NIH Clinical Trials Updates: Putting it All Together. Why the changes to NIH-funded studies involving human subjects?

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1 NIH Clinical Trials Updates: Putting it All Together Sherry Mills, MD MPH Director Office of Extramural Programs Office of Extramural Research NIH 1 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 No policies existed to make sure that the public had access to results from unpublished NIH-funded research (BMJ 2011;344:d7292 doi: /bmj.d7292 (Published 3 January 2012)) Lack of transparency in results reporting; impedes scientific progress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 2 1

2 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 3 What has changed? and what you need to do. 4 2

3 NIH Initiatives to Enhance Clinical Trial Stewardship and Human Subjects Research sirb Common Rule GCP Training Improved Research Enterprise Updated Application Forms Expanded Registration & Reporting Clinical Trial Specific FOAs Clinical Trial Review Criteria New Reforms & Initiatives 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 Research that Meets the NIH Definition of a Clinical Trial Training in Good Clinical Practice (GCP) Clinical trial-specific Funding Opportunity Announcements (FOAs) New review criteria Expanded registration and results reporting in ClinicalTrials.gov 6 3

4 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. Learn more at 7 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 healthrelated 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 8 4

5 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 9 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:

6 Determine if Your Study is an NIHdefined Clinical Trial Does your study 1. Involve one or more human participants? 2. Prospectively assign human participant(s) to intervention(s)? 3. Intend to evaluate the effect of an intervention on human participants 4. 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: 11 Determine if Your Study is an NIH-defined Clinical Trial NIH Clinical Trial Decision Tree

7 Good Clinical Practice (GCP) Training Requirement Change 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 NIHfunded Clinical Trials 13 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: extramural intranet.od.nih.gov/d/hs/gcptraining FAQs on GCP: 14 7

8 Clinical Trial-Specific Funding Opportunities Change 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 : 15 Clinical Trial-Specific Funding Opportunities 3 Types of FOAs Clinical Trials Not Allowed only accepting applications not proposing clinical trial(s) Change 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) 16 8

9 Identify Appropriate FOA FOA Title (new FOAs only) FOA Section II. Award Information Link to decision tool to help you determine if you are doing a clinical trial. 17 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 Change Study Timeline NOT-OD : New Review Criteria for Research Project Applications Involving Clinical Trials 18 9

10 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 NOT OD New NIH "FORMS E" Grant Application Forms and Instructions NOT OD New FORMS E Grant Application Instructions Available Change 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

11 Become Familiar with new HS/CT Form Review Annotated Form Set for NIH Grant Applications - FORMS-E Series 21 Protocols in Applications: Appendix Policy Change 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 22 11

12 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) Change 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 23 Single IRB for Domestic Multi-Site Research (cont d) Change 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) 24 12

13 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 25 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 26 13

14 Expanded Registration and Reporting Requirements Change Effective January 18, 2017 All NIH-funded awardees and investigators conducting clinical trials must register and report the results of their trial in ClinicalTrials.gov Relevant Policies: FDAAA/HHS Final Rule -- Applicable Clinical Trials (ACT) NIH Policy on Dissemination of NIH-Funded Clinical Trial Information extends to all NIH-funded clinical trials Learn more at 27 Expanded Registration and Reporting Requirements In order to comply with the NIH Policy on Clinical Trial Dissemination, awardees must: Submit a statement in the application that outlines a plan to comply with the expectations of the policy Register the clinical trial no later than 21 days after enrolling the first participant Update the trial with submitted information at least once a year Submit summary results no later than one year after primary completion date 28 14

15 Implementation Timeline Where Do I Go For More Information? 15

16 Public Website on Clinical Trial Requirements trials.htm 31 Public Website on Clinical Trial Requirements Video Overview of New Policies on Human Subjects Research 16

17 Public Website on Clinical Trial Requirements trials.htm 33 Public Website on Clinical Trial Requirements trials.htm 34 17

18 Decision Tool Walks Through Questions, Links to Definition FAQs and Case Studies and Provides Advice for Picking the Right FOA 35 Public Page Has Training Resources Too 36 18

19 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

20 Get Prepared! 39 20