kristoff@GENBANK.BIO.NET (Dave Kristofferson) (07/27/90)
REQUEST FOR APPLICATIONS for Research Project (R01) Grants RFA: CA-90-16 P.T. 34; K.W. 0740020, 0715035, 0765010 BIOLOGICAL AND CHEMICAL STUDIES OF TAXOL National Cancer Institute LETTER OF INTENT RECEIPT DATE: September 17, 1990 APPLICATION RECEIPT DATE: October 24, 1990 A. INTRODUCTION The Division of Cancer Treatment (DCT) of the National Cancer Institute (NCI) invites grant applications from interested investigators for chemical and/or biological studies on taxol ultimately leading either to: (1) ways to increase production of this drug; or, (2) define further its biological properties for use in improved drug design or in enhanced clinical utility. Grants are awarded to non-profit and for-profit organizations and institutions, governments and their agencies, and occasionally, to individuals. The Request for Applications (RFA) is the type of grant solicitation used when it is desired to encourage investigator-initiated research projects in areas of special importance to the National Cancer Program. Applicants funded under the RFA are supported through the customary National Institutes of Health (NIH) grant-in-aid in accordance with Public Health Service (PHS) policies applicable to research project grants. However, the RFA solicitation represents a single solicitation with specific deadlines for receipt of applications. All applications received in response to the RFA will be reviewed by the same NCI initial review group. The present RFA announcement has a specified deadline (October 24, 1990) for receipt of applications. Applications should be prepared and submitted in accordance with the aims and requirements described in the following sections: This program is described in the Catalog of Federal Domestic Assistance number 13.395. Cancer Treatment Research. Awards will be made under the authority of the Public Health Service Act, Sections 301, Public Law 78-410, as amended, 42 U.S.C. 241, as amended by Public Law 99-158, 42 U.S.C. and 285(a). This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. B. BACKGROUND INFORMATION C. RESEARCH GOALS AND SCOPE D. MECHANISM OF SUPPORT E. ELIGIBILITY F. REVIEW PROCEDURES AND CRITERIA G. METHOD OF APPLYING H. LETTER OF INTENT I. INQUIRIES B. BACKGROUND INFORMATION Taxol is an antitumor drug isolated from the Western Yew, Taxus brevifolia, and other Taxus species that has shown excellent confirmed activity against refractory human ovarian cancer and preliminary activity at other sites; it is one of the most promising new drugs in many years. It has a wholly novel mechanism of action, binding to microtubules and stabilizing them against depolymerization. Investigations of the chemistry, biology, biochemistry, and pharmacology of taxol have been limited. Many aspects of drug action and of drug production in the source plants, Taxus species, are not well understood. C. RESEARCH GOALS AND SCOPE The intention of this RFA is to encourage investigators to propose ideas which will increase our knowledge of the drug's properties and which are likely, in the long term, to contribute to large-scale drug supply and to maximally effective usage of taxol in the clinical setting. The following are undeveloped or underdeveloped areas of interest which merit particular attention: (1) biosynthesis and its regulation in Taxus sp.; (2) plant tissue culture to produce taxol and related compounds; (3) agronomics and plant genetics of taxol to enhance production; (4) evaluation of genetic engineering methods to transfer genes involved in taxol biosythesis to fast growing plants; (5) identification of the specific taxol binding site on microtubules and of the amino acid sequences involved, leading to high-resolution definition of the binding site and eventually to molecular mimics with simpler structures; (6) frequency, mechanisms, and circumvention of resistance; (7) studies of in vitro combinations of taxol with other cytotoxic agents; (8) metabolism of taxol in human tissue; (9) measurements and consequences of tissue distribution of taxol; and (10) in vivo evaluation of combination therapy using taxol in preclinical models. These areas are not meant to be restrictive and investigator-initiated proposals in all areas of taxol research relevant to the goals of this RFA, such as total chemical synthesis, are encouraged. Either single or multidisciplinary approaches may be proposed as appropriate to the topic area (see also Section I, INQUIRIES). The NCI is able to supply limited amounts of taxol for these investigations (up to 100 mg per award). Investigators needing substantial amounts of taxol for proposed studies should contact the Program Director before preparing an application (see Section I, INQUIRIES). Studies that use taxol as a reagent to isolate microtubules or to study microtubule or cycloskeletal function without therapeutic intent will not be considered responsive to this RFA. D. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) grant-in-aid. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Except as otherwise stated in this RFA, awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 82-50,000, revised January 1, 1987. This RFA is a one-time solicitation. Generally, future unsolicited competing renewal applications will compete with all investigator-initiated applications and be reviewed by the Division of Research Grants (DRG). However, should the NCI determine that there is a sufficient continuing program need, NCI may announce a request for renewal applications. Only recipients of awards under this RFA will be eligible to apply. Approximately $1,000,000 in total costs per year for five years will be committed to fund applications submitted specifically in response to this RFA. It is anticipated that five to eight awards will be made. This funding level is dependent on the receipt of a sufficient number of applications of high scientific merit. Program balance among various areas of taxol/Taxus research will be an important funding consideration. The total project period for applications submitted in response to the present RFA should not exceed five years. Foreign grants are limited to a three-year project period. The earliest feasible start date for the initial awards will be July 1, 1991. Although this program is provided for in the financial plans of the NCI, the award of grants pursuant to this RFA is also contingent upon the availability of funds for this purpose. E. ELIGIBILITY REQUIREMENTS Domestic and foreign non-profit and for-profit institutions are eligible to apply. Governments and their agencies are also eligible. F. REVIEW PROCEDURES AND CRITERIA REVIEW PROCEDURE Upon receipt, applications will be reviewed initially by the DRG for completeness. Incomplete applications will be returned to the applicant without further consideration. Evaluation for responsiveness to the RFA is an NCI program staff function. Applications will be judged to determine how well they meet the goals and objectives of the program as described in the RFA. Applications judged non-responsive will be returned by the NCI, but may be submitted as investigator-initiated research grants at the next receipt date. Questions concerning the relevance of proposed research to the RFA should be directed to program staff as described in the INQUIRIES section. In cases where the number of applications is large compared to the number of awards to be made, the NCI may conduct a preliminary scientific peer review to eliminate those applications that clearly are not competitive. The NCI will remove from competition those applications judged to be noncompetitive for award and notify the applicant and institutional business official. Those applications judged to be both competitive and responsive will be further evaluated according to the review criteria stated below for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI. The second level of review by the National Cancer Advisory Board considers the special needs of the Institute and the priorities of the National Cancer Plan. REVIEW CRITERIA The factors considered in evaluating the scientific merit of each response to this RFA will be: 1. The degree of importance of the research to one of the following: a. understanding and/or enhancement of taxol production; b. mechanism of activity of taxol as an antitumor agent; and c. potential enhancement of clinical utility of taxol. 2. The originality of the research plan from a scientific and technical viewpoint. 3. Adequacy, thoroughness, and completeness of the scientific plan. 4. Experience, training and time commitment of the Principal Investigator and staff. 5. Adequacy and availability of laboratory space and equipment required. 6. Clearly demonstrated access to all materials (i.e., chemicals, reagents, biological samples, human tissues, etc.) as are needed for the research. The review group will critically examine the submitted budget and will recommend an appropriate budget and period of support for each approved application. G. METHOD OF APPLYING The regular research grant application form PHS 398 (Revised 10/88) must be used in applying for these grants. These forms are available at most institutional business offices; from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Room 449, Westwood Building, 5333 Westbard Avenue, Bethesda, Maryland 20892; or from the NCI Program Director named below. The RFA label available in the October 1988 revision of Application Form PHS 398 must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of your application such that it may not reach the review committee in time for review. In addition, the RFA number and title should be typed on line 2 of the face page of the application form. Submit a signed, typewritten original of the application, including the Checklist, and four (4) signed, exact photocopies, in one package to the address below. The photocopies must be clear and single-sided. DIVISION OF RESEARCH GRANTS National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At time of submission, send two (2) additional copies of the application to: REFERRAL OFFICER Division of Extramural Activities National Cancer Institute Room 838, Westwood Building 5333 Westbard Avenue Bethesda, Maryland 20892 Applications must be received by October 24, 1990. If an application is received after that date, it will be returned. If the application submitted in response to this RFA is substantially similar to a research grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA which is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. H. LETTER OF INTENT Prospective applicants are asked to submit by September 17, 1990, a letter of intent that includes a descriptive title of the proposed research, the name and address of the principal investigator, the names of other key personnel, the participating institutions, the number and title of the RFA in response to which the application is being submitted. Since taxol is in very limited supply, for planning purposes, the NCI requests the applicant to indicate the amount of drug that will be required to support the proposed studies. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information it contains is extremely helpful in planning for the review of applications. It allows NCI staff to estimate the potential review workload and to avoid possible conflict of interest in the review. The letter of intent should be sent to: BY US POSTAL Dr. Matthew Suffness Program Director Grants and Contracts Operations Branch Division of Cancer Treatment National Cancer Institute Executive Plaza North, Suite 832 Bethesda, MD 20892 Telephone: (301) 496-8783 FAX: (301) 496-8333 BY DIRECT DELIVERY Dr. Matthew Suffness Program Director Grants and Contracts Operations Branch Division of Cancer Treatment National Cancer Institute Executive Plaza North, Suite 832 6130 Executive Boulevard Rockville, MD 20852 Telephone: (301) 496-8783 FAX: (301) 496-8333 I. INQUIRIES Written or telephone inquiries concerning the objectives and scope of this RFA or inquiries about whether or not specific proposed research would be responsive are encouraged and should be directed to Dr. Matthew Suffness at the above address. The Program Director welcomes the opportunity to clarify any issues or questions from potential applicants. NATIONAL RESEARCH SERVICE AWARD-INSTITUTIONAL GRANTS POLICY AND GUIDELINES RFA: DE-90-02 NATIONAL INSTITUTE OF DENTAL RESEARCH P.T. 44; K.W. 0720005, 0715148, 0785040 Application Receipt Date: December 10, 1990 AUTHORITY AND PURPOSE Under authority of Section 487 of the Public Health Service (PHS) Act as amended (42 USC 288), the National Institute of Dental Research (NIDR) awards National Research Service Award (NRSA) institutional grants (T32) to eligible institutions to develop or enhance research training opportunities for qualified individuals of the institution's selection who seek to prepare for careers in biomedical and behavioral oral health research. These Guidelines announce significant changes in both the structure and the administration of its NRSA institutional program. These changes have been endorsed by the National Advisory Dental Research Council and by the Dental Research Programs Advisory Committee. This publication contains a description of the new policies and procedures. Although the NIDR supports training in all areas of biomedical and behavioral oral health research, we intend to issue an RFA annually (each spring) in the NIH Guide for Grants and Contracts to indicate particular area(s) of emphasis. The purpose of the NRSA program is to help ensure that highly trained scientific manpower will be available in adequate numbers and in the appropriate research areas and fields to maintain the nation's biomedical and behavioral oral health research agenda. Title 42 of the Code of Federal Regulations, Part 66, is applicable to this program as are the following Catalog of Federal Domestic Assistance numbers: 13.840, 13.841, 13.842, 13.843, 13.844, 13.845, and 13.878. LEVELS OF TRAINING Applications will be accepted for research training at the predoctoral level and specialized basic science and/or clinical science training at the postdoctoral level. Research training grants are a useful mechanism for the postdoctoral training of dentists whose dental training usually provided only limited research experience. Since recent NIDR data indicate that dentists with a Ph.D. degree are more successful in obtaining subsequent independent research support than investigators with either degree alone, the NIDR requests that applicants for institutional grants propose training programs in which the training is part of a research degree program. Priority will be given to programs that offer dentists the opportunity to obtain a Ph.D. degree. However, in certain cases, proposals offering training as part of a master's degree program will be acceptable. Preapplication consultation with NIDR is highly desirable. APPLICANT ELIGIBILITY REQUIREMENTS Domestic nonprofit private or public institutions may apply for grants to support research training programs. The applicant institution(s), and any proposed consortium arrangement, must have the staff and facilities required for the proposed program. The training program director at the institution will be responsible for the selection and appointment of trainees and for the overall direction of the program. The training program must provide opportunities for individuals to carry out supervised biomedical or behavioral oral health research and to develop demonstrable research skills. Clinical departments or programs should have a significant relationship with basic scientists that will assure trainees with clinical backgrounds the opportunity to acquire the necessary foundation for future investigative work. GENERAL PROVISIONS NRSAs may not be used to support studies leading to the D.D.S. or other similar professional degrees, or to support residencies, i.e., postgraduate training for dentists providing health care directly to patients where the majority of their time is spent in non-research clinical training. However, if a specified period of full-time research training is creditable toward specialty board certification, the NRSA may support such research training if the trainee has shown a clear interest in a research career. Since dentists usually have had little or no prior research training, their training program must have, as a minimum, two years of basic research training. Research trainees are required to pursue their research training on a full-time basis, devoting at least 40 hours per week to such efforts. Research trainees in clinical areas are expected to devote their time to the proposed research training and to confine clinical duties to those which are a necessary part of the research training. TRAINEE ELIGIBILITY REQUIREMENTS The individual to be trained must be a citizen or a non- citizen national of the United States or have been lawfully admitted for permanent residence (i.e., in possession of the Alien Registration Receipt Card I-551 or I-151) at the time of appointment. Individuals on temporary or student visas are not eligible. Predoctoral trainees must have received a baccalaureate degree as of the beginning date of their NRSA appointment and must be enrolled in a graduate program leading to the award of a doctor of philosophy of science or equivalent degree in biomedical or behavioral oral health research. Individuals who wish to interrupt their dental school studies for a year or more to engage in full-time research training before completing their professional degrees are eligible; however, prior approval by the NIDR is required before their NRSA appointment is offered. Preference must be given to postdoctoral individuals who have received, as of the beginning of the NRSA appointment, a D.D.S., D.M.D., or equivalent dental degree from an accredited domestic or foreign institution. Certification by an authorized official of the degree-granting institution that all degree requirements have been met is acceptable. Individuals with a research doctoral degree (Ph.D. or equivalent) may be appointed to the training grant. However, in general, they are expected to apply for the individual postdoctoral NRSA fellowship award (F32). RECRUITMENT AND APPOINTMENT OF MINORITY TRAINEES The primary objective of this NRSA program is the preparation of qualified individuals for careers in biomedical and behavioral oral health research. Within the framework of the program's longstanding commitment to excellence and projected needs for investigators in particular areas of dental research, it is important that attention be given to recruiting individuals from minority groups that now are underrepresented nationally in these sciences. Information on plans for the recruitment of trainees should include a description of efforts to recruit individuals from underrepresented minority groups. Renewal applications should include cumulative information on the subsequent career development of all trainees, including information about their minority status. PAYBACK PROVISIONS Trainees must sign an agreement that they will fulfill the NRSA payback requirements. Recipients agree to engage in biomedical or health-related behavioral research and/or teaching for a period equal to the period of NRSA support in excess of 12 months. Once an individual has had 12 months of postbaccalaureate NRSA support, all subsequent NRSA support is subject to payback. Recipients must undertake the obligated service on a continuous basis within 2 years after termination of NRSA support. Individuals who fail to fulfill their obligation through service must pay back the total amount of NRSA funds paid to the individual for the obligation period plus interest at a rate determined by the Secretary of the Treasury. Financial payback must be completed within three years beginning on the date the United States becomes entitled to recover such amount. Under certain conditions, the Secretary of Health and Human Services may extend the period for starting service or for repayment, permit breaks in the period of service or repayment, or otherwise waive or suspend the payback obligation of an individual. Officials of the applicant organization responsible for recruitment of trainees should familiarize themselves with the terms of the service requirements and explain them carefully to prospective training candidates before an appointment at the institution is offered. PROGRAM STRUCTURE An applicant may request as many postdoctoral or predoctoral trainee positions as the proposed program can accommodate. However, training programs with fewer than five positions for postdoctoral trainees over the five-year period will not be funded. The program should be structured in such a way that acceptance of new postdoctoral trainees be limited to the first three years of the five-year award, i.e., as a minimum, two trainees the first year, another two the second year, and one the third year. A similar pattern is to be proposed by applicants requesting more than five positions. Ultimately, the number of positions awarded will be decided by the review process, program needs, and availability of funds. The NIDR will not fund more than one training grant from the same institution unless distinctly different training programs are proposed. STIPENDS AND OTHER TRAINING COSTS For predoctoral individuals at all levels of experience, the stipend level is $8,500 per annum effective October 1, 1988. For postdoctorals, the stipend for the first year of support is determined by the number of years of relevant postdoctoral experience at the time of appointment. Relevant experience may include research experience (including industrial), teaching, internship, residency, clinical practice, or other time spent in full-time studies in a health-related field beyond that of the qualifying doctoral degree. The stipend for each additional year of NRSA support is the next level on the stipend scale. Postdoctoral stipends, effective October 1, 1988, are as follows: Years of Relevant Experiences Stipend 0 $17,000 1 18,000 2 25,000 3 26,250 4 27,500 5 28,750 6 30,000 7 or more 31,500 NRSA stipends may be supplemented by an institution from non-Federal funds. Federal funds may be used for stipend supplementation only if specifically authorized under the terms of the program from which the supplemental funds are derived. An individual may make use of Federal educational loan funds or V.A. benefits when permitted by those programs. Under no circumstances may the condition of stipend supplementation detract from or prolong the training. The Tax Reform Act of 1986, Public Law 99-514, impacts on the tax liability of all individuals supported under the NRSA program. Degree candidates who, prior to the enactment of Public Law 99-514, were able to exclude all monies received under an NRSA award from their reported income, may now exclude only course tuition, fees, books, supplies, and equipment required for attendance. Non-degree candidates, who formerly were able to exclude from stipends $300 a month for a period not to exceed 3 years, will now be required to report all stipends and any monies paid on their behalf for course tuition and fees required for attendance. These new statutory requirements became effective January 1, 1987. NIH is not in a position to advise students or institutions about their tax liability. In any event, changes in the taxability of stipends in no way alter the relationship between NRSA fellows, trainees, and institutions. NRSA stipends are not now, and never have been, salaries. Trainees supported under the NRSA are not in any employer- employee relationship with NIH or the institution in which they are pursuing research training. Tuition and fees, including medical insurance, are allowable trainee costs if such charges are required of all persons in a similar training status at the institution, without regard to their source of support. Tuition at the postdoctoral level, if justifiable, is limited to that required for specific courses in support of the approved training program. Annual increments in tuition costs beyond the first year of a multi-year award (generally five years) may not exceed six percent. Trainee travel, including attendance at scientific meetings, that the institution determines to be necessary to the individual's training, is an allowable trainee cost. Institutional costs of $1,500 per year per predoctoral trainee and $2,500 per year per postdoctoral trainee may be requested to defray the cost of other training related expenses, such as staff salaries, consultant costs, equipment, research supplies, and staff travel. Also, an indirect cost allowance based on 8 percent of total allowable direct costs, or actual indirect costs, whichever is less, may be requested. Applications from State and local government agencies may request full indirect cost reimbursement. PERIOD OF SUPPORT Institutional grants are made for competitive segments of five years and are renewable. No individual trainee may receive more than five years of total NRSA support at the predoctoral level and three years of aggregate NRSA support at the postdoctoral level, including any combination of support from institutional training grants and individual fellowship awards, except under certain circumstances. Any exception to this policy requires a waiver from the NIH. Dentists requiring additional time to complete training as a participant in a Ph.D. program may anticipate favorable consideration of a waiver request, contingent upon certification of the recipient's good academic standing. REVIEW PROCESS Applications will be evaluated for merit by an NIDR initial review group (IRG). Site visits may be involved. The IRG will consider, among the criteria in its review, the following: o The proposed research training and program design: core curriculum; prescribed set of courses or seminars; the manner in which individualized guided research activities will be selected; procedures for monitoring trainees progress; the existence of a true training program (as contrasted with fellowship training for individual trainees); the appropriateness of the proposed number of trainees; the unique and/or innovative nature of the training program; resources and facilities. o Relevance to the goals of the NIDR, as described in the new NIDR Long-Range Research Plan for the Nineties, "Broadening the Scope". Copies are available by a request, in writing, to N.I.D.R., P. O. Box 54793, Washington, D.C. 20032. o The qualifications of the program director and participating faculty including the roles of specific preceptors; their time commitment; current research grant holdings and pending research grant activities; specific experience in graduate research training. o Training environment: evidence of high level of ongoing fundamental and clinical research activity; availability of equipment, facilities, and clinical resources. o Selection of trainees: plans for recruitment and criteria for the selection of trainees, including minorities, must be described fully; how will trainees be allocated to preceptors. o Past training record: it is critical to the review of both new and renewal applications that a detailed description of past performance in the training of scientists be provided; reviewers will look for demonstrated accomplishment, or potential, by the faculty in the training of scientists who will make major contributions to dental research (e.g., as indicated by success in achieving individual research grant support or recognition for outstanding scientific accomplishment); past trainee involvement in academic, clinically-oriented, and laboratory research; their ongoing productivity. For renewal applications, what is the record in filling the number of awarded trainee positions? What was the completion record of such trainee appointments? The IRG, following assessment of the quality of training grant applications and assignment of priority scores indicative of merit, will comment on each applicant's plans for attracting individuals from underrepresented minority groups to the research training program. When the application is a renewal of an award made under the new guidelines, these commentaries will cover accomplishments in recruiting individuals from underrepresented minority groups and in training them for research positions. Applications will then be reviewed by the National Advisory Dental Research Council. In addition to the recommendations made by the initial review group, the Council will include, among the information they consider, the IRG's comments on the plans for (and success in) recruitment of individuals from underrepresented minority groups into the training program. The NIDR will notify the applicant of the final Council action shortly after its meeting. Funding decisions will be made based on the review groups' recommendations, the need for research personnel in specified program areas, and the availability of funds. REVIEW SCHEDULE The NIDR has established a new policy instituting a single annual NRSA training grant receipt date and review cycle for all new and competitive renewal applications. The schedule is indicated below. It is designed to allow Program Directors time to recruit candidates during the fall/winter of the academic year for appointments to begin the following summer. Application Initial Review Council Earliest Receipt Date Meeting Meeting Award December 10 June/July July/Aug Sept 1990 1991 1991 1991 ADDITIONAL INFORMATION Effective July 1, 1990, all competing NRSA institutional training grant applications must include a description of formal or informal activities related to instruction about the responsible conduct of research to be incorporated into the proposed research training program. This announcement was published in the NIH Guide for Grants and Contracts, Vol. 18, No. 45, December 22, 1989. The NIDR expects to fund approximately five new and/or renewal institutional training awards in response to the annual RFA. For additional information, including the grounds for approving extensions of support and payback provisions, please refer to the announcement in the NIH Guide for Grants and Contracts, entitled, "National Research Service Awards - Guidelines for Individual Awards - Institutional Grants," Special Edition, Volume 13 (1), dated January 6, 1984. Additional information is available in the brochure, entitled, "National Institutes of Health - National Research Service Award, Institutional Grants (T32) - April 1989". These are usually available at the applicant institution, or contact the following person: Samuel H. Joseloff, Ph.D. Chief, Office of Grants Inquiries Division of Research Grants National Institutes of Health Westwood Building, Room 449 Bethesda, MD 20892 Telephone: (301) 496-7441 APPLICATION PROCEDURES Application should be made on Grant Application Form 398 (Rev. 10/88). This revision, which replaces Training Grant Application Form PHS 6025-1 (Rev. 1/83), contains special instructions for institutional NRSAs. Application forms are usually available at institutional offices of sponsored research or their equivalent. If not available locally, send a request accompanied by a self-addressed mailing label to Dr. Sam Joseloff at the above address. An original and four copies of the application are to be mailed to the Division of Research Grants in accordance with the instructions in the application kit. Insert the title and number of this RFA on line 2 of the application face page. The RFA label (found in the 10/88 revision of application form PHS 398) must be affixed to the bottom of the face page of the original copy of the application. Failure to use this label could result in delayed processing of your application such that it will not reach the review committee in time for review. Two information copies should be sent to: H. George Hausch, Ph.D. Chief, Scientific Review Branch National Institute of Dental Research National Institutes of Health Westwood Building, Room 519 Bethesda, MD 20892 Telephone: (301) 496-7658 Please notify the following person of your intentions to submit an application and contact for additional information: Thomas M. Valega, Ph.D. Special Assistant for Manpower Development and Training National Institute of Dental Research National Institutes of Health Westwood Building, Room 510 Bethesda, MD 20892 Telephone: (301) 496-6324