American Association of Endodontists American Association of Endodontists Foundation Request for Proposal Release Date: November 2010 Submission Deadline Date: August 1, 2011 Earliest Award Date: April 2012PurposeThe American Association of Endodontists (AAE) and the AAE Foundation (AAEF) will provide acontract to support clinical research projects that will produce high-level evidence relating to regenerativeendodontic treatment. The research focus must be pertinent to various clinical aspects of regenerativetreatment. Examples include case selection, instruments and techniques, medication, and treatmentoutcome. The research project design and methodology must adhere to stringent criteria consistent withhigh levels of evidence. When appropriate, randomized controlled trials are strongly encouraged overalternative designs. Multi-centered trials aimed at generating large sample size are also encouraged.BackgroundThe AAE is committed to incorporating regenerative procedures into the definition and scope ofendodontics. In addition, the AAE and AAEF are committed to the application of evidence basedmethodology for endodontic education, research and practice. To promote these important concepts, in2006 the AAE Board of Directors established the Regenerative Endodontics Committee (REC) as a regularstanding committee. In order to enhance and broaden the evidence for regenerative endodonticprocedures, the AAE and AAEF set out to solicit appropriate clinical research that will generate high-level evidence to support endodontic practice that incorporates regenerative procedures. The AAE RECand Research and Scientific Affairs Committee (RSAC) collaborated to develop several research questionsrelated to regenerative endodontics. After reviewing the questions, one clinical question was identifiedas a priority for investigation.Researchers have numerous options for study designs from a single researcher/institution to largemulticenter collaborations. Variables for potential designs are listed in the Statement of ResearchObjectives below.Eligibility RequirementsProposals may be submitted by U.S. and Canadian for-profit and non-profit, public and privateorganizations, such as universities, colleges, hospitals, laboratories, units of State/Province and localgovernments, and eligible agencies of the Federal government, as well as foreign academic and scientificinstitutions.Mechanisms of SupportThe mechanism of support will be a research contract between the AAE, AAEF and the principalinvestigator’s institution. It is anticipated that this contract will take place over approximately six years.Please contact the AAE or AAEF for additional contractual information.Funds AvailabilityThe estimated total funding (direct and indirect) available is in the range of $1.45-2.5 million paid overapproximately 6 years.The AAE and AAEF intend to support or contribute to the support of the contract(s) ensuing from this
RFP beginning in 2011. Grant awards will be contingent on the receipt of high quality applications. TheAAE and AAEF reserve the right not to support any proposal, if none is considered to satisfy the purposeof this RFP. For the successful proposal(s), funding beyond the first and subsequent years of the grantwill be contingent upon satisfactory progress during the preceding years and the availability of funds.The following components should be included in a detailed budget:• Database management• Principal Investigator• Endodontist plus dentist• Statistician• Dental assistant• Research coordinator• Treatment• Patient remuneration• Equipment (Requests must not duplicate any equipment in the principal investigator’s department and must be justified and essential. All equipment purchased shall remain the property of the institution. Equipment requests of $1,000 or more must include a signed statement from the university to verify need and itemized price quotes. Requests for expendable supplies must be justified and should not include supplies expected to be available from other sources.• Training, calibration, monitoringResearch ObjectivesThe objective of the RFP is to solicit clinical research to answer the following clinical research question,presented in PICO format:Population: In patients with pulpal necrosis,Intervention: does regenerative endodontic treatment,Comparison: compared to alternative treatment,Outcome: result in better outcomes?Each of the four PICO components in this multi-factorial clinical research question comprises differentoptions that lend themselves to different combinations. Patient related variables should be constant. Thefour PICO components include the following options:1. Endodontic Disease 1.1. Pulp necrosis 1.2. Apical abscess 1.3. Symptomatic or asymptomatic Apical Periodontitis 1.4. Potential for any of the above2. Endodontic Treatment (included in the categories below are variations in techniques, materials and clinical strategies; each one of these variables can be the subject of a randomized controlled trial, while the others should be controlled): 2.1. Initial (first-time) treatment 2.1.1. Number of treatment sessions 2.1.2. Irrigants – type, concentration 2.1.3. Intracanal medication – type, application period 2.1.4. Temporary seal/restoration 2.1.5. Operator’s level of training 2.2. Second Appointment 2.2.1. All of the above (2.1.1 – 2.1.5) 2.2.2. Source of stem cells 2.2.3. Scaffolds – Type
2.2.4. Growth factors – Type 2.2.5. Definitive restoration – Type, full coverage3. Alternative Treatment 3.1. Other endodontic treatment modality than the selected intervention 3.2. Variation of technique/material/strategy within the same intervention 3.3. Tooth extraction without replacement 3.4. Tooth replacement – fixed partial prosthesis, removable partial prosthesis, implant-supported prosthesis4. Assessed Outcomes 4.1. Healing 4.1.1. Radiographic measures 4.1.2. Clinical measures 4.2. Function 4.2.1. True survival 4.2.2. Absence of untoward events 4.2.3. Absence of clinical signs and symptoms 4.3. Quality of life and satisfaction perceptions, as they pertain to all aspects of endodontic disease, treatment and function of diseased/treated teeth. These outcomes may include economic, esthetic, physiologic and physical aspects, such as the quality of sensation of chewing 4.4. Patient-defined utilities 4.5. Economical 4.6. Observation period 4.6.1. 1 year 4.6.2. 2 years 4.6.3. 3 years 4.6.4. 4 years 4.6.5. 5 yearsOutcome Measures and Assessment CriteriaStandardized and validated outcome measures and assessment criteria must be used for the selectedoutcome assessment category. When appropriate, outcome assessment must observe strict rules ofcalibration and blinding. Outcome assessment should minimally occur on an annual basis for a four tofive year period.For assessment of pulpal and perioapical healing and function, the following outcome definitionsapproved by the AAE and AAEF are recommended, however, researchers are invited to provideadditional clarification of terms:1. Healed with tissue regeneration— Functional*, asymptomatic teeth with no or minimal radiographic periradicular pathosis. Radiographic evidence of new dentin/mineral tissue formation in the coronal and/or radicular portion.2. Healed without tissue regeneration -- Functional*, asymptomatic teeth with no or minimal radiographic periradicular pathosis. No radiographic evidence of new dentin/mineral tissue formation in the coronal and/or radicular portion.3. Non-healed—Nonfunctional, symptomatic teeth with or without radiographic periradicular pathosis.* Functional—A treated tooth or root that is serving its intended purpose in the dentition.Proposal ProceduresThe proposal will consist of the following elements:1. Application (ATTACHMENT A)2. Abstract of proposed study. (limit to 300 words).
3. Budget A. First year budget: provide individual components as listed on page 2 of this RFP, “Funds Availability,” as well as indirect costs. B. Total granting period: provide individual components as listed on page 2 of this RFP, “Funds Availability,” as well as indirect costs. C. Detailed justification of the proposed budget. D. Source(s) for other requested funding.4. Biographical sketches of all key personnel (4 page limit per person) with identification of the primary investigator. If this is a multi-center project, each center should have a primary contact listed along with a biographical sketch. The relevant experience and training of the key personnel in conducting similar studies should be highlighted in the biographical sketch and reprints of their relevant publications should be included in the Appendix. Research proposal should be no longer than 20 pages formatted in 12 pt font with one inch margins A. Specific aims. B. Background of question being studied and significance to endodontics/dentistry (2 page limit). C. Preliminary data. Investigators with prior experience in conducting similar studies are encouraged to present their data in order to support their ability to conduct a comprehensive and scientifically valid clinical investigation that includes a standardized and validated outcome measure of clinical success. D. Approach. This section should provide complete information necessary to evaluate the experimental approach. Methods of ascertaining the security and longevity of data should be outlined. Statistical methods should include sample size calculations, estimates of power, and a detailed plan for analyses. Use this section to justify your experimental methods and standardized outcome measures. It is expected that an appropriate data safety management board (DMSB) will be involved. Drugs to be used have to be FDA-approved; the use of investigational or new drugs (IND) has to cleared by the appropriate process. E. Time-line for research. Research milestones should be provided with 6-month intervals and are required as a basis for periodic contract performance review. F. Letter of approval from relevant Institutional Review Board (IRB) panels and the informed consent and subject enrollment documents for patient recruitment and safety monitoring.5. References6. Appendix. Include reprints of relevant publications by the key personnel of the proposal.Proposals must be sent on a CD in PDF format to the address below. Documents sent via email will notbe accepted. Sign the application form, which can be scanned and included with your proposal as a TIFFor JPEG image file. Chair, AAE Research & Scientific Affairs Committee c/o Assistant Executive Director for Development American Association of Endodontists 211 E. Chicago Ave., Suite 1100 Chicago, IL 60611-2691 firstname.lastname@example.orgProposals must be received by August 1, 2011. If a proposal is received after that date, it will be returnedwithout review.Review ConsiderationsUpon receipt, proposals will be reviewed by the AAE Research and Scientific Affairs Committee, forcompleteness and responsiveness to this RFP. Incomplete and/or non-responsive proposals will bereturned to the applicant without further consideration. If the committee deems it appropriate, special
experts such as statisticians, clinical trial researchers or other types of scientists may included in thereview process. The consultants’ comments are reviewed and forwarded to a special oversight committeecomposed of the presidents of the AAE and the AAE Foundation, the Chair of the Research and ScientificAffairs Committee and a representative from the Regenerative Endodontics Committee and the JOEeditorial Board. The Research and Scientific Affairs Committee will review the consultants’recommendations and any comments from the oversight committee and recommend a grantee/s to theAAE Foundation Board of Trustees. The reviewers will use the revised NIH scoring system (1-9 with 1being outstanding) with written critiques and the NIH criteria to evaluate the proposals. All proposalswill receive a written critique and undergo full committee review.Review CriteriaThe reviewers will evaluate the applications in the following areas in order to determine the scientific andclinical merits for possible funding.SIGNIFICANCE: Is the study addressing important problem or questions in endodontics? Are the Aimsof the study responsive to the RFP? At the conclusion of the study, what will be the benefit to thescientific, academic, and public communities in terms of their endodontic needs? Is the outcome of thestudy going to change the direction of the field in endodontics?APPROACH: Is the conceptual framework of the study sound? Are the appropriate methodologiesproposed? Are the proposed approaches feasible? Is the feasibility demonstrated in the literature orpreliminary data? Does the applicant address the potential pitfalls and alternative approaches?INNOVATION: Does the study involve new ideas, techniques, assay development, or approaches? Doesthe study have potential for broader impact to shift the paradigm in endodontics?INVESTIGATOR: Are the investigators well trained and qualified to undertake the study? Does thepublication track record support the investigators’ productivity? Do the investigators demonstrate afunding record that would help continue the project above and beyond the current RFP?ENVIRONMENT: Do the scientific environment and institution support the proposed study? Does theinstitution provide a scientific environment conducive for the success of the proposed study? Is there anyaspect of the environment uniquely suited for the proposed study and if so what is the evidence?Award CriteriaThe earliest anticipated date of award is July 1, 2011. Applicants should be aware that, in addition toscientific merit, the total cost of the proposed project and the availability of funds will be considered bythe AAE and AAEF in making funding decisions. In addition, the AAE and AAEF value complementaryfunding from other public and private sources, including foundations, corporate partners, and theapplicant’s institution. In circumstances in which proposals have similar scientific merit, but vary in cost-competitiveness, the AAE and AAEF are likely to select the more cost-competitive proposal for funding.Manuscripts based on research supported by the AAE Foundation must be submitted first to the Journalof Endodontics. The following statement must be included in any written or oral presentation of researchsupported by the AAE Foundation: This research was supported in part by a grant from the AmericanAssociation of Endodontists Foundation.ReportingAn outcomes assessment report should be provided annually, including any abstracts, posterpresentations, or manuscripts. Continued funding will be contingent on the submission of an annualprogress report. The report must contain the following information: • Actual and projected budget
• Overall status of the project including the cohort study (number of subjects enrolled, completed, withdrawn or dropped out) • List of publications including abstracts, poster presentations or manuscriptsThe report will be reviewed by the Research and Scientific Affairs Committee. Their recommendations forcontinued funding will be reviewed by the Foundation’s Board of Trustees.In addition, the status of the study cohort (number of subjects enrolled, completed, withdrawn anddropped out) should be reported annually. Annual budget reports should specify actual expenditure todate. Researchers are required to make their raw data available to the AAE after publication or within 5years following the end of funding for this project.InquiresWritten, e-mail and telephone inquiries are encouraged. The opportunity to clarify any issues orquestions from potential applicants is welcome.Direct inquiries regarding programmatic issues to: Chair, AAE Research & Scientific Affairs Committee c/o Assistant Executive Director for Development American Association of Endodontists 211 E. Chicago Ave., Suite 1100 Chicago, IL 60611-2691 Phone: 312/266-7255 or 800/872-3636, ext. 3017 Fax: 312/266-9867 or 866/451-9020 E-mail: email@example.com/26/10
ATTACHMENT A American Association of Endodontists American Association of Endodontists Foundation REQUEST FOR PROPOSAL APPLICATIONPlease type directly in the shaded areas. The box will expand as you type. Use the tab key to movefrom box to box. This form requires your signature. Please scan the signed form and include it withyour proposal as a PDF file.Title of proposed investigation/project Principal investigator/program directorName Institution Position Title Department or Equivalent Address City State/Province Zip/Postal Code Phone Fax E-mail Professional degrees/certificates, institutions conferring them, dates Animal/Human use committee approvals Enclosed Applied For (documentation enclosed) Not applicableDates of proposed period of support BudgetCosts for initial budget period (direct and indirect costs) Costs for proposed period of support (direct and indirect costs) Has other funding been received or applied for?Yes No If so, amount $
Location/s where research will be conducted Official signing application or organizationName Institution Position Title Department or Equivalent Address City State/Province Zip/Postal Code Phone Fax E-mail Principal Investigator/Program Director Assurance: I certify that the statements herein are true,complete and accurate to the best of my knowledge. I am aware that any false, fictitious, or fraudulentstatements or claims may subject me to criminal, civil, to administrative penalties. I agree to acceptresponsibility for the scientific conduct of the project and to provide the required progress reports if agrant is awarded as a result of this application.________________________________________________________________________Signature of principal investigator/program directorApplicant Organization Certificate of Acceptance: I certify that the statements herein are true, completeand accurate to the best of my knowledge. I am aware that any false, fictitious, or fraudulent statementsor claims may subject me to criminal, civil, to administrative penalties.________________________________________________________________________Signature of official signing for organizationSend this form and your proposal to Chair, AAE Research & Scientific Affairs Committee c/o Assistant Executive Director for Development American Association of Endodontists 211 E. Chicago Ave., Suite 1100 Chicago, IL 60611-2691 firstname.lastname@example.org