Part I Overview Information

Department of Health and Human Services

Participating Organizations
Agency for Healthcare Research and Quality (AHRQ), (http://www.ahrq.gov)

Components of Participating Organizations
Center for Outcomes and Evidence (COE), ( http://www.ahrq.gov)

Title:  Targeted Topic Areas in Safety and Comparative Effectiveness for the Centers for Education and Research on Therapeutics (CERTs) (U18)

Note: The policies, guidelines terms and conditions stated in this announcement may differ from those used by the NIH.

Announcement Type

New

Request for Applications (RFA) Number: RFA-HS-08-005

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four (4) weeks prior to the grant submission date. See Section IV.

Catalog of Federal Domestic Assistance Number(s)
93.226

Key Dates
Release/Posted Date: March 21, 2008
Opening Date: April 19, 2008
Letters of Intent Receipt Date(s): April 10, 2008
Technical Assistance Call: Tuesday, April 1, 2008 11:00 AM 12:30 PM Eastern time. A teleconference line will be provided by email to all CERTs Centers eligible to apply to this FOA.
NOTE: On-time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Due Date(s): May 19, 2008
Peer Review Date(s): Approximately one - two months after receipt date
Earliest Anticipated Start Date(s): September, 2008
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: May 20, 2008

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

This FOA is a limited competition. Only those institutions receiving AHRQ funding under RFA-HS-05-014 or RFA-HS-07-004 (Centers for Education and Research in Therapeutics) or RFA-HS-07-008 (Coordinating Center for the AHRQ Centers for Education and Research on Therapeutics Program) are eligible to apply. Due to the CERTs legislative mandate, their acknowledged leadership and experience in therapeutics research, and their experience as a collaborative research network, the CERTs are uniquely qualified to propose and conduct large multi-center collaborative studies in a scientifically rigorous, efficient, and timely fashion to address topics in comparative effectiveness for AHRQ and in drug safety for FDA. Under this FOA, each application must represent a collaboration of at least two, but no more than four, CERTs Centers. Each CERTs Center may participate in a total of two applications, of which only one may be as the applicant. Acceptable combinations include submission of one application and participation in another application as a collaborator, or participation in two applications as a collaborating partner. Non-CERT parties may participate only under restricted circumstances as described in Section III.3. Other- Special Eligibility Criteria.

While grant awards are made to institutions rather than individuals, this announcement and its instructions are written to inform individual researchers of this funding opportunity and facilitate the submission of grant applications by their organizations.

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
    A. Eligible Institutions
    B. Eligible Individuals
2. Cost Sharing or Matching
3. Other-Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Receipt, Review, and Anticipated Start Dates
          1. Letter of Intent
2. Technical Assistance
    B. Submitting an Application Electronically to AHRQ
  C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
     A. Cooperative Agreement Terms and Conditions of Award
       1. Principal Investigator Rights and Responsibilities
       2. AHRQ Responsibilities
       3. Collaborative Responsibilities
       4. Arbitration Process
3. Reporting

Section VII. Agency Contacts
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

This FOA is a limited competition. The purpose of this FOA is to utilize the strengths and experience of the existing CERTs Centers working as a collaborative research network to share resources in order to address targeted research needs in therapeutics safety and comparative effectiveness. Collaborations are to bring new data resources to existing population-based data systems, either in the form of existing but as-yet unlinked data resources (e.g. data available in electronic health records, laboratory values or results, and others) or through prospective data collection from institutions, providers, or patients. Such new data can enhance understanding of safety and comparative effectiveness of therapeutics by providing critical missing information about baseline disease severity or other confounders of observational analyses, such as treatment adherence, BMI, or smoking status. New data or data linkages may help to elucidate apparent differences in therapeutics effectiveness and harms, particularly among understudied subpopulations with extensive use of specific therapies or inherent vulnerabilities, disparities, or risks of serious outcomes. Topic areas for which applications are sought include: (1) antipsychotic safety and comparative effectiveness, (2) safety assessment of tumor-necrosis factor (TNF) blocking agents used in autoimmune diseases, (3) methodological work on adverse safety outcome definitions and unmeasured confounders in observational assessments of therapeutics, and (4) assessment of therapeutics use in pediatric inpatient settings and with over-the-counter acetaminophen. Improved evidence on comparative clinical effectiveness (including safety) in these topic areas will inform decisions made by patients, clinicians, payers, and regulators.

The comparative effectiveness studies proposed under this FOA will address targeted topics of clinical significance to patients, providers, and payers associated with the Medicare, Medicaid, or S-CHIP populations identified under the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) Section 1013 (42 USC 299b-7). The safety topics and methodologic issues in outcomes assessment for harms will assist in the identification of optimal and efficient methods for assessing therapeutic harms as raised in Section 905(A)(4) of the Food and Drug Administration Amendments Act of 2007 (FDAAA, Pub. L. No. 110-85).

Due to the CERTs legislative mandate, their acknowledged leadership and experience in therapeutics research, and their experience as a collaborative research network, the CERTs are uniquely qualified to propose and conduct large multi-center collaborative studies in a scientifically rigorous, efficient, and timely fashion to address topics in comparative effectiveness for AHRQ and in drug safety for FDA.

Background

The CERTs program began with the release of RFA: HS-99-004 on January 27, 1999, and the subsequent award of grants pursuant to the Food and Drug Administration Modernization Act of 1997 (FDAMA, Pub. L. No. 105-115). Section 409 of FDAMA authorized the Agency for Healthcare Research and Quality (AHRQ), in coordination with FDA, to carry out a research demonstration program to conduct research and provide objective information on drugs, biologics, and devices. AHRQ continues to manage this program in coordination with FDA under the AHRQ s 1999 reauthorizing legislation at Pub. L. No. 106-129 (See 42 USC 299b-1(b)). Among the legislative mandates of the CERTs program is to conduct research on the comparative effectiveness (which includes both benefits and harms assessments) of drugs, biological products, and devices (42 USC 299b-1(b)(2)(B)).

In 2003, the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) was enacted into law (Pub. L. No. 108-173). Section 1013 of MMA authorizes AHRQ to conduct research, demonstrations, and evaluations designed to improve the quality, effectiveness, and efficiency of Medicare, Medicaid, and the State Children's Health Insurance Program (SCHIP, 42 USC 299b-7). The essential goals of the Section 1013 mandate are to develop valid evidence, and make it easily accessible to decision makers, about the comparative effectiveness of different treatments and appropriate clinical approaches to difficult health problems. Moving beyond the synthesis of existing evidence, the research and other activities authorized by the Section 1013 provision are designed to focus on: a) understanding the outcomes, comparative clinical effectiveness, and appropriateness of health care items and services (including prescription drugs, devices, and their treatment alternatives); and b) developing strategies for improving the efficiency and effectiveness of the Medicare, Medicaid, and SCHIP programs (42 USC 299b-7(a)(1)(A)).

In consultation with relevant stakeholders, the Department of Health and Human Services (DHHS) undertook a priority setting process for identifying important topics to address the MMA Section 1013 legislation. Recommendations for research made by stakeholders were reviewed and prioritized by a steering committee composed of representatives from different components of DHHS. The Department has published an initial priority list of ten conditions under which research and related activities will be initially undertaken. The ten conditions are: 1) ischemic heart disease; 2) cancer; 3) chronic obstructive pulmonary disease/asthma; 4) stroke, including control of hypertension; 5) arthritis and non-traumatic joint disorders; 6) diabetes mellitus; 7) dementia, including Alzheimer's disease; 8) pneumonia; 9) peptic ulcer/dyspepsia; and 10) depression and other mood disorders. Research related to dementia, depression, and other mood disorders is the specific focus of the comparative effectiveness research requested under Topic Area 1 of this FOA.

In addition to evidence generation under MMA Section 1013, additional legislative activity in 2007 positioned the CERTs to address issues involving the safety assessment of the therapeutic products. P.L. 110-85, the Food and Drug Administration Amendments Act (FDAAA) was passed in 2007 to improve FDA authorities, funding, and the ultimate conduct of safety assessments for therapeutic drugs and devices (Pub. L. No. Under Section 905(4)(A) it states The Secretary shall establish collaborations with public, academic, and private entities, which

may include the Centers for Education and Research on Therapeutics under section 912 of the Public Health Service Act, to provide for advanced analysis of drug safety data described in paragraph (3)(C) and other information that is publicly available or is provided by the Secretary, in order to (i) improve the quality and efficiency of postmarket drug safety risk-benefit analysis; (ii) provide the Secretary with routine access to outside expertise to study advanced drug safety questions; and (iii) enhance the ability of the Secretary to make timely assessments based on drug safety data.

Research Objectives

The prevailing scientific approach for assessing the efficacy of therapeutic interventions is through randomized controlled trials (RCTs). RCTs, such as for drugs, are generally designed to examine the safety and efficacy of a treatment within a relatively small number and subset of affected patients and in a highly controlled setting. In such trials, treatment comparisons are often made to placebo rather than to other available treatment alternatives. While RCTs generally maximize the internal validity of a treatment investigation, trials tend to be expensive, lengthy, and yield findings that may not generalize to all patients for whom a treatment will be prescribed. As a result, the efficacy demonstrated in a randomized controlled trial may differ from the effects observed in actual clinical practice. Furthermore, most clinical trials are not designed to assess the long-term outcomes, particularly unforeseen harms (such as rare adverse events), associated with chronic medication use. As a result, there is often limited information about the full range of beneficial and harmful health outcomes, comparative effectiveness, and appropriateness of drug, device, interventional, and surgical therapies across all treatment options available to patients and their healthcare providers. This problem is especially important in the elderly and other vulnerable populations who frequently live with multiple chronic health conditions, take multiple medications, and are often excluded by protocol from participation in most clinical trials.

AHRQ recognizes that the mission of the CERTs includes comparative effectiveness research and therefore proposes this limited competition to provide additional funding to enhance the work of the Centers in this area. AHRQ will consider applications from current CERTs grantees to develop single applications representing coordinated collaborations of at least 2 CERTs Centers. Four separate research topic areas in support of the MMA Section 1013 statutory mandates on comparative effectiveness and on safety issues of high relevance to the Food and Drug Administration (FDA) will be supported. As described further in the following Research Topics section, research applications must address one of the topic areas specified below and involve data collaborations of 2 or more CERTs Centers, including the use or collection of new data resources. To understand the context of the comparative effectiveness work sought under this limited competition FOA, it is recommended that applicants consult descriptions of the issues and definitions contained in the MMA Section 1013 legislation (see http://www.medicare.gov/MedicareReform/108s1013.pdf) as well as review the activities under the Effective Health Care Program (http://effectivehealthcare.ahrq.gov/aboutUs.cfm?abouttype=program ) for Comparative Effectiveness Reports and research publications of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program.

Research Topic Areas for which Applications are Solicited

Applications are solicited in each of 4 research topic areas described below. At least one application is anticipated for funding in each topic area. For each of the first two topic areas, awards of approximately $2.5 million in total costs are anticipated. Topic areas 3 and 4 are each anticipated for funding at approximately $1 million in total costs. For each topic area application that is awarded, AHRQ anticipates one CERTs Center-led award representing and including a consortium of at least one other CERT research or coordinating center to address the topic area collaboratively. The total award pool is $7 million. All awards must be made up of collaboratives formed from the 15 currently funded CERTs centers.

Topic Area 1: Comparative Effectiveness of Antipsychotics with Special Attention to Safety

Atypical and conventional antipsychotic medications are used widely for both labeled and unlabeled indications. Neuropsychiatric illnesses treated with antipsychotics contribute significantly to morbidity, mortality, and health care expenditures through high medication costs and health care system interventions for inadequately treated disease and/or medication adverse events. For this topic, research applications are sought that will use population-based data systems supplemented with additional data collection or data linkages to increase the capture of information on antipsychotic medication use, indications, and robust measures of their harms and benefits.

Three major subtopics within this research area must be addressed by applicants. Two of these subtopics encompass vulnerable populations of patients with wide use of antipsychotics under conditions of incomplete evidence on benefits or harms: (1) pediatric populations, where there are questions of comparative effectiveness (including harms) of antipsychotics when used singly or in combinations, and (2) the institutionalized elderly, where concerns about mortality and morbidity differences by individual drugs or classes of drug are of special concern. For the third subtopic areas, applications must address at least one other population-wide safety concern of antipsychotics, such as pituitary tumors (including prolactinoma). Additional information on these three subtopic areas follows below.

Pediatric use and comparative effectiveness of single and multiple antipsychotics: In pediatric populations, antipsychotics are used for indications such as autism, mood disorders (including bipolar illness), behavioral disorders (particularly aggression), and schizophrenia. In some children, administrative data indicate multiple antipsychotic agents being prescribed concomitantly or being used as young as infancy. Use of data sources to validate the occurrence of these practices of uncertain safety and effectiveness would be helpful to multiple audiences such as Medicaid Medical Directors, as would data capturing quantifiable and valid measures of potential benefits or harms of antipsychotics used singly, in combination, or incrementally. Potential outcome measures might include hospitalizations or emergency room visits (e.g. for psychiatric or somatic events, suicide attempts, injuries, etc,) and impacts on school attendance or disciplinary actions (e.g. detentions or suspensions.) Safety issues include but are not limited to increased mortality, pituitary tumors (including prolactinoma), metabolic effects (e.g., effects on lipids and blood glucose, as well as weight gain or diabetes), tardive dyskinesia, and others. As much as possible, research and data resources should attempt to answer questions to guide optimal clinical use of individual antipsychotics or combinations in the pediatric population according to dose, duration of use, patient age or other characteristics, indication, or comorbidities.

Comparative Effectiveness and Safety of Antipsychotic Use in the Institutionalized Elderly: As part of a comparative effectiveness review of off-label uses of antipsychotics done under the AHRQ Effective Healthcare Program (http://effectivehealthcare.ahrq.gov/healthInfo.cfm?infotype=rr&ProcessID=5&DocID=64), the systematic evidence review considered the evidence for benefits and harms in using atypical and conventional antipsychotics in the treatment of dementia among the instititutionalized elderly. Concerns and questions raised in this population include questionable effectiveness in reducing agitation and psychosis, and safety concerns including mortality (due to cerebrovascular accidents and other causes), extrapyramidal side effects (EPS) including tardive dyskinesia, and sedation. Uncertainties and data gaps were noted in relation to differential risks of these outcomes across various classes and individual antipsychotic agents. Particularly in the institutionalized elderly, new or expanded linkages of data resources from nursing homes, Medicare, and Medicaid may assist in addressing these issues. Additional data may assist in discerning multi-level confounding, which may include selection factors for therapy at both the patient and facility levels.  Applications for this subtopic must propose one or more research studies to address the identified data gaps or areas of uncertain evidence, particularly with regard to mortality risks of different agents or therapeutic classes.

Safety issues with antipsychotics: Evidence from RCTs, case reports, and observational studies have raised safety concerns with the use of atypical and conventional antipsychotics. Individual agents or classes of antipsychotics may carry an increased risk of cardiovascular or cerebrovascular mortality, pituitary tumors (including prolactinoma), adverse metabolic effects (e.g., effects on lipids and blood glucose, as well as weight gain or diabetes), extrapyramidal tardive dyskinesia, and other safety issues. Research on at least one these safety risks covering all populations and age groups is required. The potential association of antipsychotics and pituitary tumors (including prolactinoma) must be addressed at a minimum.

Topic Area 2: Safety Risks of Biologic Immune Modulators

Treatment of autoimmune diseases such as rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, psoriasis, Crohn’s disease, and others often involves agents which interfere with immune function. Some products, such as TNF- alpha blockers and other biological Disease-Modifying Anti-Rheumatic Drugs (DMARDs), may pose risks of serious infections (including sepsis, pneumonia, tuberculosis or other opportunistic infections), infusion site reactions, pulmonary fibrosis, liver injury, malignancies (including T-cell and B-cell lymphomas), acute renal failure, fractures (hip and vertebral), congenital anomalies, and death. A systematic observational study, or studies, addressing a variety of populations may permit delineation of risks across patients, indications, and products themselves. Because it is likely that no single data resource could address all patient populations or outcomes of interest, proposals involving collaborative relationships to allow access to multiple databases and new data via linkages or prospective data collection are encouraged. In addition, the patient populations of interest include but are not necessarily limited to children, pregnant women, and the elderly. All indications for TNF-alpha blocker use, as well as for other biological DMARD therapy as is possible, are of interest. The ability to examine drug-specific risks is also a key feature of all desired studies. Clarification of clinical and genetic factors that can be used to predict and prevent drug adverse outcomes of DMARDs may be a focus of the study.

Findings from such a study would allow tailoring of therapeutic choices in terms of underlying risks and assist patient and provider choices by improving the understanding of different risks when initiating immune modulator therapy.

Topic Area 3: Methods Work in Safety Outcomes and Confounders

This topic area seeks research to address two related methodological issues in safety assessment: the definition and validation of adverse safety outcomes in different data systems, and the elucidation of key unmeasured confounders that may be associated with adverse outcomes. Applications to this topic area must address both issues which are described more fully below.

Relative to adverse safety outcomes definition and validation, FDA’s post-marketing safety surveillance of drug products pays particular attention to a subset of adverse medical events that are frequently described in association with medications. Examples include events such a Stevens Johnson Syndrome, ventricular arrhythmias, liver injury or failure, and acute renal failure. To help investigate these and other so-called designated medical events (listed in the following paragraph) rapidly, efficiently, and reliably in a variety of observational data systems, safety analyses need to have case definitions and validated identification mechanisms for varying populations and data sources. These may include administrative claims (using billing codes), encounter data, or electronic medical records. Having such sensitive, specific, and validated outcome definitions and coding algorithms for different data systems can improve the quality, speed, and cost of analyses by eliminating or lowering the need for additional medical record validation. To facilitate dissemination, use, and ongoing validation and improvement, all work products developed under this topic area will be placed in a common public and accessible database, such as the one being established by the Eisenberg Center of the Effective Healthcare Program. Such sharing will allow multiple investigators to use and expand the validation information as other data resources become available. For example, combination of ICD-9 codes with laboratory values might have very high sensitivity and specificity for a variety of conditions such as renal or liver failure.

Designated Medical Events (DME) include the following: 1) Congenital anomalies, 2) Acute respiratory failure, 3) Ventricular fibrillation, 4) Torsades de pointe, 5) Malignant hypertension, 6) Seizure, 7) Agranulocytosis, 8) Aplastic anemia, 9) Toxic epidermal necrolysis, 10) Liver necrosis, 11) Acute liver failure,

12) Anaphylaxis, 13) Acute renal failure, 14) Sclerosing syndromes, 15) Pulmonary hypertension, 16) Pulmonary fibrosis, 17) Confirmed or suspected transmission of an infectious agent by a marketed drug or biological product, and

18) Confirmed or suspected endotoxin shock. (Note: Listing of DMEs is adapted from "Safety Reporting Requirements for Human Drug and Biological Products; Proposed Rule" at http://www.fda.gov/OHRMS/DOCKETS/98fr/03-5204.pdf)

To address outcome definition and identification in different data systems, applications must propose how they will systematically survey the medical literature and key researchers with experience in observational studies and health-care based administrative and other data resources to develop a repository of currently validated outcomes. This repository would include published and unpublished identification algorithms for the designated medical events described above, along with all information known about their validity (e.g., sensitivity, specificity, positive predictive value) for identifying validated patient outcomes. Responsive definitions and algorithms must address multiple data systems that vary in terms of the data they capture, including but not limited to administrative claims, electronic medical records (EMRs), data systems capturing laboratory, radiologic, or diagnostic information, and procedural centers such as ambulatory surgery, infusion, or dialysis centers. The results of this effort will be placed in a common public database for reference by study investigators, study sponsors and regulatory reviewers.

A related topic to outcomes definition and validation is the methodological analysis of unmeasured confounders in comparing medications within a therapeutic class. Many observational studies do not capture information on factors that may influence patient outcomes on therapy. Such factors may include underlying disease severity, smoking status, alcohol intake, BMI, exercise, over-the-counter drug use, or multiple other lifestyle factors. When one or more products in a therapeutic class appear to have a distinctively better or worse adverse event profile relative to other agents, one question that arises is whether this may be due to differences in one or more unmeasured confounders across the drug class. For example, there may be differences in the apparent risk of thrombotic and thromboembolic phenomena across prescription contraceptives. In addition, there may be differences in risk for myocardial infarction across anti-diabetic drugs. Population-based observational research involving ancillary data from electronic medical records, patient surveys, or other reliable data sources to capture unmeasured confounders may inform the extent to which unmeasured factors account for the differences observed between medications within a class.

To address unmeasured confounders as part of applications to this topic area, applications must address how they will assess unmeasured factors from two specific patient populations. The first population of interest is women of all ages identified as using various hormonal contraceptives (particularly those products most recently approved). In addition to the lifestyle factors listed above, additional desired information would address which specific product is used (e.g., patch or pill, product lot numbers if available), the timing of product use (e.g. intermittent or continuous), and environmental factors that may influence systemic absorption (e.g. exercise, exposure to water and/or external sources of heat such as heating pads, tanning beds, etc.) The second population of interest is men and women with type 2 diabetes who are treated with various oral anti-diabetic medications. Applications addressing unmeasured confounders in contraceptives and oral anti-diabetic ages must consider including the newer drugs in prevalent use within each class, as well as a broad representation of drug classes currently used.

Topic Area 4: Characterization of Key National Drug Use Scenarios

Two critical areas where drug use patterns are poorly ascertained are in the use of pediatric inpatient drugs and Over-the-Counter (OTC) products. Filling these data gaps requires the use of novel data sources and/or prospective data collection as described below. To be responsive, applications to this topic area must address both areas.

To encourage drug research and development in the area of therapeutics use in pediatric populations, FDA and NIH have worked together under the auspices of the Best Pharmaceuticals for Children Act (BPCA) to set research priorities based upon improved understanding of how drugs are currently used to treat children across different settings of care. Although overall understanding of pediatric use of outpatient drugs has improved, it has been particularly challenging to understand the nature of pediatric drugs used in the inpatient setting. Within this topic area, applicants must propose a research study to identify and characterize in as representative fashion as is possible the universe of pediatric inpatient care in the U.S., as well as the subset of data systems available which capture drug use in this setting. These characteristics include but are not limited to patient characteristics, geography, disease mix, facility types (such as distinctions between use in pediatric hospitals and use in pediatric beds located in general hospitals) and other factors that might influence prescribing in the inpatient setting. The results of this effort can then be used to develop strategies for making scientifically valid projections of national patterns of pediatric drug use in inpatient settings, using available data. Such data can assist in priority setting for research to be conducted under the BPCA.

Although many over-the-counter (OTC) drugs are considered to be generally safe and effective for use by patients without the intervention of a learned intermediary, some OTC drug products, such as acetaminophen (APAP), can cause serious injury due to intentional or inadvertent overdosing. FDA has received case reports of serious liver injury and acute liver failure apparently due to accidental overdosing of single ingredient APAP in addition to combination APAP products. Over a 6-year study period, acetaminophen-induced acute liver failure (ALF) accounted for 46% of drug-related ALF cases reported to 22 transplant centers. Traditional drug use data sources do not capture OTC drug use other than bulk purchases, and so cannot capture even surrogates of individual patient use.

Applications addressing this topic area must seek new data sources (such as electronic medical records or patient surveys) to characterize patient use, misuse and dosing of APAP across a broad range of patient ages (including children), populations, and disease conditions. Capture of dosing with different formulations may require collection of data directly from patients in the form of surveys or other queries. Patient and consumer studies that have shown that many patients do not understand how to use acetaminophen safely or do not understand that liver injury can occur when used incorrectly; patient-level data are desirable to capture use in a variety of situations. For example, in children, it is likely to be important to capture the source of information for the user (doctor or product instructions), accuracy of dosing, ability of parents to dose by weight versus age, ability to measure dose using teaspoons (tsp.) versus milliliters (mL.) and manner of parental administration of APAP for children of various ages. In addition, it would also be helpful to examine consumers understanding of the relative safety or risks of APAP, the source of their information, and how healthcare providers instruct patients about concomitant OTC pain medicine use when prescribing narcotic/acetaminophen treatments. Previous data of this type have focused on emergency departments and clinic populations and generally have been small (100-500), so a larger and more representative assessment of use patterns is sought.

It is also important to understand the circumstances that lead to unintentional overdose and the factors that influence the severity of liver injury from patient-level data. In cases of intentional overdose to commit suicide or as a suicide gesture, it would be helpful to accurately quantify the number of cases involving acetaminophen and the percentage that develop with liver injury. In the cases of inadvertent overdose, it would be helpful to characterize the circumstances surrounding the overdose, such as lack of pain relief at labeled doses or misunderstanding of package labeling, and whether these factors differed by whether the APAP product was a prescription or OTC product.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism of Support

This Funding Opportunity Announcement (FOA) will use the Research Demonstration Cooperative Agreement (U18) award mechanism.  The individual researcher sponsored by each organizational grantee will be solely responsible for planning, directing, and executing his or her proposed projects.

AHRQ is not using the Modular Grant Application and Award Process. Applications submitted in modular format will be returned without review.

This funding opportunity will use an AHRQ cooperative agreement award mechanism. In the cooperative agreement mechanism, the PD/PI retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with AHRQ staff being substantially involved as a partner with the PD/PI, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

2. Funds Available

AHRQ plans to award a total amount of $7 million to the four targeted topic areas where research is solicited. One award is anticipated for each topic area, however awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications. The nature and scope of the proposed research are anticipated to vary among the 4 topic areas; for each of the first two topic areas (dealing with antipsychotics and TNF blockers) awards of approximately $2.5 million in total costs are anticipated. Topic areas 3 (methods) and 4 (drug use estimation) are each anticipated for funding at approximately $1 million in total costs. Although the financial plans of AHRQ provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications. Should additional funds become available, AHRQ may fund additional meritorious applications. Facilities and administrative (F&A) costs requested by applicants are included in the total cost limitation.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may only submit an application if your institution is currently receiving funding under RFA-HS-05-014, RFA-HS-07-004, or RFA-HS-07-008.

Under this FOA, each application must represent a collaboration of at least two, but no more than four, CERTs Centers. Each CERTs Center may participate in a total of two applications, of which only one may be as the applicant. Acceptable combinations include submission of one application and participation in another application as a collaborator, or participation in two applications as a collaborating partner. Non-CERT parties may participate only under restricted circumstances as described in Section III.3. Other- Special Eligibility Criteria.

You may submit an application if your institution/organization has any of the following characteristics:

AHRQ’s authorizing legislation does not allow for-profit organizations to be eligible to lead applications under this research mechanism, thus for the purpose of this FOA, AHRQ will make grants only to non-profit organizations.  For-profit organizations may participate in projects as members of consortia or as subcontractors only. Because the purpose of this program is to improve healthcare in the U.S., foreign institutions may participate in projects as members of consortia or as subcontractors only.  Applications submitted by for-profit organizations and foreign institutions will be returned without review.  Organizations described in section 501(c) 4 of the Internal Revenue Code that engage in lobbying are not eligible.

1.B. Eligible Individuals

Because this FOA builds on previous work, infrastructure, and working relationships, the PIs previously awarded funding under RFA-HS-05-014, RFA-HS-07-004, or RFA-HS-07-008 must work with their applicant organizations in submitting any application for support. If it is more appropriate for another individual to serve as PI, it must be clearly stated and the application must include a specific rationale explaining the reasons why a different PI is needed and how continuity of CERTs Program Operating Principles will be assured for research done under the FOA. Any proposed PI must be an experienced senior level individual experienced in working with the CERTs Program and AHRQ.  The PI must spend a minimum of 15% time on the proposed collaborative research topic area; this time commitment is considered distinct from existing PI time commitments obligated as part of their CERTs Center leadership.

In addition to the lead Center PI, a co-investigator from the same center must be designated and function as the deputy director and must devote no less than 25% effort in assisting in overall collaboration oversight and technical performance of the proposed research. As such, the deputy director must be a senior scientific investigator with relevant expertise to the proposed research.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her organization 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 AHRQ support.

2. Cost Sharing or Matching

This program does not require cost sharing for applications in response to this FOA.

While there is no cost sharing requirement included in this FOA, AHRQ welcomes applicant institutions, including any collaborating institutions, to devote resources to this effort. An indication of institutional support from the applicant and its collaborators indicates a greater potential of success and sustainability of the project. Examples of institutional support would include: donated equipment and space, institutional funded staff time and effort, or other resource investments. Applicant institutions must indicate institutional support by outlining the specific contributions to the project and providing assurances that their organization and any collaborators are committed to providing these funds and resources to the project.

3. Other-Special Eligibility Criteria

Definition and Requirements of Collaborations Under This Limited Competition: Collaborations of 2 to 4 CERTs centers are required for each topic application. One non-CERT collaborating institution may be proposed if it meets the conditions described below. Thus the maximum number of collaborating institutions (CERTs and non-CERT) that will be accepted is 5.

Applicants are not permitted to submit a resubmission application in response to this FOA.

Renewal applications are not permitted in response to this FOA

Section IV. Application and Submission Information

To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, use the Apply for Grant Electronically button in this FOA or link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

PDs/PIs should work with their institutions/organizations to make sure they are registered in the NIH eRA Commons.

Several additional separate actions are required before an applicant can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Registered

2) Organizational/Institutional Registration in the eRA Commons

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

Both the PD/PI and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note that if a PD/PI is also an AHRQ peer reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. AHRQ will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo -- Telephone 301-710-0267; Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to AHRQ. Some fields within the SF424 (R&R) application components, although not marked as mandatory, are required by AHRQ (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

The SF424 (R&R) application has several components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable components, required and optional. A completed application in response to this FOA includes the data in the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
Research & Related Budget (See Section IV.6., Special Instructions, regarding appropriate required budget component.)

Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

SPECIAL INSTRUCTIONS

Applications Involving Multiple Institutions 

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution must submit its budget using the Research & Related Budget component.  All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form.  See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form. 

Applications Involving Multiple Projects

The current SF424 R&R and the electronic grant application submission process do not support multiple-project budgets. If an application is structured to include multiple projects it will be necessary for the applicant to implement the following work-around to present a multiple-project budget for peer review.

Applicants are to create a spreadsheet which includes a detailed composite (overall) budget as well as separate detailed budgets for each individual project.  These budgets must use the SF424 R&R budget categories.  Any project that involves a consortium must also include a detailed budget for the consortium organization.  Each budget in the spreadsheet should be clearly labeled to indicate what it represents (e.g., Composite, Project 1 Parent organization,   Project 1 Consortium Organization A, Project 2 Organization B, etc.).  Future years must also be included.  The spreadsheet must be converted to a PDF file and be submitted as part of the budget justification section of the application (the budget justification section does not have a page limit).  Dollar figures from the composite portion of the spreadsheet must be entered into the SF424 R&R budget form that is included as a mandatory document of the grant application package.

While AHRQ will not dictate the exact format of the spreadsheet, one possible way of displaying the budget information in a consolidated way for each project and/or consortium component is to show the budget categories in rows (with individual personnel listed under the personnel category) and budget periods in columns.  A good written budget justification will be critical for explaining any fluctuations in budget categories (e.g. personnel effort levels) in future years.  If a consortium organization will participate on more than one project, a separate consortium budget page will need to be included with each project in which the consortium is involved.

3. Submission Dates and Times

See Section IV.3.A. for details.

3.A. Submission, Review, and Anticipated Start Dates
Opening Date: April 19, 2008
Technical Assistance Call: Tuesday, April 1, 2008 11:00 AM 12:30 PM Eastern time. A teleconference line will be provided by email to all CERTs Centers eligible to apply to this FOA.
Letters of Intent Receipt Date(s): April 10, 2008
Application Due Date(s): May 19, 2008
Peer Review Date(s): Approximately 1 2 months after receipt date
Earliest Anticipated Start Date(s): September, 2008

3.A.1. Letter of Intent

To allow AHRQ staff to estimate the potential peer review workload and plan the review (e.g., anticipate the nature of reviewer expertise to be required), prospective applicants may submit a letter of intent that includes an acknowledgement of interest in this funding opportunity (please refer to the number and title of this funding opportunity), a few comments on the subject of the proposed research, background expertise of key personnel, and the nature and role of participating institutions.  Please include the name and email address of the Principal Investigator.

This letter of intent is not required, is not binding, and is not considered in the review of a subsequent application.  However, these letters are administratively very helpful, as indicated above. To be most useful, the letter of intent is to be sent by the date listed above and at the beginning of this document.

The letter of intent can be sent electronically, and should be sent to:

Amy Lindinha
Center for Outcomes and Evidence
Agency for Healthcare Research and Quality
540 Gaither Road
Rockville, MD 20850
Telephone: (301) 427-1614
FAX: (301) 427-1520
Email: certsfoa@ahrq.hhs.gov

The letter of intent is to be sent by the date listed in Section IV.3.A. You will receive confirmation once the letter is received.

3.A.2. Technical Assistance

AHRQ encourages applicants to take advantage of a technical assistance conference call sponsored by AHRQ program staff. The purpose of the conference call is to provide potential applicants with background information and respond to questions about the preparation of an application in response to this FOA. The conference call will take place on April 1, 2008 at 11:00 am EDT. To register to participate in the conference call, please send an e-mail request to certsfoa@ahrq.hhs.gov) by March 28, 2008. All registrants will be sent an e-mail reply which will contain information on the call, including call-in information, by COB March 31, 2008. Potential applicants are encouraged to contact AHRQ staff with any questions (see Section VII, Agency Contacts, below).

The conference call is open to any individual or organization intending to apply. Participation is not a prerequisite to applying. Participants are encouraged to submit questions via email prior to the conference call. Please submit up to five questions with your name and the name of your institution to certsfoa@ahrq.hhs.gov by March 28, 2008. Questions of a similar topic and nature may be grouped at the sole discretion of AHRQ staff. Notes from the conference call will be posted on the AHRQ web site.

3.B. Submitting an Application Electronically to AHRQ

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp and follow Steps 1-4. Note:  Applications must only be submitted electronically.  PAPER APPLICATIONS WILL NOT BE ACCEPTED. 

In order to expedite the review, applicants are requested to notify the AHRQ Referral Office by email Gerald.Calderone@ahrq.hhs.gov when the application has been submitted.  Please include the FOA number and title, PD/PI name, and title of the application.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday Friday, excluding Federal holidays) to view the application image to determine if any further action is necessary.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH, and AHRQ. Incomplete or non-responsive applications will be returned without review.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR/SO receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific Review Group is also in the Commons. 

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on the application status in the Commons.

AHRQ will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial merit review, unless the applicant withdraws the pending application.

Institutional Review Board (IRB) approval of human subjects is not required prior to peer review of an application (see http://grants.nih.gov/grants/guide/notice-files/NOT-HS-00-003.html). However, initiation of IRB review, if necessary or applicable, is strongly encouraged to assure timely commencement of research.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

Use of CMS Data

Purchase of Centers for Medicare and Medicaid Services (CMS) public-use data, if required, should be discussed in the application narrative and included in the budget. Projects will ordinarily not use CMS (Medicare or Medicaid) data involving individual identifiers. However, for applications that propose to use Medicare or Medicaid data that are individually identifiable, applicants should state explicitly in the Research Design and Methods section of the Research Plan (form 398) the specific files, time periods, and cohorts proposed for the research.  In consultation with CMS, AHRQ will use this information to develop a cost estimate for obtaining the data. This estimate will be included in the estimated total cost of the grant at the time funding decisions are made.

Applicants should be aware that for individually identifiable Medicare and Medicaid data, Principal Investigators and their grantee institutions will be required to enter into a Data Use Agreement (DUA) with CMS to protect the confidentiality of data in accordance with the confidentiality provision in the AHRQ statute, 42 USC 299c-3(c); the Privacy rules at 45 CFR Parts 160 and 164, if applicable; and standards set out in OMB Circular A-130, Appendix III Security of Federal Automated Information Systems. The use of the data will be restricted to the purposes and time period specified in the DUA. At the end of this time period, the grantee will be required to return the data to CMS or certify that the data have been destroyed.

Unless AHRQ is able to negotiate exceptional arrangements, the DUA will include the requirement that the data user agrees to submit to CMS, a copy of all findings within 30 days of making such findings, for the sole purpose of assuring CMS that data confidentiality is maintained. The user further agrees not to submit these findings to any third party (including but not limited to any manuscript to be submitted for publication) until receiving CMS's approval to do so.

In developing research plans, applicants should allow time for refining, obtaining approval, and processing of their CMS data requests. Requests may take six months from the time they are submitted to complete. Applications proposing to contact beneficiaries or their providers require the approval of the CMS Director and may require meeting(s) with CMS staff.

CMS data are provided on IBM mainframe tapes using the record and data formats commonly employed on these computers. Applicants should either have the capability to process these tapes and formats or plan to make arrangements to securely convert them to other media and formats.

Questions regarding CMS data should be directed to the AHRQ program official listed under Agency Contacts (see Section VII).

To avoid double counting, applicants should not include the cost of the CMS data in the budget.  In the event the total costs of the project plus the cost of CMS data is greater than the total cost cap of this FOA, the budget for the project will be adjusted so that the total costs awarded to the recipient plus the CMS data costs do not exceed the cost cap. 

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

For efficient grant administration, AHRQ grant administration procedures will be used and conducted in accordance with the terms and conditions, cost principles, and other considerations described in the HHS Grants Policy Statement. The Grants Policy Statement can be found at http://www.ahrq.gov/fund/hhspolicy.htm

Pre-award costs are allowable. A grantee may, at its own risk and without AHRQ prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs are necessary to conduct the project and would be allowable under the grant, if awarded, without AHRQ prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain AHRQ approval before incurring the cost. AHRQ prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on AHRQ either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. AHRQ expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project.

6. Other Submission Requirements and Information

Applicant or Lead CERTs Center and PI Requirements: The CERT Center that submits an application representing a collaborative consortium must, as the lead CERT Center, assume overall coordination, governance, and management of the proposed research project(s). The applicant or lead Center is the only CERT Center to which an award will be made, and will be the only Center that AHRQ will communicate with and hold responsible for overall performance and completion of the proposed research.

Application Requirements: Each collaboration must address only one of the candidate topic areas in a clearly marked, single application submitted by the Lead Center; separate applications from members of a collaboration will not be accepted.

As part of each application, applicants must provide a rationale for their proposed approach to the candidate study topic, address the administrative and scientific management approaches for the proposed study or studies across the participating CERTs centers, and anticipate methodologic and translational issues in the analysis and presentation of benefits and harms of different therapies that have been assessed using observational designs. Applicants must also address how they will accommodate substantial government involvement into their proposed research.

Some research topics may build upon other funded research efforts on-going within the CERTs or AHRQ’s Effective Healthcare Program. Applicants must specifically indicate where related work is ongoing through AHRQ or other governmental funding to assure that duplication of effort or resources does not occur.

Rationale for the Approach and Proposed Collaboration to address the Topic Area: As part of any submitted application to design and conduct a study of the comparative effectiveness or solely the harms of one or more therapeutic options, applicants must provide a clear rationale that describes how the proposed approach and individual Centers in the collaboration support the scientific quality, timeliness, and impact of the proposed research project(s) for assessing the comparative effectiveness (including harms) of therapeutic options in each of the specified topic areas. Where applicable, applicants should note any provisions for examining under-studied or underserved populations, including populations served by the Medicare, Medicaid, and S-CHIP programs. Applicants must note any leveraging, synergies, or complementarities to previous, ongoing, or anticipated work funded through the CERTs or Effective Health Care programs and describe how the proposed study will contribute significant information at the margin to aid decision-making by various stakeholder groups, including but not limited to health care providers, patients, payers of health care, and drug safety regulators. Examples would include the addition of new data resources to increase the power and breadth of outcomes assessment.

Coordination and Management Plan: As part of their application, applicants must address how the collaborative effort will be coordinated by the lead CERTs Center for the research project, specifically addressing how the multiple involved institutions will contribute, communicate, and collaborate with each other productively and efficiently. Applicants must also describe how the proposed research and related activities will be integrated, if applicable, with ongoing CERTs research projects or coordinating activities of the CERTs Coordinating Center. At a minimum, applications must address how the CERTs Coordinating Center will be informed and/or involved in the proposed work. In addition, applicants must include a plan and resources to conduct an evaluation and report on the strengths, limitations, lessons learned, and best practices of the multicenter collaborative effort so as to inform the feasibility,cost, quality, and efficiency of future multicenter studies of this type. Items that may be addressed include, but are not limited to, study team assembly, conflicts of interest, protocol development, IRB and HIPAA issues, data linkage, governance, OMB review and clearance requirements if applicable, and other processes.

Methodology: The application must address methodological issues of statistical power, validity, reliability, and potential bias in the study design, data resources, data collection, and outcomes assessment measures proposed for use. With respect to comparative effectiveness, applications should address methodologic and validity issues of absolute and/or comparative benefits assessment using observational rather than randomized research designs.

Translation: Applicants must formulate and include in their applications their plans for an explicit and transparent translational research write-up that may take the form of a final report or publication that systematically discusses all studied outcome measures, whether they be harms, benefits, or both. Any final report must address the research findings in the context of clinical decision-making and consider differential outcomes associated with short-term use, long-term use, or use in subpopulations, etc. This document will describe the rationale, assumptions, and judgments in weighing the study findings in light of other available data sources such as RCTs and systematic evidence reviews that address benefits and harms. This research report should be capable of further dissemination or translation by the CERTs Partners in Therapeutics, the CERTs Educational Consortium, and/or the John M. Eisenberg Clinical Decisions and Communications Science Center of the Effective Healthcare (EHC) Program.

Substantial Government Involvement to assure Responsiveness to Federal needs and stakeholder input regarding safety and comparative effectiveness work products: The EHC program is a multi-component research and education program that is user-driven by broad public input, a Stakeholder group, a Scientific Resource Center (that informs topic relevance and feasibility and facilitates input from clinical and scientific experts), and AHRQ staff (who interact with CMS, state Medicaid agencies, FDA, and other governmental partners). The program develops actionable information for providers, payers, and patients to make evidence-based choices among competing therapeutic interventions. AHRQ staff, working in close collaboration with FDA and other governmental partners, are uniquely positioned to provide valuable input from the perspective of multiple stakeholders for the work undertaken under this limited competition. AHRQ and FDA may also be aware of pending or ongoing research and educational activities of relevance that are ongoing within various Federally-funded components.

It is anticipated for awards under this limited competition FOA that substantial government involvement will occur. Responsive applications must address how they will accommodate substantial government involvement into their planned management, coordination, and conduct of their research project(s) so as to achieve efficient, timely and high quality products for multiple users in a transparent and scientifically defensible fashion.

Research Requirements

Grantees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information".

PD/PI Credential (e.g., Agency Login)

AHRQ requires the PD/PI to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

PHS398 Research Plan Component Sections

Page limitations of the PHS398 Research Plan component must be followed as outlined in the SF424 (R&R) Application Guide. While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to AHRQ in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.   

All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporating Just-in-Time information concepts, and with the following additional requirements:

Warning: Please be sure that you observe the direct cost, project period, and page number limitations specified above for this FOA. Application processing may be delayed or the application may be rejected if it does not comply with these requirements.

Special Instructions for Modular Grant applications

AHRQ is not using the Modular Grant Application and Award Process.   Applicants for funding from AHRQ should ignore application instructions concerning the Modular Grant Application and Award Process, and prepare applications using instructions for the Research and Related Budget Components of the SF 424 (R&R).  Applications submitted in the Modular format will be returned without review.

Appendix Materials

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not comply with the required page limitations may be delayed in the review process.

Priority Populations

The Healthcare Research and Quality Act of 1999, in amending the PHS Act, directed AHRQ, in carrying out its mission, to conduct and support research and evaluations, and to support demonstration projects, with respect to the delivery of health care in inner-city and rural areas (including frontier areas), and health care for priority populations. Priority populations include low income groups; minority groups; women; children; the elderly; and individuals with special health care needs, including individuals with disabilities and individuals who need chronic care or end-of-life health care.  This authority is found at 42 USC 299(c).  To implement this statutory mandate, AHRQ published a Notice in the NIH Guide on February 28, 2003, establishing a new Agency policy on the Inclusion of Priority Populations in health services research (see http://grants.nih.gov/grants/guide/notice-files/NOT-HS-03-010.html).  Applicants under this FOA should consider and discuss including priority populations in the research design as specified in this Notice.

Publication Transmittal: General AHRQ Requirements

In keeping with the Agency's efforts to translate the results of AHRQ-funded research into practice and policy, grantees are to inform the AHRQ Office of Communications and Knowledge Transfer (OCKT) when articles from their AHRQ-supported activities are accepted for publication in the professional literature.  Grantees should also discuss any ideas about other dissemination and marketing efforts with OCKT staff.  The goal is to ensure that efforts to disseminate research findings are coordinated with other Agency activities to maximize awareness and application of the research by potential users, including clinicians, patients, health care systems and purchasers and policymakers.  This is critical when outreach to the general and trade press is involved.  Accordingly, contact with the media will take place with close coordination between OCKT and the press offices of the grantee's institutions.  In cases when products are created (such as annual or final reports, Web-based tools, CD-ROMs), grantees will be asked to submit to OCKT a brief plan describing how the product will be publicized.  An OCKT staff person will be assigned to each product and will coordinate the implementation of the plan, especially issues related to printing and electronic dissemination, and outreach to the media.

Assessment of AHRQ Grant Programs

In carrying out its stewardship of research programs, AHRQ may request information essential to an assessment of the effectiveness of Agency research programs.  Accordingly, grant recipients are hereby notified that they may be contacted after the completion of awards for periodic updates on publications resulting from AHRQ grant awards, and other information helpful in evaluating the impact of AHRQ-sponsored research.

AHRQ expects grant recipients to keep the Agency informed of publications, as well as the known uses and impact of their Agency-sponsored research. Applicants must agree to notify AHRQ immediately when a manuscript based on research supported by the grant is accepted for publication, and to provide the expected date of publication as soon as it is known, regardless of whether or not the grant award is still active.

HCUP and MEPS

Applicants are encouraged to make use of AHRQ’s Healthcare Cost and Utilization Project (HCUP) or the Medical Expenditure Panel Survey (MEPS).  HCUP is a family of health care databases and related software tools and products developed through a Federal-State-Industry partnership.  HCUP databases bring together the data collection efforts of State data organizations, hospital associations, private data organizations, and the Federal government to create a national information resource of patient-level health care data.  HCUP databases provide data beginning in 1988 and contain encounter-level information for all payers compiled in a uniform format with privacy protections in place.  HCUP include two nationwide databases, the Nationwide Inpatient Sample (NIS) and the Kids Inpatient Database (KID), and three types of State databases, the State Inpatient Databases (SID), the State Ambulatory Surgery Databases (SASD), and the State Emergency Department Databases (SEDD).  More information on HCUP can be found at http://www.hcup-us.ahrq.gov/home.jsp.

The MEPS is conducted to provide nationally representative estimates of health care use, expenditures, sources of payment, and insurance coverage for the U.S. civilian, non-institutionalized population.  MEPS is composed of three component surveys: the Household Component (HC), the Medical Provider Component (MPC), and the Insurance Component (IC).  The Household Component is the core survey, and it forms the basis for the MPC sample and part of the IC sample.  The MEPS IC collects data on health insurance plans obtained through employers and unions, including the number and types of private insurance plans offered, employer characteristics, premiums, and contributions by employers and employees.  More information on the MEPS is available at http://www.meps.ahrq.gov.

Applicants use of HCUP and/or MEPS data does not preclude the use of secondary data sources or primary data collection.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigators are planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing; the format of the final dataset; the documentation to be provided; whether or not any analytic tools also will be provided; whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use); and the mode of data sharing (e.g., under its own auspices by mailing a disk or posting data on its institutional or personal website or through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the 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 the priority score.

Section V. Application Review Information

1. Criteria 

Administrative Criteria: Upon receipt, applications will be reviewed by AHRQ for completeness and responsiveness. Applications will also be reviewed to determine whether any Center has participated in more than two applications.

Merit Review Criteria are described below.  The review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened in accordance with standard AHRQ peer review procedures that are described in 42 CFR Part 67, Subpart A.  Incomplete and/or non-responsive applications or applications not following instructions given in this FOA will be returned to the applicant without further consideration. 

As part of the initial merit review, all applications will:

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications to the same targeted topic research area. The following will be considered in making funding decisions:

In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application.

Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a meritorious 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.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the proposed research reflect key evidence needs of multiple users such as patients, clinicians, payers for health care, and Federal regulators? Is the rationale for the proposed research adequate?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well-integrated, well-reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?  Are the management plans, consortium framework, and governance structure configured to be efficient and timely in conducting and completing the proposed work? If applicable, are there appropriate plans and resources for handling OMB review and clearance? Is the methodologic approach appropriate and adequate? Are translational needs adequately addressed? Are the plans to accommodate substantial government involvement appropriate to achieve good communication, participation, and efficiency and to minimize wasteful duplication of efforts?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches or methodologies, tools, or technologies for this area?

Investigators: Is the PD/PI and other key personnel appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level(s) of the principal investigator(s) and other researchers? Does the PD/PI and investigative team bring complementary and integrated expertise to the project (if applicable)? Do the PI and designated deputy director have the necessary expertise, experience, and infrastructure to manage the coordination and governance of the proposed collaborative consortium productively? Does the application reflect the minimum time requirements for the PI and designated deputy director?

Environment: Do(es) the scientific environment(s) in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment(s), or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?  Does the proposed research collaborative (lead and/or collaborating Centers) possess any already-existing or unique environments to facilitate the proposed collaborations?

2.A. Additional Review Criteria

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

Degree of responsiveness:  How well does the application address the purpose and objectives of this FOA?  How responsive is the application to the special eligibility criteria articulated in Section IV.6, including the project requirements, noted in the FOA? Does the application conform to the submission limits, that is, participation of a CERTs Center in no more than 2 applications?

Budget: Is the proposed budget reasonable and is the requested period of support appropriate in relation to the proposed research? Are the overall and component aspects of the collaborative consortium budget reasonable?

Inclusion: Adequacy of plans to address the needs of both genders, racial and ethnic minorities (and subgroups).  Adequacy of attention to AHRQ priority populations (see above discussion on Priority Populations in section IV.6 Other Submission Requirements, and inclusion criteria included in section VIII of Required Federal Citations, below.)

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 the Human Subjects Sections of the PHS398 Research Plan component of the SF424 (R&R).

Privacy and Security Protections for Patients:  The resources and processes to be used to address privacy and security issues in the development and implementation of the research or intervention will be assessed.

Conflicts of Interest: All proposed non-governmental partnerships will be assessed for conflicts of interest in the study design, performance, or reporting of results, including conformance with the principles set forth in the CERTs Principles for Public-private Partnerships, available at http://www.certs.hhs.gov/partners/principles.html.

2.B. Additional Review Considerations

Not applicable.

2.C. Resource Sharing Plan(s)

Data Confidentiality

Pursuant to 42 USC 299c-3(c), information obtained in the course of any AHRQ supported-study that identifies an individual or entity must be treated as confidential in accordance with any explicit or implicit promises made regarding the possible uses and disclosures of such data.  There are now civil monetary penalties for violation of the confidentiality provision of the AHRQ statute 42 USC 299c-3(d).  In the Human Subjects section of the application, applicants must describe procedures for ensuring the confidentiality of the identifying information to be collected.  The description of the procedures should include a discussion of who will be permitted access to this information, both raw data and machine readable files, and how personal identifiers and other identifying or identifiable data will be restricted and safeguarded.  Identifiable patient health information collected by grantees under this FOA will also be obtained and managed in accordance with 45 CFR Parts 160 and 164, the Federal Privacy Rule developed by the Department of Health and Human Services (DHHS) pursuant to the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  These regulations serve to limit the disclosure of personally identifiable patient information by covered entities and define when and how such information can be disclosed e.g., to researchers.  Thus, health care plans ordinarily will require either patient authorization for disclosures of identifiable information to be made to researchers or waivers of such authorizations obtained from an IRB or Privacy Board (defined in the regulations), which will involve review to ensure that identifiable health information will be appropriately safeguarded by the investigators.  The DHHS Office of Civil Rights is the enforcement body for this regulation. Additional information about the regulations, their implementation, and alternative methods of permissible disclosures to researchers (limited data sets with data use agreements, de-identified data sets, data about deceased persons, and data use to develop protocols) can be obtained from: http://www.hhs.gov/ocr/hipaa/

The grantee must ensure that computer systems containing confidential data have a level and scope of security that equals or exceeds that established by the HIPAA Security Rules if applicable (see HIPAA websites in prior paragraph) and that established by the Office of Management and Budget (OMB) in OMB Circular No. A-130, Appendix III - Security of Federal Automated Information Systems. The National Institute of Standards and Technology (NIST) has published several implementation guides for this circular. They are: An Introduction to Computer Security: The NIST Handbook; Generally Accepted Principals and Practices for Securing Information Technology Systems; and Guide for Developing Security Plans for Information Technology Systems. The circular and guides are available on the web at http://csrc.nist.gov/publications/nistpubs/800-12/. The applicability and intended means of applying these confidentiality and security standards to subcontractors and vendors, if any, must be addressed in the application.

Sharing Research Resources

Rights in Data

AHRQ grantees may copyright, unless otherwise provided in grant awards, or seek patents for, as appropriate, final and interim products and materials developed in whole or in part with AHRQ funds, including, but not limited to, methodological tools, measures, software with documentation, literature searches, and analyses. Such copyrights and patents are subject to a worldwide irrevocable AHRQ license to use and permit others to use these products and materials for government purposes.  In accordance with its legislative dissemination mandate, AHRQ purposes may include, subject to statutory confidentiality protections, making project materials, databases, results, and algorithms available for verification or replication by other researchers. In addition, subject to AHRQ budget constraints, final products may be made available to the health care community and the public by AHRQ or its agents if such distribution would significantly increase access to a product and thereby produce substantial or valuable public health benefits.  Ordinarily, to accomplish distribution, AHRQ publicizes research findings but relies on grantees to publish research results in peer-reviewed journals and to market grant-supported products.  AHRQ's Office of Communications and Knowledge Transfer (OCKT) wishes to be consulted in advance of publication in order to coordinate announcements of new AHRQ-supported research results with other AHRQ dissemination activities.  Important legal rights and requirements applicable to AHRQ grantees are set out or referenced in AHRQ's grants regulation at 42 CFR Part 67, Subpart A (available in libraries and from the GPO's website at http://www.gpoaccess.gov/cfr/index.html).

3. Anticipated Announcement and Award Dates

Generally, applicants should anticipate four months between the application submission date and the earliest possible start date for this FOA.

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the NIH eRA Commons. 

If the application is under consideration for funding, AHRQ will request "Just-In-Time" information from the applicant.  Just-In-Time information generally consists of information on other support and certification of IRB approval of the project's proposed use of human subjects.  For details, applicants may refer to the "AHRQ Revised Policy for Institutional Review Board (IRB) Review of Human Subjects Protocols in Grant Applications" (http://grants.nih.gov/grants/guide/notice-files/not-hs-00-003.html). 

A formal notification in the form of a Notice of Award (NOA) will be provided to the applicant organization. Once all administrative and programmatic issues have been resolved, the Notice of Award will be generated via email notification from the awarding component to the grantee business official. The NOA signed by the grants management officer is the authorizing document.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NOA are at the recipient’s risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See also Section IV.5., Funding Restrictions.

2. Administrative and National Policy Requirements

All AHRQ grant and cooperative agreement awards are subject to AHRQ s grants regulations at 42 CFR Part 67, Subpart A, and are subject to the requirements of the HHS Grants Policy Statement that are applicable based on the recipient type and the purpose of this award (see http://www.ahrq.gov/fund/hhspolicy.htm).

Activities conducted under this award that involve the collection of information e.g., conducting surveys or requesting responses to uniform questions from nine or more persons, establishments or other entities, are currently required by HHS to be cleared by OMB under the Paperwork Reduction Act (PRA) (44 USC 3501-3521). Submissions for clearance under PRA are through AHRQ and HHS. Therefore, affected grantees with proposals where the PRA applies must include the effort and time in their proposed timelines to develop materials and receive necessary clearances. It typically takes at least six months from date of initial submission to AHRQ to receive clearances, and sometimes much longer if submissions are incomplete or the justification for the proposed data collection plans are questioned during the clearance process. Information collection that requires PRA clearance may not begin until grantees receive written notification via e-mail from AHRQ that clearance has been obtained. Detailed information on the PRA can be found at http://www.hhs.gov/ocio/policy/collection/. AHRQ will consider reasonable requests from grantees to extend the period of performance or to carryover funding to accommodate unavoidable delays in OMB clearance and processing.

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to otherwise applicable OMB administrative guidelines, DHHS grant administration regulations 45 CFR Parts 74 or 92 (Part 92 is applicable for State and local Governments), and other DHHS, PHS, and AHRQ grant administration policy statements.  AHRQ will use these procedures in evaluating and administering the cooperative agreements under this FOA.

The administrative and funding instrument used for this program will be the cooperative agreement Research Demonstration Mechanism U18, an "assistance" mechanism (rather than an "acquisition mechanism), in which substantial AHRQ programmatic involvement with the grantees is anticipated during the performance of the activities.  Under the cooperative agreement, the AHRQ purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities.  Consistent with this concept, the dominant role and prime responsibility resides with the PD/PI for the project as a whole, although specific tasks and activities may be shared between a grantee and AHRQ as described in this subsection of the FOA. Cooperative activities are intended to strengthen the individual grantee activities through the facilitation of data sharing, data access and communications.

All cooperative activities that include significant government involvement will require prior approval by the AHRQ Program Officer.

2. A.1. Principal Investigator Rights and Responsibilities

The PD/PI of the CERT Center that submits an application representing a collaborative consortium will, as the lead CERT Center, have the primary responsibility for the overall coordination, governance, and management of the proposed research project(s). The applicant or lead Center will communicate with AHRQ and be held responsible for overall performance and completion of the proposed research, including the following items:

Grantees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and AHRQ policies.

2. A.2. AHRQ Responsibilities

AHRQ program staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

The AHRQ PO may participate in component activities of the proposed research to provide scientific and policy input to activities of the study team. Component activities in which the AHRQ PO may participate include, but are not limited to, the following:

2.A.3. Collaborative Responsibilities

The PI of the CERTs Center for the research project will coordinate and manage the collaborative effort and assure that the multiple involved institutions will contribute, communicate, and collaborate with each other productively and efficiently so as to integrate their component efforts. The lead CERTs Center PI is responsible for communication of key information to the CERTs National Steering Committee and, as appropriate, with the CERTs Coordinating Center. The PI will be responsible for assuring conformance with the agreed upon plan to evaluate and report on the strengths, limitations, lessons learned, and best practices of the multicenter collaborative effort in order to inform the feasibility, cost, quality, and efficiency of future multicenter studies of this type. Items that may be addressed include, but are not limited to, study team assembly, conflicts of interest, protocol development, IRB and HIPAA issues, data linkage, governance, OMB review and clearance if applicable, and other processes.

2.A.4. Arbitration Process

Any disagreement that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the AHRQ may be brought to arbitration.  An Arbitration Panel composed of three members will be convened.  It will have three members: a designee of the Steering Committee, one AHRQ designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual grantee.  This special arbitration procedure is not intended to deny the grantee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and DHHS regulations 45 CFR Part 16.

3. Reporting

Grantees funded under this FOA must participate in quarterly meetings of the CERTs Steering Committee and briefly report on research progress. A midpoint progress report must be submitted no later than the halfway point of the project period; for a 12 month project period, this must be no later than 7 months after award, and for an 18 month project period, this must be no later than 10 months after award. At minimum, monthly phone calls discussing progress with the AHRQ Program Official must be held.

The Midpoint Progress Report must include Sections a through f in the general PHS form 2590 instructions, as well as sections g through j as described in Section IV of the 2590 instructions. The Midpoint Progress Report is to include descriptive and evaluative comments on both completed activities and plans for the remainder of the project period, including any changes foreseen in the future.  At a minimum, the report must include descriptive comments on:  progress to date measured against project aims; methodological changes implemented; key preliminary findings; significant problems and resolutions; inclusion of priority populations; and project related publications, presentations, and dissemination activities. 

Financial Status Reports (FSRs; SF 269) are required annually (i.e. every 12 months) by AHRQ for ALL grant programs.  An annual FSR must be submitted no later than 90 days after the close of each 12 month period of funding.  A hard copy of the report must be submitted to the AHRQ FSR Coordinator in AHRQ Grants Management.

A final Progress Report and Financial Status Report are required when an award ends, as required in the HHS Grants Policy Statement (see http://www.ahrq.gov/fund/hhspolicy.htm).

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research (program), peer review, and financial or grants management issues.

1. Scientific/Research Contact(s):

AHRQ welcomes the opportunity to clarify any issues or questions from potential applicants who have read the FOA. Written and telephone inquiries concerning this FOA are encouraged.

Direct your questions about general FOA issues, including information on the targeted research topics or the inclusion of women, minorities, children, and other priority populations to:

Anne Trontell, M.D., M.P.H.
Center for Outcomes and Evidence
Agency for Healthcare Research and Quality
540 Gaither Road
Rockville , MD 20850
Telephone: (301) 427-1607
FAX: 301-427-1640
Email: certsfoa@ahrq.hhs.gov

2. Peer Review Contact(s):

Direct your questions about peer review issues of grant applications made in response to this FOA to:

Carl Ohata
Office of Extramural Research, Education, and Priority Populations
540 Gaither Road, Room Number
Rockville, MD 20850
Telephone: (301) 427-1549
FAX: (301)-427-1562
E-mail address:Carl.Ohata@ahrq.hhs.gov

3. Financial/Grants Management Contact(s):

Direct inquiries regarding financial or grant management matters to:

Michelle Burr
Office of Performance, Accountability, Resources and Technology
Grants Management
540 Gaither Road,  
Rockville, MD 20850
Telephone: (301) 427-1451
FAX: (301) 427-1462
Email: Michelle.Burr@ahrq.hhs.gov

Section VIII. Other Information

Required Federal Citations

Inclusion of Women and Minorities in Research Study Populations:

Women and members of minority groups are included in all AHRQ-supported research projects involving human subjects, unless a clear and compelling rationale and justification are provided that inclusion is inappropriate, e.g., because of the lack of connection between the study and the health of women or particular minorities.

All investigators proposing research involving human subjects should read the UPDATED "NIH Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research," published in the NIH Guide for Grants and Contracts on August 2, 2000 (http://grants.nih.gov/grants/guide/notice-files/not-od-00-048.html). A complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm. To the extent possible, AHRQ requires adherence to these NIH Guidelines.

Investigators may obtain copies from the above sources or from the NIH Guide Web site at http://grants.nih.gov/grants/guide/index.html.  AHRQ Program staff may also provide additional information concerning these policies (see Section VII, Agency Contacts).

Human Subjects Protection:

Federal regulations at 45 CFR Part 46 require that applications and proposals involving human subjects research must be evaluated in accordance with those regulations, 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 (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).
 
Standards for Privacy of Individually Identifiable Health Information:

The Department of Health and Human Services (DHHS) "Standards for Privacy of Individually Identifiable Health Information", regulation was mandated by the Health Insurance Portability and Accountability Act (HIPAA) of 1996 which governs the protection of individually identifiable health information.  It is administered and enforced by the DHHS Office for Civil Rights (OCR). The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools that may be used to determine whether a researcher is a staff member of a covered entity. Compliance with the Privacy Rule for those classified under the Rule as "covered entities" is mandatory.  Decisions about applicability and implementation of the Privacy Rule reside with covered entities.  Project Officers will assist grantees in resolving questions about the applicability of HIPAA requirements.

Access to Research Data through the Freedom of Information Act:

The OMB Circular A-110 has been revised to provide access to research data developed with Federal support through the Freedom of Information Act (FOIA) in certain 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. If no Federal action is taken having the force and effect of law in reliance upon an AHRQ-supported research project, the underlying data are not subject to this disclosure requirement.  Furthermore, even if a Federal regulatory action is taken in reliance on AHRQ-supported research data under FOIA, 5 USC 552(b), disclosure of confidential identifiable data from such study is statutorily protected under 42 USC 299c-3(c), and thus is exempted from disclosure under "the (b)(3) exemption in FOIA.  It is important for applicants to understand the scope of this requirement and its limited potential impact on data collected with AHRQ support.  Proprietary data might also be exempted from FOIA disclosure requirements under "the (b)(4) exemption", for example, if they constitute trade secrets or commercial information.  NIH has provided general related guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm which does not include discussion of the exception applicable to confidential identifiable data collected under AHRQ's authorities.

Should applicants wish to place data collected under this FOA in a public archive, which can provide protections for the data (e.g., as required by confidentiality provisions of the statute applicable to AHRQ-supported projects, 42 USC 299c-3(c) and manage the distribution of non-identifiable data for an indefinite period of time, they may. The application should include a description of any archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should consider how to structure informed consent statements or other human subject protection procedures to permit or restrict disclosures of identifiable data, as warranted.

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 health improvement priorities for the United States. AHRQ encourages applicants to submit grant applications with relevance to the specific objectives of this initiative. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:

This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authority of 42 USC 299 et seq. and, Federal Regulation, 42 CFR Part 67 and in accordance with 45 CFR Parts 74 or 92 and other referenced applicable statutes and regulations.  All awards are subject to the terms and conditions, cost principles, and other considerations described in the HHS Grants Policy Statement. The HHS Grants Policy Statement can be found at http://www.ahrq.gov/fund/hhspolicy.htm.

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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