ClinicalTrials: An introduction Presented by : Tracy Gatlin, B.S., CT Administrator

1. ClinicalTrials.gov: An introduction Presented by: Tracy Gatlin, B.S., CT.gov Administrator Date: September 20, 2017

2. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator 2 Terms to know: ACT-Applicable Clinical Trial. ICMJE-International Committee of Medical Journal Editors. CMS-Center for Medicare and Medicaid Services NIH-National Institute of Health. FDAMA-Food and Drug Administration Modernization Act of 1997 FDAAA-Food and Drug Administration Amendments Act of 2007

3. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator CT.gov: Historical Timeline 3 1997: Congress Passes Law (FDAMA) Requiring Trial Registration 2000: NIH Releases ClinicalTrials.gov Web Site 2005: International Committee of Medical Journal Editors Requires Trial Registration 2006: World Health Organization Establishes Trial Registration Policy 2007: Congress Passes Law (FDAAA) Expanding ClinicalTrials.gov Submission Requirements 2015: CMS requires NCT # for all billable research claims 2016: Final Rule for FDAAA 801 Issued 2016: Final NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information Issued

4. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator 4 Why do I have to register? • It is the law. • Your ability to publish could be affected. • Your funding as an investigator and for the institution could be affected. • Civil monetary penalties up to $11,569.00 for all violations in a single proceeding. • $11,569.00/day after 30 day period that the violation is uncorrected. • HHS may withhold remaining or future grants • NIH may post notices of non-compliance and issue penalties.

5. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator 5 Agencies Requiring Registration: • FDA/NIH-Applicable Clinical Trials (ACTs) • NIH-2016 Policy • ICMJE-Publication • CMS-Billing Medicaid Note: All 4 agencies have the ability to affect funding and publication for noncompliance.

6. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator 6 Determining A Trial For Registration: • CLARA submission • Is the study investigator initiated vs industry or cooperative group? • What is the study phase? • Is UAMS the main site? • What is the funding source? • Would this be an ACT? • Is the study already registered?

7. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator 7 Determining A Trial For Registration (Cont): • Determination is made • Not Applicable • Required under the law • Required under NIH policy • Not required but recommended for publication purposes (ICMJE) • Pending review of other committees • Investigator receives notification thru the CLARA system once a final determination has been made.

8. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator 8 CT.gov Database Modules: • Protocol Section • Study Status • Oversight • Study Description • Study Design • Outcome Measures • Results • Participant Flow • Baseline Characteristics • Outcome Measures and Statistical Analysis • Adverse Events

9. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator 9 Investigator Responsibilities: • Contact Administrator if assistance is needed: • New User Account • CT.gov Training • Register study prior to the first subject being enrolled, unless request placed for Administrator help with registration. • Keep study updated a minimum of every six months or as requested by the Administrator • Enter in results within one year of the Primary Completion Date

10. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator 10 CT.gov Administrator Responsibility: • Make determination for registration requirements in CLARA and notify the PI. • Assign new user accounts • Assist PI as requested • Send reminders via email/telephone • Review and release studies.

11. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator 11 Is my study an Applicable Clinical Trial? • Generally: • Study type: Interventional • Study Phase/Primary Purpose: Other than Phase 1/other than feasibility • Studies a U.S. FDA-regulated drug/device product • One or more of the following • At least one facility location with the U.S./U.S. territory • Clinical trial has an IND or IDE • A drug/device produyct under investigation is a product manufactured and exported from the U.S

12. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator 12 Is my study a clinical trial under the NIH policy? • Does the study involve human participants? • Are the participants prospectively assigned to an intervention? • Is the study designed to evaluate the effect of the intervention on the participants? • Is the effect being evaluated a health-related biomedical or behavioral outcome? If the answer to ALL 4 questions is yes then the study would be considered a clinical trial according to the NIH definition.

13. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator 13 ClinicalTrials.gov: What’s New? • Individual Participant Sharing Statement • Plan to Share Data and Plan Description have been added to the Protocol Section. • This section is optional under the law but is required under ICMJE • Documents Section • Allows for upload of study documents into CT.gov. • The study protocol and the Statistical Analysis Plan are required to be uploaded as part of the results information submission for all studies labeled as ACTs or that fall under the NIH policy with a Primary Completion Date on or after January 18, 2017. • Study documents must be in PDF/A format.

14. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator ORRA CT.gov Available Services: • Review for possible registration • Individual trial registration • Assistance with CT.gov conference call • Trial maintenance assistance Contact Tracy at tlgatlin@uams.edu for assistance 14

15. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator 15 • Tips! • Know your study • Acronyms and misspellings • Outcome measures • Primary outcome must be specific and measurable • Primary outcome must be one thing • Use the Description fields for detail, leave detail out everywhere else • No verbs and pronouns • Make it easy on yourself and copy/paste where you can • Ask for help.

16. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator • Resources: • Information on registering clinical trials: • http://prsinfo.clinicaltrials.gov • Revised FAQ section • https://clinicaltrials.gov/ct2/manage-recs/faq#act • The International Committee of Medical Journal Editors policy on trial registration: • http://www.icmje.org/clin_trialup.htm • NIH Policy on the Dissemination of Clinical Trial Information • http://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-149.html 16

17. ORRATracy L. Gatlin, B.S.UAMS ClinicalTrials.gov Administrator Contact Information: Tracy Gatlin, UAMS ClinicalTrials.gov Administrator Office of Research Regulatory Support, Slot 813 Phone: 686-6803 Email:tlgatlin@uams.edu 17