WRNMMC SCIENTIFIC REVIEW PANEL William D. Watson, MD, PhD CDR MC USN Vice-Chair, NNMC SRP

1. National Naval Medical CenterDirectorate for Professional EducationClinical Investigation Department WRNMMC SCIENTIFIC REVIEW PANEL William D. Watson, MD, PhD CDR MC USN Vice-Chair, NNMC SRP Director of Neurology Labs, USUHS Director, Comprehensive National Neuroscience Program (CNNP) “The National Naval Medical Center is an approved provider of continuing nursing education by the Navy Medicine Manpower, Personnel, Training and Education Command, an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation.”

2. Disclosure Statement This CE/CME activitydoes not have commercial support, and has no conflicts of interest. Research Course

3. Learning Objectives • Discuss the genesis of Scientific Review Panel (SRP) • Administrative structure – where does SRP fall in review process • Discuss composition of SRP, review principles and criteria for SRP approval of research 4. Helpful Tips for Successful Transitioning Through the IRB Process Research Course

4. Learning Objective 1: Discuss the genesis of Scientific Review Panel (SRP) • Several protocol violations late 1990’s and early 2000’s, including several protocols at civilian institutions with Navy PIs • BUMED annual Inspector General review 2002 recommended separating IRB review into 2-step process - Scientific review (Scientific Review Panel) - Human Protections review (Institution Review Board) Research Course

5. Learning Objective 1: Discuss the genesis of Scientific Review Panel (SRP) • Two step review performed at most institutions in U.S. • Considered gold standard • Helps to optimize benefit to risk ratio of research proposals • SRP and IRB instituted at all Navy MTF’s with IRB authority (Surgeon General in 2004) Research Course

6. Discuss the genesis of Scientific Review Panel (SRP). Purpose of the SRP • Ensure scientific validity of all submitted protocols, which is essential to protecting human and animal research • Poorly designed research places subjects at risk and wastes resources • PI not objective about own research • Underestimate risks; overestimate benefits Research Course

7. Commander Director for Graduate Education Clinical Investigations Department RESPONSIBLE CONDUCT OF RESEARCH SERVICES ADMINISTRATIVE SUPPORT Nursing Research Research Resources SCIENTIFIC REVIEW PANEL INSTITUTIONAL REVIEW BOARD Simulation Center Learning Objective 2: Administrative structure – where does SRP fall in review process Research Course

8. Administrative structure – where does SRP fall in review process SRP Administrative Structure • Three Co-Chairs CDR Sam Wanko, MD LCDR Alex Bustamante, MD LCDR Todd Gleeson, MD • Up to two Vice-Chairs and “No fewer than 9 anonymous members” • Administrative support from Responsible Conduct of Research Services (RCRS) provided by Ms. Wendy Gilbert (wendy.gilbert@med.navy.mil, phone 301-295-2268) Research Course

9. Learning Objective 3:Discuss composition of SRP, review principles and criteria for SRP approval of research Composition of SRP - The NNMC Scientific Review Panel (SRP) consists of the 11 primary reviewers. - Reviewers are senior researchers Research Course

10. Discuss composition of SRP, review principles and criteria for SRP approval of research SRP review principles and criteria Each submitted protocol shall meet the following criteria: 1. The protocol format must be followed (Human Use Protocol Application could be found at http://www.bethesda.med.navy.mil/professional/research/Responsible_Conduct/Forms/index.aspx) 2. The research question is articulated in a clear and precise manner. Research Course

11. SRP review principles and criteria (cont.) 3. The research question is relevant to Military Medicine. 4. The background section informs the reviewers why the research question is important. 5. The literature search is comprehensive and complete. Research Course

12. SRP review principles and criteria (cont.) • The study design is appropriate for the research question a. Are the controls adequate? b. Will the design produce a credible answer to the research question? 7. The research methods are feasible (time frame, personnel, resources) Research Course

13. SRP review principles and criteria (cont.) 8. Sample size calculations are provided (if needed) and the proposed statistical analysis is valid 9. The entire proposal is well written, logical, and clear 10. All references must be complete and accurate Research Course

14. Learning Objective 4:Helpful Tips for Successful Transitioning Through the IRB Process Revised 30 October 2008 Standard Operating Procedure for SRP review • Electronic format (e-mail) • 2 reviewers/protocol, 10 consecutive days to complete review • Co-Chair receives 2 reviews and administrative review and writes summary review for RCRS • Ms. Wendy Gilbert is the SRP administrator • NNMC Building 1(Tower), 4th floor, RCRS. • wendy.gilbert@med.navy.mil, phone 301-295-2268 Research Course

15. Standard Operating Procedure for SRP review (cont.) • Co-Chair summarizes reviews and is final authority on forwarding to IRB • Co-Chair or Vice Chair alone reviews Expedited protocols Expedited Categories (9) - Collection of hair, nails, teeth (non-disfiguring) - Secretions (i.e., sweat) - Recording physical data, 18+ yo (excludes hi energy or invasive procedures) - Blood collection, 18+ yo - Dental plaque collection - Voice recording (i.e., speech defects) - Moderate exercise in healthy volunteers - Existing data - Behavior, group or individual where research does not manipulate behavior and does not involve stress to subjects Research Course

16. Helpful Tips for Successful Transitioning Through the IRB Process SRP Review Template The Scientific Review Template (Word) can be found at http://www.bethesda.med.navy.mil/professional/research/Responsible_ Conduct/Forms/Scientific_Review.doc • Reference (a): Commander, BUMED Ltr 3900 Ser M00R/06UM00R201 of 9 Aug 06 (BUMED Site Visit from 28 to 31 March 2006 of the NNMC Human Research Protection Program) • Per reference (a), protocols must be scientifically sound prior to review by the institutional review board (IRB); therefore, investigators must address the requirements of the scientific review before proposals are forwarded to the IRB for consideration of human subject protection issues. Please review the SRP Template - shows you the basis upon which your proposal will be scientifically reviewed Research Course

17. Helpful Tips for Successful Transitioning Through the IRB Process Review Template Reference (a): Commander, BUMED Ltr 3900 Ser M00R/06UM00R201 of 9 Aug 06 (BUMED Site Visit from 28 to 31 March 2006 of the NNMC Human Research Protection Program) Title of Research Protocol: Protocol CIP#: Principal Investigator: Reviewer Code: 1. Is the research question articulated with clarity and precision? Yes No Comments: . 2. Is the research question relevant to Navy Medicine? Yes No Comments: 3. Does the background section inform us why this question is important? Yes No Comments: Research Course

18. Helpful Tips for Successful Transitioning Through the SRP Process • Proofread yourself, and by others • Spell correctly and use proper grammar • Fully spell out acronyms with first use in abstract and body of protocol • Write with clarity and precision. Clear prose flows from clear thought • This is a formaldocument. Do not use slang phrases or terms • Always explain fully. Don’t assume that the reviewer is an expert in your area or that she/he will know what is inside your head Research Course

19. Helpful Tips for Successful Transitioning Through the SRP Process The following typical pitfalls must be avoided: • The Human Use Protocol format has not been followed precisely • Abstracts have not met main requirement: they must be concise summaries of protocol • Researchers have not met with NNMC biostatistician Research Course

20. Helpful Tips for Successful Transitioning Through the SRP Process ABSTRACT A brief summary of the essential elements of the research proposal. Typically the LAST part of the proposal written. Should encapsulate proposal Introduction to genesis of idea/importance/history State research question(s) seeking to answer Briefly state method(s) to answer the research question(s) State suspected results State potential implications of your research Research Course

21. Helpful Tips for Successful Transitioning Through the SRP Process INTRODUCTION AND HYPOTHESIS/OBJECTIVES • Introduce and clearly state your research hypothesis or objectives, whichever is appropriate. • If performing a descriptive study where no population will be tested against a control using statistical analysis, then objectives or specific aims are appropriate (i.e., no hypothesis is being tested) Research Course

22. Helpful Tips for Successful Transitioning Through the SRP Process BACKGROUND AND SIGNIFICANCE Place your research question(s) in context Why your question(s) is (are) important Review for the reader in plain speak, the pertinent literature that leads to your research hypothesis Provide a statement regarding why your research question is relevant to Military Medicine Research Course

23. Helpful Tips for Successful Transitioning Through the SRP Process Literature Search Tips • For animal research, databases required for review prior to submission: FEDRIP (Federal Research in Publication), and Agricola (database of National Agricultural Library). Both of these databases are mediated access only. You may also wish to search BIOSIS (Biological Abstracts online), another mediated access. • Thorough literature searches are required for scientific integrity and validity, and prevent redundancy. • Redundant protocols require detailed analysis of prior study flaws and how these are overcome in current proposal. Research Course

24. Case Study: DATABASE Literature Search. “A comprehensive literature search was performed from July - November 2006, with the final literature search prior to protocol re-submission on November 10, 2006. Using PUBMED database, we used search terms including “Acinetobacter baumannii (997),” “Acinetobacter baumannii AND Operation Iraqi Freedom OIF (1),” “war wounded infections (176),” “Acinetobacter baumannii AND epidemiology (297),” “Acinetobacter baumannii AND Iraq (8),” “Acinetobacter baumannii AND resistance (590),” “Acinetobacter baumannii AND genome (71),” “Acinetobacter baumannii AND epidemiology AND Iraq (5).” All articles were read in detail, with only five found to be related to this protocol. Although each of these articles are epidemiological studies of Acinetobacter baumannii in Iraq since the outbreak of the Iraq conflict, none has more than 15 cases, complete patient histories to include mechanism of injury, dates of antibiotics, sensitivity and resistance studies, as well as PCR strain identification. This protocol intends to fill a significant gap in the literature by providing a comprehensive epidemiological study on Acinetobacter baumanii species as determined by PFGE on 80 specimens collected on OIF/OEF casualties who have been provided care at NNMC through retrospective analysis of what we hope will be much more complete patient histories. Research Course

25. Case Study: DATABASE Literature Search. • “A literature search using the Medline Ovid search engine was performed on 30JUN2007 from 1950 until the present using the search terms traumatic intracranial aneurysm, traumatic aneurysm, traumatic pseudoaneurysm. A total of 1143 entries returned. These results were initially screened for those that were English language entries leaving 944. Titles were then screened and an additional 855 entries were excluded secondary to relevancy leaving 89. Complete papers corresponding to each abstract were then obtained and read in detail. Papers were then rejected based on their relevance to vascular injury associated with military penetrating brain and spinal injury leaving 5 studies. These articles characterize an experience encompassing 75 cases of traumatic central nervous system arterial injury. Though valuable, they offer no reference to the rate of rupture or resolution, and limited reference to endovascular interventions. This study proposes to fill this significant gap.” Research Course

26. Helpful Tips for Successful Transitioning Through the SRP Process RESEARCH DESIGN AND METHODS • Begin with a declarative statement telling the reader what your study design is (prospective, randomized, double blind study) • Then take the reader step-by-step through exactly what you intend to do (with references as needed) • Control groups • Detail data points to be collected • Ensure you are collecting data on potential confounders • Data collection sheets = an appendix (page numbers) Research Course

27. Helpful Tips for Successful Transitioning Through the SRP Process RESEARCH DESIGN AND METHODS • State primary and secondary outcomes • Seek statistical consultation • Address sample size calculation including what assumptions you made to arrive at your proposed sample size Research Course

28. Helpful Tips for Successful Transitioning Through the SRP Process HUMAN USE JUSTIFICATION • Please state what data will be collected (hard copy/electronic), PHI? • Who will have access to data (usually PI and AI), • Where it will be stored (typically locked cabinet in PI’s office), • Electronic data usually kept on password protected computer accessible by PI and AI only with backup disk and printout created monthly, at termination of data analysis or all study completion all study data including master key is to be turned into NNMC RCRS department for long-term storage. Research Course

29. Helpful Tips for Successful Transitioning Through the SRP Process Funding Scores Funding for protocols which request funding is scored on a 100 point merit system: - Each reviewer scores protocol, with Chair submitting final summary score. - Just because you ask for it does not mean it will be funded (laptops, equipment warranties, etc) - Typically $2-8,000 total, and must justify amount requested. Research Course

30. References • NNMC Scientific Review Panel Standard Operating Procedure (SOP), revised 30 October 2008. Copies on file in Responsible Conduct of Research Services Department, 4th floor of building 1. 2. Principles and Practice of Clinical Research. edited by Gallin, J.I., Ognibene, F.P. 2nd edition. Burlington: Academic Press Publications, 2007. 3. WRNMMC Protocol template Research Course

31. QUESTIONS???? Research Course

32. Thank You My contact Information: William D. Watson, MD, PhD CDR MC USN Director of Neurology Labs, USUHS Director, Comprehensive National Neuroscience Program (CNNP) Bethesda, MD 20889 wwatson@usuhs.mil phone 301-295-0390 Research Course