Abstract
The NCI-Rapid Access to Intervention Development (RAID) program is designed to assist translation to the clinic of novel anticancer therapeutic interventions, either synthetic, natural product, or biologic, arising in the academic community. Applications to RAID must be submitted electronically, using our secure on-line form. The electronic submission process benefits the applicant as it assures that each application contains all required application components, and eliminates the need to make multiple copies of the application. The applications are brief (the equivalent of 20 pages or less), and should clearly outline the resources required to ready the proposed therapeutic agent for clinical trials.
Applications are accepted twice yearly, and must be submitted no later than midnight ET on February 1 and August 1 (or the first business day after if the deadline falls on a weekend). The applications are reviewed by a panel of extramural experts within two to three months of receipt. Review criteria include strength of the scientific hypothesis, scientific novelty, and cost/benefit considerations afforded by the proposal.
RAID is not a grant mechanism. Approved applications to RAID gain access to the drug development contract resources of the Developmental Therapeutics Program. The output of these studies is provided to the originating investigator, and may include GMP synthesized material, formulation research, pharmacological methods, or IND-directed toxicology, for support of an investigator-held IND application and clinical trials. RAID does not sponsor clinical trials.
Table of Contents
I. About RAID
- Background
- Distinctions Between RAID and Other DTP Programs
- Services
- Eligibility
- Intellectual Property Rights
III. Review Process
IV. Oversight
I. About RAID
A. Background
RAID is a program designed to facilitate translation to the clinic of novel, scientifically meritorious therapeutic interventions originating in the academic community. It will do this by making available to the academic research community, on a competitive basis, NCI resources for the pre-clinical development of drugs and biologics. RAID is intended to remove the most common barriers between laboratory discoveries and clinical trials of new molecular entities. The goal of RAID is clinical "proof of principle" that a new molecule or approach is a viable candidate for expanded clinical evaluation.
Why RAID?
There are novel ideas and candidate molecules in the academic community that deserve expeditious clinical testing. Often an alliance with a corporate partner will adequately and expeditiously achieve this goal. Where private-sector capacity is limited, RAID will help academic institutions bridge the gap between discovery and clinical testing, so that efficient translation of promising discoveries may take place even in the absence of development capacity or clinical expertise in the institution where the discovery was made. RAID should therefore enable entry into the clinic of promising molecules that are not otherwise likely to receive an adequate and timely clinical test. The goal of RAID is the rapid movement of novel molecules and concepts from the laboratory to the clinic for proof-of principle clinical trials with scientific priority focusing on the disproportionate unmet needs such as:
- rare cancers
- pediatric cancer
- clinical/molecular pharmacodynamics
- certain specified classes of biologics
- natural products
- small molecule and antibody development for concomitant imaging studies
What RAID is not:
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RAID is not intended to be a pipeline for materials for NCI-held INDs. It is assumed that most of the products in the RAID program will be studied clinically under investigator-held INDs within the originating (or a collaborating) institution.
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RAID is not an unconditional commitment to develop a particular compound for the clinic. 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.
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RAID is not meant to assist industry in its development projects in the absence of an academic partner. "Pure" industrial collaborations with the NCI are encouraged through its Drug Development Group (DDG) .
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RAID is not a grant program to a particular laboratory. It is expected that the great majority of resources committed through RAID will be through use of NCI new-agent development contracts and of NCI staff expertise in service of highly meritorious projects originating in academia. It may happen that some steps in the process are best carried out in the originating laboratory, in which case NCI will initially attempt to provide necessary support through existing suitable funding vehicles, but this pathway for support may not be the ultimate avenue used. The focus will be on using NCI staff expertise to define the most effective and cost-efficient means of accomplishing the necessary tasks.
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RAID is not intended to support provision of materials for Phase II and III clinical trials.
B. Distinctions between RAID and the DDG
The NCI Drug Development Group (DDG) considers drug development opportunities from the NCI intramural, extramural corporate, or extramural academic communities where the originators are certain at the outset that NCI's holding of the resulting IND and managing clinical trials is a desired goal. By contrast, the products of the RAID program will, in general, be returned directly to the originating investigator for the proof-of-principle clinical trials that are the object of the program.
Distinction between NCI-RAID and NIH-RAID
The NIH-RAID program is patterned after the NCI-RAID program. It was established to make available, on a competitive basis, certain critical resources needed for the development of new small molecule therapeutic agents.
C. Services
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, NCI staff will interact directly with the Principal Investigator (PI). NCI contractors perform the RAID-approved tasks under the direction of NCI staff. In the event of licensure to an eligible small business, the licensee will be welcome to participate in project meetings with the permission of the PI, but NCI will at all times consider the PI the main point of contact for the project. Which tasks will be necessary to accomplish in any particular case will vary from project to project. In some cases RAID will support only the 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 tasks needed to file an IND. Examples of tasks that can be supported by RAID include, but are not limited to:
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Definition or optimization of dose and schedule for in vivo activity
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Development of pharmacology assays
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Conduct of pharmacology studies with a pre-determined assay
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Acquisition of bulk substance (GMP and non-GMP)
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Scale-up production from lab-scale to clinical-trials lot scale
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Development of suitable formulations
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Development of analytical methods for bulk substances
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Production of dosage forms
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Stability assurance of dosage forms
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Range-finding initial toxicology
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IND-directed toxicology, with correlative pharmacology and histopathology
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Planning of clinical trials
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Regulatory affairs, so that FDA requirements are likely to be satisfied by participating investigators seeking to test new molecular entities in the clinic
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IND filing advice
The output of 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.
RAID does not sponsor clinical trials. If it is the applicant's intent to apply to NIH for grant support to fund the clinical trial, there should be careful coordination of the timing of the applications for RAID support and clinical trials support. If the clinical trials support is acquired too early, a significant part of the life of the grant may elapse waiting for production of material and conduct of toxicology studies. If the clinical trials support is acquired too late, a significant part of the shelf life of the product may elapse waiting for the receipt of funding. We encourage applicants to review our data on timelines for completion of projects in order to obtain a realistic expectation of when they can expect to receive product and data from RAID. We also encourage discussion with RAID staff and your grants program director if you have questions.
Exchange of data and product will be under the terms of an NCI Materials Transfer Agreement (see E. Intellectual Property below). For those projects approved for production of a clinical batch, the final vialed drug product will be delivered in a single shipment; RAID cannot distribute drug product in multiple shipments or on a per patient basis.
D. Eligibility
RAID is intended for use by academic discovery laboratories and not-for-profit organizations. It is expected that most applicants for activities funded by RAID will have an appointment in an institution with an NIH-assured Institutional Review Board or formal collaborations with a staff member of such an institution.
Can companies use RAID?
Since RAID is designed to facilitate access of academic centers to clinical trial opportunities arising from their research, ideas arising solely from a corporate source without academic collaborators are not eligible. The following types of interactions between RAID applicants and industry will allow funding of successful applicants by the RAID program:
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research collaborations between the originating academic investigator and a corporate collaborator of any size, where the product in the RAID request is NOT yet licensed to a company;
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licensed products of the originating laboratory, where the licensee is a "small business" in the sense of the Small Business Innovation Research-SBIR grant definition (fewer than 500 employees).
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licensed products of the originating laboratory, where the licensee is not SBIR eligible but where the licensee has provided a written statement that they do not intend to develop the product for anticancer indications and have no objection to the NCI's participating in the product's development.
The academic collaborator must in all cases be the submitter of the application.
Products from an originating laboratory that are licensed to a non-SBIR eligible firm, or originating in a non-SBIR eligible firm and the subject of research in an academic laboratory are NOT eligible for RAID support if the non-SBIR eligible firm intends to pursue or has already pursued clinical trials-oriented development.
Does RAID discourage company involvement?
Not at all. Applicants are still free to negotiate with companies for licensing opportunities while RAID projects are under way. In the event of successful licensure to a non-SBIR-eligible firm, the RAID project(s) currently active will be drawn to an orderly conclusion in collaboration with the originating laboratory and the licensee, the data made available, and/or an actual product transferred to the originating laboratory.
Is RAID open to non-U.S. applicants?
Yes, provided the applicant meets all the other eligibility criteria. Additionally, please note that the U.S. DHHS Office of Human Research Protections (OHRP) requires that the recipient of any tangible product intended for human use have an OHRP assurance number, regardless of the recipient's location. If the applicant's institution does not already have an OHRP assurance number, their institution will need to obtain one prior to NCI's manufacture of vialed drug product.
E. Intellectual Property Rights
It is expected that originating parties will have acquired or be in the process of acquiring intellectual property protection prior to involvement of NCI. Normally, NCI will not acquire intellectual property rights to inventions made by its employees with Research Materials under RAID, unless the originating investigator and NCI mutually agree that to do so would be in the best interest of the project. If the NCI does file a patent application, the originating investigator will be given the opportunity to negotiate for an exclusive license under procedures set forth in 37 CFR Part 404.
As noted previously, many RAID tasks will be accomplished by the use of NCI's development contracts. Normally, an NCI contractor may elect to retain rights under the Bayh-Dole Act for any contributions it makes that rise to the level of invention. NCI contractors have, as a term of their funding agreement, agreed to offer a first option to the originating investigator for license negotiation. Certain other contractors or subcontractors may be subject to a Determination of Exceptional Circumstances through which their rights in subject inventions made using Research Materials may be assigned to the originating investigator. Should an invention occur the originating academic party will thereby have acquired a valuable potential ally in commercializing the subject of the research and may have acquired additional intellectual property if the latter was derived from collaborative research. An NCI Materials Transfer Agreement will be put into place at an appropriate time after the approval of a project and will form the basis for sharing confidential information with NCI [See example of RAID MTA (PDF-32K). Please do not submit this document with your application.].
Applicants will be expected to make available any excess reagents or products of the RAID process to requesting parties.
II. Application Process
A. Overview
NCI will receive proposals submitted using our on-line submission process, twice per year (February 1 and August 1) or first business day after if deadline falls on weekend). Proposals will consist of an application, a PI biosketch, and, if required, a letter of commitment from the investigator's institution indicating support for the clinical trial (see B. Application for additional details). The application exclusive of the questionnaire, PI biosketch, letter of clinical commitment, and appendix should be no more than the equivalent of 20 single-spaced pages (PHS grant application materials ARE NOT required and the use of a PHS398 form is NOT required). Paper copies will not be accepted.
No more than two requests for support from the same principal investigator may be received on any one receipt date. An individual product has two chances to be approved by RAID. After the initial application and one resubmission,, subsequent requests focusing on the same product will be returned without review.
B. Application Components (RAID Online Submission Application)
Full Contact Information: full name, title, mailing address, phone, fax and e-mail address for the applicant.
Abstract: 300 words or less.
Background: a summary of the field to allow appropriate understanding of the scientific and medical context from which the opportunity emerges.
Hypothesis: a clear statement of the hypothesis(ses) to be tested with entry of the relevant molecule into the clinic. In accord with NCI's emphasis on molecular targeted drug development (Ann Oncol 1999 Nov; 10(11):1287-91), RAID applications must provide a hypothesis-driven therapeutic with the opportunity for hypothesis-based testing in the clinic. Proposals must meet the Developmental Therapeutics Program's criteria for targeted therapies and will undergo internal review on such matters.
Specific Request: a clear statement of the tasks specifically being requested from NCI to allow a test in the clinic. Also, a clear statement about the anticipated future role of the applicant or applicant institution in the development of the project once the NCI becomes involved. Applications for a RAID project which would result in a clinically usable dose form, with supporting toxicology, for a Phase I study must have a letter of commitment from the institution indicating its support for conducting the clinical study (please see below for more information on the letter of commitment).
Justification: reasons why the project under consideration represents a particularly innovative or promising approach to the treatment, prevention, diagnosis, or detection of cancer.
Uniqueness: a discussion by the applicant of related or similar molecules already under development by NCI or known to be in development under industrial sponsorship, and why the NCI should undertake development in light of this.
Additional Support: a clear statement by the applicant of all current, anticipated, and hoped for sources of support for the project. This includes a summary of the status of past, planned, or ongoing negotiations with companies related to licensure or future development of the product. This section should also include information on any peer-reviewed grants and/or grant applications pertaining to the project (e.g., SPORE grant which will support the intended clinical trial with the product). The applicant should be sure to indicate how RAID support would complement, not duplicate, other sources of support. Please see Section C: Services above for suggestions on the timing of RAID support with clinical trials grant support.
Feasibility and Production Issues: a general discussion of the overall properties of the product and the requirements necessary for the specific requests. Completion of the appropriate small molecule or biologic (generic, mammalian cell products, oligonucleotide, peptide, viral vector) questionnaire is required.
Intellectual Property: a statement by the applicant 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 an application requires the use of non-commercially available technology/material which is patented by a third party, applicant must provide documentation that the patent holder does not object to the applicant's use.
NIH Biosketch:
All submissions are required to have a completed PHS 398
(
http://grants.nih.gov/grants/funding/phs398/phs398.html) for the Principal
Investigator.
Letter of Commitment: All investigators requesting production of clinical lot and/or IND-directed toxicology must provide a letter of commitment from their institution. The letter is intended to insure the reviewers and NCI that the products and data produced by RAID have a clinical outlet, and as such the letter should indicate that the institution is committed to the filing of an IND and conduct of a clinical trial once RAID activities are completed. The letter of commitment should be signed by the head of the cancer center at the institution, the director of clinical research at the institution, or other party with obvious authority to commit the institution to conducting a clinical trial. Further, if neither the signatory of the letter or the applicant is a practicing medical oncologist, the letter of commitment should indicate the identity of the clinician who will be the principal investigator of the clinical trial; it may be advisable for the applicant to include a supplemental letter from the clinician indicating that they are willing to undertake the trial.
Appendix: background preprints or reprints (maximum of five; not included in the page limitation).
C. Further Details
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Applications are NOT expected to request specific funds or even estimate costs. A central function of NCI staff in the RAID Review Process will be to outline costs utilizing U.S. Government internal or external contract sources to achieve the desired goals.
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A resubmitted proposal must include a response to reviewer critiques of the original application.
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Where re-application is made to RAID for continuation of a previously completed task, summaries of the relevant completed NCI studies should be included in the "Background" section as a specifically indicated basis for the current application.
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In the event that a RAID investigator relocates to a new academic institution, he/she must provide appropriate documentation in order for NCI's development of the project to continue. This documentation needs to:
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If the PI and institution are unable or unwilling to complete the RAID project, NCI will have the right to continue development without changing IP status.
III. Review Process
Requests for support will undergo a two-stage review, initially by a specially constituted RAID Special Emphasis Panel Subcommittee consisting of outside experts from academia and industry. Recommendations will be forwarded to and discussions held by the full SEP for all the applications received. Members of the RAID SEP and its subcommittees are bound by confidentiality agreements customary for review of NIH grants.
A. Review Criteria
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Strength of the Hypothesis: the extent to which this discovery is associated with a compelling hypothesis that strongly merits a clinical test.
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Novelty: the extent to which this discovery will enable clinical testing of new approaches to cancer that has not been adequately explored and are NOT likely to be explored without RAID assistance.
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Costs and Benefits: appropriateness of the anticipated costs in light of the possible payoffs.
Review will result in assignment of the following numeric scores between 1 and 5:
1 = Outstanding
2 = Excellent
3 = Good
4 = Acceptable
5 = Defer
Composite scores will be tabulated based on:
40% on Strength of the
Hypothesis
40% on Novelty
20% on Cost and Benefits
B. Overview
The RAID SEP has the authority to scale back an applicant's request based on development or feasibility concerns and to recommend approval of only a portion of the requested tasks. Reviewers will score the proposal based on the revised set of tasks. NCI will commit to develop 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.
Review will be completed by May 15 and November 15 for requests received February 1 and August 1, respectively. Successful applicants will be invited to meet with NCI staff and present a seminar on their project, after which a milestone approach identifying tasks for the project will be developed.
IV. Oversight
The RAID Special Emphasis Panel will periodically review the status of all projects conducted in the RAID program. This will include assessment of progress and determination of whether particular projects should be continued or terminated, based on progress, likely progress, or difficulties in reaching the desired project goal.
V. How to Contact Us
If you have questions about any aspect of the RAID program, please contact:
RAID Program
Coordinator
Developmental Therapeutics Program
6130 Executive Blvd., RM 8022
Rockville, MD 20852
Telephone: 301-496-8720
Fax: 301-402-0831
Email: raid@dtpax2.ncifcrf.gov