NIH Forms E Town Hall 1.17.2018

SF424 Forms E Major Changes Removal of Human Subjects Sections from the Research Plan and other form pages Protections Data Safety Monitoring Plan Inclusion/Enrollment Introduction of Human Subjects & Clinical Trials form https://grants.nih.gov/grants/funding/Grant_Application_Form_Update-FORMS-E.pdf

Why Changes to Clinical Trial Policies? Government Accountability Office recommended: NIH better track number of funded clinical trials Improve data collection overall Ensure results are published and/or reported in a public database

New Policies & Regulations Primary Aims: Enhance application and award processes to increase NIH’s ability to assess the merits and feasibility of clinical trial applications Improve oversight and transparency Increase the sharing of clinical trial results

Am I doing Human Subjects Research? https://humansubjects.nih.gov/questionnaire

Is my submission a Clinical Trial? https://grants.nih.gov/ct-decision/index.htm

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 a placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

SF424 Forms E Program Announcements All FOAS will specify the allowability of clinical trials in Section II. Award Information All clinical trials FOAs will specify allowability of clinical trials in FOA title FOAs that accept clinical trials will incorporate specific review criteria to ensure that reviewers appropriately consider clinical-trial related information

SF424 Forms E Weill Research Gateway

SF424 Forms E Human Subjects & Clinical Trial Form

SF424 Forms E Human Subjects & Clinical Trials Form

SF424 Forms E Human Subjects & Clinical Trials Study Record Form Section Information Example HS Required? CT Required? 1 Basic Information Study Exemptions; Human Participants Yes 2 Study Population Study Focus; Inclusion Enrollment 3 Protection and Monitoring Plans Protection of Subjects; DSMB Partial 4 Protocol Synopsis Narrative, Intervention Type No 5 Other CT Attachments Upload Link

Human Subjects & Clinical Trial Form Section 1 – Basic Information

EXEMPT RESEARCH CATEGORIES 8 new categories defined in 45 CFR 46.104(d) (effective January 19, 2018) Commonly used exempt categories: “Research, conducted in established or commonly accepted educational settings, that specifically involves normal educational practices that are not likely to adversely impact students’ opportunity to learn required educational content or the assessment of educators who provide instruction.” [Category 1] “Research that only includes interactions involving educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior (including visual or auditory recording)” that meet one of three criteria. [Category 2] “Research involving benign behavioral interventions in conjunction with the collection of information from an adult subject through verbal or written responses (including data entry) or audiovisual recording if the subject prospectively agrees to the intervention and information collection…” that meet one of three criteria. [Category 3] “Secondary research for which consent is not required: Secondary research uses of identifiable private information or identifiable biospecimens” that meet one of four criteria. [Category 4]

Am I doing Human Subjects Research? https://humansubjects.nih.gov/questionnaire

Human Subjects & Clinical Trial Form Section 1 – Basic Information https://grants.nih.gov/policy/clinical-trials/definition.htm

Human Subjects & Clinical Trial Form Section 1 – Basic Information 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. Interventions 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. E.g., drugs/small molecules/compounds; surgical techniques, delivery systems such as face-to-face strategies, strategies to change health-related behavior (e.g., diet, cognitive therapy), treatment strategies, prevention strategies, diagnostic strategies. Health-related Biomedical or Behavioral Outcomes The pre-specified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status on quality of life. E.g., positive or negative changes to physiological or biological or psychological parameters, or disease process, or changes to quality of life.

Human Subjects & Clinical Trial Form Section 2 – Study Population Characteristics

Recruitment & Retention Plan Tailored based on target population, research design, research procedures, etc. and include thorough “SWOT”-like analysis. Recruitment considerations: feasibility plan (e.g. recruiting subjects from ED without prior discussions with ED leadership), targeted strategies, tailored recruitment tools, Retention plans should be proactive (electronic reminders for visits, frequent communications, reimbursement for subject transportation costs, video conference, etc.) Retention considerations: subject population, sufficient staff

Human Subjects & Clinical Trial Form Section 3 – Protection & Monitoring Plans

Single IRB Review and Data Safety Monitoring Multi-Site/Center Applications: Single IRB (“IRB of Record”) discussion with IRB office PRIOR to submitting grant application Requires submission to WCM IRB office (in eIRB) regardless of where IRB review is taking place Suggested language for inclusion in applications

WCM Data and Safety Monitoring Board (DSMB) Independent committee safeguarding clinical trial participants monitoring interim safety and efficacy outcomes data in ongoing trials Provides expertise, including recommendations regarding the continuation, modification, or termination of any or all arms of a study Monitors 65 studies, including 29 IND holders and 21 multi-site studies Meets on a monthly basis dsmb@med.cornell.edu

Data and Safety Monitoring Plan (DSMP) All protocols require a DSMP commensurate with the degree of risk and complexity of the protocol Greater than minimal risk studies require a Data and Safety Monitoring Board A DSMP should include: Monitoring of risk (adverse events (SAEs, UAEs, UPs) including frequency and attribution) Monitoring of data (aggregate data, accrual information, protocol deviations, interim analysis (if applicable)) Rules for study termination, including stopping rules for participants How the monitoring will be conducted, how often, by whom (PI, DSMB, medical monitor) Description of the composition of the DSMB, if applicable, including expertise of members

Human Subjects & Clinical Trial Form Section 4 – Protocol Synopsis

Human Subjects & Clinical Trial Form Section 4 – Protocol Synopsis

Human Subjects & Clinical Trial Form Section 5 – Other Clinical Trial-related Attachments Provide additional trial-related information only if your FOA specifically requests it

Other NIH Mechanisms Training Awards Fellowship Awards Do not support clinical trials (with the exception of some D43 and K12 awards) All Training FOAs will be designated as “Clinical Trial Not Allowed” but will indicate that appointed trainees are permitted to obtain research experience in a clinical trial led by mentor/co-mentor Some D43 and K12 FOAs will be designated as “Clinical Trial Optional’ Fellowship Awards All will be designated as ‘No Independent Clinical Trials,’ but will indicate that applicants are permitted to propose research experience in a clinical trial led by sponsor/co-sponsor Career Development Awards FOAs that indicate ‘Clinical Trial Required’ will support independent clinical trials conducted by the applicant FOAs that indicate “No Independent Clinical Trials” permit the applicant to propose research experience in a clinical trial led by a sponsor/co-sponsor

SF424 Forms E Human Subjects & Clinical Trials Resources Walkthrough Video https://www.youtube.com/watch?v=nz9NWFhYOG8 SF424 Application Guide https://grants.nih.gov/grants/how-to-apply-application-guide.html NIH e-Protocol Template https://e-protocol.od.nih.gov/#/home NIH Definition of Clinical Trial Case Studies https://grants.nih.gov/policy/clinical-trials/case-studies.htm

Weill Cornell Resources IRB http://researchintegrity.weill.cornell.edu/institutional_review_board/ DSMB http://researchintegrity.weill.cornell.edu/dsmb/ Joint Clinical Trials Office Standardized Protocol Template https://jcto.weill.cornell.edu/sites/default/files/downloads/iit_protocol_template_-_wcm_-_version_2.0.doc   Joint Clinical Trials Office Subject Recruitment and Activation https://jcto.weill.cornell.edu/investigators/study-activation-and-conduct/researchers-toolbox Clinical & Translational Science Center http://weill.cornell.edu/ctsc/services_and_resources/ Weill Research Gateway Guides https://its.weill.cornell.edu/guides/wrg-sponsored-programs-guides

Contact Information Office of Sponsored Research Administration https://research.weill.cornell.edu/about-us/leadership-directory/osra-directory IRB/Office of Human Research Protections & DSMB http://researchintegrity.weill.cornell.edu/ORI_staff/index.html Joint Clinical Trials Office https://jcto.weill.cornell.edu/ Study Recruitment jctosrc@med.cornell.edu