FAQ Concerning the Orphan Products Clinical Trials Grants Program
The deadline for submissions is June 25, 2019.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date. Applicants should be aware that on-time submission means that an application is submitted error free (of both Grants.gov and eRA Commons errors) by 11:59 PM Eastern Time on June 25, 2019.
A Letter of Intent in not required, is non-binding, and does not enter into the review of a subsequent application. However, the information that it contains allows FDA staff to estimate the potential review workload and plan the review. No responsiveness decision will be made based on the letter of intent.
Prospective applicants are asked to submit the letter of intent with information contained in the RFA by 11:59 PM Eastern Time on May 25, 2019.
The grants are available to any foreign or domestic, public or private, for-profit or nonprofit entity (including state and local units of government). Federal agencies may not apply.
Of the estimated FY funding of approximately $15 million, approximately $10 million will fund noncompeting continuation awards, and approximately $5 million will fund new awards, subject to availability of funds. Application budgets are not limited, but need to reflect the actual needs of the proposed project. An applicant planning to submit a grant application with $500,000 or more in direct costs for any year is required to provide this notification in writing to the FDA OOPD Orphan Products Clinical Trials Grants Director at least 4weeks prior to the grant application submission deadline (i.e., by May 28, 2019 by 11:59 PM Eastern Time). The applicant must receive a letter in response from OOPD confirming approval to include in an appendix of the submitted grant application. Please see the following for more information: https://grants.nih.gov/grants/how-to-apply-application-guide/forms-e/general-forms-e.pdf
The scope of the proposed project should determine the project period. The maximum project period is 4 years. However, the length of support will depend on the nature of the study.
For those studies with an expected duration of more than 1 year, a second, third, or fourth year of noncompetitive continuation of support will depend on the following factors: (1) Performance during the preceding year; (2) compliance with regulatory requirements of investigational new drug (IND)/investigational device exemption (IDE), if applicable; and (3) availability of Federal funds.
Products that qualify for this grant program are drugs, biologics, medical devices, and foods for medical purposes that are indicated (used) for a disease or condition that affects fewer than 200,000 people in the United States. Diagnostics and vaccines will qualify for the program only if the United States population to whom they will be administered is fewer than 200,000 people per year.
No. A drug or biologic product does NOT have to hold orphan drug designation to be eligible for the grant program. The Background and Significance section of the application must contain information documenting the prevalence, not incidence, of the population to be served by the product is fewer than 200,000 individuals in the United States. The applicant should include a detailed explanation supplemented by authoritative references in support of the prevalence figure.
Diagnostic tests and vaccines will qualify only if the population to whom they will be administered is fewer than 200,000 individuals in the United States per year. The orphan drug designation process is the mechanism by which sponsors of drugs and biologics for rare diseases may qualify for incentives of the Orphan Drug Act such as tax credits and marketing exclusivity. Orphan drug designation is encouraged, especially if there is a question as to whether the proposed disease or condition would be eligible for orphan drug status or in cases where the estimated prevalence of the population is close to 200,000.
Only clinical studies of products for rare diseases with an unmet medical need qualify for this funding opportunity. These clinical studies should evaluate safety and/or effectiveness of medical products in a way that will substantially contribute to the body of evidence needed to support marketing approval or provide essential data to facilitate medical product development for rare diseases.
Use of innovative efficient trial designs is encouraged under the funding opportunity announcement. For example, seamless trial designs, which compress the phases of a trial into one continuous trial, as well as basket, umbrella and platform trials, which allow for testing of multiple drugs and/or multiple diseases using a common infrastructure. Early stages of product development can also hold significant promise for the advancement of curative treatments for rare diseases. Consideration should also be given to the use of real world data, which has the potential to allow for more efficient design and conduct of clinical trials in the health care setting to answer questions previously though infeasible. Real world data can also, in certain cases, be analyzed to support medical product development and approval using novel analytical approaches.
In addition, applications that propose adaptive trial designs, simulations, and modeling used toward the study of safety and effectiveness of a product are encouraged. For example, modeling and simulation allow for organization of diverse data sets, optimization of product dosing based on individual physiology and genetics, and can provide a vital tool to help evaluate new treatments in rare diseases where patient populations are inherently difficult to study because of their small size. Many of these approaches are appropriate in the early stages of product development and may hold significant promise for the advancement of therapeutic treatments for rare diseases. Early engagement with FDA review divisions to discuss the use of these innovative tools is recommended prior to submitting a grant application.
Yes, an IND/IDE is needed, except for medical foods that do not need premarket approval and medical devices that are classified as non-significant risk (NSR). Applicants studying an NSR device should provide a letter in the application from FDA's Center for Devices and Radiological Health indicating the device is an NSR device.
Protocols involving an approved drug that would otherwise be eligible for an exemption from the IND regulations must be conducted under an IND to qualify for funding under this program. The proposed clinical protocol (the same protocol that is included in the grant application) should be submitted to the applicable FDA IND/IDE review division a minimum of 30 days before the grant application deadline. Be sure to indicate in the IND cover letter that you are applying for an orphan product grant. To qualify for programmatic/scientific review, the study protocol proposed in the grant application must be under an active IND or IDE (i.e., not on clinical hold).
No. The clinical protocol that is being submitted in the grant application for the product for the disease/condition being studied through the proposed trial must be submitted to the appropriate FDA review division a minimum of 30 days before the grant application deadline.
If you are not the sponsor on the IND/IDE, then you must have a formal collaborative agreement with the company or individual who is the official sponsor of the IND and should include documentation of such a relationship in your grant application.
Yes. The grants are available to any foreign or domestic, public or private, for-profit or nonprofit entity (including State and local units of government).
Foreign applications must indicate how the proposed project has specific relevance to the mission and objectives of FDA and has the potential for significantly advancing science in the United States.
Yes. All institutions engaged in human subject research financially supported by HHS must file an assurance of protection for human subjects with the Office of Human Research Protections (OHRP) (45 CFR part 46). Applicants are advised to visit the OHRP Web site for guidance on human subject protection issues. Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained.
The requirement to file an assurance applies to both awardee and collaborating performance site institutions. Awardee institutions are automatically considered to be engaged in human subject research whenever they receive a direct HHS award to support such research, even where all activities involving human subjects are carried out by a subcontractor or collaborator. In such cases, the awardee institution bears the responsibility for protecting human subjects under the award.
The awardee institution is also responsible for, among other things, ensuring that all collaborating performance site institutions engaged in the research hold an approved assurance prior to their initiation of the research. No awardee or performance site institution may spend funds on human subject research or enroll subjects without the approved and applicable assurance(s) on file with OHRP. An awardee institution for multi-site research must, therefore establish a single IRB of record and assurance. The single IRB of record may be an IRB already being used by one of the performance sites, but it must specifically be registered as the single IRB of record with OHRP.
The clinical protocol should comply with Good Clinical Practice Consolidated Guidance which sets an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects. All human subject research regulated by FDA is also subject to FDA's regulations regarding the protection of human subjects (21 CFR parts 50 and 56). Applicants are encouraged to review the regulations, guidance, and information sheets on human subject protection and good clinical practice. Responsibilities of Sponsor-Investigators can also be found in the online presentation which provides awareness to sponsors and investigators of important responsibilities to adequately conduct clinical trials. For further information, applicants should review the section on human subjects in the application instructions of the Request for Applications (RFA).
No. IRB approval is not required at the time of the submission of grant application. However, documentation of IRB approval for the single IRB of record must be on file with the FDA grants management office before an award to fund the study will be made.
Yes. The protocol should be submitted in the application as an appendix. Informed consent and assent forms should be provided as an appendix as well.
All applications must be submitted electronically through Grants.gov. The applications must be prepared using the SF424 (R&R) application forms along with the SF424 (R&R) Application Guide for this funding opportunity as well as any program-specific instructions. Please use the link from the Orphan Products Clinical Trials Grants Program website to the current NIH Guide for Receipt Dates and follow the Required Application Instructions in the Detailed RFA.
The earliest submission date for the RFA is April 25, 2019. The application submission deadline for the RFA is June 25, 2019 by 11:59 PM Eastern Time. A letter of intent is required a minimum of 30 days prior to the application due date (i.e. by May 25, 2019). Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
Applicants should be aware that on-time submission means that an application is submitted error free (of both Grants.gov and eRA Commons errors) by 11:59 PM Eastern Time on the application due date. Late applications will not be accepted for this funding opportunity.
Application Review Process and Timelines
FDA grants management and program staff will review all applications. To be responsive, an application must be submitted in accordance with the requirements of the Request for Applications (RFA). Applications found to be non-responsive will be returned to the applicant without further consideration. Responsive applications will be peer reviewed and evaluated for scientific and technical merit by a panel of experts in the subject field of the specific application. Consultation with the relevant FDA review division may also occur during this phase of the review to determine whether the proposed study will provide acceptable data that could contribute to product approval. A score will be assigned to each application based on the scientific/technical review criteria. The review panel may advise the program staff about the appropriateness of the proposal to the goals of the grant program.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit.
1. Rationale: The soundness of rationale in relation to the current understanding of the rare disease(s) and the likelihood the proposal will facilitate medical product development to address an unmet medical need in a rare disease(s) or provide highly significant improvements in treatment or diagnosis and assist or substantially contribute to market approval of the proposed product(s).
2. Study Design and Inclusion of Patient Input: The quality and appropriateness of the study design, research methodology, and data analyses to accomplish the specific aims of the proposed study. Patients and caregivers are highly encouraged to be involved in the planning of the design and development of these clinical studies. Their perspectives contribute to improved protocol design and medical product development through understanding of disease and treatment burden, impact on daily living and quality of life issues which may be otherwise overlooked.
3. Investigator(s): The qualifications of the Principal Investigator(s) (PIs), collaborators, and other support staff.
4. Infrastructure and Resources: The probability of success of the proposed project given the environment in which the work will be done.
5. Ability to Advance the Current Field: The ability of the project to shift current research or clinical practice paradigms towards future product development and to exert a significant influence on product development.
In addition, reviewers will evaluate the following additional items while determining scientific and technical merit:
· Budget and Period of Support
· Protections for Human Subjects
· Inclusion of Women, Minorities, and Children
· Resource Sharing Plans
· Foreign Organizations
See the RFA for further information.
Applicants will usually be notified of the review results via a summary statement approximately 6 months from the application deadline.
Once the grant applications are reviewed and scored by the ad hoc panel of experts, a cut-off score for funding will be established. Those applications within the anticipated fundable range will be ranked in order of their score with the earliest possible funding start date beginning November 2019 based on availability of funds.
All responsive applications will be issued scores and summary statements following the review of the applications. If your grant application received a favorable/competitive score you will be sent a cover memo and a Pre-Funding Certification Form (PCF) along with a copy of the Summary Statement. You will be required to complete and return the PCF and accompanying information (including your responses to the Summary Statement critiques, the current IRB approval letter, Federal Wide Assurance documentation and verification of product availability) by the date specified in the cover memo. This is not a guarantee that you will receive funding.
If you receive grant funding, you will receive a formal Notice of Grant Award. Your grant will be assigned an OOPD grant Project Officer (PO) who will be your main contact. You will be required to keep the PO informed throughout the grant of any issues and changes including protocol changes, adverse events, changes in key study personnel, etc. If you have any questions or concerns about the grant or the study, you may contact the PO for assistance. Additionally, if you experience any difficulties in patient enrollment, OOPD may be able to assist or suggest options.
You will receive a congratulatory letter from the PO outlining your roles, responsibilities, and requirements as a grantee. You will be required to follow and be in compliance with Good Clinical Practices and Current Good Manufacturing Practices. You will be required to maintain regulatory requirements such as IRB approvals, up to date FWA, IND requirements including submission of IND annual reports and appropriate adverse event reporting, up to date clinicaltrials.gov information (for applicable or voluntarily registered trials), etc.
To assist in monitoring your grant, your PO will establish enrollment and progress goals for each funding year with you upon initial funding. You will also be required to submit Quarterly Reports and Annual Reports to OOPD. There will be at least one grant evaluation with OOPD during the lifetime of your grant. OOPD should be contacted before any protocol changes are made (including Key Personnel and Performance Site changes). Publication of study results is encouraged.
Once the grant is funded, Quarterly Reports will be required typically every three months from the date the grant was issued. These reports should include an update on the overall progress of the study, monitoring of the study, and for “applicable clinical trials” and voluntarily registered trials an update on the ClinicalTrials.gov entry for the study. Additional information that should be reflected in these updates include enrollment, adverse events, changes in protocol, publications, and presentations.
In addition, an annual Report in the form of a Research Performance Progress Report (RPPR) is required.
At the end of the grant, a Final Report will be due within 90 days after the end date of the project period.
Questions regarding financial aspects of a proposed application and a funded grant should be addressed to:
Daniel Lukash, FDA/Office of Acquisitions & Grant Service
E-mail: Daniel Lukash
Scientific and Research questions should be addressed to: Katherine Needleman, FDA/Office of Orphan Products Development
E-mail: Katherine Needleman
Technical questions regarding submitting through grants.gov should be submitted to:
eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
o Finding Help Online: https://grants.nih.gov/support/index.html
o Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
o Contact Center Telephone: 800-518-4726
o Email: firstname.lastname@example.org