The National Institute of Diabetes & Digestive & Kidney Disease

About Type 1 Diabetes - Rapid Access to Intervention Development (T1D-RAID)

Background

T1D-RAID is a cooperative program of the NIDDK and NCI designed to facilitate translation to the clinic of novel, scientifically meritorious therapeutic interventions. It will do this by making available, on a competitive basis, NCI resources for the pre-clinical development of drugs, natural products, and biologics. A partial listing of those services includes: high-throughput screening, studies in animal models, formulation, pharmacology and toxicology studies, and bulk substances acquisition.

T1D-RAID is intended to remove the most common barriers between laboratory discoveries and clinical trials of new molecular entities. The goal of T1D-RAID is to support the preclinical work needed for the clinical "proof of principle" which is the study that will determine if a new molecule or novel approach is a viable candidate for expanded clinical evaluation.

Why T1D-RAID?

There are novel ideas and candidate molecules in the scientific community that deserve expeditious clinical testing. Often an alliance with a corporate partner will adequately and expeditiously achieve this goal. However, where resources or priorities are limiting progress, T1D-RAID will help bridge the gap between discovery and clinical testing. This will facilitate efficient translation of promising discoveries even in the absence or lack of availability of development capacity or clinical expertise in the organization where the discovery was made. T1D-RAID should therefore enable entry into the clinic of promising molecules that are not otherwise likely to receive an adequate and timely clinical test.

What T1D-RAID is not:

• T1D-RAID is not intended to be a pipeline for materials for NIH-held INDs. It is assumed that most of the products in the T1D-RAID program will be studied clinically under investigator-held INDs within the originating (or a collaborating) institution.
• T1D-RAID is not an unconditional commitment to develop a particular compound for clinical use. Development will proceed sequentially in a logical order and the start of one segment of the process (e.g., toxicology) will depend on satisfactory completion of preceding segments (e.g., formulation). Insurmountable difficulties in one segment may force abandonment of individual projects, as they do in any development program.
• T1D-RAID is not a grant program to a particular laboratory. It is expected that the great majority of resources committed through T1D-RAID will be through use of NCI new-agent development contracts and of NIDDK and NCI staff expertise in service of highly meritorious projects. It may happen that some steps in the process are best carried out in the originating laboratory, in which case NIDDK will advise on other mechanisms available for support of this work. The focus will be on using NIDDK and NCI staff expertise to define the most effective and cost-efficient means of accomplishing the necessary tasks.
• T1D-RAID is not intended to support provision of materials for larger Phase II and III clinical trials.

Services

T1D-RAID is designed to accomplish the tasks that are rate-limiting in bringing discoveries from the laboratory to the clinic. Once a project has been approved, NIDDK staff interact directly with the Principal Investigator (PI). NCI contractors perform the T1D-RAID-approved tasks under the direction of NIDDK and NCI staff. The required tasks will vary from project to project. In some cases T1D-RAID will support only one or two key missing steps necessary to bring a compound to the clinic; in other cases it may be necessary to supply the entire portfolio of development requirements needed to file an IND. Examples of tasks that can be supported by T1D-RAID include, but are not limited to:

1. Definition or optimization of dose and schedule for in vivo activity
2. Development of pharmacology assays
3. Conduct of pharmacology studies with a pre-determined assay
4. Acquisition of bulk substance (GMP and non-GMP)
5. Scale-up production from lab-scale to clinical-trials lot scale
6. Development of suitable formulations
7. Development of analytical methods for bulk substances
8. Production of dosage forms
9. Stability assurance of dosage forms
10. Range-finding initial toxicology
11. IND-directed toxicology, with correlative pharmacology and histopathology
12. Planning of clinical trials
13. Regulatory affairs, so that FDA requirements are likely to be satisfied by participating investigators seeking to test new molecular entities in the clinic
14. IND filing advice

For more information on services that may be available, visit http://dtp.nci.nih.gov/docs/raid/raid_index.html

The output of T1D-RAID activities will be both products and information that will be made fully available to the originating investigator for support of an IND application and clinical trials. T1D-RAID does not sponsor clinical trials. However, NIDDK has other programs such as the Type 1 Diabetes TrialNet (http://www.diabetestrialnet.org/en/public/index.html) and Immune Tolerance Network (http://www.immunetolerance.org/) that may provide support for subsequent clinical trials.

Eligibility

The following are acceptable types of organizations that can request program resources:

• Academic institutions
• Non-profit research institutions
• Biotechnology and pharmaceutical companies
• U.S. and non-U.S. entities

Investigators whose projects are supported through T1D-RAID must first provide a Statement of Commitment to development of the supported project, setting out milestones to move the development progressively toward IND clinical trials. The Statement of Commitment should include a description of the product(s) or method(s) to be developed through T1D-RAID, and for each product or method to be developed, a description of expected product research and development, including, where relevant, major preclinical, clinical, regulatory, manufacturing and marketing stages; monetary and personnel commitments for each development stage; and the project time to accomplish each stage of commercial development.

In exchange for the support provided by the T1D-RAID program, the Investigator's Organization must agree that in the event that the Organization's commitment to development toward IND clinical trials ceases for a progressing project, as evidenced by a lack of commitment of resources to achieve the milestones set out in the Statement of Commitment as initially provided, or as amended and accepted by the NIDDK, the Organization will grant to the NIDDK a royalty-free, irrevocable, nonexclusive license under any patent on such compound or product or process for use of such, to manufacture and/or use the invention for purposes related to or connected with therapy or diagnosis of type 1 diabetes and its complications. Further, in such event, the Organization agrees that at the request of the NIH, Organization will license responsible applicants to manufacture and/or use the invention for purposes related to or connected with therapy or diagnosis of type 1 diabetes and its complications, including for commercial purposes, under terms that are reasonable under the circumstances.

Intellectual Property Rights

It is anticipated that the majority of Requests submitted will involve a potential therapeutic that either already has protected intellectual protection or will be in the public domain. Please contact T1D-RAID@niddk.nih.gov for more information about intellectual property rights.

As noted previously, in conducting a portion of the T1D-RAID research, it may be necessary for NIDDK or NCI to use the services of one of the NIDDK's or NCI's contractors or subcontractors under a funding agreement as defined by 35 U.S.C. §201(b). Under the Bayh-Dole Act (35 U.S.C. §200 et. seq.), a contractor may elect and retain title to subject inventions developed under a funding agreement. As a term and condition of their funding agreements, certain NCI and NIDDK contractors involved with the RAID programs have agreed to offer Provider a first option to negotiate a license to subject inventions made using the Research Material(s). Certain other NCI contractors or subcontractors may be subject to a Determination of Exceptional Circumstances (35 U.S.C. §202(a)(ii)), through which their rights in subject inventions made using the Research Material(s) may be assigned to the Provider. Should an invention occur with one of these contractors, the Organization will thereby have acquired a valuable potential ally in commercializing the subject of the research and may have acquired additional intellectual property if it was the result of collaborative research. NIH Materials Transfer Agreements will form the basis for sharing confidential information with NIDDK and NCI [see example of NIDDK T1D-RAID MTA (24KB-PDF)].

Request Process

Overview

NIDDK will receive requests twice per year (April 1 and November 1). A letter of intent is encouraged one month prior to submission of a Request. Requests will consist of a written description of the request, a technology transfer form, and, if required, a letter of commitment from the investigator's institution indicating support for the clinical trial (see B. Components of the Request for additional details). The Request itself should be no more than 15 single-spaced pages (Public Health Service grant application materials ARE NOT required). No more than two requests for support from the same principal investigator may be received on any one receipt date. An individual product has three chances to be approved by T1D-RAID. After three unsuccessful attempts, subsequent requests focusing on the same product will be returned without review.

Components of the Request (15 pages, not including appendices)

Abstract: 300 words or less.

Background: Provide a summary of the field to allow appropriate understanding of the scientific and medical context from which the opportunity emerges (usually no more than 1 page).

Novelty: Discuss of why the product/strategy represents a particularly innovative or promising approach to treatment of type 1 diabetes and its complications. Discuss related or similar molecules already under development or known to be in development, and why the NIDDK should undertake development in light of this. Hypothesis: State a clear hypothesis(ses) to be tested with entry of the relevant molecule into the clinic. T1D-RAID requests must provide a hypothesis-driven therapeutic with the opportunity for hypothesis-based testing in the clinic.

Specific Request: Very clearly specify the tasks being requested from NIDDK to allow a test in the clinic. It is not necessary to describe in detail study design for toxicology, stability, and other commonly performed preclinical development tasks. A description of the type of study needed and for the reason it is needed is sufficient. Also, a the Request should include clear statement about the anticipated future role of the investigator or investigator's organization in the development of the project once the NIDDK becomes involved. Requests for T1D-RAID support for preparation of clinical materials for a Phase I study must be accompanied by a letter of commitment from a clinical investigator in which the source of clinical trial funding is identified or from a collaborating clinical trials organization such as Type 1 TrialNet or the Immune Tolerance Network. It is assumed that any project at a stage to require clinical supplies materials will have supporting toxicology already completed.

Criteria for proceeding: Delineate the desired outcome from the specific request with a description of criteria for progressing or NOT progressing to the next stage.

Research and Development Plan: Assuming the criteria to proceed is attained, outline the steps you envision as necessary for advancement of the proposed product/strategy to clinical practice. Summarize how you and your collaborators have/will be contributing to the implementation of this development plan beyond NIH's efforts. Describe potential sources of financial support for the project, including a summary of your interactions with companies related to licensure or future development of the product. Be sure to include all current, anticipated, and hoped for sources of support for the project. Also include information on any peer-reviewed grants and/or grant applications pertaining to the project Be sure to indicate how T1D-RAID support would complement, not duplicate, other sources of support.

Feasibility and Production Issues:

If small molecule, provide a proven synthesis route to the desired product, describe yields of the largest quantity previously purified, and specify how the product is characterized and the desired/required level of purity.

If biologic agent, indicate from which organism(s) the desired product has been isolated previously and in what production quantities (e.g. g/ml). Provide (or reference) the sequence of required vectors. Describe an assay that can be used to define the product's activity and specifications for the product's performance. In many cases, the investigator can expect to receive a more detailed feasibility questionnaire from T1D-RAID program staff after the Request has been received but prior to the review of the Request.

If natural products isolate, provide a proven purification scheme to the desired product. Describe yields of the largest quantity previously purified and how the product is defined/characterized. Specify the desired/required level of purity.

For safety evaluations with Good Laboratory Practices (GLP) indicate whether there are sufficient quantities of Good Manufacturing Practices (GMP) manufactured material available to conduct these studies.

Appendix: Provide a biographical sketch of the applicant (1-2 pages). Include any background preprints or reprints (maximum of five; not included in the page limitation) and relevant patents. Attach relevant letters of collaboration. Provide any analytical characterization (e.g. proof of identity, purity) or any product for which biological data is provided.

Intellectual Property: A statement by the investigator of any patents issued or pending with respect to either the product or to any non-commercially available technology/material required for the development of the product. In the event that the Request requires the use of non-commercially available technology/material which is patented by a third party, the investigator must provide documentation that the patent holder agrees to the investigator's use. Each T1D-RAID Request must include the form provided below signed by an authorized staff member overseeing intellectual property and/or technology transfer for their affiliated institution. This form verifies that they have reviewed the T1D-RAID request and that the technology is or is not eligible for consideration by the T1D-RAID program. If the technology is found not to be eligible for use in the T1D-RAID Request, and is central to the investigator's plan, Request to the T1D-RAID program is not encouraged. (Please see the T1D-RAID Technology Transfer Form available formats (17KB-PDF).)

Important Information:


• Requests are NOT expected to ask for specific funds or even estimate costs. A central function of NIDDK and NCI staff in the T1D-RAID Review Process will be to outline costs utilizing U.S. Government internal or external contract sources to achieve the desired goals.
• Requests should not include colored graphics, glossy photographs, or other materials that cannot be accurately reproduced as black and white photocopies. If absolutely essential, please be aware that not all reviewers will have access to the color copies.
• Resubmitted Requests must include a response to reviewer critiques of the original Request.
• If re-request is made to T1D-RAID for continuation of a previously completed task, summaries of the relevant completed NIDDK studies should be included in the "Background" section as a specifically indicated basis for the current Request.
• If a T1D-RAID investigator relocates to a new academic institution, he/she must provide appropriate documentation in order for NIDDK's development of the project to continue. This documentation needs to:
1. Verify that the intellectual property which is the subject of the T1D-RAID project can be developed at the new institution, or
2. Identify a new Principal Investigator at the current institution who will take responsibility for completion of the project.

Submission Information

Requests can be submitted electronically from IBM-compatible computers in MS Word. Alternatively, three complete copies of each request should be submitted to:

T1D-RAID
Myrlene Staten, MD
Senior Advisor, Diabetes Translational Research
Division of Diabetes, Endocrinology and Metabolic Diseases, NIDDK, NIH
6707 Democracy Boulevard
Bethesda, MD 20892-5460

e-mail: T1D-RAID@niddk.nih.gov

Review Process

Requests will be reviewed for support by a specially convened T1D-RAID Review Panel consisting of outside experts from academia and industry. NIDDK staff will participate in an advisory capacity, and not as voting members of the T1D-RAID Review Panel. T1D-RAID Review Panel members are bound by confidentiality agreements customary for review of NIH grants.

Review Criteria

The number of projects to be supported in any review cycle will be a function of:

1. the level of scientific merit assigned to the Requests
2. NIH programmatic issues, and
3. the projected costs of each aspect of the projects Requests will receive two levels of review (external and internal), which are described below. Each requestor will receive a copy of review comments and notification of the level of assistance NIDDK will be offering in response to the request.

External Review

A specially convened ad hoc T1D-RAID Review Panel of experts from academia and industry will initially evaluate the Requests in a confidential manner for scientific and technical merit. The T1D-RAID Panel will review and prioritize each Request on the basis of the following evaluation criteria:

• Strength of the hypothesis: the extent to which the Request is associated with a compelling hypothesis that strongly merits exploration.
• Novelty: the extent to which the Request will enable preclinical development of new therapeutic and prevention strategies that have not been adequately explored.
• Research & Development plan and feasibility/production issues: the clarity and appropriateness of the R & D plan and the likelihood that the planned tasks can be accomplished in a straight forward fashion. The Review Panel reserves the right to scale back an investigator's request based on development or feasibility concerns and may recommend approval of only a portion of the requested tasks.

Internal Review

Requests will receive a secondary level of review by the NIDDK internal oversight committee. NIDDK and NCI projects will be compared with tasks currently assigned to NIH contractors and a final prioritization of projects will be made taking into consideration the following additional factors:

• Importance of projects in addressing NIDDK and NCI research agendas
• Portfolio diversity (e.g., multiple projects directed against the same molecular target may be less favored than projects addressing diverse modes of action).
• Contract capacity (e.g., an individual contract may be better able to initiate a less expensive, but lower priority project due to funding limitations).

Special Considerations for Biopharmaceuticals

Projects that request production of biological materials require additional review by a T1D-Biological Resources Branch Oversight Committee (T1D-BRB-OC) The T1D-BRB-OC addresses technical and feasibility issues unique to the production of biopharmaceuticals.

Timelines

Timelines for Requests		Dates
Submission of letters of intent	March 1	October 1
Submission deadline for Requests	April 1	November 1
Notification of review outcome to applicants	By July 31	By March 30

NIDDK staff will be in contact with successful requestors, and timelines will be under development by August 15 or May 15 of each cycle (timelines for approved biological projects will depend on T1-BRB-OC meeting dates).

Implementation of Supported Requests


The T1D-RAID Review Committee has the authority to scale back an investigator's request based on development or feasibility concerns and to recommend approval of only a portion of the requested tasks. Reviewers will score the Request based on the revised set of tasks. NIDDK will commit to development of those projects accorded high merit by the Review Process. The number of projects to be supported in any review cycle will be a function of the level of merit and availability of funds.

In the event that a T1D-RAID project is encountering problems or overrunning its projected budget in a way that will not readily lead to a desired data endpoint or clinical trials candidate, a status review group will be convened to consider the likelihood that further work in the project area will be fruitful. The investigator and NIDDK staff will present progress to date in a face-to-face forum to between three and five extramural scientists knowledgeable in the area and bound by identical conflict of interest guidelines. Following the presentations, the review group will meet in closed session to determine whether T1D-RAID efforts should continue with new project milestones or the project should be concluded.

Oversight

The NIDDK expects to convene a T1D-RAID Oversight Committee consisting of outside advisers and a subgroup of its own members. This group will periodically review the progress and direction of the T1D-RAID program and explore opportunities for program development and enhancement.

How to Contact Us

If you have questions about any aspect of the T1D-RAID program, please contact: