1. Melissa McCarey, MPH Jefferson Clinical Research Institute (JCRI) Melissa.McCarey@jefferson.edu Clinicaltrials.gov: What is it? What do I need to know?

2. What is Clinicaltrials.gov?

3. Evolution of Clinical Trial Disclosure Requirements 1997:FDAMA establishes ClinicalTrials.gov 2000:ClinicalTrials.gov launched 2005:ICMJE requires registration of trials (including at ClinicalTrials.gov) 2007:FDAAA expands ClinicalTrials.gov to require registration of more studies and results and adds penalties for noncompliance 2008:ClinicalTrials.gov adds basic results modules, including adverse events 2014: CMS billing rule implemented requiring NCT # (Full obligatory compliance required as of 1/1/2015) 2014:Notice of Proposed Rulemaking (NRPM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials made available for public comment Adapted from http://clinicaltrials.gov/ct2/about-site/historyhttp://clinicaltrials.gov/ct2/about-site/history 3

4. Why Should I Register? It’s the Law! - FDAAA If you want to publish your results! ICJME Requirements CMS Billing Rule – Mandatory reporting of NCT# on claims for items and services in “qualified clinical trails” for Medicare coverage Increases Research Transparency Helps people (patients, caregivers, providers, general public) find ongoing clinical trials

5. FDAAA FDAAA - Registration Required for “Applicable Clinical Trials”: Interventional studies (drugs, biologics, devices) Phase 2 – 4 (not phase 1 drug; not small feasibility device;) US FDA jurisdiction (e.g., IND/IDE or US site) Studies initiated after September 27, 2007, or initiated on or before that date and were still ongoing as of December 26, 2007 When: Within 21 days of enrollment of 1 st subject Update at least every 12 months (30 days for Recruitment Status and Primary Completion Date) http://clinicaltrials.gov/ct2/manage-recs/fdaaa 5

6. ICMJE ICMJE – Registration: Which studies? Required for Prospective studies that: Assign subjects to an intervention or concurrent comparison or control groups Study the cause/effect relationship between medical intervention and a health outcome. ICMJE scope is much broader than the scope of FDAAA: Interventions include procedures, behavioral treatments, dietary interventions Health outcomes include any biomedical or health-related measure obtained in participants, including pharmacokinetic measures and adverse events 6 Source: http://www.icmje.org/about-icmje/faqs/clinical-trials-registration/http://www.icmje.org/about-icmje/faqs/clinical-trials-registration/

7. Responsible Party FDAAA Definition Industry Sponsored multi-center trials Sponsor is responsible for determining and fulfilling requirements Site Investigators – check to ensure trials are registered Investigator Initiated Trials Principal Investigator is responsible for registering trials ICMJE & CMS Anyone may register, but for ICMJE the author is responsible for ensuring complete registration

8. Penalties for Failure to Register FDAAA Public notices of noncompliance and violations Withholding of NIH funds FDA sanctions Civil monetary penalties (up to $10,000/day)CMS Billing will be affected: delayed or deniedICMJE Cannot publish in journals following ICMJE policy, and other select journals

9. How do I Register my Trial? Contact your clinicaltrials.gov administrator (That’s Me!) for an account Make sure you have all required info: Status: not yet recruiting, enrolling, active, not recruiting etc Estimated Start Date & Primary Completion Dates Study Description – Key words, inclusion/exclusion, phase, study design, interventions and controls, number of arms and description Outcomes– Primary, secondary outcomes and timeframes Entry Complete – Entry is sent to Administrator I am always available to answer questions!!

10. FDAAA FDAAA – Results Submission Required for: Applicable Clinical Trials In which the study product is approved (for any use) by FDA When: Within 12 months of Primary Completion Date (final data collection for primary endpoint) If product not approved by Primary Completion Date but is approved later, then results due 30 days after approval Delays are possible, primarily for manufacturer or under limited special circumstances o Pending publication is NOT considered a good cause for delay http://clinicaltrials.gov/ct2/manage-recs/fdaaa 10

11. Results Section: Required Data Elements Participant Flow and Recruitment details Arm/Group assignment Completed/Lost to Follow-Up Baseline characteristics Outcome Measures Primary/Secondary/Post-Hoc Time points Unit of Measure Measures of Central Tendency Units of Dispersion Not Available – Explanation required

12. Questions