NIH Clinical Trial Initiatives: - PowerPoint Presentation

1. NIH Clinical Trial Initiatives: “Putting it All Together”1

2. Why the changes to NIH-funded studies involving human subjects?No policies existed to make sure that the public had access to results from unpublished NIH-funded research (BMJ 2011;344:d7292 doi: 10.1136/bmj.d7292 (Published 3 January 2012))Lack of transparency in results reporting; impedes scientific progressdishonors research participantswastes tax-payers’ research funding 2

3. Why the changes to NIH-funded studies involving human subjects?New NIH Clinical Trial Initiatives will help to :Maximize use of knowledge from clinical trialsFacilitate clinical trials design and reduce duplicationPromote dissemination of research information and resultsFoster responsible stewardship of public’s research investment3

4. 4What has changed?…and what you need to do.

5. GCP TrainingsIRBCommon RuleClinical Trial Specific FOAsClinical Trial Review CriteriaExpanded Registration & Reporting Updated Application Forms Improved Research EnterpriseNIH Initiatives to Enhance Clinical Trial Stewardship and Human Subjects Research

6. New Reforms & InitiativesAll Research Involving Human ParticipantsNew forms to collect human subjects information Use of a single Institutional Review Board (IRB) for domestic multi-site studiesResearch that Meets the NIH Definition of a Clinical TrialTraining in Good Clinical Practice (GCP)Clinical trial-specific Funding Opportunity Announcements (FOAs)New review criteriaExpanded registration and results reporting in ClinicalTrials.gov6

7. Know NIH Definition of a Clinical TrialA research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.Learn more at https://grants.nih.gov/policy/clinical-trials/definition.htm 7

8. NIH Definition of a Clinical TrialProspectively Assigned: a pre-defined process (e.g., randomization) specified in an approved protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervention, placebo, or other control) of a clinical trial.Intervention: a manipulation of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints. Examples include: drugs/small molecules/compounds, biologics, devices procedures (e.g., surgical techniques); delivery systems (e.g., telemedicine, face-to-face interviews)strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits) treatment strategies, prevention strategies, and diagnostic strategies8

9. NIH Definition of a Clinical TrialHealth-related Biomedical or Behavioral Outcome: the pre-specified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life. Examples include: positive or negative changes to physiological or biological parameters (e.g., improvement of lung capacity, gene expression) positive or negative changes to psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers, reading comprehension and/or information retention) positive or negative changes to disease processes positive or negative changes to health-related behaviors positive or negative changes to quality of life9

10. NIH Definition of a Clinical TrialDefinition was clarified in October 2014Encompasses a wide range of types of trials, including:MechanisticExploratoryPilot/FeasibilityBehavioralWith broader definition, many more studies are classified as clinical trials Notice: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html10

11. Determine if Your Study is an NIH-defined Clinical TrialDoes your study…Involve one or more human participants?Prospectively assign human participant(s) to intervention(s)?Intend to evaluate the effect of an intervention on human participantsHave a health-related biomedical or behavioral outcome? If “yes” to ALL of these questions, your study is considered a clinical trialClinical Trial Interactive Decision Tree: https://grants.nih.gov/ct-decision/index.htm11

12. Determine if Your Study is an NIH-defined Clinical Trial12NIH Clinical Trial Decision Treehttps://grants.nih.gov/ct-decision/index.htm

13. Good Clinical Practice (GCP) Training RequirementEffective January 1, 2017 –NIH-funded clinical investigators and NIH staff who are involved in the design, conduct, oversight, or management of clinical trials are to be trained in Good Clinical Practice (GCP)13NOT-OD-16-148​ Policy on Good Clinical Practice Training for NIH Awardees Involved in NIH-funded Clinical TrialsChange

14. Good Clinical Practice (GCP) RequirementReceive GCP training if you are or expect to be involved in design, conduct, oversight, or management of clinical trials. Training could be:Class or courseAcademic training programCertification from a recognized clinical research professional organizationNIH GCP trainingRetain documentation of trainingRefresh training at least every three years14Some GCP training options: https://nih-extramural-intranet.od.nih.gov/d/hs/gcptrainingFAQs on GCP:https://grants.nih.gov/grants/policy/faq_nih_good_clinical_practice.htm#5162 

15. Clinical Trial-Specific Funding OpportunitiesApplications/proposals involving clinical trials (due dates on or after January 25, 2018) must be submitted to an FOA/RFP that accepts clinical trials15NOT-OD-16-147: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-147.htmlNOT-OD-17-043: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-043.htmlChange

16. Clinical Trial-Specific Funding Opportunities3 Types of FOAs Clinical Trials Not Allowed – only accepting applications not proposing clinical trial(s)Clinical Trials Required – only accepting applications proposing clinical trial(s)Clinical Trials Optional – accepting applications that either propose or do not propose clinical trial(s)16Change

17. Identify Appropriate FOAFOA Title (new FOAs only)FOA Section II. Award Information17Link to decision tool to help you determine if you are doing a clinical trial.

18. Changes to the Review Criteria 18For Research Project (R) applications proposing clinical trials:Clinical trial-related questions in addition to standard review criteria:Significance InvestigatorsInnovationApproachEnvironmentStudy Timeline ChangeNOT-OD-17-118: New Review Criteria for Research Project Applications Involving Clinical Trials

19. Changes to the Review Criteria 19For Career Development (K) applications proposing clinical trials:Clinical trial-related questions in addition to standard review criteria:Candidate Research PlanMentors, co-mentors, consultants, collaboratorsEnvironment & Institutional Commitment to CandidatStudy Timeline for Clinical TrialsChangeNOT-OD-17-121 New Review Criteria for Career Development Award Applications Involving Clinical Trials 

20. Changes to the Review Criteria 20For Fellowship (F) applicants proposing to gain research experience in a sponsor or co-sponsor led clinical trial:Clinical trial-related questions in addition to standard review criteria:Sponsors, Collaborators, and ConsultantsResearch training planChangeNOT-OD-17-122: New Review Criteria for Ruth L. Kirschstein National Research Service Award (NRSA) Individual Fellowship Applications Involving Research Experiences in Clinical Trials

21. Changes to the Review Criteria 21For Training (T) applications if appointee(s) propose to gain research experience in a mentor or co-mentor led clinical trial:Clinical trial-related questions in addition to standard review questions:Preceptors/mentorsChangeNOT-OD-17-123: New Review Criteria for Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grants Involving Research Experiences in Clinical Trials

22. New Human Subjects and Clinical Trials Information FormRequired for all applications with due dates on or after January 25, 2018Consolidates human subjects and clinical trial information into one placeExpands information required for studies meeting definition of NIH clinical trialCollects information at the study levelAligns with ClinicalTrials.govChangeNOT-OD-17-062 New NIH "FORMS-E" Grant Application Forms and InstructionsNOT-OD-17-119 New “FORMS-E” Grant Application Instructions Available

23. Become Familiar with new HS/CT Form23Take a video tour of the new form. Review High Level Summary of Form Changes: FORMS-E to learn about other form changes.

24. Become Familiar with new HS/CT Form24Review Annotated Form Set for NIH Grant Applications - FORMS-E Series

25. Protocols in Applications: Appendix PolicyProtocols only allowed in appendix when required by FOARequirement associated with review criteriaOnly placed in appendix, when required by FOAPlacement elsewhere results in return on application25Change

26. Single IRB for Domestic Multi-Site Research26NIH-funded multi-site domestic studies involving non-exempt human subjects research are expected to use a single IRB (sIRB)Effective for applications/proposals with due dates/solicitations published on or after January 25, 2018NOT-OD-16-094  Final NIH Policy on the Use of a Single Institutional Review Board for Multi-Site ResearchNOT-OD-17-076 Revision: Notice of Extension of Effective Date for Final NIH Policy on the Use of a Single Institutional Review Board for Multi-Site ResearchNOT-OD-16-109 Scenarios to Illustrate the Use of Direct and Indirect Costs for Single IRB Review under the NIH Policy on the Use of a Single IRB for Multi-site ResearchChange

27. Single IRB for Domestic Multi-Site Research (cont’d)27Exceptions to sIRB policy include:Foreign sitesCareer development (K), Research Training (T), and Fellowship (F) awardsSites where review by sIRB is prohibited by federal, tribal, or state law, regulation, or policyWhen there is a compelling justification (very rare)Change

28. In Single IRB plan, include:Name of the sIRB (if known)Indicate that, if funded:All sites, including any added after award, agree to rely on sIRBSites will sign reliance agreement that will include a communication planIndicate who will maintain records of this agreement Applications/Proposals28

29. ExceptionsFor legal, regulatory, or policy-based exceptions: provide specific citation and indicate which sites are impactedSpecial consideration, “ad hoc” exceptions, provide compelling justificationSeveral protocols may have one sIRB plan for allIf delayed onset, in justification include statement that awardee will follow the policy and will provide sIRB info prior to startApplications/Proposals29Budget as if no ad hoc exception

30. Implementation Timeline

31. Where Do I Go For More Information?

32. https://grants.nih.gov/policy/clinical-trials.htm 32Public Website on Clinical Trial Requirements

33. Public Website on Clinical Trial RequirementsVideo Overview of New Policies on Human Subjects Research

34. https://grants.nih.gov/policy/clinical-trials.htm 34Public Website on Clinical Trial Requirements

35. https://grants.nih.gov/policy/clinical-trials.htm 35Public Website on Clinical Trial Requirements

36. Decision Tool Walks Through Questions, Links to Definition FAQs and Case Studies and Provides Advice for Picking the Right FOA36

37. Public Page Has Training Resources Too37

38. What You Should DoContact a Program OfficerRead/select FOA carefullyAre clinical trials allowed?Additional review criteria?Protocol submission required?Apply early to FOARead/become familiar with application instructionsNew Human Subjects/Clinical Trials form38

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40. GCP TrainingClinical Trials FOAsUpdated Application FormsSingle IRBCommon RuleExpanded registration and reporting40Get Prepared!