The purpose of this solicitation is to identify promising agents for preclinical efficacy testing of type 1 diabetes (T1D) using standardized protocols developed by the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) in conjunction with the current contractor, BRM (Biomedical Research Models, Inc). Preclinical testing will monitor prevention, delay, reversal or amelioration of T1D in well characterized rodent models.
NIDDK seeks applications for specific compounds to be included in its initial round of testing. These proposals can be submitted directly to this program (
http://t1diabetes.nih.gov/T1D-PTP/) for animal testing (efficacy and mechanistic studies) or through the T1D-RAID program (
http://www.niddk.nih.gov/fund/diabetesspecialfunds/T1D-RAID/) if additional preclinical drug development resources are needed (toxicology, formulation, stability, etc). Each compound will have a proponent/sponsor who will be expected to participate in the design and justification of the specific intervention protocol and who collaborates in evaluating the results. Proponents can be individuals, nonprofit or academic groups, biotechnology and pharmaceutical companies, U.S and non-U.S. entities. NIDDK is responsible for the supervision and costs of the experimentation that would be performed by the contractor. It is important to emphasize that this is not a grant mechanism. Approved requests gain access to the contractor’s facility and resources for the necessary testing according with the nature of the agent recommended. There is no direct funding provided to the sponsor.
Animals involved in this study will be housed at the BRM, Inc animal facilities. The program is designed to involve collaborations with investigators that have performed initial pre-clinical evaluation of biological/pharmacological interventions that might prevent/delay the onset of T1D and revert or ameliorate the disease process. The animal models used by the contractor will primarily be the NOD mouse and the BB rat. It is likely that this program will accept up to 2 different interventions for testing in the first year of the program and add 4–5 more in each subsequent year.
Intervention Proponents
The T1D-PTP program invites scientists to recommend interventions they believe have sufficient therapeutic potential to proceed toward preclinical drug development. Each intervention has a proponent who should provide the following information:
- A rationale for the choice of intervention including strong preliminary data showing evidence of efficacy on animal models of T1D, other organ specific autoimmune diseases and/or data derived from human studies.
- Recommendations about proper dosage and timing of the intervention.
- Methods for documenting the intervention has the expected biochemical and/or physiological effects.
- Methods to assay pharmacokinetics of the compound to ensure that is stable and reaches expected blood serum levels.
- Information, if available for mechanistic studies which could lead to biomarkers useful for monitoring efficacy in clinical trials.
NIDDK welcomes the involvement of the proponent with appropriate expertise relevant to particular agents to help finalize the testing protocol.
Study
If the intervention is selected for study, its proponent may participate in the conduction of the research in collaboration with NIDDK staff and the contractor. The protocol should provide sufficient statistical power to detect significant differences in terms of prevention, delay, reversal or amelioration of T1D. In addition, compounds may be tested to determine possible mechanisms of action and whether biomarkers/surrogate markers that quantitatively assess their beneficial effects or the organism response to them may be identified (immune response and function, beta cells/islet function markers, markers of insulitis progression/beta cell autoimmune destruction, metabolic parameters, etc).
Study results will be made available to the public.
Intellectual Property, Data Publication and Further Investigation
Testing will verify efficacy and/or mechanistic aspects of the potential intervention. Regarding use of the technology, publications etc, confidential agreements and/or material transfer agreements (MTA) will be developed with the institutions involved in this program. If the proponent is recommending the testing of a non-commercially available agent in development, it should provide a statement describing the intellectual property position of the investigator relevant to the agent to be tested.
If the agent to be tested is the property of a commercial entity or company willing to donate the material for testing, the company must sign a MTA which will include a Statement of Intent to further development towards clinical testing, if the agent demonstrates a mutually agreed-upon level of efficacy.
Request Process
The proponents who wish to recommend a specific intervention (single agent or combination of agents) to be considered by the NIDDK review panel for testing by the contractor should send a request prepared according with the format described below. Individuals or groups who wish to recommend more than one intervention for consideration are encouraged, but should use separate requests for each intervention.
Request forms—in Microsoft Word format—should be sent to this program. The Request itself should be no more than 15 single-spaced pages.
Request Format
Proponents should submit a request in Microsoft Word format. The request should address the following, in this order:
Title of the Request
The title of the request is typically the name of the substance(s) or formulation being tested and its purpose.
Contact Information
This information includes the name, institutional address, telephone, fax, and e-mail of the individual submitting the request. If the institution is an academic entity the request must be cosigned by an appropriate official and should acknowledge that there is no direct funding provided to the proponent.
Background Information
This section should describe concisely the reason why the compound(s) deserves to be evaluated for potential beneficial effects on the prevention, delay or reversal of T1D. The rationale may include:
- Theoretical framework
- Pilot data in animal models or humans if available
- Pharmomacokinetic, pharmacodynamic and toxicity data if available.
- Clinical Potential
- Other justification
- If this section includes unpublished data, include enough information (i.e., figures, tables, protocols) to permit its evaluation. If the section includes published data, include similar information and a reference citation to the publication(s) from which the data are derived. The background section should be no longer than five pages (including figures and tables).
Suggested Intervention Protocol
This section should provide a detailed description of the compound(s) being tested and the rationale for the protocol proposed. This information is necessary in order to develop a final testing protocol. The following should be addressed:
- Nature and proposed biological activity of the agent.
- Route of administration of the agent and justification. Dosage and frequency of administration.
- Source and suggested suppliers. Cost estimate.
- What is the best way to monitor or test whether the agent produces the expected physiological or pharmacological effects in the animal model? Will this require blood tests or other fluid samples, or will it require that some of the animals be sacrificed to obtain internal tissues? If a blood test is required, how much blood is needed? At what age, or at what time after treatment initiation, should the test be performed? How expensive is the test to conduct? If the test requires specialized expertise or equipment not provided by the contractor, is this available in the sponsor's laboratory, other locations?
- At what age should the intervention be initiated? Is there a range of ages that would be acceptable? Duration of the treatment and rationale for study design must be provided.
- Expected outcome.
- Data analysis and interpretation.
Animal Safety
This section should describe what is known about potential harmful side effects the treatment might have on rodents. If the sponsor knows of any pilot data based on either short-term or long-term exposure of rodents or other mammals to the treatment, the request should state this and describe any harmful side effects noted in the previous study. If the applicant knows of toxicity data related to other doses of the compound or to related compounds, this should be summarized for evaluation by an institutional animal use committee.
Costs of Testing
The T1D-PTP provides support to BRM, Inc. for animal acquisition, animal housing, testing, statistical analysis, and purchase, or cost-shared purchase, of test agents.
The Proponent should provide information on the source and cost of the agent(s) to be studied: (1) If the agent is available from commercial sources, will it be donated or what is the estimated cost to obtain a sufficient supply of the agent for the number of animals to be tested? (2) Can the proponent provide the agent to the program at no cost? or (3) If the agent is not available commercially and cannot be provided by the proponent, the proponent should: (a) provide a justified cost estimate of a sufficient supply of the compound to treat the number of animals proposed for the duration of the treatment and (b) state the proportion of the cost that the program is requested to provide.
*SPECIAL COST CONSIDERATION: If cost is associated with the acquisition of the agent(s) and you have a negotiated General Services Administration (GSA) rate, please apply this rate to any and all costs.
Statement of Understanding
The request should include the following statement of understanding:
In submitting this request, I agree to the following:
- I understand all information presented in the request can be freely shared with members of the NIDDK external review and evaluation panel during its evaluation of requests, but will otherwise be considered confidential. If approved, the information will also be shared with the contractor in order to design the appropriate testing studies.
- I understand that NIDDK intends to make the results of all supported studies—regardless of whether they produce data showing positive or negative effects on the prevention, delay or reversal of T1D— publicly available and can be used in applications for further research support by anyone. I also will be free to use NIDDK generated data in the context of applications for research support or for any other purpose.
- Include only if applicable: The agent/compound recommended makes use of materials that are not yet freely available and whose production depends on proprietary or unpublished methods. If my request is approved for incorporation in this program, a mutually acceptable Materials Transfer Agreement that would permit me to provide the contractor with the compound(s) needed for the experimentation will be developed with the institutions involved in this program.
Review
Requests will be reviewed by an External Review Panel convened by NIDDK that will consist of experts from academia and industry. An internal NIDDK Review Panel will also discuss the submissions. Review Panel members are bound by confidentiality agreements customary for review of NIH grants. The review criteria will be similar to the ones listed for review panels convened by the T1D-RAID program but will reflect an emphasis on fostering development of T1D therapeutics and relevant animal preclinical efficacy testing. Acceptance into the program will be based on scientific merit, programmatic relevance, perceived translational potential and availability of resources.
Program Oversight
The NIDDK expects to convene an oversight/evaluation committee consisting of outside advisers and a subgroup of its own members. This group will periodically review the progress and direction of the T1D-PTP and explore opportunities for program development and enhancement.
How to Apply
Requests prepared in MS word format can be submitted electronically to contact personnel. Alternatively, three complete copies of each request should be submitted to the addresses indicated below.
Recommended Requests Receipt Dates
Requests will be accepted at any time, but the recommended target dates for review are April 30 th and November 5 th, 2008
For more information, contact:
Guillermo Arreaza-Rubín, M.D.
Division of Diabetes, Endocrinology, and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd. Rm. 6101
Bethesda, MD 20892-5460
Telephone: (301) 594-4724
FAX: (301) 480-2688
E-mail: arreazag@mail.nih.gov
Lisa Spain, Ph.D.
Division of Diabetes, Endocrinology, and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd. Rm. 695
Bethesda, MD 20892-5460
Telephone: (301) 451-9871
FAX: (301) 480-2688
E-mail: spainl@mail.nih.gov
