SBIR/STTR TECHNOLOGIES FOR MONITORING AND PERFORMING RESUSCITATION RELEASE DATE: February 5, 2004 PA NUMBER: PA-04-059 (This PA has been reissued, see PA-06-126 and PA-06-127) EXPIRATION DATE: January 23, 2006 Department of Health and Human Services (DHHS) PARTICIPATING ORGANIZATION: National Institutes of Health (NIH) ( COMPONENT OF PARTICIPATING ORGANIZATION: National Heart, Lung and Blood Institute (NHLBI) ( CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.837, 93.838, 93.839 APPLICATION RECEIPT DATE(S): Applications submitted in response to this program announcement will be accepted at the standard application deadlines [April 1, August 1, December 1] THIS PA CONTAINS THE FOLLOWING INFORMATION: o Purpose of the PA o Research Objectives o Mechanism(s) of Support o Project Period and Amount of Award o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Where to Send Inquiries o Submitting an Application o Supplementary Instructions o Peer Review Process o Review Criteria o Award Criteria o Receipt and Review Schedule o Required Federal Citations NOTICE: This program announcement (PA) must be read in conjunction with the current Omnibus Solicitation of the National Institutes of Health, Centers for Disease Control and Prevention, and Food and Drug Administration for Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Grant Applications. The solicitation (see [PDF] or (MS Word] contains information about the SBIR and STTR programs, regulations governing the programs, and instructional information for submission. All of the instructions within the current SBIR/STTR Omnibus Solicitation apply. PURPOSE OF THE PA This announcement is to encourage small businesses to participate in the research and development of new approaches, tools, methods, devices, and biomaterials to provide bioengineering-based methodologies for monitoring and performing resuscitation. Ultimately, the goal of this program is to reduce morbidity and mortality from circulatory, hypoxemic or traumatic arrest. For this purpose, this announcement is interested in fostering better systems and methods for out-of-hospital and basic resuscitation research that 1) enables monitoring of genetic, molecular, biochemical, physical or metabolic derangements associated with circulatory, hypoxemic, or traumatic arrest; and 2) elucidates the unique pathophysiology of irreversible injury following multiple organ or whole-body ischemia and reperfusion, Applications should address critical cardiac, vascular, pulmonary, or hematologic and/or surgical strategies and propose research that will significantly improve clinical outcomes of resuscitation efforts. Research plans should emphasize specialties such as medicine, surgery, imaging, computer science, bioengineering and materials science, chemistry and physics. RESEARCH OBJECTIVES For the purpose of this solicitation resuscitation research will include the population of patients who collapse as a consequence of sudden circulatory, hypoxemic, or traumatic arrest. Circulatory, hypoxemic or traumatic arrest is a significant public health problem cutting across age, race, and gender. It often occurs without warning in persons who are healthy prior to their collapse. The national estimated mortality for all cause arrest is 350,000 lives per year, with economic costs for trauma related injuries estimated at over $400 billion dollars per year, in productive life years. In contrast to most problems in cardiovascular medicine, current death rates have not improved significantly despite scientific advances throughout medicine. In recognition of this public health burden, in June 2000, the NHLBI led a multi-agency conference entitled, "Post-Resuscitative and Initial Utility in Life Saving Efforts" (PULSE) co-sponsored by the National Institute of Child Health and Human Development (NICHD), the National Institute of General Medical Sciences (NIGMS), the National Institute of Neurological Disorders and Stroke (NINDS), of the National Institutes of Health (NIH), the Food and Drug Administration (FDA), and the Department of Defense (DOD). Nearly 200 conference participants, from the domestic and international scientific and practice community, spanning basic, applied, and trauma science expertise, met for two and a half days to identify obstacles and to forge a research agenda that would save lives and restore arrest victims to their pre-event neurologic and physical condition. Conference participants concluded new therapies and technologies to increase survival outcomes in resuscitation are realistic and should be fostered. A key obstacle for contemporary treatment strategies is the acutely limited time window for effective treatment. Beyond ten minutes after victim collapse, the likelihood of complete physical and neurologic recovery with conventional resuscitation is very low and overall survival for arrest victims is less than ten percent. Extension of therapeutic time windows and support of critical physiologic functions provides an opportunity to expand strategies for the treatment of arrest syndromes and for dramatic improvement in survival. The need to stimulate the development of enabling technology and new scientific avenues to expand basic and applied resuscitation research was a recurring theme throughout the Workshop deliberations. It became a key recommendation of the conference, and is the basis for this solicitation. The theoretical basis for cardiopulmonary resuscitation (CPR) practice, closed chest compressions and ventilation, was established in the 1960's. The fundamental strategies for CPR have not changed since these original concepts emerged and there is a paucity of contemporary CPR research. Outcomes in trauma related battlefield statistics have not improved significantly since the Civil War. Recognition of ventricular fibrillation, a common cause of circulatory arrest, and the efficacy of cardioversion in restoration of normal conduction and spontaneous circulation occurred in the 1940's. Despite numerous advances in the identification of patients at risk and the use of therapeutic interventions including drugs and devices the outcome of resuscitation efforts for arrest victims remains poor. Even with contemporary use of the automated external defibrillator to enhance resuscitation efforts, successful hospital discharge rates in controlled studies remains less than five percent. Success is significantly lower if complete neurologic recovery is included. Existing strategies known to restore circulation, shorten ischemia, and save lives should be refined to encourage and facilitate rapid, widespread and effective out-of-hospital application and are encouraged by this announcement. Current investigations are limited by underutilization of systems correlations and understanding of interrelated factors which contribute to irreversible cellular, vascular and organ damage in arrest states. Expansion of basic and applied research with a goal of identifying new therapies to minimize or tolerate whole-body ischemic insults holds promise for a dramatic improvement in survival rates. Scientific evidence exists to support assumptions that metabolic modulation of cellular and tissue systems could improve survival. New therapeutic interventions are likely to be derived from an understanding of cellular biology and gene expression that provide protection or tolerance to ischemia, reperfusion injury and other derangements of inadequate perfusion. A critical obstacle to improve survival, particularly for out-of-hospital arrest, is the lack of methods and systems to identify, monitor, and trend physiologic (biochemical, metabolic or cellular) parameters. Noninvasive or minimally invasive devices to be applied in the field to detect blood and tissue oxygen, carbon dioxide levels, pH, blood pressure, and assess vital organ perfusion are desperately needed. These devices need to be interrelated and should not impede resuscitation efforts. Such technology would facilitate research, identify critical markers, or trends of these markers, and provide critical baselines for monitoring and assessment of arrest victims during resuscitation efforts. Rapid out-of-hospital application of a percutaneous, or noninvasive continuous flow circulatory support system with the ability to administer fluids and deliver medications could be vital to survival of arrest victims. Enhancement of survival outcomes following resuscitation and development and piloting of innovative strategies which may, directly or indirectly, affect this outcome is the primary goal of this announcement. The primary potential target is the control and/or alleviation of whole-body ischemia and reperfusion injury before, during, and following resuscitation. Several factors contribute to the eventual demise of heart, lung or vascular cells, including oxidant stress, calcium overload, osmotic stress, energy depletion, and inflammation. New therapeutic interventions may focus on addressing mechanisms of regional or whole-body ischemia and reperfusion to improve survival. Hypothermia successfully preserves cells, tissue, organs and organ systems in a variety of settings, however, there are hypothermia-related complications, including changes in electrical stability of the heart, clotting factors, blood chemistries and tissue oxygen that need further investigation. Research projects to evaluate novel methods to induce controlled hypothermia in the field or during resuscitation efforts, offer novel opportunities to increase the functional time window in resuscitation victims and significantly improve survival in some settings. Investigations in hibernation, birth, and shock, that are associated with sudden profound changes in circulation, metabolism, and basal physiologic processes may provide insight for new therapeutic or protective strategies for complete physiologic and neurocognitive recovery. Trauma arrest victims provide unique challenges and opportunities for resuscitation research. Thrombosis and hemorrhage control are critical in the care of trauma victims. Resuscitation can be successful only if hemostasis is achieved and delivery of critical substrate is adequately restored. The identification, development, and testing of an optimal resuscitation fluid, which can prolong tissue viability, whether a temporary or long-term substitute for blood derived products, would be a boon for trauma resuscitation survival outcomes. Innovative strategies or systems to provide rapid vascular access and appropriate replacement fluid delivery will be a major advance in reducing trauma related deaths. Noninvasive or minimally invasive imaging techniques providing rapid assessment of multiple vital organ function, volume status, or cellular or organ perfusion rates during resuscitation efforts is critical to assess patient status and would provide timely feedback to implement and assess appropriate treatment. Unwitnessed arrest or collapse in a public facility presents another critical resuscitation challenges. Instantaneous interactive communications systems are needed as a rapid alert system for paramedical personnel and to provide bystanders with instructions for initiation of life-saving resuscitation measures. This PA seeks to encourage potential applicants to take full advantage of the SBIR/STTR program mechanism for multi-disciplinary research projects that develop monitoring systems and approaches to perform resuscitation that are safe and effective for use in humans. In the pre-clinical or clinical development phases, collaborations between basic scientists with approved animal facilities and healthcare organizations may be required. Research proposals should focus on improving out-of-hospital resuscitation, but the need to evaluate specific technologies and approaches in the clinic during design development is recognized. This program seeks innovative projects to provide new capabilities in systems and methods. Projects that offer only incremental advances of existing in-hospital technologies will not be responsive to this PA. Examples of topics the research and clinical communities have identified are listed below: however this program announcement is not limited to these examples and is open to all relevant, meritorious research ideas: o Develop improved defibrillator technology. o Develop enabling technologies for research of whole body ischemia and reperfusion injury in appropriate animals models and humans. o Develop methods to augment rapid delivery and transfer of oxygen to cells, tissues and organs. o Develop methods for rapid functional restoration of circulation, both neurologic and cardiovascular, during cardiac, hypoxemic and/or traumatic arrest. o Develop methods for rapid vascular access and delivery of medications and resuscitation fluids, either traditional or novel synthetic preparations o Develop materials and methods for rapid induction of controlled hypothermia o Develop alternative methods to traditional CPR to maintain vital organ blood flow and nutrient delivery during cardiac, hypoxemic, and/or traumatic arrest. o Develop biosensors, using natural and synthetic substrates, for acquisition and monitoring of critical vital organ function, (e.g. cardiac, neurologic, cellular and tissue oxygen levels). o Develop methods to rapidly identify and implement hemostasis in trauma victims. o Develop ultra fast methods for recognition and identification of patient collapse and location. MECHANISM(S) OF SUPPORT This PA uses the SBIR and STTR mechanisms, which are set-aside programs. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. Future unsolicited, competing-continuation applications based on this project will compete with all SBIR/STTR applications and will be reviewed according to the customary peer review procedures. This PA uses just-in-time concepts. It also uses the modular budgeting format. Specifically, if you are submitting an application budget of $100,000 total costs (direct, F&A and fee) or less, use the modular format and instructions as described in the current SBIR/STTR Omnibus Solicitation. Otherwise follow the instructions for non-modular budget research grant applications. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at Except as otherwise stated in this PA, awards will be administered under NIH grants policy as stated in the NIH Grants Policy Statement, December 2003, available at Applications may be submitted for support as Phase I STTR (R41) or Phase I SBIR (R43) grants; Phase II STTR (R42) or Phase II SBIR (R44) grants; or the SBIR/STTR FAST-TRACK option as described in the SBIR/STTR Omnibus Solicitation. Phase II applications in response to this PA will only be accepted as competing continuations of previously funded NIH Phase I SBIR/STTR awards. The Phase II application must be a logical extension of the Phase I research but not necessarily a Phase I project supported in response to this PA. PROJECT PERIOD AND AMOUNT OF AWARD The SBIR/STTR Omnibus Solicitation indicates the statutory guidelines of funding support and project duration periods for SBIR and STTR Phase I and Phase II awards. For this PA, budgets up to $150,000 total costs per year and time periods up to 2 years for Phase I may be requested. Budgets up to $500,000 total costs per year and up to 3 years may be requested for Phase II. Total costs include direct costs, F&A, and a profit/fee. ELIGIBLE INSTITUTIONS Eligibility requirements are described in the SBIR/STTR Omnibus Solicitation. Only small business concerns are eligible to submit applications. A small business concern is one that, on the date of award for both Phase I and Phase II agreements, meets ALL of the criteria as described in the SBIR/STTR Omnibus Solicitation. INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. On an SBIR application, the principal investigator must have his/her primary employment (more than 50%) with the small business at the time of award and for the duration of the project. The PI on an STTR application may be employed with the small business concern or the participating non-profit research institution as long as s/he has a formal appointment with or commitment to the applicant small business concern, which is characterized by an official relationship between the small business concern and that individual. WHERE TO SEND INQUIRIES We encourage your inquiries concerning this PA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into two areas: scientific/research and financial or grants management issues: o Direct your questions about scientific/research issues to: Suzanne Goldberg, M.S.N., R.N. Division of Heart and Vascular Diseases National Heart, Lung and Blood Institute Two Rockledge Center, Rm 9174 6701 Rockledge Dr., MSC 7940 Bethesda, MD 20892-7940 Telephone: (301) 435-0532 Fax: (301) 480-1336 E-mail: Ms. Ann Rothgeb Division of Lung Diseases National Heart, Lung, and Blood Institute Rockledge II, Room 10114, MSC 7952 Bethesda, MD 20892-7952 Telephone: (301) 435-0202 Fax: (301) 480-3557 Email: Phyllis Mitchell, M.S. Division of Blood Diseases and Resources National Heart, Lung and Blood Institute Rockledge II, Room 10163 MSC 7950 Bethesda, MD 20892-7950 Telephone: (301) 435-0481 Fax: (301) 480-1060 Email: Lawton Cooper, M.D. Division of Epidemiology and Clinical Application National Heart, Lung and Blood Institute Rockledge II, Room 8124 MSC 7936 Bethesda, MD 20892 Telephone: (301) 435-3077 Fax: (301) 480-1669 Email: o Direct your questions about financial or grants management matters to: Ms. Shelia Ortiz Division of Extramural Affairs Grants Operations Branch National Heart, Lung, and Blood Institute Rockledge II, Room 7154, MSC 7926 Bethesda, MD 20892-7926 Telephone: (301) 435-0166 Fax: (301) 480-3310 Email: SUBMITTING AN APPLICATION The PHS 398 research grant application must be used for all SBIR/STTR Phase I, Phase II and Fast-Track applications (new and revised.) Effective October 1, 2003, applications must have a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The DUNS number can be obtained by calling (866) 705-5711 or through the web site at The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 is available at Prepare your application in accordance with the SBIR/STTR Omnibus Solicitation and the PHS 398. Helpful information for advice and preparation of the application can be obtained at: The NIH will return applications that are not submitted on the 5/2001 version of the PHS 398. For further assistance contact GrantsInfo, Telephone: (301) 710-0267, Email: The title and number of this PA must be typed on line 2 of the face page of the application. SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: This PA uses the modular budgeting format. Specifically, if you are submitting an application budget of $100,000 total (direct, F&A and fee) or less, use the modular format and instructions as described in the SBIR/STTR Omnibus Solicitation. SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the application, including the checklist, and five signed photocopies in one package to: Center for Scientific Review National Institutes of Health 6701 Rockledge Drive, Room 1040, MSC 7710 Bethesda, MD 20892-7710 (FOR USPS EXPRESS or REGULAR MAIL) Bethesda, MD 20817 (FOR EXPRESS/COURIER NON-USPS SERVICE) APPLICATION PROCESSING: Applications must be received by or mailed on or before the receipt dates described on the first page of this program announcement. The CSR will not accept any application in response to this PA that is essentially the same as one currently pending initial review unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an unfunded version of an application already reviewed, but such application must include an Introduction addressing the previous critique. Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within 8 weeks. PEER REVIEW PROCESS Applications submitted for this PA that are complete will be assigned on the basis of established PHS referral guidelines. Appropriate scientific review groups convened in accordance with the standard NIH peer review procedures ( will evaluate applications for scientific and technical merit. As part of the initial merit review, all applications will: o Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score o Receive a written critique o Receive a second level review by the appropriate advisory council or board. REVIEW CRITERIA The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals: o Significance o Approach o Innovation o Investigator o Environment ALL SBIR/STTR APPLICATIONS 1. Significance: Does the proposed project have commercial potential to lead to a marketable product or process? Does this study address an important problem? What may be the anticipated commercial and societal benefits of the proposed activity? If the aims of the application are achieved, how will scientific knowledge be advanced? Does the proposal lead to enabling technologies (e.g., instrumentation, software) for further discoveries? Will the technology have a competitive advantage over existing/alternate technologies that can meet the market needs? 2. Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Is the proposed plan a sound approach for establishing technical and commercial feasibility? Does the applicant acknowledge potential problem areas and consider alternative strategies? Are the milestones and evaluation procedures appropriate? 3. Innovation: Does the project challenge existing paradigms or employ novel technologies, approaches or methodologies? Are the aims original and innovative? 4. Investigators: Is the Principal Investigator capable of coordinating and managing the proposed SBIR/STTR? Is the work proposed appropriate to the experience level of the Principal Investigator and other researchers, including consultants and subcontractors (if any)? Are the relationships of the key personnel to the small business and to other institutions appropriate for the work proposed? 5. Environment: Is there sufficient access to resources (e.g., equipment, facilities)? Does the scientific and technological environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following items will be applied to ALL applications in the determination of scientific merit and the priority score: PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. (See additional information and criteria included in the section on Federal Citations, below). INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. (See additional information and Inclusion Criteria in the sections on Federal Citations, below). Human Subjects: 1. Protection of Human Subjects from Research Risks - for all studies involving human subjects. See instructions and "Guidance for Preparing the Human Subjects Research Section. If an exemption is claimed, is it appropriate for the work proposed? If no exemption is claimed, are the applicant's responses to the six required points appropriate? Are human subjects placed at risk by the proposed study? If so, are the risks reasonable in relation to the anticipated benefits to the subjects and others? Are the risks reasonable in relation to the importance of the knowledge that reasonably may be expected to be gained? Are the plans proposed for the protection of human subjects adequate? 2. Inclusion of Women Plan - for clinical research only. Does the applicant propose a plan for the inclusion of both genders that will provide their appropriate representation? Does the applicant provide appropriate justification when representation is limited or absent? Does the applicant propose appropriate and acceptable plans for recruitment/outreach and retention of study participants? 3. Inclusion of Minorities Plan - for clinical research only. Does the applicant propose a plan for the inclusion of minorities that will provide their appropriate representation? Does the applicant provide appropriate justification when representation is limited or absent? Does the applicant propose appropriate and acceptable plans for recruitment/outreach and retention of study participants? 4. Inclusion of Children Plan - for all studies involving human subjects. Does the applicant describe an acceptable plan in which the representation of children of all ages (under the age of 21) is scientifically appropriate and recruitment/retention is addressed realistically? If not, does the applicant provide an appropriate justification for their exclusion? 5. Data and Safety Monitoring Plan for clinical trials only. Does the applicant describe a Data and Safety Monitoring Plan that defines the general structure of the monitoring entity and mechanisms for reporting Adverse Events to the NIH and the IRB? CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to be used in the project, the required five items described under Vertebrate Animals (section f of the Research Plan instructions) will be assessed. If vertebrate animals are involved, are adequate plans proposed for their care and use? Are the applicant's responses to the five required points appropriate? Will the procedures be limited to those that are unavoidable in the conduct of scientifically sound research? BIOHAZARDS: Is the use of materials or procedures that are potentially hazardous to research personnel and/or the environment proposed? Is the proposed protection adequate? ADDITIONAL REVIEW CONSIDERATIONS: The following items may be also be considered by reviewers but will not be included in the determination of scientific merit. SHARING RESEARCH DATA: Applicants requesting $500,000 or more in direct costs in any year of the proposed research must include a data sharing plan in their application. The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or priority score. BUDGET: The reasonableness of the proposed budget may be considered. For all applications, is the percent effort listed for the PI appropriate for the work proposed? On applications requesting up to $100,000 total costs, is the overall budget realistic and justified in terms of the aims and methods proposed? On applications requesting over $100,000 in total costs, is each budget category realistic and justified in terms of the aims and methods? PERIOD OF SUPPORT: The appropriateness of the requested period of support in relation to the proposed research. PHASE II APPLICATIONS In addition to the above review criteria: 1. How well did the applicant demonstrate progress toward meeting the Phase I objectives, demonstrating feasibility, and providing a solid foundation for the proposed Phase II activity? 2. Did the applicant submit a concise Commercialization Plan that adequately addresses the seven areas described in the Research Plan item J? 3. Does the project carry a high degree of commercial potential, as described in the Commercialization Plan? AMENDED APPLICATIONS In addition to the above criteria, the following criteria will be applied to revised applications. 1. Are the responses to comments from the previous SRG review adequate? 2. Are the improvements in the revised application appropriate? PHASE I/PHASE II FAST-TRACK APPLICATION REVIEW CRITERIA For Phase I/Phase II Fast Track applications, the following criteria also will be applied: 1. Does the Phase I application specify clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II? 2. Did the applicant submit a concise Commercialization Plan that adequately addresses the seven areas described in the Research Plan, item J? 3. To what extent was the applicant able to obtain letters of interest, additional funding commitments, and/or resources from the private sector or non-SBIR/ STTR funding sources that would enhance the likelihood for commercialization? 4. Does the project carry a high degree of commercial potential, as described in the Commercialization Plan? Phase I and Phase II Fast-Track applications that satisfy all of the review criteria will receive a single rating. Failure to provide clear, measurable goals may be sufficient reason for the scientific review group to exclude the Phase II application from Fast-Track review. AWARD CRITERIA Applications submitted in response to a PA will compete for available funds with all other recommended SBIR and STTR applications. The following will be considered in making funding decisions: o Scientific merit of the proposed project as determined by peer review o Availability of funds o Relevance to program priorities For FAST-TRACK applications, the Phase II portion may not be funded until a Phase I final report and other documents necessary for continuation have been received and assessed by program staff that the Phase I milestones have been successfully achieved. RECEIPT AND REVIEW SCHEDULE See REQUIRED FEDERAL CITATIONS HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained. DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for all types of clinical trials, including physiologic, toxicity, and dose- finding studies (phase I); efficacy studies (phase II), efficacy, effectiveness and comparative trials (phase III). The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risk to the participants. (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible. Investigators should seek guidance from their institutions, on issues related to institutional policies, local IRB rules, as well as local, state and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score. INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 2001 (; a complete copy of the updated Guidelines are available at The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects that is available at REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. You will find this policy announcement in the NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on hESCs can be found at and at Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (see It is the responsibility of the applicant to provide, in the project description and elsewhere in the application as appropriate, the official NIH identifier(s)for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review. PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at Applicants may wish to place data collected under this PA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The Department of Health and Human Services (DHHS) issued final modification to the Standards for Privacy of Individually Identifiable Health Information , the Privacy Rule, on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR). Those who must comply with the Privacy Rule (classified under the Rule as covered entities ) must do so by April 14, 2003 (with the exception of small health plans which have an extra year to comply). Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website ( provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on Am I a covered entity? Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal Domestic Assistance at and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284)and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the 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 routine 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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