Opportunities and Resources
- Small Businesses: Improve HIV Envelope Protein Expression, Yield, and Purification
- A New Opportunity to Advance HIV Therapeutic Vaccine Science
- Help Improve Anti-HIV Dosing Intervals by Discovering and Identifying Sustained Release Products
In The News
- The "Nature" of Appeals
- You Will Still Use Cover Letters, but Not for Assignment Requests
- News Briefs
- Just for "U": A Closer Look at Cooperative Agreements
- Reader Questions
New Funding Opportunities
You’ve probably been hearing more talk lately about phased awards, which may have caused you to wonder what they are and how they work.
You’re in luck. Here you’ll find some of the basics surrounding phased innovation awards.
What Are Phased Awards?
Phased awards are a type of grant used to support high-risk research and development of promising and viable candidate products or technology (e.g., drugs, vaccines). Thus, phased grant award mechanisms, such as an R21/R33 grant, are used for early-stage research and discovery, preclinical development of candidate products, and exploratory projects.
The benefit of phased awards is that unlike other grant mechanisms—think R01 grants—the ultimate risk of failure is greatly reduced as is the monetary risk to NIH since additional funding is directed to only the most promising projects.
How do Phased Awards Work?
Rather than giving a select few grantees large-sum awards for their projects, phased awards allow NIH to issue small award amounts to a larger number of grantees for Phase I of an award. At the end of Phase I, NIAID will evaluate a grantee’s research and analysis progress to determine if his or her project has met the pre-determined transition milestones and other requisites that would allow the grantee to continue to Phase II of the award.
Continuing on to Phase II of the award is often referred to as “transitioning to Phase II.” And as you can probably guess, approval to transition to Phase II coincides with the grantee's receiving additional funding to continue work on his or her project. In some instances, Phase II award amounts can be substantially more than the grant amount awarded in Phase I.
But transitioning to Phase II is not easy. In fact, under some funding opportunity announcements (FOAs), only half of the grantees that receive a Phase I award meet the milestones and other requirements necessary to progress to Phase II. The estimated odds of transitioning are usually mentioned in the FOA.
How Are the Milestones Set?
Many of the parameters for setting phased award milestones are provided in the FOA. Applicants use the parameters listed in the FOA to propose reasonable milestones that they’d consider indicative of the Phase I success needed to transition to Phase II. Applicants then submit their proposed transition milestones as part of their initial grant application package.
Next, peer reviewers assess the applicant’s grant package, paying special attention to the proposed milestones. The reviewers consider the quality, rigor, and suitability of the milestones and capture their opinions and recommendations in a summary statement. The summary statement is then provided to the applicant after the grant package review concludes.
NIAID program staff also receive a copy of the summary statement, which they use to consider the reviewers’ recommendations, along with the programmatic objectives. If necessary, program staff will also work with the applicant to negotiate changes to the proposed milestones before funding.
Once program staff and the applicant come to an agreement, the authorized organizational representative submits the final approved transition milestones to NIAID, which are then referenced in the Notice of Award, and Phase I funding is awarded after all the usual requirements for making an award are satisfied. The applicant (now a “grantee”) can then begin work on Phase I of his or her project.
Once a Grantee Meets the Phase I Milestones, Is He or She Automatically Approved to Transition to Phase II?
Not exactly. Here’s where the process can begin to get complicated.
As stated earlier, some phased awards may be constructed so that no more than half of the grantees who receive awards for Phase I will be approved to transition to Phase II. That said, all of the grantees that were issued an award for Phase I of a project are evaluated simultaneously as one group at the end of that phase (normally, one or two years after the initial award).
A panel of NIH program staff is convened to evaluate and rank the “Phase II Transition Packages” of the grantees. In addition to assessing whether each grantee has met the milestones as originally outlined, other determining factors are also weighed heavily in this review; for instance, whether or not the grantee’s project still fits within the scientific priorities of the program division or how well the grantee’s candidate product or technology is prepared for further development.
All of the above factors and more are thoroughly considered when evaluating grantee transition packages. At the conclusion of the panel evaluation, the grantees that rank in the top half of the group transition to Phase II and receive additional funding for their projects. Grantees that place in the bottom half do not transition to Phase II and may even have their Phase I awards closed out at that point, depending on how the FOA is set up.
Additionally, grantees who don't successfully transition to Phase II cannot 1) reapply to another phased award for the same project or 2) file an appeal against the evaluation panel’s decision, which is final.
What Happens After Phase II Ends?
At the end of the Phase II project period, if a grantee’s project has been successful and shows promise beyond “proof of principle,” the grantee would then be poised to apply to subsequent FOAs (e.g., R01s, Small Business Innovative Research grants) for additional funding.
The best news here is that if a grantee is able to successfully procure a subsequent research project award, the grantee will undoubtedly have access to much more substantive resources to continue his or her project.
Opportunities and Resources
If your small business can improve expression, yield, and rapid purification for multiple HIV envelope immunogen components, you may be the ideal candidate for a Phase I, Phase II, or Fast-Track grant through funding opportunities for Small Business Innovation Research (SBIR) or Small Business Technology Transfer (STTR).
We seek innovative technologies and strategies that would meet regulatory requirements for use in HIV vaccine clinical studies. Such technologies should have commercial potential.
Your application must propose research to improve the expression yield in a specific cell culture system and the purification yield using specific purification regimens designed for HIV envelope proteins suitable for use as clinical immunogens. Your project may focus on any step of envelope expression and yield, improvement of substrates, or development of purification platforms.
Read the funding opportunity announcements (FOAs) linked below for examples of the following:
- Approaches you might evaluate to improve HIV envelope expression and yield
- Areas of focus for your project
- Protein purification methodologies that work for all HIV envelopes
The examples in the FOAs are not your only options; you may propose other appropriate projects that are highly innovative or enhancements of current approaches. Whatever approach you choose, it should significantly advance the current state of the art and have commercial potential.
Note that the opportunities do not support clinical trials, non-envelope protein vaccines, or lectin-based purification schemes.
Duration and Budget Requirements
The normal expectations for small business awards, based on statutory guidelines from Congress, are as follows:
- Your total funding support (direct costs, indirect costs, and fees for the life of the award) should not exceed $150,000 for Phase I awards and $1 million for Phase II awards. With additional justification, you may request $225,000 for Phase I awards and $1.5 million for Phase II awards.
- Phase I awards should not exceed six months and Phase II awards should not exceed two years.
That said, if you anticipate a budget or project period greater than the normal guidelines, contact NIAID's program official listed below. NIAID can fund Phase I applications with budgets of up to $300,000 annual total costs for up to two years and Phase II or Phase IIB applications with budgets of up to $1 million annual total costs for up to three years. We must request a waiver from the Small Business Administration to do so; therefore, your application’s budget must be extremely well justified and its scientific area must be included in the list of NIH, CDC, FDA, and ACF Program Descriptions and Research Topics.
Ultimately, we encourage you to propose a budget and duration that are reasonable and appropriate for your project.
Keep in mind that even if your budget is within the normal expectations, your application's review committee may recommend budget cuts. In addition, NIAID may reduce the length of an award or the review committee's recommended budget for administrative, programmatic, or budgetary reasons.
The number of awards depends on NIH's appropriation and whether we get enough high-quality applications.
Other Application Information
The first due date for both opportunities is September 5, 2016. After that, use NIH's SBIR/STTR Standard Due Dates for Competing Applications until the opportunities expire on April 6, 2019. Don't forget that the standard due dates for small business applications changed in September 2015.
Send your questions about the FOAs to Dr. Jeff Pullen, NIAID's scientific program contact.
Do you have an interest in understanding the links between vaccine regimens, immune responses, and HIV virologic control? If so, look no further.
NIH seeks applications for a funding opportunity announcement (FOA) that aims to advance the understanding of vaccine regimens and immune responses that sustainably suppress viral loads in HIV-infected individuals. This FOA will support hypothesis-driven mechanistic studies using small, comparative, multi-arm, clinical trials of virologically suppressed, HIV-infected individuals on combination antiretroviral therapy (cART).
Specific research areas of interest include:
- Comparisons of vaccine vectors, HIV immunogen constructs, vaccine adjuvants, vaccine or adjunct dosages, or the order and timing of treatments
- Endpoints based on correlations between measures of immunity and virologic criteria
- Other immunotherapeutic approaches
Read the FOA for additional responsive areas of interest, as well as research areas that will be considered nonresponsive and therefore will not be reviewed.
This FOA will support both an initial and a follow-on clinical trial designed to confirm the observed correlations between specific vaccine-induced immune response and virologic control, and to further optimize the response. The goal is to develop effective therapeutic vaccination strategies by methodically increasing the understanding of protective responses, then working to improve the potency of those responses.
As such, your application should propose clinical trials designed to identify correlations between levels of induced immune response and HIV virologic control.
Refer to the FOA for a list of activities related to conducting clinical trials that may be supported, as well as a list of clinical trial planning activities that will not be supported. Pay close attention to the requirements for clinical research funded by the Division of AIDS.
This FOA will be funded through a U01 cooperative agreement. Application budgets are not capped but should reflect the actual needs of the proposed project.
The maximum project period is five years. Your application should contain a milestone plan, to include opening enrollment within 12 months of award and completing the clinical trial within the period of award. NIAID may reduce funds or the period of performance based on lack of achievement of yearly milestones.
Applications are due July 28, 2016. Apply early to allow adequate time to correct any errors found in your application during the submission process.
NIAID aims to develop oral, implantable, injectable, or transdermal anti-HIV sustained-release products (SRPs) with a minimum dosing interval of once a week; monthly or three-month intervals would be better still. To do so, we will fund research projects to identify existing anti-HIV molecules or discover new, highly potent, selective anti-HIV small molecules with potential relevance to extending dosing intervals.
The R01 funding opportunity announcement (FOA) identifies several example areas of interest:
- Discovery, through chemical synthesis, of new active pharmaceutical ingredients (APIs) that exhibit highly potent and selective in vitro anti-HIV activity.
- Design and development of existing APIs with established antiviral activity and HIV resistance patterns in combination.
- Chemical and physical characterization of selected APIs and drug delivery systems.
- In vitro and in vivo studies designed to assess the potential toxicity and safety of selected APIs and drug delivery systems.
- Pharmacokinetic and pharmacodynamics studies designed to characterize in vivo release of an SRP for a proposed dosing interval.
- SRP studies to assess local tissue concentrations of the API and document local cellular and tissue reactions.
At the same time, the FOA provides a list of nonresponsive areas of research. Be sure to review the full list by following the link below. Examples include:
- Random or bulk screening of chemical or natural product libraries and collections to "discover" SRP candidates.
- Developing intravaginal rings or products to be delivered exclusively by topical delivery to the male or female genital or gastrointestinal tracts.
- Developing or using genetically modified organisms or bacterial, fungal, or viral vectors to deliver SRP candidates.
Deadlines and Requirements
The maximum project period is five years. Your application budget is not limited but must reflect the actual needs of your proposed project.
The program will make use of milestones and Go/No-Go criteria to guide research leading to the selection of candidate APIs and drug delivery systems. Propose milestones in your Research Strategy and include a summary Gantt chart to help reviewers understand the flow of your proposed Specific Aims and the interrelatedness of your development plan’s components.
Send an optional letter of intent by July 1, 2016. Applications are due August 3, 2016.
For complete details, read the April 6, 2016 Guide announcement.
Also, check out the Long-Acting/Extended Release Antiretroviral Resource Program (LEAP), created by NIAID's Division of AIDS to provide investigators access to scientific, pharmaceutical, and regulatory expertise, as well as computer-based modeling and simulation services.
A recent item in Nature titled Under Appeal may have caught your eye and gotten you thinking that appealing peer review results might be, well, appealing. You may want to think again.
The outcome described in the Nature piece was a positive one for the U.K.-based scientist, but note that it is a rare case. In general, successfully challenging review results is uncommon and can be time- and energy-consuming. Those appeals that are successful result in a "re-review," and the outcome of that re-review is final. However, at NIH, most appeals are unsuccessful and result in the applicant having to revise and resubmit his or her application.
You may appeal if you have evidence of bias, lack of appropriate expertise, reviewer errors of a factual nature, reviewer conflicts of interest, or other flaws in the peer review process that would have had a significant impact on your application's final overall impact score.
An appeal cannot be based on a difference of scientific opinion. Such an appeal does not increase the chance of being funded. It will, however, delay funding further than if you had revised and resubmitted your unsuccessful application without going through the appeals process.
To learn more, read our Appeals of Scientific Review of Grant Applications SOP and Should You Appeal?
In March, we told you that Policy Changes Accompany the FORMS-D Changeover. One of those changes, the new PHS Assignment Request Form, merits further discussion.
Beginning with applications due on or after May 25, 2016, you have the option of completing the new PHS Assignment Request Form. On this form you can:
- Identify any NIH institutes or centers as an awarding component, both positively ("assign to") and negatively ("do not assign to").
- Make study section or special emphasis panel requests, both positively and negatively.
- List potential reviewers in conflict and explain why.
- List scientific expertise needed to review your application.
The form is not a requirement—you could even choose to complete only one of the fields listed above and leave the rest blank.
Keep in mind, if you list potential reviewers in conflict, acceptable explanations are conflict of interest, competitor, or long-standing scientific disagreement. Ultimately your scientific review officer (SRO) will decide whether to exclude reviewers.
Read for our full advice on how to approach your assignment request.
As before, you must have a cover letter for the following applications:
- Approvals to submit. For applications requiring our approval to submit, state that you have attached a copy of the NIAID acceptance letter to the PHS 398 Cover Letter attachment for:
- Grants requesting $500,000 or more in direct costs for any year
- Conference Grants (R13 or U13)
- Investigator-initiated clinical trial planning and implementation awards
- Generation of data per the NIH Genomic Data Sharing Policy. State that studies will generate large-scale human or nonhuman genomic data as detailed in the NIH Genomic Data Sharing Policy.
- Corrected applications. Include a complete cover letter if you did not pass validations and submitted a corrected application.
- Late applications. See the Late Applications section in Submission Policies.
- Continuous submission. Indicate that you are a member of an NIH study section qualified to submit at a nonstandard time.
- Video. Indicate that you plan to send video files later. Read more at Plan Ahead for Video.
You can also still use the cover letter to:
- Point out requests for applications and program announcements. State the title if you're responding to an initiative.
- Note special areas. Note the involvement of human subjects, select agents, or other areas with special requirements.
- Note a subaward that will be active for only some of the grant's years.
For more about cover letters, see Cover Letter Attachment. In the past, only NIH's Division of Receipt and Referral and SRO would see your cover letter, not the reviewers or program officer. The same will be true of the new PHS Assignment Request Form.
If you plan to apply for the HIV Vaccine Research and Design (HIVRAD) Program (P01), your budget request cannot exceed $2 million in annual direct costs. We intend to fund one or two awards in FY 2017 and FY 2018. The next application due date is July 15, 2016.
You've probably come across funding opportunity announcements (FOAs) that use activity codes starting with a "U," for example, U01 and U19. The "U" designates a cooperative agreement.
If you're not familiar with or want to know more about "U"s, here's some information you may find helpful.
What Is a Cooperative Agreement?
A cooperative agreement is a support mechanism that NIH frequently uses for high-priority research areas that require a level of involvement from NIH staff that is higher than for a typical research project (R) grant. This substantial involvement is usually needed for oversight, coordination, or facilitation; we explain the term "substantial staff involvement" in more depth, below.
Cooperative agreements are usually awarded in response to requests for applications (RFAs), which outline the scientific scope, required activities under the grant, any special peer review considerations, the nature of NIH staff involvement in the award, and specific responsibilities of NIH staff and the project director/principal investigator (PD/PI) during the project period.
What Is Meant by "Substantial Staff Involvement"?
Fundamentally, NIH staff work jointly with the PD/PI, acting as a partner to support and stimulate the research. Staff are not meant to play a dominant role nor assume direction or primary responsibility for awardee activities.
Examples of substantial staff involvement include:
- Participating in protocol design, data collection, and data analysis and interpretation
- Approving a stage of a clinical trial or other collaborative project before the next stage starts
- Coordinating or providing training to grantee staff
For additional descriptions, see Substantial Staff Involvement at Determining When to Use a Cooperative Agreement.
Before Applying, Points to Ponder
When you're thinking about applying for an NIAID-supported, "U" funding opportunity, keep in mind a couple of key points.
Why a Cooperative Agreement?
First, consider why the Institute is using a cooperative agreement rather than an R series grant and what that will entail for you as PD/PI.
As we mentioned, a cooperative agreement allows our staff significantly more involvement in the project, but that covers a wide range of tasks.
For instance, we sometimes use the U mechanism to form a study group or collaborative network centered on a particular topic. In such a case, the day-to-day feel of the project won’t differ much from a typical R grant. However, when we use a cooperative agreement for clinical trials, the PD/PI and our staff will be working very closely together several hours a week to develop and execute a trial and associated studies.
Check Out the FOA for Need-to-Know Information
Since cooperative agreements are generally used for complex or targeted projects that require the close coordination of multiple grants or resources, you should go through the FOA thoroughly and take into account the experience, intensity, and level of collaboration required to manage the cooperative agreement.
When reading a cooperative agreement FOA, pay special attention to the following sections of Part 2. Full Text of Announcement:
- Section I. Funding Opportunity Description—covers requirements for applications that might include access to resources, certifications, definitions, milestones, or special considerations. Note certain areas of research that may be required or excluded, as well as other mandatory items, such as participating in meetings or workshops and using specific databases.
- Section IV. Application and Submission Information, 2. Content and Form of Application Submission—has instructions for Other Attachments and the Research Strategy and may provide details about where you should put certain information.
- Section V. Application Review Information—often includes special or additional review considerations for cooperative agreements to focus reviewer attention on the critical aspects needed for a project's success.
- Section VI. Award Administration Information—contains the Cooperative Agreement Terms and Conditions of Award that 1) outline specific special terms of award and 2) define and describe the responsibilities of the PD/PI and NIH staff. Be sure you can abide by the provided framework since this information will also be in the Terms of Award, which will be part of your Notice of Award.
Check In With the FOA Contact, Too
Though a FOA will give you essential information, you should talk to the scientific/research contact listed in the announcement to truly understand the motivations of our using a cooperative agreement and the expectations we have of the PD/PI.
Application Submission, Peer Review, and Other Considerations
Given the complex requirements of a cooperative agreement, you'll likely spend more time preparing for and writing your application. If you have questions or concerns along the way, we encourage you to communicate with the appropriate contacts listed in the FOA.
Other processes for cooperative agreement applications are "business as usual":
- Application submission—you'll submit electronically.
- Peer review—as with most applications in response to an RFA, a special emphasis panel will review the applications using the criteria described in the FOA. Reviewers will be aware of the need for NIAID staff involvement. Like other RFAs, applications will not be assigned a percentile.
- Funding—applications submitted in response to an RFA are funded by a pay plan, not a published payline. A pay plan is the list of meritorious applications that were received and scored and that program officials have selected for funding. The number of grants awarded depends on the total funds set aside for the RFA.
- Just-in-time—will be similar to any other application submitted in response to a FOA.
During an Award and After
Given the nature of cooperative agreements, you can expect NIAID staff to work more closely with you and schedule more frequent communications than they would for a PD/PI on a research project grant. You may also need to get their approval to initiate or continue stages of work, as we mentioned above.
Note that administering cooperative agreements may also differ slightly from R-series awards; for example, carryover of unobligated funds in cooperative agreements is not automatic and must be requested and justified.
As you near the end of your project period, you may wonder about submitting a renewal application to continue the funding of your research. The FOA will specify whether renewals are permitted. Since cooperative agreements are generally used to target and support high-priority areas of science, the option for renewing depends on NIAID's continued interest and funding availability.
Bottom line for renewing a cooperative agreement: Don't plan on the same program being continued in five years. In most cases, applicants will submit a new application at the end of their award.
Feel free to send us a question at firstname.lastname@example.org. After responding to you, we may ask your permission to include your question in the newsletter, incorporate it into the Find a Funding Opportunity site, or both.
“If my proposed project for a K23 award is HIV-related, should I apply following the K series or the AIDS and AIDS-related due dates?”—anonymous reader
You will follow the standard due dates for AIDS and AIDS-Related Applications.
The next due date is May 7, 2016, a Saturday, so it rolls forward to May 9. For that date, apply to PA-14-049 using FORMS-C. The subsequent due date is September 7, 2016, for which you'll apply to PA-16-198 using FORMS-D.
“Can I add a submitted (but not yet accepted) publication in the Publication List linked to a renewal application?”—anonymous reader
No, you shouldn’t add any publications that haven’t yet been accepted by a journal.
However, if your manuscript is accepted after you've sent your application but before the initial peer review, we will accept that news as post-submission material no later than 30 calendar days before the review meeting. Email the scientific review officer a PDF attachment stating the authors, institutional affiliations, title of the article, the journal that accepted it, and the expected time of publication. Don’t attach the article itself.
Learn more at NIH's Post-Submission Materials Policy Frequently Asked Questions.
- NIAID-DAIDS-RFP-NIHAI2015050, NIAID HIV and Other Infectious Diseases Clinical Research Support Services (CRSS)
- BAA-NIAID-NIHAI2016064, Advanced Development of Multivalent Vaccine Candidates for Filovirus and Lassa Fever
See other announcements at NIAID Funding Opportunities List.