Applied Research on Antimicrobial Resistance (AR): Estimates of Economic Cost for Antimicrobial Resistant Human Pathogens of Public Health Importance

Announcement Type: New.

Funding Opportunity Number: 04094.

Catalog of Federal Domestic Assistance Number: 93.283.

Key Dates:

Letter of Intent Deadline: May 17, 2004.

Application Deadline: June 14, 2004.

I. Funding Opportunity Description

Authority: Sections 319E(d) of the Public Health Service Act, [42 U.S.C. 247d-5(d)], as amended.

Purpose: The purpose of the program is to provide assistance for applied research aimed at prevention and control of the emergence and spread of antimicrobial resistance in the United States. This program addresses the “Healthy People 2010” focus area of Immunization and Infectious Diseases.

Measurable outcomes of the program will be in alignment with the following performance goals for the National Center for Infectious Diseases: Protect Americans from infectious diseases and reduce the spread of antimicrobial resistance.

The program's design must implement A Public Health Action Plan to Combat Antimicrobial Resistance (Part I: Domestic Issues) (Action Plan). For Research Objective I, measurable outcomes need to be consistent with item (16) in Focus Area I, Surveillance of the Action Plan: to provide health care system administrators and other decision makers with data on the impact of drug-resistant organisms (e.g., outcome, treatment costs) and on effective prevention and control measures. For Research Objective II, measurable outcomes need to be consistent with one or more of the following action items: Focus Area II. Prevention and Control, Item 23, 30 or 50. The Action Plan is available at Internet site: www.cdc.gov/drugresistance/actionplan/index.htm . Applications should address Research Objective I or Research Objective II.

Research Objectives I: The priority objective of this program is to create estimates of the economic costs of antimicrobial resistance in human pathogens of public health importance by providing information needed to prevent and control AR. This should include:

• Analysis of data on incidence, prevalence, and antimicrobial susceptibility of specific infectious diseases.
• Development of methods to determine costs which are simple and reproducible for different antimicrobial resistant organisms.
• Calculation of economic costs (direct and indirect) of infections that are resistant to one or more antimicrobial agents compared with infections that are susceptible to those agents.

Activities: Awardee activities for this program must include ALL of the following:

• Assemble retrospective clinical data from a sample of people infected with a specific organism (e.g., Streptococcus pneumoniae, Staphylococcus aureus, Neisseria gonorrhoeae), some susceptible and others resistant (as defined and outlined in NCCLS document M100-S13) to specific antimicrobial agents or classes of antimicrobial agents (e.g., penicillin, semi-synthetic penicillins, erthromycin, macrolides, ciprofloxacin, fluroquinolones). Clinical data include, but are not limited to demographic information, morbidity, mortality, treatment, hospitalization, laboratory testing results, and infection control measures and must be linked to individual patients (that is, for a single patient, treatment and laboratory data must be available; summary data for treatments and antimicrobial susceptibility are not acceptable). Provide estimate, original or from existing data sources, for burden of disease(s).
• Provide a method for defining and calculating costs of treatment and hospitalization and other relevant aspects of care regarding infections with chosen organisms and which can be readily reproduced for organisms in other situations (e.g., in a spreadsheet format). This could include, but is not limited to treating given resistant infection(s) with a drug to which a pathogen is susceptible, likelihood of culturing, hospitalization or other treatment, and transmission within households or healthcare facilities or among contacts, and indirect costs as applicable.
• Analysis of data to answer the questions:

—What is the cost of antimicrobial resistance in the chosen situation?

—How accurate is this method of data collection and analysis?

—Under what circumstances is this method of data collection and analysis reliably reproducible?

• Partnerships among an economist, statistician, clinician and epidemiologist or others may be necessary to ensure appropriate information is included in dataset and appropriate analysis are conducted.

Research Objective II: Awardee activities for this program must include research that addresses at least one of the following Action Items found in A Public Health Action Plan to Prevent Antimicrobial Resistance: Focus Area II. Prevention and Control, items 23 (Evaluate the relationship between prescribing behavior and specific antimicrobial drug marketing and promotional practices. Assess the public health effects of these practices in collaboration with partners.), 33 (Evaluate the potential impact of improved diagnostic tests, including rapid point-of-care tests on antimicrobial drug use and patient care, and assess their financial implications. Take into account tests that distinguish between bacterial and viral infections, tests that identify resistant pathogens, and tests that distinguish common clinical entities such as bacterial sinusitis and acute bacterial otitis media from illnesses with similar manifestations for which antimicrobials are not beneficial.), and 50 (Conduct additional research to further define the effects of using various veterinary drugs on the emergence of resistant bacteria that infect or colonize food animals of different species, using various animal husbandry practices. Identify risk factors and preventive measures. Assess the associated risk of: Transmission of AR infections to humans; Clinical disease in humans; and Transfer of resistance factors from animal flora to human flora.) In proposals that concern action items 23, 30, or 50, research proposals must address a current and compelling problem of antimicrobial resistance that is of high public health importance and for which research is needed. Such proposals must provide arguments why results of the proposed research could provide substantial impact and improvement to the current methods of prevention and control of the stated antimicrobial resistance problem. (Examples include but are not limited to problems in community-associated, healthcare-associated and foodborne-associated resistant infections).

II. Award Information

Type of Award: Grant.

Fiscal Year Funds: 2004.

Approximate Total Funding: $1,000,000.

Approximate Number of Awards: Five.

Approximate Average Award: $200,000 (This amount is for the first 12-month budget period, and includes both direct and indirect costs).

Floor of Award Range: None.

Ceiling of Award Range: None.

Anticipated Award Date: August 30, 2004.

Budget Period Length: 12 Months.

Project Period Length: Two Years for the economic research proposal, Research Objective I; two years for Research Objective II, unless a compelling argument is presented that describes why research cannot be completed in less than three years. Throughout the project period, CDC's commitment to continuation of awards will be conditioned on the availability of funds, evidence of satisfactory progress by the recipient (as documented in required reports), and the determination that continued funding is in the best interest of the Federal Government.

III. Eligibility Information

III.1. Eligible Applicants

Applications may be submitted by public and private nonprofit organizations and by governments and their agencies, such as:

• Public nonprofit organizations
• Private nonprofit organizations
• Universities
• Colleges
• Research institutions
• Hospitals
• Community-based organizations
• Faith-based organizations
• Federally recognized Indian tribal governments
• Indian tribes
• Indian tribal organizations
• State and local governments or their Bona Fide Agents (this includes the District of Columbia, the Commonwealth of Puerto Rico, the Virgin Islands, the Commonwealth of the Northern Marianna Islands, American Samoa, Guam, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau)
• Political subdivisions of States (in consultation with States)

A Bona Fide Agent is an agency/organization identified by the state as eligible to submit an application under the state eligibility in lieu of a state application. If you are applying as a bona fide agent of a state or local government, you must provide a letter from the state or local government as documentation of your status. Place this documentation behind the first page of your application form.

III.2. Cost Sharing or Matching

Matching funds are not required for this program.

III.3. Other

CDC will accept and review applications with budgets greater than the ceiling of the award range. If your application is incomplete or non-responsive to the requirements listed in this section, it will not be entered into the review process. You will be notified that your application did not meet submission requirements.

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 CDC programs.

Note:

Title 2 of the United States Code section 1611 states that an organization described in section 501(c)(4) of the Internal Revenue Code that engages in lobbying activities is not eligible to receive Federal funds constituting an award, grant, or loan.

IV. Application and Submission Information

IV.1. Address to Request Application Package

To apply for this funding opportunity, use application form PHS 398 (OMB number 0925-0001 rev. 5/2001). Forms and instructions are available in an interactive format on the CDC Web site, at the following Internet address: www.cdc.gov/od/pgo/forminfo.htm .

Forms and instructions are also available in an interactive format on the National Institutes of Health (NIH) Web site at the following Internet address: http://grants.nih.gov/grants/funding/phs398/phs398.html .

If you do not have access to the Internet, or if you have difficulty accessing the forms on-line, you may contact the CDC Procurement and Grants Office Technical Information Management Section (PGO-TIM) staff at: 770-488-2700. Application forms can be mailed to you.

IV.2. Content and Form of Application Submission

Letter of Intent (LOI): Your LOI must be written in the following format:

• Maximum number of pages: five
• Font size: 12-point unreduced
• Double spaced
• Paper size: 8.5 by 11 inches
• Page margin size: One inch
• Printed only on one side of page

• Written in plain language, avoid jargon Your LOI must contain the following information:
• Descriptive title of the proposed research
• Name, address, E-mail address, and telephone number of the Principal Investigator
• Names of other key personnel
• Participating institutions
• Number and title of this Program Announcement (PA)

Application: Follow the PHS 398 application instructions for content and formatting of your application. For further assistance with the PHS 398 application form, contact PGO-TIM staff at 770-488-2700, or contact Grants Info, Telephone (301) 435-0714, E-mail: GrantsInfo@nih.gov.

Your research plan should address activities to be conducted over the entire project period.

You are required to have a Dun and Bradstreet Data Universal Numbering System (DUNS) number to apply for a grant or cooperative agreement from the Federal government. Your DUNS number must be entered on line 11 of the face page of the PHS 398 application form. The DUNS number is a nine-digit identification number, which uniquely identifies business entities. Obtaining a DUNS number is easy and there is no charge. To obtain a DUNS number, access www.dunandbradstreet.com or call 1-866-705-5711. For more information, see the CDC Web site at: http://www.cdc.gov/od/pgo/funding/pubcommt.htm.

This PA uses just-in-time concepts. It also uses the modular budgeting as well as non-modular budgeting formats. See: http://grants.nih.gov/grants/funding/modular/modular.htm for additional guidance on modular budgets. Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular budget format. Otherwise, follow the instructions for non-modular budget research grant applications.

Additional requirements that may require you to submit additional documentation with your application are listed in section “VI.2. Administrative and National Policy Requirements.”

IV.3. Submission Dates and Times

LOI Deadline Date: May 17, 2004.

CDC requests that you send a LOI if you intend to apply for this program. Although the LOI is not required, not binding, and does not enter into the review of your subsequent application, the LOI will be used to gauge the level of interest in this program, and to allow CDC to plan the application review.

Application Deadline Date: June 14, 2004.

Explanation of Deadlines: Applications must be received in the CDC Procurement and Grants Office by 4 p.m. eastern time on the deadline date. If you send your application by the United States Postal Service or commercial delivery service, you must ensure that the carrier will be able to guarantee delivery of the application by the closing date and time. If CDC receives your application after closing due to: (1) carrier error, when the carrier accepted the package with a guarantee for delivery by the closing date and time, or (2) significant weather delays or natural disasters, you will be given the opportunity to submit documentation of the carriers guarantee. If the documentation verifies a carrier problem, CDC will consider the application as having been received by the deadline.

This announcement is the definitive guide on application submission address and deadline. It supersedes information provided in the application instructions. If your application does not meet the deadline above, it will not be eligible for review, and will be discarded. You will be notified that your application did not meet the submission requirements.

CDC will not notify you upon receipt of your application. If you have a question about the receipt of your application, first contact your courier. If you still have a question, contact the PGO-TIM staff at: 770-488-2700. Before calling, please wait two to three days after the application deadline. This will allow time for applications to be processed and logged.

IV.4. Intergovernmental Review of Applications

Your application is subject to Intergovernmental Review of Federal Programs, as governed by Executive Order (EO) 12372. This order sets up a system for state and local governmental review of proposed federal assistance applications. You should contact your state single point of contact (SPOC) as early as possible to alert the SPOC to prospective applications, and to receive instructions on your state's process. Click on the following link to get the current SPOC list: http://www.whitehouse.gov/omb/grants/spoc.html.

IV.5. Funding Restrictions

Restrictions, which must be taken into account while writing your budget, are as follows: None.

If you are requesting indirect costs in your budget, you must include a copy of your indirect cost rate agreement. If your indirect cost rate is a provisional rate, the agreement should be less than 12 months of age. Awards will not allow reimbursement of pre-award costs.

IV.6. Other Submission Requirements

LOI Submission Address: Submit your LOI by express mail, delivery service, fax, or e-mail to: Barbara Stewart, Public Health Analyst, Centers for Disease Control and Prevention, National Center for Infectious Diseases, 1600 Clifton Road, NE., Mailstop C-19, Atlanta, GA 30333, Telephone: 404-639-0044, Fax: 404-639-2469, e-mail: bsg2@cdc.gov.

Application Submission Address: Submit the original and five hard copies of your application by mail or express delivery service to: Technical Information Management-PA# 04094, CDC Procurement and Grants Office, 2920 Brandywine Road, Atlanta, GA 30341.

Applications may not be submitted electronically at this time.

V. Application Review Information

V.1. Criteria

You are required to provide measures of effectiveness that will demonstrate the accomplishment of the various identified objectives of the grant. Measures of effectiveness must relate to the performance goals stated in the “Purpose” section of this announcement. Measures must be objective and quantitative, and must measure the intended outcome. These measures of effectiveness must be submitted with the application and will be an element of evaluation.

The goals of CDC-supported research are to advance the understanding of biological systems, improve the control and prevention of disease and injury, and enhance health. In the written comments, reviewers will be asked to evaluate the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals.

The scientific review group will address and consider each of the following criteria in assigning the application's overall score, weighting them as appropriate for each application. The application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative, but is essential to move a field forward.

The criteria for review are the same for applications for either Research Objective except where noted and are as follows:

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field?

Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? Does the proposed research consider all the activities listed in either “Research Objective I” or “Research Objective II”?

Innovation: Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies?

Investigator: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)?

Environment: Does the scientific 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? Is there evidence of institutional support?

Additional Review Criteria: In addition to the above criteria, the following items will be considered in the determination of scientific merit and priority score:

Applications for Research Objective I: Are there plans for analysis of relevant epidemiological data, for development of methods that can be readily reproduced for organisms in other situations, and for analysis of data to answer questions on cost, accuracy and reproducibility?

Are the measurable outcomes of the program consistent with Action Item 16 (Provide health care system administrators and other decision makers with data on the impact of drug-resistant organisms (e.g., outcome, treatment costs) and on effective prevention and control measures.) in Focus Area I, Surveillance of A Public Health Action Plan to Combat Antimicrobial Resistance (Part I: Domestic Issues)?

Applications for Research Objective II: Does the proposed research help implement at least one of the following Action Items found in A Public Health Action Plan to Prevent Antimicrobial Resistance (Part I: Domestic Issues): Focus Area II, Prevention and Control, Action Items 23 (Evaluate the relationship between prescribing behavior and specific antimicrobial drug marketing and promotional practices. Assess the public health effects of these practices in collaboration with partners.), 33 (Evaluate the potential impact of improved diagnostic tests, including rapid point-of-care tests on antimicrobial drug use and patient care, and assess their financial implications. Take into account tests that distinguish between bacterial and viral infections, tests that identify resistant pathogens, and tests that distinguish common clinical entities such as bacterial sinusitis and acute bacterial otitis media from illnesses with similar manifestations for which antimicrobials are not beneficial.), and 50 (Conduct additional research to further define the effects of using various veterinary drugs on the emergence of resistant bacteria that infect or colonize food animals of different species, using various animal husbandry practices. Identify risk factors and preventive measures. Assess the associated risk of: Transmission of AR infections to humans; Clinical disease in humans; and Transfer of resistance factors from animal flora to human flora.) Does the research address a current and compelling problem of antimicrobial resistance that is of high public health importance and for which research is needed?

Protection of Human Subjects from Research Risks: Does the application adequately address the requirements of title 45 CFR part 46 for the protection of human subjects? This will not be scored; however, an application can be disapproved if the research risks are sufficiently serious and protection against risks is so inadequate as to make the entire application unacceptable.

Inclusion of Women and Minorities in Research: Does the application adequately address the CDC Policy requirements regarding the inclusion of women, ethnic, and racial groups in the proposed research? This includes: (1) The proposed plan for the inclusion of both sexes and racial and ethnic minority populations for appropriate representation; (2) The proposed justification when representation is limited or absent; (3) A statement as to whether the design of the study is adequate to measure differences when warranted; and (4) A statement as to whether the plans for recruitment and outreach for study participants include the process of establishing partnerships with community(ies) and recognition of mutual benefits.

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research.

V.2. Review and Selection Process

Applications will be reviewed for completeness by the Procurement and Grants Office (PGO) and for responsiveness by the National Center for Infectious Diseases. Incomplete applications and applications that are non-responsive to the eligibility criteria will not advance through the review process. Applicants will be notified that their application did not meet submission requirements.

Applications that are complete and responsive to the PA will be evaluated for scientific and technical merit by an appropriate peer review group or charter study section convened by the National Center for Infectious Diseases in accordance with the review criteria listed above. As part of the initial merit review, all applications may:

• Undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of the applications under review, will be discussed and assigned a priority score.
• Receive a written critique.
• Receive a second level review.

Award Criteria: Criteria that will be used to make award decisions include:

• Scientific merit (as determined by peer review)
• Availability of funds
• Programmatic Priorities

V.3. Anticipated Award Date

August 30, 2004.

VI. Award Administration Information

VI.1. Award Notices

Successful applicants will receive a Notice of Grant Award (NGA) from the CDC Procurement and Grants Office. The NGA shall be the only binding, authorizing document between the recipient and CDC. The NGA will be signed by an authorized Grants Management Officer, and mailed to the recipient fiscal officer identified in the application.

Unsuccessful applicants will receive notification of the results of the application review by mail.

VI.2. Administrative and National Policy Requirements

45 CFR Part 74 and Part 92

For more information on the Code of Federal Regulations, see the National Archives and Records Administration at the following Internet address: http://www.access.gpo.gov/nara/cfr/cfr-table-search.html.

The following additional requirements apply to this project:

• AR-1—Human Subjects Requirements
• AR-2—Requirements for Inclusion of Women and Racial and Ethnic Minorities in Research
• AR-7—Executive Order 12372
• AR-10—Smoke-Free Workplace Requirements
• AR-11—Healthy People 2010
• AR-12—Lobbying Restrictions
• AR-15—Proof of Non-Profit Status
• AR-22—Research Integrity
• AR-23—States and Faith-Based Organizations
• AR-25—Release and Sharing of Data

Additional information on these requirements can be found on the CDC Web site at the following Internet address: http://www.cdc.gov/od/pgo/funding/ARs.htm.

VI.3. Reporting

You must provide CDC with an original, plus two hard copies of the following reports:

1. Interim progress report, (use form PHS 2590, OMB Number 0925-0001, rev. 5/2001 as posted on the CDC Web site) no less than 90 days before the end of the budget period. The progress report will serve as your non-competing continuation application, and must contain the following elements:

a. Current Budget Period Activities Objectives.

b. Current Budget Period Financial Progress.

c. New Budget Period Program Proposed Activity Objectives.

d. Budget.

e. Additional Requested Information.

f. Measures of Effectiveness.

2. Financial status report no more than 90 days after the end of the budget period.

3. Final financial and performance reports, no more than 90 days after the end of the project period.

These reports must be mailed to the Grants Management Specialist listed in the “Agency Contacts” section of this announcement.

VII. Agency Contacts

For general questions about this announcement, contact: Technical Information Management Section, CDC Procurement and Grants Office, 2920 Brandywine Road, Atlanta, GA 30341, Telephone: 770-488-2700.

For scientific/research issues, contact: Mary Lerchen, DrPH, MS, Extramural Program Official, National Center for Infectious Diseases, 1600 Clifton Road, NE., Atlanta, GA 30333, Telephone: 404-639-0043, E-mail: mll0@cdc.gov.

For questions about peer review, contact:

Barbara Stewart, Public Health Analyst, National Center for Infectious Diseases, 1600 Clifton Road, NE., Atlanta, GA 30333, Telephone: 404-639-0044, E-mail: bsg2@cdc.gov.

For financial, grants management, or budget assistance, contact:

Sharon Robertson, Grants Management Specialist, CDC Procurement and Grants Office, 2920 Brandywine Road, Atlanta, GA 30341, Telephone: 770-488-2748, E-mail:sqr2@cdc.gov.

VIII. Other Information

None.