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

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No policies existed to make sure that the public had access to results from unpublished NIH-funded research (BMJ 2011;344:d7292 doi: /bmj.d7292 (Published 3 January 2012))
Lack of transparency in results reporting;
impedes scientific progress
dishonors research participants
wastes tax-payers’ research funding

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 trials
Facilitate clinical trials design and reduce duplication
Promote dissemination of research information and results
Foster responsible stewardship of public’s research investment

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

5. Improved Research Enterprise
NIH Initiatives to Enhance Clinical Trial Stewardship and Human Subjects Research
GCP Training
Updated Application Forms
sIRB
Common Rule
Expanded Registration & Reporting
Improved Research Enterprise
Clinical Trial Specific FOAs
Clinical Trial Review Criteria

6. New Reforms & Initiatives
Research that Meets the NIH Definition of a Clinical Trial
All Research Involving Human Participants
New forms to collect human subjects information
Use of a single Institutional Review Board (IRB) for domestic multi-site studies
Training in Good Clinical Practice (GCP)
Clinical trial-specific Funding Opportunity Announcements (FOAs)
New review criteria
Expanded registration and results reporting in ClinicalTrials.gov

7. Know NIH Definition of a Clinical Trial
A 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.
Before we can dive into the details, we must first understand what research falls under these reforms and how NIH defines a clinical trial.
Learn more at

8. NIH Definition of a Clinical Trial
Prospectively 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 strategies

9. NIH Definition of a Clinical Trial
Health-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 life

10. NIH Definition of a Clinical Trial
Definition was clarified in October 2014
Encompasses a wide range of types of trials, including:
Mechanistic
Exploratory
Pilot/Feasibility
Behavioral
With broader definition, many more studies are classified as clinical trials
Notice:

11. Determine if Your Study is an NIH-defined Clinical Trial
Does 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 participants
Have a health-related biomedical or behavioral outcome?
If “yes” to ALL of these questions, your study is considered a clinical trial
Clinical Trial Interactive Decision Tree:

12. Determine if Your Study is an NIH-defined Clinical Trial
NIH Clinical Trial Decision Tree

13. Good Clinical Practice (GCP) Training Requirement
Change
Good Clinical Practice (GCP) Training Requirement
Effective 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)
NOT-OD ​ Policy on Good Clinical Practice Training for NIH Awardees Involved in NIH-funded Clinical Trials

14. Good Clinical Practice (GCP) Requirement
Receive GCP training if you are or expect to be involved in design, conduct, oversight, or management of clinical trials. Training could be:
Class or course
Academic training program
Certification from a recognized clinical research professional organization
NIH GCP training
Retain documentation of training
Refresh training at least every three years
Some GCP training options:
FAQs on GCP:

15. Clinical Trial-Specific Funding Opportunities
Change
Clinical Trial-Specific Funding Opportunities
Applications/proposals involving clinical trials (due dates on or after January 25, 2018) must be submitted to an FOA/RFP that accepts clinical trials
NOT-OD :
NOT-OD :

16. Clinical Trial-Specific Funding Opportunities
Change
Clinical Trial-Specific Funding Opportunities
3 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)

17. Identify Appropriate FOA
FOA Title (new FOAs only)
FOA Section II. Award Information
There are two primary places that your FOA will indicate whether it accepts clinical trials or not
Link to decision tool to help you determine if you are doing a clinical trial.

18. Changes to the Review Criteria
For Research Project (R) applications proposing clinical trials:
Clinical trial-related questions in addition to standard review criteria:
Significance
Investigators
Innovation
Approach
Environment
Study Timeline
NOT-OD : New Review Criteria for Research Project Applications Involving Clinical Trials

19. Changes to the Review Criteria
For Career Development (K) applications proposing clinical trials:
Clinical trial-related questions in addition to standard review criteria:
Candidate
Research Plan
Mentors, co-mentors, consultants, collaborators
Environment & Institutional Commitment to Candidat
Study Timeline for Clinical Trials
NOT-OD New Review Criteria for Career Development Award Applications Involving Clinical Trials 

20. Changes to the Review Criteria
For 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 Consultants
Research training plan
NOT-OD : 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
For 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/mentors
NOT-OD : 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 Form
Change
New Human Subjects and Clinical Trials Information Form
Required for all applications with due dates on or after January 25, 2018
Consolidates human subjects and clinical trial information into one place
Expands information required for studies meeting definition of NIH clinical trial
Collects information at the study level
Aligns with ClinicalTrials.gov
<recap benefits of new data collection strategy and close out video>
NOT-OD  New NIH "FORMS-E" Grant Application Forms and Instructions
NOT-OD New “FORMS-E” Grant Application Instructions Available

23. Become Familiar with new HS/CT Form
Take 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 Form
Review Annotated Form Set for NIH Grant Applications - FORMS-E Series

25. Protocols in Applications: Appendix Policy
Change
Protocols in Applications: Appendix Policy
Protocols only allowed in appendix when required by FOA
Requirement associated with review criteria
Only placed in appendix, when required by FOA
Placement elsewhere results in return on application
Another recent policy update that is somewhat related to this new HS/CT form is the updated appendix policy. Because the new HS/CT form will collect key elements from the protocol, the option to submit this protocol with the appendix will be removed.
For Parent FOAs, our default option will be not to allow the inclusion of the protocol in the application, and if it’s included, the application will be sent back.
But for IC-issued FOAs, the FOA must state that it’s a requirement to include the protocol in the appendix (not in the new HS/CT form). This requirement must also be added to the review criteria.

26. Single IRB for Domestic Multi-Site Research
Change
Single IRB for Domestic Multi-Site Research
NIH-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, 2018
NOT-OD   Final NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research
NOT-OD  Revision: Notice of Extension of Effective Date for Final NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research
NOT-OD  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 Research

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

28. Applications/Proposals
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 sIRB
Sites will sign reliance agreement that will include a communication plan
Indicate who will maintain records of this agreement

29. Applications/Proposals
Exceptions
For legal, regulatory, or policy-based exceptions: provide specific citation and indicate which sites are impacted
Special consideration, “ad hoc” exceptions, provide compelling justification
Several protocols may have one sIRB plan for all
If delayed onset, in justification include statement that awardee will follow the policy and will provide sIRB info prior to start
Budget as if no
ad hoc exception

30. Implementation Timeline

31. Where Do I Go For More Information?

32. Public Website on Clinical Trial Requirements

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

34. Public Website on Clinical Trial Requirements

35. Public 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 FOA

37. Public Page Has Training Resources Too

38. What You Should Do Contact a Program Officer Read/select FOA carefully
Are clinical trials allowed?
Additional review criteria?
Protocol submission required?
Apply early to FOA
Read/become familiar with application instructions
New Human Subjects/Clinical Trials form

40. Get Prepared! GCP Training Clinical Trials FOAs Single IRB Common Rule
Updated Application Forms
Single IRB
Common Rule
Expanded registration and reporting
Get Prepared!