intramural investigators. If your application includes such a collaboration, you may not request funds for the support of the intramural scientist. For further details, read Applications Involving the NIH Intramural Research Program under the FOA's Section IV. Application and Submission Information.
Find complete information on both opportunities in the June 4, 2014, R01 and R21 Guide notices. Applications for both are due on standard AIDS dates.
For pepole infected with HIV, viral hepatitis progresses more rapidly. To address priority areas in the Action Plan for the Prevention, Care, and Treatment of Viral Hepatitis and advance the research on this topic, we are seeking research on HIV/HBV and HIV/HCV co-infection through two new companion funding opportunity announcements (FOAs).
Six NIH institutes are participating in these FOAs, which inform their call for multidisciplinary approaches. Each institute has its own areas of research interest. NIAID, in particular, aims to:
- Understand the pathogenic interactions between HIV disease and HCV infection or HBV infection;
- Study host and risk factors and mechanisms associated with spontaneous clearance of HCV and sustained virologic response to HCV or HBV treatment in HIV coinfected individuals;
- Identify host and risk factors and mechanisms associated with co-morbidity;
- Study factors associated with acquisition of HBV or HCV in HIV-infected individuals (and vice versa);
- Identify predictors for HBV or HCV perinatal transmission in HIV-coinfection;
- Study effectiveness of interferon-free direct-acting antiviral drug regimens to treat HIV/HCV coinfection.
To see lists of all six institutes’ research interests, read the June 10, 2014, R01 and R21 Guide notices. Applicants are encouraged to contact the scientific/research contacts listed in the FOAs to discuss areas of interest with particular institutes.
For both the R01 and R21, the multiple application deadlines follow NIH's standard AIDS dates. The first deadline is September 7, 2014 (which rolls forward to September 8, 2014).
If you missed the June 2, 2014, meeting of our advisory Council, read on for a few notes of interest to extramural researchers.
NIAID Director Dr. Anthony Fauci announced that the president's FY 2015 budget proposal is essentially flat, which translates into a net loss of buying power as the costs of biomedical research continue to rise without the equivalent increase in our budget. We can't say what this will mean for our paylines, but if Congress passes a budget at or around that level, we're unlikely to increase paylines significantly, if at all.
He also announced the appointment of Dr. Maria Giovanni as associate director for genomics and bioinformatics for NIAID, making her the head of NIAID's genomics and bioinformatics programs—and your program contact for research involving genomic sequencing and big data.
Other topics included a list of NIAID intramural scientists who'd won prestigious honors and awards, changes to NIAID's Division of Intramural Research, news from recent scientific conferences that NIAID participated in, and a rundown of recent scientific developments that affect NIAID's research priorities.
For all of Dr. Fauci's remarks, watch the NIAID Advisory Council Meeting.
Learn more about NIAID's priorities and initiatives from Council subcommittee meetings, where our staff discuss extramural research programs with advisory Council members. See below for video of these subcommittees' open sessions:
- AIDS Research Advisory Committee
- Division of Allergy, Immunology and Transplantation Subcommittee
- Division of Microbiology and Infectious Diseases Subcommittee
You might also be interested in hearing more about new Council members who came on board in January 2014, for whom this was their second Council meeting:
- DAIDS Subcommittee
- Chris Wilson, M.D., director of the Global Health Discovery and Translational Sciences Program at the Bill and Melinda Gates Foundation
- DAIT Subcommittee
- Anita S. Chong, Ph.D., professor of surgery at the University of Chicago
- Arlene Sharpe, M.D., Ph.D., George Fabyan Professor of Comparative Pathology at Harvard Medical School, head of the Division of Immunology in the Department of Microbiology and Immunobiology, and co-director of the Harvard Institute of Translational lmmunology
- DMID Subcommittee
- Larry S. Schlesinger, M.D., Samuel Saslaw Professor and chair of the Department of Microbial Infection and Immunity in the College of Medicine at The Ohio State University
These members will serve until October 31, 2017. Learn more about them at Biographical Sketches of NIAID Council Members.
While we're on the topic of Council, if you're not tuned into our concepts, you might be missing out on big insights into NIAID's strategic thinking.
Before NIAID announces a new initiative, such as a request for applications (RFA), a program announcement (PA), or a request for proposals (RFP), our advisory Council must first approve a corresponding concept.
While there is no guarantee that a concept will become an initiative, savvy applicants often gear their investigator-initiated applications toward NIAID's research interests.
To see a list of approved concepts, go to Concepts: Potential Opportunities. Find our most recent concepts on the following pages:
- June 2014 DAIDS Council-Approved Concepts
- June 2014 DAIT Council-Approved Concepts
- June 2014 DMID Council-Approved Concepts
For more about how concepts work, read Concepts May Turn Into Initiatives in the NIAID Funding Opportunity Planning and the Budget Cycle.
Get our advice on using concepts to your advantage at Use Our Concepts List, Blend Approaches and other sections of Choose Approach and Find FOAs in the Strategy for NIH Funding.
Upcoming Webinar on Human Subjects Incident Reporting. On July 24, 2014, the Office for Human Research Protections is hosting a Webinar to give Guidance on Reporting Incidents to OHRP. To watch, simply go to the event's videocast page (use the preceding link) 5 to 10 minutes before the event begins at 2:00 p.m. Eastern.
As you prepare to write your multiple PI application, give time and attention to the required Leadership Plan.
Reviewers judge its scientific merit and whether it promotes enough coordination and communication among PIs. They consider the appropriateness and quality of the plan in their evaluation and scoring of the investigators as well as the overall impact of the application.
Given all this, your plan needs to be as sound as possible, but how do you fill such a tall order? The following pointers may help.
Address What's Required
Before discussing your plan, much less writing it, you and your fellow PIs must know what items you should cover.
- Rationale and justification for choosing the multiple PI approach.
- Governance and organizational structure of the team.
- Procedures for resolving conflicts.
- Process for making decisions on scientific direction and allocating resources and funds.
For the rest of the list, go to Multiple PI Facts, linked below.
We expand on a few of the required items in the section Know What Reviewers Want, Like, and Expect.
Follow a Few Tips
Here is some general advice to keep in mind as you approach and write your plan.
Ask questions. Approach the Leadership Plan as you would the Research Plan. That is, ask yourself and the other PIs some basic questions, such as: Why are we going to the trouble of making this a multi-PI application? How will we organize and execute the overall project? What will we do if we run into problems? What provisions can we make ahead of time against potential pitfalls?
Do more than what's required. While good plans address several points required by NIH, e.g., rationale for using the multi-PI approach, governance, conflict resolution, the best plans go a step further. They cover additional ground by discussing potentially sensitive issues, such as data sharing between PIs, collaborative publication policies, contingency plans in case one PI changes institutions, and procedures for allocating resources.
Get organized. Just like exemplary Research Plans, the best Leadership Plans are typically organized into succinct sections or paragraphs with informative headings, for example, Rationale, Organizational Structure, and Procedures for Resolving Conflicts.
Dividing into sections and clearly labeling them not only makes for easy reading (which is important for reviewers who have many applications to evaluate), but also lets reviewers follow the applicants’ thought processes and find answers to questions they may have.
Since the Leadership Plan has no page limit and does not count toward the Research Strategy page limit, use the lack of space constraints to include what you need and present the information in an easy-to-find way. Do not use this section as a way to circumvent the page limit for the Research Strategy section.
Avoid pitfalls. Weaker Leadership Plans tend to suffer pitfalls: poor organization, lack of specifics on roles and responsibilities, omitting critical information like plans for deciding scientific direction or resolving conflicts, and projecting an attitude of “trust us, we’ve been working together for years.”
Another major pitfall is stating that all PIs will take joint responsibility for everything—finances, project direction, and necessary scientific expertise. Reviewers know that even the closest collaborations can run into problems and that there will be times when PIs do not agree. Therefore, reviewers will appreciate a sensible division of responsibilities much more than a frequently implemented conflict resolution procedure.
Plans with faults like these may sometimes pass scrutiny by reviewers, but you don’t want to take a chance on undermining their confidence in your application by simply recycling a plan from another application.
Know What Reviewers Want, Like, and Expect
As we mentioned at the outset, you should cover several required bases in your Leadership Plan.
We focus on a few of those here and provide advice on how you might address them based on what reviewers expect to see.
Why Multiple PIs?
Reviewers like to see a solid, scientifically based answer to this question. Since the multiple PI option is for collaborative, usually multidisciplinary, research, they must understand why your proposed research requires bringing in and working with other PIs with distinct and complementary expertise.
In the absence of a clear scientific rationale, reviewers will likely question why you wouldn't be able to complete the research without the other PIs.
What to do. Provide a strong rationale and justification for choosing the multiple PI approach. For instance, describe why the Specific Aims of the project could not be accomplished without the combined leadership and expertise of all the PIs.
Who Will Do What?
Reviewers expect to see Leadership Plans that clearly and specifically delineate the PIs' respective roles and responsibilities. Those that do may receive more favorable evaluations than those that don't.
What to do. We touched on this above, but it's worth repeating. Rather than stating that the PIs will share all responsibilities equally, which reviewers usually view as unrealistic, describe specific "assignments": PI #1 will be responsible for Specific Aim #1 and be responsible for doing X, PI #2 will work on Specific Aim #2 and be in charge of Y, and so on.
Also, be sure to say who will serve as contact PI, the person who will coordinate 1) communication among all PIs and NIH and 2) the progress report.
Reviewers look for a sound organizational and governance plan. In the absence of one, they'll be concerned that the level of coordination and communication among the PIs might be insufficient to fully realize the collaborative aspects of the project.
In instances where a multiple PI application includes an established researcher and a more junior investigator, reviewers will look for and carefully evaluate the time commitment and plans for decision making and resource allocation to determine whether they are appropriate and equitable. Keep in mind that while the level of effort of each PI on a multi-PI application does not have to be the same (whether established or junior), it does need to be appropriate and justified for the work proposed.
What to do. In your governance plan, describe the process for deciding scientific direction and communication procedures, for example, regularly scheduled meetings of the PIs, periodic evaluation of research progress and finances, and publication policies.
Reviewers like to see a carefully considered conflict resolution plan, which preferably includes the involvement of well-respected people outside of the project to mediate disputes if the PIs are unable to resolve the issues by themselves.
What to do. Disputes are likely to arise, so you'll need to describe how you'll handle them. If you can't come to an agreement, will you bring in an arbitration committee? If so, who and how many will be on it? Will you give a timeframe in which the conflict must be resolved?
- Examples of Project Leadership Plans for Multiple PI Grant Applications on the Multiple Principal Investigators page
- Strategy for NIH Funding
Feel free to send us a question at firstname.lastname@example.org. After responding to you, we may include your question in the newsletter, incorporate it into the NIAID Research Funding site, or both.
List every publication (or manuscript accepted for publication) that was supported by your grant during the reporting period (in other words, those since your last progress report that weren’t previously reported), unless otherwise indicated in the terms of award. Include this information in response to question C.1 Publications in the RPPR.
A number of investigators have been submitting more than what is required—years’ worth of publications from their grant. In other cases, investigators are including everything they published in the past year, including those from other grants. Not only does this inundate our staff, but based on the additional publications that they list, they may signal to us that their research has made an unauthorized change in scope or other action that requires prior approval. This can create additional paperwork and delay awards.
If it’s not in scope, you should not be citing the grant in the publication. For a list of all actions that constitute a change in scope, see Change in Scope in Section 8 of the NIH Grants Policy Statement.
If you want to mention other publications to put some of your work in context, be clear that these publications are supported otherwise in the discussion.
In addition, if you include a publication that’s not part of your award in response to question C.1, you’ll run the risk of a delay in award if the publication isn’t compliant with the Public Access Policy.
We’re also finding that some PIs are delegating publication reporting to their junior colleagues, for whom erring on the side of caution may mean including every publication in the PI’s bibliography. Since this is what we would like to avoid, PIs should verify that progress reports do not include extraneous publications. Both PIs and signing officials are responsible for ensuring the publications are compliant with the Public Access Policy.
"Do I still qualify as an early-stage investigator if my collaborators are established principal investigators?"—anonymous reader
Yes. We encourage new and early-stage investigators (ESIs) to choose expert consultants, collaborators, and coinvestigators.
This is distinct from having an established investigator as one of the principal investigators (PIs) on a multiple PI application. If your multiple PI application includes an established investigator as one of the PIs, it cannot benefit from your new PI/ESI status. For example, it wouldn’t qualify for the New PI payline. In this scenario, you would lose your personal new PI or ESI status if your multi-PI application is funded.
You can have an established investigator act as a coinvestigator on a multi-PI application without forfeiting your new PI/ESI benefits, so long as the established investigator is not one of the PIs.
Read How to Qualify for New and Early-Stage Investigator Status to verify your eligibility.
- RFA-AI-14-026, Development of Novel Therapeutics for Select Pathogens
- RFA-AI-14-020, Innovative Assays to Quantify the Latent HIV Reservoir
See other announcements at NIAID Funding Opportunities List.