Full Text DE-95-004 HEALTH EFFECTS OF DENTAL AMALGAMS IN CHILDREN NIH GUIDE, Volume 24, Number 11, March 24, 1995 RFA: DE-95-004 P.T. 34 Keywords: Dentistry Biomaterials Toxicology National Institute of Dental Research Letter of Intent Receipt Date: May 22, 1995 Applications Receipt Date: August 24, 1995 PURPOSE The National Institute of Dental Research (NIDR) invites applications for cooperative agreements for a multidisciplinary clinical trial addressing the health effects of dental amalgams in children. Public concerns about the safety of dental amalgam fillings containing mercury continues despite assurances from the public health community. The general purpose of the trial is to investigate the possible relationship between lowdose exposure to mercury vapor from dental amalgam restorations and the occurrence of specific health conditions in children. To accomplish this the NIDR is interested in supporting a prospective, randomized clinical trial involving children from high risk caries populations needing restorative dental treatment with dental amalgam. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Health Effects of Dental Amalgams in Children, is related to the Priority area of oral health. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001- 00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit, non-profit, public and private organizations, such as dental or medical schools, universities and research institutions. Applications from foreign institutions are not eligible, however, applications may have international components. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or principal investigator should be included with the application. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to undertake this program will be a cooperative agreement (U01), which is an assistance mechanism, rather than an acquisition mechanism. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by collaborating and otherwise working jointly with the award recipient in a partnership role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships and governance of a study funded under a cooperative agreement are discussed later in this document under the section "Terms and Conditions of Award." The cooperative agreement mechanism of support will be used because substantial NIDR programmatic staff involvement with the awardee is necessary to facilitate coordination of a multidisciplinary approach to the research topic, to assist in protocol development, particularly in the selection of appropriate health endpoints, in quality control procedures, and to play an active role in monitoring the safety of study participants. FUNDS AVAILABLE This RFA is a one-time solicitation. At least one application is expected to be funded as a result of this RFA. However, in the event that a multicenter trial is needed to obtain sufficient numbers of subjects and to provide standardized analysis of biological samples, additional awards will be made. In either case, the funds available for the first year of support for the RFA are expected to total no more than $500,000. This level of support is conditional upon the receipt of applications of high scientific merit. Awards are expected to be made in Fiscal Year 1996. Although the financial and programmatic plans of the NIDR provide for support beyond the initial five year award, awards pursuant to this RFA are also contingent upon the availability of funds. RESEARCH OBJECTIVES Background Dental amalgam, a mixture of approximately equal parts of elemental mercury and other metals including silver, tin, copper, zinc and palladium or indium, has been in continuous use as a dental restorative material for well over a century. It has been the material of choice in restoring posterior teeth because of its strength, durability and relative low cost. It is estimated that approximately one-half of the 200 million restorative procedures performed in 1990 utilized amalgam as the material of choice. Mercury is widely found in the environment with trace levels present in air, water, and food. The toxicity of elemental mercury and its compounds is widely recognized. Experimental studies on animals, and biopsy observations in humans based on occupational exposure to organic mercury can affect the immune system to produce a nephrotic syndrome. Research on animals indicate large strain differences in susceptibility to the autoimmune response to mercury. In humans signs and symptoms associated with mercury intoxication from elemental mercury include tremor, ataxia, personality change, loss of memory, insomnia, fatigue, depression, headaches, irritability, slowed nerve conduction, weight loss, appetite loss, psychological distress, and gingivitis. Several review articles have indicated that few large scale human studies have been conducted investigating the potential adverse effects of dental amalgams. One large study of Swedish women was reported in which none of the correlations between number of amalgam fillings and clinical symptoms or complaints were found to be positive. Most of the signs and symptoms of mercury toxicity have been associated with longterm occupational exposure to air concentrations of mercury greater than 50 fg/m3, reflected by urinary mercury concentrations greater than 100 ng/ml. While clinically significant effects have not been reported below air concentrations of 100 fg/m3, preclinical manifestations consisting of short term memory loss and slowed peripheral nerve conduction have been reported below this level. No clinical findings on impairment of kidney function have been found in persons exposed to airborne concentrations of mercury below 100 fg/m3. Purported public concerns over the release of mercury from dental amalgam fillings have been recurring for many years. However, recent concerns have intensified with the discovery that small amounts of mercury vapor may be released from amalgam restorations and eventually absorbed into body tissues. Although, with the exception of allergic or hypersensitive reactions in a small number of patients, no adverse health effects have been demonstrated following the placement of dental amalgam fillings in humans. Nevertheless, there is a concern over the margin of safety between known toxic levels of mercury, regardless of source, and those levels in individuals having numerous amalgam fillings. A Health Assessment Program sponsored by the American Dental Association (ADA) was initiated in 1975. Each year, at the annual ADA meeting, practicing dentists volunteer to participate in this screening program. Questionnaires are given to all volunteers and urinary samples are collected for mercury assays. Between 1975 and 1983 over 9400 dentists participated in this program. Urine specimens were collected from 4272 of these dentists, 3793 of whom were general dentists. Their average urinary mercury concentration was 14.2 ng/ml, 4.8% had concentration levels over 50 ng/ml, 1.3 percent levels over 100 ng/ml. A subsequent report of the findings for 19851986 showed a decrease in urinary mercury concentration, averaging 5.8 ng/ml and 7.6 ng/ml. Although some five percent to seven percent of these professionals had high urinary mercury concentrations (over 20 ng/ml) no abnormal glomerular or tubular kidney dysfunction was reported. In 1991, the ADA reported results of a survey of 1000 adults which showed that nearly one-half believed that health problems could develop from dental amalgam. In the same year, the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) separately convened panels of experts to evaluate the current state of knowledge regarding amalgam-related hazards. Both panels of experts agreed that current research information does not demonstrate a causal relationship between dental amalgam and a human health problem. Subsequent to these meetings the Swedish Medical Research Council held a scientific conference in 1992 on the biological consequences of mercury released from dental amalgam and reported that it does not, according to available data, contribute to systemic disease, toxicological or teratological effects. In contrast, a symposium on the toxicity of mercury vapor from dental amalgam, held in 1992 under the auspices of the Society of Toxicology, reported that more remains to be learned about the effects of chronic, low level mercury exposure associated with dental amalgams. Attendees called for more research in the areas of neurologic, reproductive, developmental and renal effects, and the mechanisms that underlie them. The need for additional research was echoed by the Public Health Service when in 1991, at the direction of the Assistant Secretary for Health, it brought together subject matter experts as well as specialists in risk and benefits assessment on the Committee to Coordinate Environmental Health and Related Programs (CCERHP) to reach an independent judgment about the degree of health risk, if any, posed by the use of dental amalgam as a restorative material. These experts determined that current research did not demonstrate a health hazard for the vast majority of individuals exposed to mercury vapor at levels commonly encountered. In a 1993 report from CCERHP, the Assistant Secretary for Health, reaffirmed the position enunciated earlier by PHS that there are no data to compel a change in the current use of dental amalgam. Nevertheless, given the available scientific evidence, the possible adverse health effects resulting from the use of dental amalgam cannot be fully discounted. The strongest evidence documenting any potential hazards of amalgam restorations would be obtained from prospective cohort clinical studies, especially a clinical trial involving an amalgam restorative material in children. In particular, given the current state of knowledge, information is needed to try to define more precisely the human dose response relationship of low dose mercury exposure from dental amalgam restorative materials. Children in the mixed dentition stage have been selected as the subjects of choice because of the importance of establishing a baseline in a group with little or no exposure to mercury. Further, the NIDR is interested in studying a population that experiences caries at a high rate, who have received little or no restorative treatment prior to entry into the prospective trial, and in which there is a high likelihood of need for amalgam restorations. Finally, a childhood population of this age group will allow at least seven years, and hopefully more, of followup, a period that should prove sufficient to detect even the most subtle effects, if any, of amalgam. Objectives and Scope The aims of this clinical trial are to investigate the following: 1. Potential neurological, psychological/behavioral, renal, endocrine or other relevant organ system impairments or dysfunctions in children that are attributable to exposure to amalgam restorations; 2. Degree to which Hg concentrations in urine, blood or other relevant tissues differ in children with and without exposure to amalgam restorations; and 3. Progression of Hg concentrations in urine, blood or other relevant tissues over time in children beginning with the time of the initial placement of amalgam restorations. It is anticipated that the clinical trial would be performed in populations at high risk for dental caries consisting of individuals that have received little or no previous treatment and which are in need of restorative treatment. Such populations may come from within the U.S., outside of the U.S., or a combination of the two. It is anticipated that routine restorations of carious teeth supplemented by an aggressive caries prevention and education program consistent with appropriate standard of care would be instituted for the study population throughout the study period. Due to the nature of the trial, a multidisciplinary approach including the appropriate mix of experts from epidemiology, biostatistics, neurology, behavioral sciences/child psychology, toxicology, and other relevant specialties is believed to be essential to its success. To accomplish the objectives within the multidisciplinary context, substantive NIDR scientific input is viewed as essential during both the developmental and operational phases of the project. Consensus is necessary regarding specific neurological, psychological/behavioral, and/or other appropriate health endpoints as well as for the length of time, estimated to be in the range of five to seven years, for study subject followup during which even the most subtle psychological or physiological changes could be detected. SPECIAL REQUIREMENTS The organizational structure of the study may take one of several forms depending on the ability to recruit sufficient numbers of subjects, to perform analyses on biological samples, and to perform data entry and analysis. These functions may all be able to be performed at one institution or with subcontracts to individual centers under a single award. On the other hand, it may be necessary to fund multiple sites with individual awards. In the latter case, it may also be necessary to fund a coordinating center to insure efficient conduct of the trial. In the event that multiple sites are required to carry out the trial, it is imperative that principal investigators of the individual centers agree to follow a single clinical protocol as well as to make measurements in a uniform and prescribed manner. Specific rationale should accompany the suggested outcome measures recommended as primary response variables. The variables selected should be specific enough to pertain to mercury vapor exposure. If multiple primary outcome measures are recommended, the methodology for combining results should be addressed to avoid confusion regarding procedures used for interpreting statistically significant findings (i.e., explain how positives will be validated). The importance of identifying and documenting the availability of an adequate population of subjects for this trial cannot be overemphasized. The assumptions made in the calculation of sample size determination must be made explicit with supportive documentation provided whenever possible. Procedures for soliciting diverse subpopulations will be required as will specific procedures for monitoring and managing the trial, including any quality control procedures. If more than one country or cultural/ethnic group is involved, a detailed description of precautions that will be taken to ensure that all instruments used will be valid across the various subgroups is necessary. Administrative responsibility needs to be documented in detail including responsibility for recruitment and enrollment, eligibility requirements, and criteria for determining whether a field center qualifies for inclusion in the study. Special attention must be given to the potential attrition problem during the study period, indicating the methods that will be used to encourage subjects to remain in the study, the techniques used for monitoring dropout rates at individual study sites, and the possible corrective actions that will be employed. The method of providing restorative care for all participants at the conclusion of the study must be specified. Appropriate level of dental care will have to be provided to all participants requiring restorative care as a result of participating in this study or coincident to participating in the study. Terms and Conditions of Award These special Terms of Award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR parts 74 and 92, and other HHS, PHS, and NIH Grant Administration policy statements. The administrative and funding instrument used to undertake the project is a cooperative agreement (U01), an "assistance" mechanism (rather than an "acquisition" mechanism) in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient in a partner role, but it is not to assume direction, prime responsibility or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity resides with the awardee(s) for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardees and the NIDR Project Scientist who is the Assistant Director for Program Development, Extramural Program. Awardees will have the usual responsibilities of award recipients, including protocol development, participant recruitment and followup, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and preparation of publications, as well as responsibilities for collaboration with other awardees, as appropriate, and collaboration with the NIDR Project Scientist. Awardees will have lead responsibilities for the project as a whole and it is anticipated that the awardees will have lead responsibilities in all joint tasks and activities, except it is anticipated that the NIDR Project Scientist(s) will have lead responsibilities in quality control and catalyzing interim monitoring of data and safety and may, consistent with publication policy to be adopted by the Steering Committee as well as NIH publication policy, have lead responsibilities in the preparation of some publications. Awardees will retain custody of and have primary rights to the data developed under these awards, subject to Federal government rights of access consistent with current HHS, PHS, and NIH policies. In addition to the NIDR Project Scientist, a representative from the Epidemiology and Oral Disease Prevention Program (EODPP) will have responsibilities in protocol development, quality control, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, collaboration with awardees, and project coordination. The main governing body of the study will be the Steering Committee. The Committee will have primary responsibility for developing common protocols, facilitating the conduct and monitoring of studies, and reporting the study results. The composition of the Committee will depend on the final organization of the trial. For a multicenter trial, the Committee will be composed of the principal investigator, representatives from each of the recruitment centers, a representative of the coordinating center, representatives from each of the analytic centers, the NIDR Project Scientist and a representative of the EODPP. For a single center trial, the Committee will consist of the PI, representatives from any analytic centers, the NIDR Project Scientists and a representative of the EODPP. Each member of the Committee will have one vote except for representatives from the NIDR who, together, shall have only one vote. The Chairperson, who will be someone other than an NIDR staff member, will be selected by the Committee. Subcommittees will be established by the Steering Committee, as it deems appropriate. The collaborative protocol will be developed by the Steering Committee and followed by all awardees. This protocol may be reviewed by an external committee convened by NIDR. The protocol will be implemented only with the concurrence of the awardee(s) and NIDR. Data will be submitted centrally to the Coordinating Center. The protocol will define rules regarding access to data and publications. An independent Data and Safety Monitoring Board (DSMB), to be appointed by NIDR, will review progress at least annually and report to NIDR. The DSMB will examine data for any untoward effects of the treatment procedure or of Hg amalgam on subjects as well as for statistically significant increases in Hg between baseline and subsequent measurements. The DSMB will have the responsibility of reporting to the NIDR the occurrence of untoward effects of Hg amalgam, any human subject ethical issues, or if statistical significance is reached in one of the major study endpoints before the planned end of the trial. The NIDR reserves the right to terminate or curtail the study (or an individual award in the event of (a) failure to develop or implement a mutually agreeable collaborative protocol, (b) substantial shortfall in participant recruitment, follow up, data reporting, quality control, or other major breach of the protocol, (c) reaching a major study endpoint substantially before schedule with persuasive statistical significance, or (d) human subject ethical issues. Any disagreement that may arise in scientific/programmatic matters within the scope of the award, between award recipients and the NIDR may be brought to arbitration. An arbitration panel will be composed of three members one selected by the Steering Committee (with the NIDR members not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by the NIDR, and the third member selected by the two prior members. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with the PHS regulations at 42 CFR part 50, Subpart D and HHS regulation at 45 CFR part 16. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (Section 492 of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Minorities in Study Populations) which have been in effect since 1990. The new policy contains some new provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines for inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513), and reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators may obtain copies from these sources or from program staff or contact the person listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTERS OF INTENT Prospective applicants are asked to submit, by May 22, 1995, a letter of intent that includes a descriptive title of the proposed center(s), the name, address and telephone number of the center director(s), the identities of other key personnel and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications. It allows NIDR staff to estimate the potential review workload and to avoid possible conflict of interest in the review. The letter of intent is to be addressed to Dr. Norman S. Braveman at the address listed under INQUIRIES. APPLICATION PROCEDURES Prospective applicants are advised to communicate with program and grants management staff of the NIDR as early as possible in the planning phase of application preparation. NIDR staff are available to assist applicants to ensure that the objectives, structure, and the budget format for the proposed study are acceptable. The research grant application form PHS 398 (rev. 9/91) is to be used in applying for this cooperative agreement. These forms are available at most institutional offices of sponsored research; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/710-0267; and from the program administrator listed under INQUIRIES. The RFA label available in the form PHS 398 must be affixed to the bottom of the face page of the original application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed in item 2a of the face page of the application form and the YES box checked. The instructions accompanying form PHS 398 must be followed to the extent possible, but some modification will be necessary. For example, a new Table of Contents must be prepared giving page numbers for all items in the application. Pagination must be consecutive throughout the application. A consolidated budget for the complete project for the entire project period must be presented (see page 5, form PHS 398). Separate detailed, annual and total budgets for the entire project period for each center must be presented (use pages 4 and 5, form PHS 398). Direct and indirect costs are to be given. Funds may be requested for professional, technical, and administrative personnel; consultant services; equipment; supplies; travel; patient costs directly related to the research; minor renovations and other costs. Detailed justification of the budget requests will be required. Under Research Plan, describe the goals of the center(s) and discuss the background and significance of the topics being addressed. Explain how the proposed research will accomplish the objectives. Describe the organizational and administrative structure, the responsibilities of the principal investigator and other investigators, and the proposed mechanisms for monitoring scientific progress. Address issues raised under the "Special Requirements" and "Terms and Conditions" sections of the RFA. An abstract (page 2, form PHS 398) must be completed for the entire application. Submit a signed, original of the application, including the Checklist, and three signed, exact photocopies, in one package to: Division of Research Grants National Institutes of Health 6701 Rockledge Drive, Room 1040 - MSC 7710 Bethesda, MD 20892-7710 Bethesda, MD 20817 (for express or courier service) At the time of submission, two additional copies also must be sent to: Dr. H. George Hausch Division of Extramural Research National Institute of Dental Research Natcher Building, Room 4AN-44F 45 Center Drive MSC 6402 Bethesda, MD 20892-6402 Applications must be received by August 24, 1995. If an application is received after that date, it will be returned to the applicant. REVIEW CONSIDERATIONS General Considerations All applications will be judged on the basis of the scientific merit of the proposed protocols and the documented ability of the PI and the research team to conduct the essential study components as broadly outlined in the RESEARCH OBJECTIVES of the RFA. Although technical merit of the application is important, it will not be the sole criterion for selection. Other considerations such as importance and timeliness of the proposed trial, access to patients, and multidisciplinary nature of the studies will be part of the evaluation criteria. Review Method Upon receipt, applications will be reviewed by NIH staff for completeness and responsiveness. Applications that are incomplete or nonresponsive to this RFA, or exceed the first year budget limit of $500,000 in direct costs, including any indirect costs associated with consortium arrangements, will be returned to the applicant without further consideration. Waivers of the receipt date deadline and budget limitation will not be granted. Those applications that are complete and responsive will be evaluated in accordance with the criteria stated below for scientific and technical merit by a special review committee convened by the NIDR Scientific Review Office. As part of the initial merit review, a process (triage) may be used by the initial review group in which applications will be determined to be competitive or non-competitive based on their scientific merit relative to other applications received in response to the RFA. Applications judged to be competitive will be discussed and assigned a priority score. Applications judged to be noncompetitive will be withdrawn from further consideration and the Principal Investigator and the official signing for the applicant organization will be notified. Review Criteria Applicants are encouraged to submit and describe their own ideas on how best to meet the goals and objectives of the RFA. They are expected to address issues identified under SPECIAL REQUIREMENTS of the RFA. Applications will be judged primarily on the scientific quality of the application, the appropriateness, importance and timeliness of the proposed approach, adequacy of facilities, access to patients, the multidisciplinary nature of the study, the approach to cost containment, the discussion of considerations relevant to the RFA, the expertise of the investigators, their capability to perform the proposed research, and a demonstrated ability to work as part of a multidisciplinary team as well as with the NIDR project scientists. The review group will assess the scientific merit of the protocols and related major factors, including: 1. The rationale for and prioritization of the primary health outcome variables proposed for the trial. 2. The appropriateness of the study design regarding length of study, composition and size of study groups, anticipated number of centers needed, inclusion of appropriate control group(s), and entry criteria of subjects required at participating centers. 3. Documentation (e.g., pilot study results) relative to the feasibility of the study population proposed for use in the trial, including susceptibility to dental caries, need for restorative treatment, lack of previous exposure to amalgam fillings or exposure to mercury from other environmental or dietary sources. 4. The adequacy of the identified study population, including the potential for enrollment, participation by females and minorities as study subjects, participant access for the duration of the trial period, and stability of participants for the duration of the study. Adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. 5. The scientific and administrative qualifications, experience and commitment of the identified investigators to conduct this study. The adequacy of the proposed interdisciplinary team to conduct this trial. The expertise and experience of the data management team identified by the applicant, including the quality control procedures suggested for data entry, editing, storage and processing procedures. The quality and thoroughness of the analytical plan suggested in the study protocol. 6. The extent to which the investigators have anticipated potential problems; the loss of a senior investigator, change of an administrative head at a study site controlling access to a large group of study participants, difficulties in recruiting participants, corrective actions for clinics experiencing difficulty during the study period. 7. The technical expertise, demonstrated experience and capabilities of the laboratory to perform the mercury assays at the sensitivity level required for this study. The technical merit and justification for other core resources requested and the appropriateness of the budget for each component. 8. The thoroughness and adequacy of quality control procedures for accuracy and reliability of the clinical and laboratory data, monitoring the adherence to the study protocol by all investigators, and safety of procedures used. 9. The strategy for conducting longterm followup of the study participants should this be desired later including provisions for treatment of exiting participants from the study, during or at its conclusion, including providing for any restorative treatment needs. AWARD CRITERIA The NIDR appreciates the value of complementary funding from other public and private sources, including foundations and industrial concerns, for activities that will complement and expand those supported by the NIDR. Such support is encouraged to supplement funding for this trial. Applications recommended for funding by the National Advisory Research Dental Council will be considered for award based upon: (a) scientific and technical merit as determined by peer review, importance of the proposed clinical trial, timeliness, multidisciplinary nature of the study, and the requirements explicitly stated in the RFA; (b) in the case of a multicenter trial, compatibility of the various elements to make a successful collaborative program a reasonable likelihood; and (c) availability of funds. Letter of Intent Receipt Date: May 22, 1995 Application Receipt Date: August 24, 1995 NARDC Review: January 1996 Anticipated Award Date: March 1996 INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding scientific program issues to: Norman S. Braveman, Ph.D. Division of Extramural Research National Institute of Dental Research Natcher Building, Room 4AN 24B 45 Center Drive MSC 6402 Bethesda, MD 20892-6402 Telephone: (301) 594-2089 FAX: (301) 480-8318 Email: BravemanN@de45.nidr.nih.gov Direct inquiries concerning fiscal policy matters to: Ms. Theresa Ringler Division of Extramural Research National Institute of Dental Research Natcher Building, Room 4AS-55 45 Center Drive MSC 6402 Bethesda, MD 20892-6402 Telephone: (301) 594-4800 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.121. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. [Part 92 applies when state and local governments are eligible to apply as "domestic organization."]. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routing education, library, day care, health care or early childhood development services are provided to children. This is consistent with the phs mission to protect and advance the physical and mental health of the american people. .
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