WHAT IS NEW AT NIH & OTHER UPDATES - PowerPoint Presentation

1. WHAT IS NEW AT NIH & OTHER UPDATESOctober 25, 2017Frances Payne Bolton School of NursingCenter for Research & Scholarshiphttps://sites.google.com/a/case.edu/new-at-nih_10-25-17/

2. Summary of NIH Changes: 12.7.16 - 1.25.18 TopicEffective DateSummary of ChangeWebsiteClinical Trial Definition & Specific Application (NOT-OD-17-043)25-Jan-181. Need to ensure that you follow guidelines for clinical trial. (Answer 4 questions).2. Can only submit applications involving clinical trials if the specific RFP or FOA specifically calls for clinical trials.https://grants.nih.gov/policy/clinical-trials/CT-decision-tree.pdfhttps://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-043.htmlhttps://clinicaltrials.gov/ct2/manage-recs/how-registerClinical Trials: New Review Criteria(NOT-OD-17-118) 25-Jan-18Additional review criteria for clinical trialshttps://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-118.htmlNew NIH "FORMS-E": Clinical Trials(NOT-OD-17-062)25-Jan-18Expansion and use of discrete form fields for clinical trial informationhttps://grants.nih.gov/policy/clinical-trials/new-human-subject-clinical-trial-info-form.htmhttps://grants.nih.gov/grants/ElectronicReceipt/files/Annotated_Forms_General_FORMS-E.pdfNew NIH "FORMS-E": Human Subjects(NOT-OD-17-062)25-Jan-18Consolidation of human subjects, inclusion enrollment, and clinical trial information.https://grants.nih.gov/policy/clinical-trials/new-human-subject-clinical-trial-info-form.htmhttps://grants.nih.gov/grants/ElectronicReceipt/files/Annotated_Forms_General_FORMS-E.pdf

3. DEFINITION OF A CLINICAL TRIAL

4. Summary of NIH Changes: 12.7.16 - 1.25.18 TopicEffective DateSummary of ChangeWebsiteElimination of Appendix for Clinical Trials Applications(NOT-OD-17-098)25-Jan-18All information required for the peer review process must be contained within those designated sections of the application image, unless the FOA specifies otherwise.https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-098.htmlNIH Policy on the Dissemination of NIH-Funded Clinical Trial Information(NOT-OD-16-149)18-Jan-17All NIH-funded clinical trials are expected to register and submit results information to Clinicaltrials.gov.https://clinicaltrials.gov/ct2/home

5. Summary of NIH Changes: 12.7.16 - 1.25.18 TopicEffective DateSummary of ChangeWebsitePolicy on Post-Submission Materials(NOT-OD-17-066)25-Sep-17Post-submission materials are submitted after submission of the grant application but prior to initial peer review. They are not intended to correct oversights or errors discovered after submission. See website for complete list of materials.https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-066.htmlIssuing Certificates of Confidentiality(NOT-OD-17-109)17-Sep-17Certificates automatically apply to all funded studies.https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-109.htmlAppendix Policy(NOT-OD-17-035)25-Jan-17Special policy for clinical trials. For other applications, ONLY blank consent forms, blank surveys and/or data collection instruments. If your application DOES NOT meet these criteria, it will be deemed to be ineligible.https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-035.html

6. Summary of NIH Changes: 12.7.16 - 1.25.18 TopicEffective DateSummary of ChangeWebsiteGood Clinical Practice (GCP) Training: Clinical Trials(NOT-OD-16-148)16-Sep-16All NIH-funded investigators and staff who are involved in the conduct, oversight, or management of clinical trials should be trained in GCP.https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-148.htmlhttps://osp.od.nih.gov/clinical-research/clinical-trials/RECOMMENDED SITES FOR GCP Training16-Sep-16Society of Behavioral Medicine: Good, easy to use, practical site.CITI site more complex but you can get CREC credits.http://www.sbm.org/training/good-clinical-practice-for-social-and-behavioral-research-elearning-coursehttps://about.citiprogram.org/en/series/good-clinical-practice-gcp/Rigor and TransparencySex as a Biologic Variable25-Jan-16For most research grants and RPPRs, application requirements aim to enhance reproducibility of research findings through increased scientific rigor and transparency. https://grants.nih.gov/grants/peer/guidelines_general/Reviewer_Guidance_on_Rigor_and_Transparency.pdfhttps://grants.nih.gov/reproducibility/index.htmExplain how relevant biological variables are factored into research designs & analyses.https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-102.html https://grants.nih.gov/grants/peer/guidelines_general/SABV_Decision_Tree_for_Reviewers.pdf

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9. Rigor & ReproducibilityScientific PremiseScientific Rigor (Design)Biological Variables (SABV)Authentication

10. 4 AREAS OF FOCUSWHAT DOES “SCIENTIFIC RIGOR” MEAN?WHERE SHOULD IT BE INCLUDED IN THE APPLICATION?Scientific PremiseThe scientific premise for an application is the research that is used to form the basis for the proposed research question(s). Describe the general strengths and weaknesses of the prior research being cited as crucial to support the application. Consider discussing the rigor of previous experimental designs, as well as the incorporation of relevant biological variables and authentication of key resources.Research StrategySignificanceScientific Rigor(Design)Scientific rigor is the strict application of the scientific method to ensure robust and unbiased experimental design, methodology, analysis, interpretation and reporting of results. Emphasize how the experimental design and methods proposed will achieve robust and unbiased results.Research StrategyApproach

11. 4 AREAS OF FOCUSWHAT DOES IT MEAN?WHERE SHOULD IT BE INCLUDED IN THE APPLICATION?Biological VariablesBiological variables, such as sex, age, weight, and underlying health conditions, are often critical factors affecting health or disease. In particular, sex is a biological variable that is frequently ignored in animal study designs and analyses, leading to an incomplete understanding of potential sex-based differences in basic biological function, disease processes and treatmentresponse. Explain how relevant biological variables, such as the ones noted above, are factored into research designs, analyses, and reporting in vertebrate animal and human studies. Strong justification from the scientific literature, preliminary data or other relevant considerations must be provided for applications proposing to study only one sex.Research StrategyApproachSex as a Biologic Variablehttps://grants.nih.gov/grants/peer/guidelines_general/SABV_Decision_Tree_for_Reviewers.pdfNIH Review Criteria: Evaluate adequacy of research plan with regarding to SABV

12. 4 AREAS OF FOCUSWHAT DOES IT MEAN?WHERE SHOULD IT BE INCLUDED IN THE APPLICATION?AuthenticationKey biological and/or chemical resources include (but are not limited to) cell lines, specialty chemicals, antibodies, and other biologics.Briefly describe methods to ensure the identity and validity of key biological and/or chemical resources used in the studies. These resources may or may not be generated with NIH funds and:May differ from lab to lab over timeMay have qualities and/or qualifications that could influence the research dataAre integral to the proposed researchThe authentication plan should state in one page or less how you will authenticate key resources, including the frequency, as needed for your research. Examples: https://www.uab.edu/ccts/images/R2T_Appendix_Documents/Pollock_Authentication_Appendix.pdfOther Research Plan Section:Include as an attachmentDo not include in the Research Strategy

13. Summary of NIH Changes: 12.7.16 - 1.25.18 TopicEffective DateSummary of ChangeWebsiteAuthentication of Key Biological and/or Chemical Resources(NOT-OD-17-068)25-May-17For research grants, use of a new "Authentication of Key Biological and/or Chemical Resources" attachmenthttps://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-068.htmlNIH Public Access Policy(NOT-OD-15-091)-Public Access Policy Progress Reports-How Papers Get into PMC18-Mar-14All investigators funded by NIH submit or have submitted to the National Library of Medicine's PubMed Central, an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication.https://publicaccess.nih.gov/policy.htmhttps://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-091.htmlhttps://www.ncbi.nlm.nih.gov/pmc/about/submission-methods/https://www.nihms.nih.gov/db/sub.cgi?process_auth=1&login=myNCBIData and Safety Monitoring Plans-Definitions, Guidelines-Templates for DSMB/C25-May-16A separate attachment to emphasize the importance and facilitate systematic enforcement of the Data and Safety Monitoring Plan.https://www.nia.nih.gov/research/dgcg/clinical-research-study-investigators-toolbox/data-and-safety-monitoring

14. NEW NIH MECHANISMSNew MechanismDescriptionWebsitesR34 (PAR-17-133)Applications that propose the complete planning, design, and preparation of the documentation necessary for implementation of investigator-initiated clinical trials. The application should propose the developmental work to be performed that would enhance the probability of reaching definitive outcomes in a clinical trial.Supports planning for clinical trials that address high-priority research questions related to the mission and goals of the funding agency. Sufficient pre-clinical data to support the planning of the clinical trial should be available prior to submission of the R34 grant application. The proposed trials should be hypothesis-driven and milestone-defined.https://grants.nih.gov/grants/guide/pa-files/PAR-17-133.htmlhttps://grants.nih.gov/grants/peer/r_awards/R34_guide_for_reviewers.pdf

15. NEW NIH MECHANISMSNew MechanismDescriptionWebsitesR61/R33(PAR-16-405)Supports applications to develop and implement phase II and beyond investigator-initiated single-site clinical trials. Applications must be relevant to the research mission of the NHLBI and meet the NIH definition of a clinical trial.The award is bi-phasic and milestone-driven. Applications must present the scientific rationale for the clinical trial and a comprehensive scientific and operational plan that describes the conduct of the trial, as well as plans for project management, subject recruitment and retention, performance milestones, scientific conduct of the trial, and dissemination of results.The multiple PD/PI model is strongly encouraged but not required. Applicants are encouraged to include a PD/PI with expertise in biostatistics, clinical trial design, and coordination.https://grants.nih.gov/grants/guide/pa-files/PAR-16-405.htmlhttp://www.nhlbi.nih.gov

16. UPDATES: Data Use Agreement-CWRUKey AspectsDescriptionWhat is a data use agreement (DUA)?A Data Use Agreement (DUA) is a contractual document used for the transfer of data that have been developed by nonprofit, government or private industry, where the data are nonpublic or are subject to some restrictions on its use.When is a DUA needed?When a member of a research team leaves CWRU or the research team wishes to have access to the data which belongs to CWRU.When an individual who is not an employee of CWRU requests access to and use of the data which belongs to CWRU.Who manages the DUAs at CWRU?Technology Transfer Office at CWRU. Current contact person: Andy Jarrell at 368-1401 or amj29@case.edu What are the steps of submitting DUA?Complete & submit a DUA Review Form to Technology Transfer (See Google Site)Technology Transfer composes the actual agreement & obtains approval from CWRU legalObtain needed signaturesIssues to ConsiderDifferent considerations if data are de-identified vs not de-identifiedNeed clear understanding of where data are currently housed & where data by requesting individual will be housedNeed clear understanding of what requested data will be used for

17. TRAINING SLIDES FOR NIH REVIEWERS ARE ATTACHED TO ADD ADDITIONAL CLARIFICATION REGARDING SCORING CRITERIA FOR nih GRANTS

18. CSR Core Reviewer Training Slides August 19, 2017Training Resources CommitteeDr. Karyl Swartz, Chair

19. Overall Impact and SignificanceOverall Impact is the likelihood for the project to exert a sustained, powerful influence on the research field.Evaluation is driven by the importance of the problem in the field.Overall Impact can be influenced by all five scoreable criteria (significance, investigator, innovation, approach, environment) and score-driving criteria, prioritized according to reviewer judgment.Significance is a key score-driving review criterion that evaluates the potential effect on the field if the aims are SUCCESSFULLY completed. Evaluate if project is based on a strong premise, or scientific foundation.Assuming successful completion of aims, evaluate how much the project will move the field forward.Describe specific advancement in knowledge, technology, or clinical practice that the project will bring, NOT the importance of the topic, field, or disease.6

20. Examples of projects with potential high significance and high overall impact:studies of fundamental properties of basic biological processes without any translational aimprojects that study rare diseasesprojects that use in silico, in vitro, or in vivo models (cell lines, invertebrate or vertebrate animal models, or human subjects)non-hypothesis driven, exploratory studiestechnological, methods development, models creation, data analytic and analytic methods development effortsdata collecting, cataloguing, cohort building or other resource development projectsAn application need not have a direct link to health nor be hypothesis-driven to have significanceNote: Mission of NIH includes basic & clinical research7

21. Investigator(s): evaluate productivity of the investigators in terms of impact of their work on the field, not just by number of publications or the impact factor of the journalsevaluate PI’s ability to lead a major project but not their independence a collaboration should be supported by a letter and/or a history of previous collaboration, not necessarily by requesting budget supportInnovation: conceptual and/or technological use of appropriate methodology that may not be innovative is not a weaknessApproach: address scientific rigor and relevant biological variables including sexevaluate whether strategy, methods and preliminary data support feasibilityconsider whether pitfalls and alternative strategies are discussedEnvironment: evaluate if the specific resources available are appropriate for the needs of the project, not the prestige of the institutionOther Scored Criteria8

22. Rigor and ReproducibilityRationale: To support the highest quality of research, public accountability, and social responsibility in the conduct of science, scientific community makes a special effort to advance rigor in designing and performing research and the ability to reproduce biomedical research findings. NIH’s Rigor and Reproducibility policy clarifies expectations and highlights four areas that need more explicit attention by applicants and reviewers. Scientific Premise is the scientific foundation of the project, including the quality and strength of prior research. As defined by NIH, premise is distinct from a hypothesis or justification; it is a retrospective consideration of the foundation for the application. Under Significance, explain how specifically the underlying preliminary data and/or published literature support the scientific question (score-driving). Needs to be a scientific justification if both sexes are NOT included. State whether data will be disaggregated by sex or other biologic variables.2. Scientific Rigor is the strict application of the scientific method that supports robust and unbiased approach in design, analysis, interpretation, and reporting of results. Sufficient information should be provided for the study to be assessed and reproduced. Animal numbers and other statistics should be included in the Research Plan. Scientific Rigor is addressed under Approach (score-driving).9

23. 3. Relevant Biological Variables, including sex: all studies involving human subjects or vertebrate animals should account for sex and other relevant biological variables (age, source, weight, or genetic strain). Should be explicitly addressed under Approach (score-driving).State whether humans and/or vertebrate animals of both sexes are includedIf only one sex is being used, state whether and how this is scientifically justified. Cost, absence of known sex differences, aggressiveness of male mice are not adequate justifications State whether the data will be disaggregated according to sex and other biological variables4. Key biological and/or chemical resources: cell lines, specialty chemicals, antibodies and other biologics that may differ from laboratory to laboratory or over time. Provide specific evaluation of the processes used to validate quality of key resources to avoid unreliable results This is a non score-driving review consideration addressed in separate section of critique, but severe concerns may affect ApproachRigor and Reproducibility10

24. Human Subjects Protections and Inclusions: Score-DrivingRegardless of whether application designates Yes or No for Human Subjects, evaluate whether human subjects are involved and whether exemptions may apply.If research involves human subjects (but does not qualify for IRB Exemptions), evaluate four points:the risk to subjectsthe adequacy of protection against riskpotential benefits of the research to subjects and othersthe importance of the knowledge to be gainedIf the application proposes a clinical trial, consider if the application describes an appropriate Data and Safety Monitoring Plan. (*NIH has its own definition of clinical trial). Can be in Human Subjects section. Secondary data analyses are usually considered as Human Subjects research. Need data use agreements. If claiming an exemption, then need to include details/process regarding how they will de-identify data.If research involves human subjects (but does not qualify for IRB Exemptions), evaluate if the proposed inclusion of women, minorities, and children under 18 years of age is scientifically justified.11

25. Vertebrate Animals and Biohazards: Score DrivingFor any proposed use of live vertebrate animals, comment on four points:description of procedures, including species, strains, ages, sex, and total number of animals (justification of animal numbers is now part of Research Plan)justification for the choice of speciesminimization of pain and distress method of euthanasia is now included in the PHS form D Cover Page Supplement; if not consistent with the recommendations of the AVMA Guidelines for the Euthanasia of Animals, a description and scientific justification of the method should be provided in the text boxBiohazards are research components known in the professional community to pose a risk to research personnel and/or the environment (biological organisms, toxins, radioactivity, dangerous chemicals, or recombinant DNA). Applications do not contain a separate section on Biohazards. They can be addressed throughout the application, including the Facilities sectionDetermine whether proper handling procedures and adequate protections are addressed (personnel training, safety protocols, containment facilities, waste disposal)12

26. Resubmission (A1) is an unfunded application that has been modified following initial review and resubmitted for new consideration. Evaluate & Score the application presented. Comment on the quality of changes made in response to the initial review (summarized in Introduction). Have they addressed prior concerns sufficiently or are there still issues?Current score should not be influenced by the score from the previous submissionRenewal is an application requesting additional funding for a period subsequent to that provided by the current award. Evaluate progress made in the last period of support, not necessarily by publications in high impact journals, but in terms of achieving the previous goals and the impact this has had on the fieldResubmission and Renewal: Score Driving13

27. Applications from Foreign Organizations – evaluate if other countries present special opportunities not available in the USSelect Agents are hazardous materials that pose a severe threat to public as listed by DHHS (not general Biohazards)Resource Sharing Plans relate to unique developed tools such as model organisms or genomic data. If budget >$500K for one year or using Genomic data—a resource sharing plan is required to share information with other researchers. Should reviewers be concerned if this is developing something that could be commercialized? Is there a plan to share this “app” (or commercialized product) with other PIs.Authentication of Key Biological and/or Chemical Resources. Needs to be authentication (biologic variables)—especially if not using a kit.Budget and Period of Support – if proposing changes in time or amount, make specific recommendations, and comment on potential overlap14Assigned reviewers should evaluate and comment on Additional Non Score-Driving Review Considerations

28. Overall ImpactScore1 2 34 5 67 8 9HighMediumLowEvaluating Overall ImpactEvaluating Overall Impact: Consider the 5 criteria: significance, investigator, innovation, approach, environment (weighted based on reviewer’s judgment) and other score influences (e.g. human subjects)5 is a good medium-impact application, and the entire scale (1-9) should always be considered.e.g. Applications may be addressing a problem of high importance in the field, but weaknesses in the criteria bring down the overall impact to medium.e.g. Applications may be addressing a problem of moderate importance in the field, with some or no weaknesses.e.g. Applications may be addressing a problem of moderate/high importance in the field, but weaknesses in the criteria bring down the overall impact to low.e.g. Applications may be addressing a problem of low or no importance in the field, with some or no weaknesses.e.g. Applications are addressing a problem of high importance/interest in the field. May have some or no weaknesses. Overall Impact: The likelihood for a project to exert a sustained, powerful influence on research field(s) involved15