Guidelines for a Request for Proposal (RFP)

Neurocognitive Changes in Patients undergoing General Anesthesia during Surgery in the Head-Above-Heart Position

APPLICATION INSTRUCTIONS

The Anesthesia Patient Safety Foundation (APSF) is soliciting research proposals designed to elucidate the nature and potential etiological factors of unexpected neurocognitive deficits in patients undergoing general anesthesia during surgery in non-supine positions. There have been an increasing number of reports of severe neurological injury in previously healthy patients having shoulder surgery in the beach chair position.  The incidence and mechanisms of the observed neurocognitive effects are unknown. Prior cases of severe CNS injury have been reported in healthy patients undergoing sitting neurosurgical procedures, under general anesthesia with induced or inadvertent hypotension, during normovolemic hemodilution, and in other situations in which the injury may have been preventable. APSF believes this is a major patient safety issue that warrants rigorous study. For these reasons, APSF is proposing the following:

• An award up to $200,000.00 for a period not to exceed 2 years to study this question.  It is anticipated the study will begin within 90 days of APSF making the award.
• The proposed study should be a prospective observational clinical trial with a matched and/or parallel control group (e.g., similar patients having similar surgery in the supine position). The use of validated preoperative and postoperative tests of neurocognitive function are required. Additional intraoperative and/or postoperative testing (e.g., neurological function monitoring, biomarkers) is encouraged.
• A contract mechanism will be used and funds will be awarded to a single institution. The contract for the RFP will be made to a sponsoring institution, not to individuals or to departments. Any qualified member of a sponsoring institution (hospital, university, clinic, etc) in the United States or Canada may apply.
• The principal investigator must be an experienced scientist from a North American institution.
• The RFPs will be evaluated by a scientific review committee selected by APSF. Proposals will be assessed for merit based primarily on their likelihood of meeting the contractual objectives outlined in the RFP as well as the proposed study's scientific rigor, innovation, cost-effectiveness, and the probability of producing generalizable knowledge that can be disseminated widely.
• Proposed studies that cannot reliably be initiated by July 1, 2010 will not be considered.
• Funding will be contingent on acceptable modifications to the proposal based on feedback from the APSF review committee as well as appropriate IRB and institutional approvals.

 

DETAILED APPLICATION INSTRUCTIONS

A complete RFP Application Packet will consist of the following documents, arranged in the following order:

A.  Cover Page(s)

B.  Project Summary

C.  Research Narrative

D.  References Cited

E.  Human subjects approval letter or submitted IRB application

F.  Budget and budget justification

G.  Applicants? curriculum vitae

H.  Departmental Chair's letter of support

I.  Consultants? Letters of Support and Statement of Work

J.  Allowed supplemental materials

 

General Formatting Requirements

Applications that fail to comply with the formatting requirements will be returned without review! All applications must use a serif font that is no smaller than TIMES 12 point. All application pages will be single-spaced and use 1 inch margins on all sides. Except as specifically stipulated below, no supplemental materials, appendices, addenda, websites, or additional documents will be accepted. Number all pages (bottom right corner) sequentially, starting with the cover page

 

A. Cover Page

The Cover Page shall include the following in this order:

1. Title of research project
2. Name of applicant (Principal Investigator) with academic degrees, office address, phone number, fax number and e-mail address
3. Names and affiliations of all investigators and consultants
4. Name, office address, and phone number of departmental chairperson
5. Sponsoring institution and name, office address, phone number and e-mail address of the responsible institutional financial officer
6. Total amount of funding requested (including institutional overhead)
7. Start and end dates of proposed project

 

B. Project Summary

  The Project Summary should explain the proposed research study in language understandable to the average clinical anesthesiologist. The summary may not exceed 100 words and will used primarily for promotional purposes.

 

C. Project Narrative

The Project Narrative should provide the reviewers with sufficient information to assess the proposed project?s objectives, methodological details, limitations, and likely impact. Note that a traditional ?Background & Significance? is not required since this is a targeted RFP. The reviewers generally appreciate well-designed figures and tables which more effectively illustrate or summarize the project?s design, the point(s) being made, methods being used, etc.

The Project Narrative must include the following sections presented in the following order:

1. Hypothesis and Specific Aims (maximum 300 words). After a brief introduction, this section must articulate the Aims of the study and the hypotheses to be tested. All hypotheses must be stated in a way that they can be tested with empiric data.
2. Evidence of Ability of Investigators to Conduct the Study (maximum 1000 words). This section should include descriptions and citations of the investigators? previous relevant research. Any relevant preliminary results should be included here.
3. Detailed Proposed Methods (maximum 2000 words). This section must include a detailed description of the proposed experimental design, the numbers and nature of study participants, the procedures to be employed, the independent variables to be manipulated, the dependent variables to be measured, and any covariates that will be included. Importantly, this section must include a detailed description of the neurocognitive (and other) tests or monitors to be used. This description should include a rationale for the choice of each test/monitor that addresses the alternatives, benefits and limitations, and how the resulting data will be processed and interpreted.
4. Statistical Plan and Power Analysis (maximum 500 words). This section must include a data management plan (including evidence of HIPPA compliance, data privacy and data security), a detailed analytical plan, and a sufficiently robust power analysis to convince the reviewers of a low likelihood of either Type 1 or Type 2 error. In addition to total sample size, the plan should include a statement of the number of eligible subjects in the study site?s patient population and the feasibility of adequate recruitment during the study period. It would be prudent to provide evidence of the initial and planned ongoing involvement of an experienced biostatistician.
5. Interpretation of Results (maximum 500 words). This section should describe how the results will address the stated hypotheses, how alternative findings will be interpreted, what the team will do if the findings do not confirm the original hypothesis (this is especially important in multi-part studies or aims that depend on each other), and the clinical significance of the results.
6. Study Limitations (maximum 500 words). This critical section must provide a comprehensive and realistic description of the study limitations and the methods by which the investigators have (or will) mitigate these limitations.
7. Project Management and Detailed Timeline (maximum 250 words plus Gantt chart). This section must describe how the PI will organize, plan, and oversee the proposed research. When a team of scientists will be involved, the Project Management plan should describe how the team will communicate and interact. Finally, this section should describe how the team will assure that the project is completed on time and within the proposed budget. The project timeline should be presented in a Gantt chart that includes specific detailed milestones and deliverables.

 

D. List of Literature Cited (maximum 1 page).

This section should provide evidence that the investigators are familiar with the literature and will take a rigorous and scholarly approach to the proposed research. Please cite only the most relevant and important literature. References should be cited in the order in which they appear in the Project Narrative and should use the format approved by the journal Anesthesia and Analgesia.

 

E. Protection of Human Subjects.

This section must include a letter from the Institutional Review Board (IRB) indicating either that the study has been approved or that it has been submitted for review. In the latter case, the full IRB proposal must be included with the application (the IRB proposal will not count toward the application page limits). If medical devices are to be used on patients in the study in ways that are not currently FDA-approved, the investigators must confer with their IRB regarding the need for an IDE. Similarly, if drugs are to be used in the study in ways that are not currently FDA-approved, the investigators must confer with their IRB regarding the need for an IND.

 

F. Budget and Budget Justification.

The budget request must not exceed $200,000 (including a maximum of 15% institutional overhead). The proposed projects must not exceed 2 years in duration. Unused funds must be returned to APSF if funds remain after completion of the project (i.e., actual expenditures were less than the budgeted funding) or the project is not completed within the approved time period. Enumerate in an itemized spreadsheet table all proposed expenditures broken down by year of the proposal.

Project proposals that include institutional in-kind support (e.g., contributed effort of investigators or other research personnel, use of equipment, test assays, etc.) suggest a real institutional commitment to the research team and the project and thus will be viewed more favorably by the Committee. Any institutional support must be enumerated specifically in the budget (in a separate column from what is being requested from APSF).

The following items cannot be included in the budget for this RFP: Travel, Construction costs, Administrative expenses of any type, manuscript preparation costs, telecommunication or internet access charges, literature search costs, maintenance fees or contracts.

The following budget categories should be listed:

1. Personnel. All investigators and staff should be listed even if no funds from APSF are requested. Salaries must be limited to current NIH Guidelines. Benefits must comply with institutional guidelines and federal regulations. A biostatistician should be included.
2. Consultants. ?Internal Consultants? must be listed as Co-Investigators in the Personnel section. External consultant use must be well justified. In the Justification (see below) detail the use and rationale of each consultant, the number of hours to be worked, the cost per hour, and how the consultant will participate in the research team. For each consultant, a separate letter of support is required (see below).
3. Equipment. This category is only for durable equipment exceeding $2,000. Multicomponent equipment systems are considered in aggregate. Only absolutely essential equipment purchases will be allowed. In general, the APSF expects institutions to provide desk or laptop computers for research projects. Proposed equipment purchases must be thoroughly justified including rationale and alternatives. Equipment-related supplies should be listed in Supplies.
4. Supplies. This category should include all research supplies necessary to complete the project. Costs of assays or reagents should be included in this category.
5. Patient Care or Volunteer Costs. Volunteers may be reimbursed for reasonable (e.g., travel) expenses and provided reasonable incentives for their participation in a study. Patients who participate in the study should generally not receive additional compensation except in circumstances that can be well justified and have been approved by the local IRB. The APSF does not expect to have to pay for patient care-related costs (i.e., clinical care supplies) unless the study requires special research equipment or a well-justified substantial deviation from standard-of-care processes and procedures.
6. Other Costs. List any other approved costs that may be incurred to complete the study.
7. Total Direct Costs.
8. Institutional Overhead (Indirect Costs). May not exceed 15%. Note that institutional overheads of less than 15% will be viewed as institutional in-kind support.
9. Total Costs by year and overall

 

Budget Justification. The Budget Justification must provide, in a well-organized narrative format, a full detailed justification for all proposed expenditures. The committee will evaluate particularly carefully any proposed purchases of equipment. The use of proprietary software, supplies, or equipment is allowed but the Committee will question such use if there is a reasonable likelihood it could yield a significant future benefit to a for-profit entity.

 

G. Applicants? Curriculum Vitae.

This should include CV in NIH-format of the Principal Investigator and of all Co-Investigators. CVs must be a maximum of 4 pages each and should include current positions, relevant honors/awards, relevant national service, recent and relevant peer-reviewed publications (do not list submitted papers or any abstracts), and current research funding from any external source.

 

H. Department Chair?s Letter of Support.

The letter from the Departmental Chair must include the following information:

1. A statement that the Chair has read the proposal and agrees with its content.
2. The number of working days per week available to the PI (and applicable Co-Investigators) for the proposed research and the degree of involvement of the applicant in other research projects
3. The Chair's degree of enthusiasm for the proposed project including a statement about the ability of the team to accomplish the project as proposed.
4. The availability of facilities and patient population essential to the completion of the proposed research.
5. A statement that the Department will assure that the project will be completed on time and within budget.
6. A statement of the Chair?s agreement to return any unused funds if the applicant fails to complete the project, and any remaining funds after the completion of the study.

 

I.  Consultants? Letters of Support and Statement of Work.

Each proposed Consultant must write and sign a letter on his/her institutional letterhead that confirms their willingness to participate in the project as stipulated in the proposal. The letter should at a minimum include an indication that the consultant has read the proposal and agrees with its content, a detailed description of how the consultant will contribute to the project, evidence that the consultant is qualified to contribute in this manner, the number of hours the consultant will commit to the project, the consultant?s expected remuneration for his/her efforts, and a statement of how (and how often) the consultant will communicate with the PI and the research team.

 

J.   Allowed Supplemental Materials.

In general, the Committee does not seek additional materials beyond the items specified above and, if submitted, these will NOT be reviewed. However, if the investigator proposes the use of novel or particularly complex data instruments that cannot otherwise be included in the Project Narrative (every effort should be made to do so), then these instruments may be included as an Appendix. Note that for this RFP data instruments that have not already been demonstrated to be valid and reliable should not be used unless no other such instrument is available and the project plan includes a specific and detailed method to demonstrate the novel instrument?s validity and reliability.

 

SUBMISSION OF RFP APPLICATION

The entire RFP package must be converted to Adobe PDF format and merged as a SINGLE file. Please name the PDF Application Packet file as: PI Lastname.Firstname-RFP-2010 (example: Smith.John-RFP-2010.pdf).

The RFP application must be submitted electronically to Stoelting@apsf.org no later than 5PM (EST) on Monday, February 01, 2010.