Recovery Act Limited Competition: Methodology Development in Comparative Effectiveness Research (RC4)
National Institute on Drug Abuse
This NIH Funding Opportunity Announcement (FOA), supported by funds provided to the NIH and AHRQ under the American Recovery & Reinvestment Act of 2009 ("Recovery Act" or "ARRA"), Public Law 111-5, invites applications to enhance, develop, or evaluate methodologies to improve the efficiency, validity, and credibility of comparative effectiveness research (CER) studies. CER encompasses a wide array of methodologies, including technology assessment, meta-analysis, systematic reviews, observational studies, and experimental trials. Each of these methodologies suffers from substantial weaknesses that limit their ability to rapidly provide information sought by patients, clinicians, and other stakeholders to make robust evidence-based decisions on clinical practice and public policy. Research is needed to develop better methods for measuring or reducing these weaknesses, which include, for example, confounding bias in observational studies and selection bias in randomized trials. Research in methodology development focuses on approaches to design, implement, analyze, and report CER, as opposed to CER projects that focus on comparing specific interventions for preventing or treating a given medical condition. It is hoped that this line of research will lead to significantly greater efficiency, validity, and credibility of CER among researchers, health care providers, and policy makers, and therefore will enhance the quality of the nation's health.
This initiative is one of several being offered to help fulfill the goals of the American Recovery and Reinvestment Act (ARRA) to help stimulate the economy through support of biomedical and behavioral research. Additional information the Recovery Act and related NIH opportunities is available through the Office of Extramural Research (http://grants.nih.gov/recovery/ )
Participating NIH Institutes:
This FOA invites applications to enhance, develop, or evaluate methodologies to improve the efficiency, validity, and credibility of comparative effectiveness research (CER) studies. Research to improve CER methods is seen to be necessary given the well-known limitations of commonly applied methods, ranging from technology assessments to prospective observational studies and large-scale randomized trials. Recent advances in the capacity and uptake of information technology and statistical sciences present a unique opportunity to address a number of long-standing barriers to expansion of CER and CER findings, including assessing and limiting confounding biases in observational studies and improving efficiency and generalizability of randomized trials. These advances, however, have not been adequately studied in the area of comparative effectiveness, leaving a substantial opportunity for improvement that could be met in part by successful applications to this FOA.
For the purposes of this FOA, the definition of comparative effectiveness research will adhere to that adopted by the Federal Coordinating Council given at http://wayback.archive-it.org/3909/20130926125230/http://www.hhs.gov/recovery/index.html: "Comparative effectiveness research is the conduct and synthesis of research comparing the benefits and harms of different interventions and strategies to prevent, diagnose, treat and monitor health conditions in "real world" settings. The purpose of this research is to improve health outcomes by developing and disseminating evidence-based information to patients, clinicians, and other decision-makers, responding to their expressed needs, about which interventions are most effective for which patients under specific circumstances.
- To provide this information, comparative effectiveness research must assess a comprehensive array of health-related outcomes for diverse patient populations and subgroups.
- Defined interventions compared may include medications, procedures, medical and assistive devices and technologies, diagnostic testing, behavioral change, and delivery system strategies.
- This research necessitates the development, expansion, and use of a variety of data sources and methods to assess comparative effectiveness and actively disseminate the results."
The term "comparative" refers to comparisons of interventions and strategies to prevent, diagnose, treat, and monitor health conditions. The term "effectiveness" refers to applicability "to real-world needs and decisions faced by patients, clinicians, and other decision makers" within "real-world settings," i.e. not the ideal settings created in efficacy investigations. CER investigations compare two or more interventions and strategies that are currently available to practicing clinicians (i.e., not innovative or experimental drugs, devices, or approaches that might more typically be part of an FDA-regulated efficacy study). These interventions and strategies can include "medications, procedures, medical and assistive devices and technologies, diagnostic testing, behavioral change, and delivery system strategies." As examples, CER investigations could:
- Compare two or more different existing, available drugs for prevention of major morbidity or mortality in a given medical condition
- Compare for a given medical condition the clinical outcomes of medical and surgical strategies, where all medications or surgical techniques are already available in practice
- Compare for a given medical condition the clinical outcomes of existing medical and lifestyle strategies within the framework of different health care delivery approaches
Priority-Setting Process and Inputs for use of ARRA OS Funds
There were four main inputs for priorities for ARRA OS CER funds: public input, an internal Departmental workgroup, the FCC report, and the IOM report. The FCC identified the following as minimum threshold criteria which must be met to be considered for funding:
- Included within statutory limits of ARRA and the Council's definition of CER;
- Potential to inform decision-making by patients, clinicians or other stakeholders;
- Responsiveness to expressed needs of patients, clinicians or other stakeholders;
- Feasibility of research topic (including time necessary for research).
The CER-CIT will require the use of the FCC's prioritization criteria for scientifically meritorious research and investments for all projects funded with OS ARRA funds. These criteria are:
- Potential impact (based on prevalence of condition, burden of disease, variability in outcomes, costs, potential for increased patient benefit or decreased harm),
- Potential to evaluate comparative effectiveness in diverse populations and patients sub-groups and engage communities in research,
- Addresses existing uncertainty within the clinical and public health communities regarding management decisions and variability in practice,
- Addresses a need or is unlikely to be addressed through other organizations,
- Potential for multiplicative effect.
Finally, investments funded from this appropriation must address at least one of the following topic areas:
- One of the 100 IOM topic recommendations or the 10 general recommendations and/or
- An issue within one the MMA 14 priority conditions identified by AHRQ which are not currently addressed;
- Fall into one of the AHRQ identified evidence gaps or be identified in the FCC report to the Congress.
The current list of priority conditions includes:
- Arthritis and nontraumatic joint disorders (Muscle, bone, and joint conditions)
- Cancer (Cancer)
- Cardiovascular disease, including stroke and hypertension (Heart and blood vessel conditions)
- Dementia, including Alzheimer's Disease (Brain and nerve conditions)
- Depression and other mental health disorders (Mental health)
- Developmental delays, attention-deficit hyperactivity disorder, and autism (Developmental delays, ADHD, autism)
- Diabetes mellitus (Diabetes)
- Functional limitations and disability (Functional limitations and physical disabilities)
- Infectious diseases including HIV/AIDS (Infectious diseases and HIV/AIDS)
- Obesity (Obesity)
- Peptic ulcer disease and dyspepsia (Digestive system conditions)
- Pregnancy including preterm birth (Pregnancy and childbirth)
- Pulmonary disease/asthma (Breathing conditions)
- Substance abuse (Alcohol and drug abuse)
Scope: This FOA solicits applications for 3-year projects proposing innovative approaches to enhance, develop, or evaluate methodologies to improve the efficiency, validity, and credibility of CER studies. (Note: this FOA does not target establishment of new CER findings, but rather research of CER methods.)
There are a wide range of valid CER study types and methods that are legitimate targets for research. Broad areas of methodology research include (but are not limited to) control for confounding and bias in observational studies, systematic combination of data from randomized and observational studies to streamline comparative assessments, linkage and use large amounts of data derived from practice-based warehouses, health economics, decision analysis, altered treatment effects in the setting of multiple comorbidities, value-of-information research and CER simulations, robust sub-group or personalized treatment interactions, rapid roll-out of observational studies and pragmatic trials within integrated health care systems or existing large-scale registries, use of Internet platforms to perform mega-randomized trials at low cost, and innovative approaches for rapid and efficient design, implementation, and completion of large-scale pragmatic trials and implementation studies, including Bayesian, adaptive, and cluster designs.
When appropriate, this FOA encourages investigators to produce publicly available CER tools, such as software, computerized trial algorithms, and web tools for study management.
Applicants should be aware of the fact that any proposed project should be feasible within a three year period and a total costs budget of $1.5 million.
The scope of possible approaches to CER methods has also been left open. The general guideline is that the results of grants following from this RFA could set the stage for other, future studies establishing the value of the methods proposed.
This initiative is supported by funds provided to the NIH under the American Recovery & Reinvestment Act of 2009 ("Recovery Act" or "ARRA"), Public Law 111-5. Contingent upon the submission of a sufficient number of scientifically meritorious applications, NIH intends to commit at least $10 million in response to this FOA. We anticipate that 6-7 awards will be made in fiscal year 2010, pending the number and quality of applications and availability of funds. Although the size of award may vary with the scope of research proposed, applications must stay within the budgetary guidelines for this FOA. Budget proposals are limited to $500,000 total costs per year over three years and the total cannot exceed $1,500,000.
Grants that are awarded will have to use a non-modular budget. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
This program is supported by funds provided to the NIH and AHRQ under the Recovery Act. The purpose of the Recovery Act is to stimulate the American economy through job preservation and creation, infrastructure investment, energy efficiency and science, and other means. Consistent with these goals, domestic (United States) institutions/organizations planning to submit applications that include foreign components should be aware that requested funding for any foreign component should not exceed 10% of the total requested direct costs or $25,000 per year (aggregate total for a subcontract or multiple subcontracts), whichever is less.
Eligible Institutions: Consistent with the purposes of the Recovery Act (in particular, to preserve and create jobs and promote economic recovery in the United States, and to provide investments needed to increase economic efficiency by spurring technological advances in science and health), applicants must be a domestic (United States) institution/organization. Foreign organizations/institutions are not permitted as the applicant organization.
- More than one PD/PI (i.e., multiple PDs/PIs) may be designated on the application
- This is a one-time-only solicitation, resubmissions are not permitted.
- The RC4 application Research Strategy component of the PHS398 (Items 3-5) may not exceed 12 pages, including tables, graphs, figures, diagrams, and charts.
Release/Posted Date: December 28, 2009
Opening Date: January 26, 2010 (Earliest date an application may be submitted to Grants.gov)
Application Due Date(s): February 26, 2010
Peer Review Date(s): May/June 2010
Earliest Anticipated Start Date(s): August 31, 2010
Expiration Date: February 27, 2010
Michael S. Lauer, MD
Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 8128
Bethesda, MD 20892
Telephone: (301) 435-0422
Fax: (301) 480-7971