Research Grants: Request for applications

2011 RESEARCH GRANTS PROGRAM

REQUEST FOR APPLICATIONS

DATE OF ISSUE: APRIL 6, 2011

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Since its founding in 1987, the CFIDS Association of America (“Association”) has supported research into the biological basis of chronic fatigue syndrome (CFS) through direct grants to investigators, sponsorship of scientific symposia and meetings, fostering collaborations and, most recently, establishing the SolveCFS BioBank. Over the past few years, CFS research has received high-profile media attention, generating both increased interest and unprecedented opportunities for progress.

To meet the unequivocal need for a more robust scientific enterprise for CFS, in late 2007 the Association’s Board of Directors announced the Campaign to Accelerate CFS Research to fuel a more intensive search for biomarkers, better diagnostics and more effective treatments. The current purpose of the Association’s research program is to build, support and link a critical mass of innovative and credible researchers focused on early detection, objective diagnosis and effective treatment and to create, identify and leverage new private and commercial funding sources and opportunities for CFS investigators.

EXECUTIVE SUMMARY
This 2011 Request for Applications (RFA) solicits research proposals that will advance objective diagnosis and effective treatment of CFS.

• The CFIDS Association of America intends to commit approximately $600,000 to this RFA for award of successful applications responsive to this announcement.
• Interested investigators are invited to submit a Letter of Intent (LOI) in English using the form provided at: http://www.cfids.org/research/loi-2011.pdf. The deadline for receipt of the fully completed LOI is 17:00 (U.S. Eastern time) on June 3, 2011. Investigators are expected to adhere to the LOI format, provide all requested information and are limited to five pages in length (including budget) plus two additional pages for supporting documentation and/or pilot study data. Other formats or attachments beyond the stated page limit will not be evaluated. Letters of Intent and allowable attachments should be submitted in a single electronic portable document format (PDF) file to research@cfids.org.
• Investigators who submit LOIs for projects consistent with funding priorities and budgetary guidelines of this RFA and meet all other eligibility guidelines will be invited to submit a comprehensive research grant application. Notification of the outcome of the review of LOIs will be made by June 24, 2011. Full applications will be due by 17:00 (U.S. Eastern time) on September 30, 2011.
• Awards issued under this RFA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications. Funding decisions will be communicated to applicants by January 13, 2012 and may be subject to conditions identified in the review process that will be required to be satisfied in order for funding approval to be conferred.
• It is anticipated that 4-6 awards will be issued under this RFA. The earliest date on which funding will begin is February 1, 2012.
• The maximum award is $100,000 in total costs. Research grants are generally made to cover the direct costs of such items as salaries for professional and technical personnel, patient costs, equipment, supplies, travel to present findings at research meetings and other miscellaneous items. Institutional indirect costs cannot exceed 10%.
• The maximum term of awarded grants will be 18 months. A timeline for the proposed project is required as part of the LOI.
• There is no limit to the number of applications that an institution/organization may submit in response to this RFA.
• Applications may be submitted by nonprofit, public and commercial institutions with no restrictions as to geographic location.

NATURE OF THE RESEARCH OPPORTUNITY
CFS is an illness with strong biological underpinnings yet its cause(s) has not been identified. Diagnosis is based on a characteristic symptom pattern and exclusion of alternative explanations for symptoms. Treatments are aimed at controlling co-morbid conditions and symptom relief. Even though treatments are not currently targeted at CFS etiologies, effective symptom relief may provide clues to the cause(s) of CFS. Well-designed research that uses standard operating procedures is needed to systemically and successfully identify and validate biomarkers that can be used for the objective diagnosis efficacy of treatments for CFS.

At least one million people in the U.S. have CFS. The lack of validated biomarkers for objective diagnosis and treatment efficacy represents a huge unmet medical need with substantial public health burden. To attract greater industry and commercial interest to address this disease burden requires research that is reproducible and reliable.

The CFIDS Association intends to bridge the gap between bench discoveries and clinical implementation by funding research aimed at discovery and replication of diagnostic and treatment biomarkers and exploring new drug targets and treatments for CFS. Knowledge acquired from research funded under this RFA will be used to attract pharmaceutical and biotech study and commercialization as well as augment the evidence base for clinical practice and health policy (i.e., insurance reimbursement, documentation of vocational disability, etc.).

RESEARCH GOALS AND OBJECTIVES
The objective of this RFA is to solicit research proposals that will advance objective diagnosis and effective treatment of CFS. Topics of specific interest include, but are not limited to:

• Treatment targeted at possible cause(s) of CFS including antimicrobial and antiviral therapies.
• Effective therapeutic approaches to symptom management or underlying pathophysiology, including exploration of existing and off-label medications, orphan or novel drug families.
• Methods of preventing or treating documented viral infection or reactivation from latency.
• Markers, surrogate endpoints or clinical endpoints that reproducibly and reliably quantify and predict the clinical effects of specific treatments.
• Enhanced treatment decision-making using FDA-approved pharmacogenomic test for drug metabolism with respect to medications and treatments for CFS.
• Targeted treatment and symptom relief based on genomic variation.
• Laboratory, clinical, imaging or genomic (gene expression profiling, multigene test panels, etc.) markers that can be used to objectively diagnose, delineate CFS subtypes and target treatment.
• Markers and/or strategies for objective identification of CFS subtypes that will advance diagnosis and therapy.
• Genetic studies of families with multiple members affected with CFS.
• Identification of susceptibility alleles for viral infections.
• Identification of susceptibility alleles for immune dysfunction.
• Identification of epigenomic biomarkers that have potential for early detection and indicators of CFS severity.
• Epigenetic modifications as a result of infection and subsequent development of CFS.
• Global analysis of antibody reactivities to an array of various molecules including self-molecules.
• Known and novel infectious triggers for CFS, including in vitro and animal model systems and computer simulations of infection and/or immune response coupled with laboratory data that will yield markers for biological conditions that result in the individual’s inability to recover from the illness arising from an acute infection.
• Microbiome analysis of relevant body systems.
• Computerized assessments for quantifying cognitive impairment.

Proposals that leverage existing resources and infrastructures, including but not limited to the SolveCFS BioBank (see overview of biobank below and http://www.solvecfs.org/SOLVECFSBIOBANK/tabid/99/Default.aspx), for subject enrollment and sample collection are highly encouraged and will be given additional weight. Proposals with robust biomarkers requiring validation and investigational therapeutics or off-label treatments with strong potential to enhance clinical practice for CFS are highly encouraged and will be given additional weight.

OVERVIEW OF THE SOLVECFS BIOBANK RESEARCH RESOURCE
The SolveCFS BioBank has been fully operational with an integrated clinical registry and biorepository since receiving ethical approval from the Genetic Alliance (GA) Institutional Review Board in March 2010. As of March 2011, the SolveCFS BioBank has consented and enrolled 628 people that include: 448 CFS patients and 140 controls that have consented to provide clinical information and biological samples (blood and buccal swabs). Of the 448 consented CFS patients, 170 patients have been referred by CFS specialty care clinics to ensure the accuracy of their CFS diagnosis and extensive documentation of their clinical characteristics.

The SolveCFS BioBank uses an online questionnaire composed of standardized and validated instruments to collect clinical information using a secure web-based platform. Demographic information is collected using questions from national surveys so results can be compared to population norms. Other information includes 36 items assessing health-related quality of life, physical and mental fatigue, symptom severity and frequency, pain, sleep, depressive symptoms, medical history, medication use and family history. Common data standards (e.g., HL7, SnoMed, ASTM), controlled language and vocabulary are used to limit variability and to enhance comparability across disease categories.

The biorepository component uses automation for sample collection, storage and processing as much as possible. Collection kits are customized based on type and quantity to ensure and maintain the quality of the biological sample. Kits contain instructions, collection tubes and pre-addressed containers that meet shipping specifications for biological hazard material. All collection tubes are labeled with unique identifiers and are bar-coded for accurate tracking and inventory. Kits can be customized for the collection and storage of blood and blood components, DNA, RNA, cells, tissue and organs. All collection kits can be tracked and easily accessioned. Once collection kits are received by the biorepository, biological samples are processed according to FDA-established Good Laboratory Practices (Federal Registry 43 FR 59985-60020) using documented standard operating procedures. Sample quality assurance procedures are conducted on all biological sample types.

When submitting a Letter of Intent, investigators who propose utilizing assets of the SolveCFS BioBank will be required to include a detailed description of the information or type of sample needed to successfully complete the project. If the project otherwise meets all criteria responsive to the RFA, the investigators’ needs will be compared against the SolveCFS BioBank resources to generate an estimate for the number of subjects meeting specific selection criteria (i.e., acute illness onset for studies of viral triggers, participants within a specific age group for studies of endocrine factors, etc.). Association staff will generate an estimate of direct costs to cover custom sample collection and/or processing, addition of supplementary items to the clinical questionnaire or collection of information at specific time points, etc. to provide to the investigative team. In the full application, these costs will be reflected in the total budget request. If the application is funded, the amount of the award will be reduced by these costs and the funds retained by the Association to perform the required services through the SolveCFS BioBank. Additional instructions are provided in the Letter of Intent form and will be included in the full application.

INSTRUCTIONS TO INTERESTED INVESTIGATORS
Eligibility: Letters of Intent may be submitted by nonprofit, public and commercial institutions with no restrictions as to geographic location. If invited to submit a full research application, the applicant’s institution will be required to demonstrate that it is a viable ongoing concern with which the Association can confidently enter into a granting relationship. All financial information will be kept strictly confidential in accordance with the confidentiality requirements stated herein.

Current members of the Association's Board of Directors are not eligible to receive Association research grants as principal investigators. However, they may serve as unpaid consultants or collaborators for Association-supported projects and may seek grants once their service has ended. Multidisciplinary and collaborative efforts are encouraged.

Postdoctoral fellows are eligible to submit Letters of Intent as principal investigators under this RFA. However, any postdoctoral fellow who applies is required to collaborate with an Administrative Principal Investigator (PI) who serves as the director of the laboratory or facility in which the research will be conducted. The Administrative PI will be responsible for assisting in providing all institutional documents required for the project and will be required to sign any award. Responsibility for the planning, direction and execution of the proposed project will be solely that of the principal investigator. Training- or mentoring-only proposals are not appropriate for this RFA. For proposals involving postdoctoral fellowships as applicants, biographical information is required for both the postdoctoral fellow and the Administrative PI.

Letters of Intent Submission Procedures: Interested applicants should submit a Letter of Intent (LOI) in English due by 17:00 U.S. Eastern time on June 3, 2011. Please adhere to the format of the LOI (http://www.cfids.org/research/loi-2011.pdf), provide all requested information and limit the LOI to five pages (including preliminary budget). Supporting documentation and/or pilot study data can be provided but must be limited to 2 additional pages. Other formats or attachments beyond the stated page limit will not be evaluated.

Letters of Intent and allowable attachments should be submitted in a single electronic portable document format (PDF) file to research@cfids.org. If submission by postal mail is preferred/required by the PI/institution, please mail to: Research Program, CFIDS Association of America, PO Box 220398, Charlotte, NC 28222-0398. Electronic submissions must have a time/date stamp before 17:00 U.S. Eastern time on June 3, 2011. Postal submissions must be mailed in time to be received by June 3, 2011. LOIs received after the stated deadline will not be reviewed.

Investigators who submit LOIs describing scientifically sound proposals designed to ensure the consistency and reliability and reproducibility of results that fall within the funding priorities and budgetary guidelines of this RFA and meet all other eligibility guidelines will be invited to submit a comprehensive research grant application. Notification of the outcome of the review of LOIs will be made by June 24, 2011. Full applications will be due by 17:00 (Eastern time) on September 30, 2011.

Review of Complete Applications: Only those investigators invited to submit full grant applications will be eligible for review of their applications. Peer reviewers will review grant applications based on scientific merit. The peer reviewers’ comments and scores will be utilized to make a supplemental evaluation of strategic issues related to funding and other factors relevant to the overall research program. The scientific and strategic merit scores will be used by the Executive Committee of the Association’s Board of Directors for the purpose of making fully informed funding decisions about the applications.

Award of Grants: Grant decisions rest with the Executive Committee of the Association’s Board of Directors, based on a composite of scientific and strategic factors. Funding may be contingent on the submission of additional information or revisions to the approved proposal.

Duplication of Support: When requests for the support of a project are submitted to more than one granting agency, support from the Association cannot duplicate other support. However, Association support is permitted to supplement support from other institutions.

Funds Available: Funds of up to $600,000 have been projected for this program in 2012; however, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of applications of high scientific merit that meet the requirements of this RFA. Applicants may request a project period of up to 18 months and maximum total budget of $100,000 including direct costs and indirect costs. Indirect expenses for funded grants are capped at 10% of the total grant award. In the event of collaboration between multiple institutions, indirect costs are only paid once – either to the PI’s institution as a percentage of total direct costs or, in the case of multiple PIs and multi-site studies, one institution will be assigned as the administrative center and will receive and be responsible for distributing funds including indirect costs. In no case may the total of all indirect costs paid exceed 10% of the total award.

Confidentiality of Information: In processing and reviewing Letters of Intent or full applications, the Association will use its best efforts to not disclose confidential or proprietary information submitted. Members of the Association's Board of Directors, professional staff and external peer-reviewers are required to sign non-disclosure agreements. However, the Association has no other mechanisms to maintain or guarantee the confidentiality of information, and as a not-for-profit corporation, does not have the financial resources to: (a) sustain liability for disclosure of information, nor (b) institute mechanisms to maintain the confidentiality of information. Submission of a Letter of Intent is deemed to verify acceptance of these provisions.

The CFIDS Association of America treats all Letters of Intent, applications, financial information, research projects and associated research information (collectively, the “Confidential Information”) in confidence using no less than reasonable care in protecting such Confidential Information from disclosure to third parties who do not participate in the grant review process. All Confidential Information will be used by the Association and its grant reviewers only internally for the purposes of reviews and assessments, and will be shared only in accordance with its sharing policy stated herein. Notwithstanding the Association’s and its reviewers’ obligations regarding such Confidential Information, such obligations cover any information retained in their unaided memories and may not be used without the permission of the disclosing party. Notwithstanding the foregoing, the obligations governing the disclosure and use of Confidential Information do not apply with respect to Confidential Information that it can be demonstrated:

1. was generally known to the public prior to the effective date of this RFA; or
2. becomes generally known to the public through no unlawful or unauthorized act of omission by any recipient of Confidential Information, or in violation of this RFA; or
3. was independently developed by any recipient prior to the effective date of this RFA; or
4. was disclosed to a recipient by a third party who has the right to make such disclosure.

If any recipient of Confidential Information is requested to produce any of the Confidential Information pursuant to a legal or governmental proceeding, such recipient shall give the applicant or other owner of such Confidential Information (the “Discloser”) as much prior notice of such requirement as is reasonably practicable under the circumstances and shall use its reasonable efforts to assist the Discloser of such Confidential Information in objecting to such request. If a recipient is compelled to disclose any of the Confidential Information pursuant to such legal or governmental proceeding, such recipient shall use its reasonable efforts to assist Discloser in obtaining confidential treatment for such Confidential Information, will disclose only that portion of the Confidential Information which is responsive to the order, and will provide the Discloser with any copies of Confidential Information so disclosed; provided that such Confidential Information shall remain confidential until it falls into one of the categories specified above.

Conflicts of interest: Principal investigators and their paid collaborators submitting applications to this RFA will be excluded from serving as reviewers on their proposal. However, non-applicants who are invited to serve as reviewers may still have a conflict of interest that arises during the grant review process. A reviewer is judged to have a conflict of interest if (1) he or she is a collaborator, subcontractor and/or consultant with an investigator on the grant application; (2) the application is from the reviewer's own institution, regardless of whether or not the reviewer has had any involvement in preparing the application; (3) the reviewer, his/her immediate family or close professional associate(s) has a financial or vested interest in the outcome of the proposed research (even if no significant involvement is apparent in the proposal being considered); or (4) the reviewer has been involved in discussions regarding the application, is a provider of services, cell lines, reagents or other materials, or is the author of a letter of reference for the applicant.

When a conflict of interest is deemed to be present, the reviewer will be ineligible to review the proposal. Reviewers are also urged to avoid any actions that might give the appearance that a conflict of interest exists, even though he or she believes there may not be an actual conflict of interest.

Requirements for Funded Grants: Those investigators whose projects described in the Letter of Intent are deemed to be responsive to the research objectives of the RFA will receive a full grant application and a set of the Association’s Policies Governing the Award of Research Grants. It is important for those submitting Letters of Intent to understand at the outset of the application process that support for approved applications will require the Principal Investigator and his/her institution to agree to:

• define selection methods for cases and controls, including which case definition is used and how it is applied. At a minimum, all CFS subjects must fulfill the 1994 case definition (Fukuda et al, http://www.annals.org/content/121/12/953.abstract). Whenever possible, cohorts should be selected using post-exertional malaise/relapse as an inclusion criterion
• conduct and report research using documented standard operating procedures according to Good Laboratory Practices where applicable;
• submit data accumulated with these funds to a secure bioinformatics platform designed as a permanent archive and data repository for use by approved investigators in the CFS research community;
• submit detailed quarterly progress reports once funding begins;
• participate in quarterly assessment conferences once funding begins;
• submit detailed quarterly financial reports on expenditures related to the grant once funding begins;
• agree to an equitable arrangement to share intellectual property if a new discovery is made using funds from a CFIDS Association award and/or materials from the SolveCFS Biobank;
• grant a non-exclusive, perpetual, irrevocable, world-wide, royalty-free license with a right to grant sublicenses to practice the claims of the patent for purposes of non-commercial research in the event that a previous discovery is validated or commercialized as a result of using funds from a CFIDS Association award and/or materials from the SolveCFS Biobank; and,
• publish the results of funded research as rapidly as possible in the open scientific literature indexed for MEDLINE, consistent with high standards of scientific excellence and rigor, and to include acknowledgement of the funding provided by the CFIDS Association of America in all manuscripts and publications resulting from its support.

Non-compliance with any of these requirements may result in suspension of funding, revocation of the award and/or ineligibility for future support. Letters of Intent submitted by former Association grantees will be screened on the basis of how well the PIs met reporting and publication guidelines in force at the time of their earlier award(s).

Important Dates:

Please direct inquiries regarding this Request for Applications to:

Suzanne D. Vernon, PhD
Scientific Director
The CFIDS Association of America, Inc.
PO Box 220398
Charlotte, NC 28222-0398
E-mail: research@cfids.org
Web: www.cfids.org

RFA: http://www.cfids.org/research/rfa-2011.pdf
LOI Form: http://www.cfids.org/research/loi-2011.pdf