Prevention Epicenter Program

Announcement Type: Competitive Supplemental.

Funding Opportunity Number: 04100.

Catalog of Federal Domestic Assistance Number: 93.283.

Key Dates: Application Deadline: June 14, 2004.

Executive Summary: This announcement encompasses two distinct projects.

(1) Microbiology laboratory errors. Errors in the laboratory can occur during the pre-analytical, analytical, and post analytical phases of specimen management. Most studies on laboratory errors focus on the analytical (testing) phase; however, preliminary data from a pilot study conducted by CDC suggests that there are a significant numbers of errors that occur with antimicrobial susceptibility testing results in the post analytical reporting phase. This program focuses on assessing the impact of both testing and reporting errors on patient management and outcomes.

(2) C. difficile associated disease. C. difficile associated disease (CDAD) is an important, yet under recognized, public health problem that results in significant patient morbidity and increased healthcare costs. Recent estimates of the scope and magnitude of CDAD suggest its incidence among acute care hospital patients, results in over 500 million dollars in excess healthcare costs annually. Moreover, various data sources suggest its incidence is increasing. It is hypothesized that changing antimicrobial use patterns and resistance may be contributing to this increasing incidence. In addition, programs that include new methods of infection control (such as novel methods of environmental disinfection, novel strain typing methods and hand washing using alcohol-base products) as well as improved laboratory detection and reporting methods may be impacting the incidence of CDAD.

I. Funding Opportunity Description

Authority: Section 317(k)(2) of the Public Health Service Act [42 U.S.C. 247b(k)(2)], as amended.

Purpose: The purpose of these supplemental awards is twofold: (1) To determine the number and types of laboratory errors associated with identification and antimicrobial susceptibility testing of bacteria isolated from cultures of blood and sterile body sites of hospitalized patients; and (2) to determine if recently introduced antimicrobial agents and infection control practices are impacting rates of C. difficile-associated disease and whether antimicrobial resistance could be emerging. This program addresses the “Healthy People 2010” focus area of Immunization and Infectious Diseases.

Measurable outcomes of the program will be in alignment with one or more of the following performance goal(s) for the National Center for Infectious Diseases: Protect Americans from infectious diseases, Reduce the spread of antimicrobial resistance, and Protect Americans from death and serious harm caused by medical errors and preventable complications of healthcare.

Research Objectives: (1) Microbiology laboratory errors. Errors in the laboratory can occur during the pre-analytical, analytical, and post analytical phases of specimen management. Most studies on laboratory errors focus on the analytical (testing) phase; however, preliminary data from a pilot study conducted by CDC on laboratory reports concerning bacterial pathogens causing bloodstream infections suggest that there are a significant numbers of errors that occur with antimicrobial susceptibility testing results in the post analytical reporting phase. This program focuses on assessing the impact of both testing and reporting errors on patient management and outcomes.

The knowledge gained through this research will help define what interventions need to be made in laboratories to improve the accuracy and utility of antimicrobial susceptibility tests reports (such as cascading of results) to reduce errors and improve patient outcomes. The objectives of this program are to:

• Determine the number and types of microbiology laboratory errors associated with processing cultures from blood and sterile body sites (such as cerebrospinal fluid (CSF)) of hospitalized patients;
• Determine the accuracy of bacterial identifications by participating laboratories;
• Determine the accuracy of the antimicrobial susceptibility patterns of the bacteria recovered from the blood and sterile body sites; and
• Determine the accuracy and appropriateness of the reports issued to the patients' charts, along with the outcomes of the patients for which errors are noted.

One possible study design would be to identify a series of positive blood and body fluid cultures, to include both Gram-positive and Gram-negative pathogens, and to track the flow of information from the laboratory to the patients' chart, while concomitantly sending the isolates and a copy of the microbiology results to a reference laboratory for confirmation. The appropriateness of the antimicrobial agents tested and reported, given the identification of the organism to genus and species level, is critical. Thus, attention should be paid to reporting of results for inappropriate antimicrobial agents (e.g., nitrofurantoin for blood cultures), or reporting results for fourth generation cephalosporins or carbapenems, for organism that are susceptible to first generation cephalosporins.

(2) C. difficile associated disease. (CDAD) According to national data from hospital discharges, CDAD rates are increasing and CDAD is now responsible for substantial patient morbidity and excess healthcare costs. Because antimicrobial agents are a major risk factor for CDAD, it is unknown whether the introduction and widespread use of certain newer antimicrobials, especially those with anti-anaerobic activity, may lead to increased rates of CDAD. In addition, certain infection control practices, such as the use of alcohol gels for hand hygiene, also may contribute to increasing rates of CDAD, whereas hospitals that use bleach as a disinfectant for environmental surfaces may have better controlled rates of CDAD. A rationale for introducing new antimicrobial use guidelines and/or infection control policies will require knowing the excess costs associated with CDAD and cost effectiveness of prevention strategies. Finally, it is unknown whether the pathogen C. difficile itself may be developing resistance to the antimicrobial agents commonly used to treat CDAD (i.e. metronidazole and vancomycin).

The scientific knowledge to be achieved through this project includes addressing each of the above questions and information gaps regarding the contemporary epidemiology of CDAD in U.S. hospitals. To this end, objectives for this project include the following:

• Identify current antimicrobial agents that may be risk factors for CDAD in several U.S. healthcare facilities.
• Determine the antimicrobial susceptibility of at least 100 recent isolates of Clostridium difficile.
• Determine whether infection control practices, including hand hygiene with alcohol gel (vs. soap and water) and environmental cleaning with bleach, are risk or protective factors for CDAD.
• Determine the excess healthcare costs of CDAD.

The types of research and experimental approaches to be considered in answering these questions and achieving the objectives include: Case-control and/or cohort studies to determine risk factors for CDAD and the attributable costs of CDAD; isolation of C. difficile from the stool of CDAD patients followed by identification and susceptibility testing of isolates; and environmental and hand sampling for C. difficile and/or intervention studies to determine the impact of different infection control strategies on either surface contamination or incidence of CDAD.

Depending on current capabilities and needs, recipients may request support under this supplement for one or both of the following projects:

• Microbiology Errors Associated with Processing Blood and Sterile Body Site Cultures.
• The Impact of New Forms of Antimicrobial Use, Resistance, Laboratory Methods, and Infection Control Practices on the Incidence of Clostridium difficile and Associated Patient Morbidity and Healthcare Costs.

Activities: Awardee activities for this program are as follows:

Microbiology Errors Associated With Processing Blood and Sterile Body Site Cultures

• Determine the number and types of microbiology laboratory errors associated with processing cultures from the blood and sterile body sites (such as CSF) of hospitalized patients.
• Identify the bacteria isolated.
• Identify the accuracy of the antimicrobial susceptibility patterns of the bacteria.
• Determine the accuracy of the reports issued to the patients' charts. Patients' charts should be reviewed and assessed, along with the outcomes of the patients for which errors are noted.
• Identify at least 10 microbiology laboratories in different healthcare institutions that can serve as study sites. Identify a central reference laboratory for confirmation of the identification and antimicrobial susceptibility pattern of the isolates (this could include the Division of Healthcare Quality Promotion (DHQP) reference laboratories at CDC).
• Prospectively collect at least 10 bacterial isolates from each study site (at least 5 gram-positive and 5 gram-negative organisms) for which routine antimicrobial susceptibility tests are typically performed (excludes organisms such as Neisseria meningitidis, Group B streptococci, or Haemophilus influenzae). Send organisms, along with a copy of the organism's identification and antimicrobial susceptibility test report when completed by the study site laboratory, to the central laboratory for testing.
• Assess whether the appropriate cultures were collected for the suspected infection (i.e., the appropriate number and timing of blood cultures, appropriate CSF tubes delivered to microbiology laboratory within the designated time period established by the laboratory).
• Assess whether the report of culture results and antimicrobial susceptibility test results on the patients' charts were accurate and appropriate (e.g., no reports of antimicrobial agents that are used for urinary tract infections for bacteria from cerebrospinal fluid).
• Assess clinician's response to laboratory data (i.e., changes in antimicrobial chemotherapy based on susceptibility test results).
• Assess adverse patient outcomes based on inaccurate or inappropriate reporting of culture and susceptibility results.
• Develop an educational program for reducing the laboratory errors associated with testing and reporting results for bacteria isolates from blood and sterile body fluids.

The Impact of New Forms of Antimicrobial Use, Resistance, Laboratory Methods, and Infection Control Practices on the Incidence of Clostridium difficile and Associated Patient Morbidity and Healthcare Costs

• Determine if recently introduced antimicrobial agents (such as fluoroquinolones) or new modes of antimicrobial use (such as clindamycin for community-associated Staphylococcus aureus infections) constitute risk factors for C. difficile associated disease (CDAD).
• Determine whether there is emerging resistance to the drugs of choice (i.e., vancomycin and metronidazole) in C. difficile that could impede effective treatment.
• Determine if new infection control measures (such as hand washing with alcohol-based products or new disinfectants) may impact the incidence of CDAD (e.g., risk factors for infection).
• Determine the impact of new laboratory methods (such as the use of assays that detect both toxin A and toxin B), efforts to reduce turnaround time of assay or culture results, or improved reporting methods, impact the incidence of CDAD.
• Determine the patient morbidity and healthcare costs associated with the excess or reduced number of cases of CDAD resulting from any or all of these factors.

In a cooperative agreement, CDC staff is substantially involved in the program activities, above and beyond routine grant monitoring.

CDC Activities for the two projects are as follows:

• Collaborate with the recipient in all stages of the program, and provide programmatic and technical assistance.
• Collaborate with the recipient in all aspects of the science.
• Participate in the dissemination of findings and information stemming from the project.
• Participate in improving program performance through consultation with recipient.
• Facilitate communication of data and results among stakeholders.
• Assist in the development of research protocols for IRB review by all cooperating institutions participating in the research project. The CDC IRB will review and approve the protocol initially and on at least an annual basis until the research project is completed.

II. Award Information

Type of Award: Cooperative Agreement.

CDC involvement in this program is listed in the Activities Section above.

Fiscal Year Funds: 2004.

Approximate Total Funding: $634,000.

Approximate Number of Awards: Four (two per project).

Approximate Average Award: $158,500 (This amount is for the first 12-month budget period, and includes both direct and indirect costs).

Floor of Award Range: $157,000.

Ceiling of Award Range: $160,000.

Anticipated Award Date: August 16, 2004.

Budget Period Length: 12 months.

Project Period Length: Two 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

Eligibility is limited to the seven current Prevention Epicenter Program grantees. They are: Harvard Pilgrim Health Care, Washington University, Northwestern University, University of Iowa, McGuire Research Institute, Memorial Sloan-Kettering Institute for Cancer Research, and Johns Hopkins University. No other applications are solicited.

Eligibility is limited to the Prevention Epicenters in order to maximize the use of available funds by building on existing infrastructure for evaluating healthcare-associated infections and adverse events and utilizing highly demonstrated expertise in infection control procedures and practices. The proposed supplemental projects will complement activities associated with the established Prevention Epicenter Program, which includes projects designed to develop, implement, and evaluate the effectiveness of epidemiologically-based strategies to improve healthcare quality and assure patient safety.

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.

This program is designed and intended to support research, therefore only research will be supported under this cooperative agreement. Any applications proposing anything other than research will be considered non-responsive.

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: http://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

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 GrantsInfo, Telephone (301) 435-0714, E-mail: GrantsInfo@nih.gov.

Your research plan should address activities to be conducted over the entire project period (through 1/31/2006).

Submit one application that includes one or both of the proposed projects. Each project should be clearly identified in the application. Provide a line-item budget and narrative justification for all requested costs, and separate line-item budgets for each proposal submitted.

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 http://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

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

Application Submission Address: Submit the original and five hard copies of your application by mail or express delivery service to: Technical Information Management—PA#4100, 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 cooperative agreement. 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 that will be used to evaluate each project 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?

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: None

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 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 by CDC senior staff.

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

Award Date: August 16, 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-22—Research Integrity
• 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 website) 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 and annual progress 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: Dr. Mary Lerchen, Acting Director, Office of Extramural Research, Centers for Disease Control and Prevention, National Center for Infectious Diseases, 1600 Clifton Road, NE., Mailstop C-19, Atlanta, GA 30333, Telephone: 404-639-0043, E-mail: mll0@cdc.gov.

For questions about peer review, contact: Barbara Stewart, 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, E-mail: bsg2@cdc.gov.

For financial, grants management, or budget assistance, contact: Yolanda Sledge, Grants Management Specialist, CDC Procurement and Grants Office, 2920 Brandywine Road, Atlanta, GA 30341, Telephone: (770) 488-2787, E-mail: YSledge@cdc.gov.