ClinicalTrials.gov and FDAAA for NIH Grantees NIH Regional Seminar – May 2016 Rebecca J. Williams, Pharm.D., MPH Assistant Director, ClinicalTrials.gov National Library of Medicine http://ClinicalTrials.gov

Overview Introduction to Section 801 of the Food and Drug Administration Amendments Act of 2007 (FDAAA) Rationale Requirements ClinicalTrials.gov Practical Considerations FDAAA Next steps Protocol Registration and Results System (PRS) Resources NIH Office of Extramural Research (OER) Resources and Tips

Rationale for Trial Registration & Summary Results Reporting

Why Conduct Clinical Trials? To obtain new and generalizable knowledge Key component of the body of scientific evidence that is used to inform medical decision making

How It’s Supposed to Work Clinical Trials Journals FDA Reviews Systematic Reviews Meta-analyses Guidelines Informed Decisions Health Outcomes

Three Key Issues Not all trials are published Publications do not always include all pre-specified outcome measures Unacknowledged changes are made to the trial protocol that would affect the interpretation of the findings e.g., changes to the pre-specified outcome measures

Zarin CTSA Webinar (10-21-09) Kaplan-Meier estimates for ulcer complications according to traditional definition. Results are truncated after 12 months, no ulcer complications occurred after this period. Adapted from Lu 2001. Source: Jüni P, Rutjes AW, Dieppe PA. BMJ. 2002 Jun 1;324(7349):1287-8. ClinicalTrials.gov / NLM 7

Summary of Findings Fewer than half of NIH funded trials registered at ClinicalTrials.gov after September 2005 and completed by December 2008 were published in a peer reviewed biomedical journal indexed by Medline within 30 months of trial completion After a median of 51 months after study completion, a third of NIH-funded trials in the sample remained unpublished BMJ 2011;344:d7292 doi

Public Benefits of Access to Clinical Trial Data Meet ethical obligation to human subjects (i.e., that results will be used to help others/inform science) Inform future research and research funding decisions Mitigate information bias (e.g., non publication) Evaluate research integrity (e.g.,adherence to protocol) Prevent duplication of trials of unsafe or ineffective interventions Provide access to data to support evidence-based medicine Enhance patient access to enrollment in clinical trials All contribute to increased public trust in clinical research

Levels of Transparency Zarin CTSA Webinar (10-21-09) Levels of Transparency 11 Zarin DA, Tse T. Science. 2008. ClinicalTrials.gov / NLM

About ClinicalTrials.gov Clinical studies registry and results database Over 210,000 studies (trials & observational studies) Studies with locations in all 50 states and 193 countries Privately and publicly funded studies involving humans Study information submitted by study sponsors or investigators Web Site & registry launched in February 2000 Results database, in September 2008 Over 21,000 studies with results Database updated daily Usage 65,000 unique visitors per day

FDAAA and Other Trial Disclosure Policies

Why Register and Report Results? Required by most medical journals (ICMJE*) Registration for all clinical trials (all interventions) http://www.icmje.org/publishing_10register.html It is Federal law! (FDAAA 801**) Registration & results submission for “applicable clinical trials” http://www.clinicaltrials.gov/ct2/manage-recs/fdaaa Encouraged for all NIH-supported trials Registration & results submission, even if not subject to FDAAA 801 http://grants.nih.gov/ClinicalTrials_fdaaa/ New NIH Policy Proposal to make this *required* * International Committee of Medical Journal Editors ** Section 801 of the Food and Drug Administration Amendments Act of 2007

Other reasons … Center for Medicare and Medicaid Services (CMS) requires NCT Number for coverage of routine costs of qualifying clinical trials U.S. Department of Veterans Affairs (VA) requires registration and results reporting of clinical trials funded by the VA Office of Research & Development U.S. National Cancer Institute (NCI) requires results reporting in a peer-reviewed scientific journal or ClinicalTrials.gov https://clinicaltrials.gov/ct2/manage-recs/background#WhyRegister

And more reasons… European Union requires registration and results reporting of certain drug and biologic clinical trials Declaration of Helsinki states that all research studies involving human subjects must be registered & researchers have a responsibility to make research results publicly available World Health Organization (WHO) considers registration a “scientific, ethical and moral responsibility” and states that there is an ethical imperative to report results And others!! https://clinicaltrials.gov/ct2/manage-recs/background#WhyRegister

“Medical advances would not be possible without participants in clinical trials,” said NIH Director Francis S. Collins, M.D., Ph.D. “We owe it to every participant and the public at large to support the maximal use of this knowledge for the greatest benefit to human health. This important commitment from researchers to research participants must always be upheld.” http://www.nih.gov/news/health/nov2014/od-19.htm

NIH Policy Proposal Guide Notice: NOT-OD-15-019 NIH-funded awardees & investigators conducting clinical trials, funded in whole or in part by NIH NIH-funded clinical trials must be registered and have summary results, including adverse event information, submitted to ClinicalTrials.gov NIH revised definition of clinical trial (Oct 2014) Includes Phase 1, all intervention types (broader than “ACT”) Same type of registration and results data and in the same timeframes as the trials subject to FDAAA Comment period closed March 2015 NIH Policy Proposal: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-019.html Revised NIH Definition of “Clinical Trial”: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html

NCI Clinical Trial Access Policy Guide Notice: NOT-CA-15-011 Released: January 28, 2015 http://grants.nih.gov/grants/guide/notice-files/NOT-CA-15-011.html Final Trial Results are expected to be reported in a publicly accessible manner (peer-reviewed scientific journal or ClinicalTrials.gov) within twelve (12) months of the Trial’s Primary Completion Date regardless of whether the clinical trial was completed as planned or terminated earlier Will be incorporated as a Term and Condition of the award NCI = U.S. National Institutes of Health, National Cancer Institute

What does FDAAA 801 require? The responsible party for an applicable clinical trial (ACT) subject to FDAAA must : Register the ACT in ClinicalTrials.gov no later than 21 days after enrollment of the first participant; Update the ACT in ClinicalTrials.gov at least once every 12 months (Recruitment Status and Primary Completion Date within 30 days) Submit summary results (including adverse event information) for certain trials not later than 1 year after the trial’s Primary Completion Date. Delays allowed in some circumstances 20

The Clinical Trial Lifecycle & ClinicalTrials.gov

What Studies to Register? All Clinical Trials (ICMJE) “Applicable Clinical Trials - ACTs”* (FDAAA 801) Interventional study of drug, biologic, or device Exception: Phase 1 drug trials and small feasibility device trials US FDA jurisdiction (e.g., US site or IND/IDE) ACTs initiated on or after 9/27/07 or ongoing as of 12/26/07 *Complete definitions at: http://prsinfo.clinicaltrials.gov/ElaborationsOnDefinitions.pdf

Where to Register? ClinicalTrials.gov Protocol Registration and Results System (PRS) Log-in at: https://register.clinicaltrials.gov Interactive data entry or XML upload Tool also available for cancer centers submitting protocol information to NCI Clinical Trials Reporting Program (CTRP) Studies conducted outside the U.S. Be aware of all local requirements! May also be required to register in local trial registry

Prior to Trial Initiation Identify roles and responsibilities Responsible Party* (FDAAA 801) Sponsor IND/IDE holder; if none, then Person or entity who “initiated” the trial Funding recipient if grant or sponsored research agreement Funder if procurement funding agreement (contract) Sponsor may designate the Principal Investigator (PI) as Responsible Party if PI meets certain requirements (e.g., has access to and control over data, right to publish) *Complete definition at http://prsinfo.clinicaltrials.gov/ElaborationsOnDefinitions.pdf IND/IDE= Investigational New Drug Application/Investigational Device Exemption

Prior to Trial Initiation (cont.) Register the trial at ClinicalTrials.gov Before 1st participant is enrolled (ICMJE) Within 21 days of 1st participant enrolled (FDAAA 801) Tip: Enter NIH Grant number in record (Secondary ID) FDA Informed Consent Regulations (21 CFR§50.25(c)) A statement must be included in informed consent documents of applicable clinical trials initiated on or after March 7, 2012 regarding availability of information at ClinicalTrials.gov 21 CFR 50.25(c): http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.25 FDA Guidance: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM291085.pdf

While the Trial is Ongoing Updates to ClinicalTrials.gov Required at least once every 12 months (FDAAA 801) Update/verify “active” trials once every 6 mo. (ClinicalTrials.gov) Consider any protocol amendments that impact registration Recruitment status and (primary) completion date must be updated within 30 days of a change (FDAAA 801)

Throughout Trial Lifecycle Certification of Compliance to FDA Form 3674 must accompany human drug, biological, and device product submissions CMS Medicare National Coverage Determination (NCD) for Routine Costs in Clinical Trials* Must provide NCT Number if submitting claims for routine costs that occur during a clinical trial Mandatory as of January 1, 2015 Support Materials: http://www.clinicaltrials.gov/ct2/manage-recs/resources

Throughout Trial Lifecycle (cont.) Certification of Compliance to NIH All grants supporting ACTs; whether grantee is RP or not See: http://grants.nih.gov/clinicaltrials_fdaaa/certify-compliance.htm Competing awards (applications): SF 424: Part II, section 4.1.6 PHS 398: Part II, section 4.1.6 Non-competing continuation progress reports: Research Performance Progress Report (RPPR): All SNAP and non-SNAP awards Section 6.7 of RPPR Instruction Guide available at: http://grants.nih.gov/grants/rppr/rppr_instruction_guide.pdf Unrelated to the FDA certification of compliance

NIH Certification of Compliance: Competing applications and PHS 2590 In the “Human Subjects” section: Add a heading entitled “ClinicalTrials.gov” Under the heading, registered trials provide: NCT number/s Brief Title/s ID and contact info for the RP Under the heading, trials not yet registered: Include a clear statement that the project includes an ACT which will require registration in ClinicalTrials.gov.

NIH Certification of Compliance: RPPR Section G. Special Reporting Requirements G.4.c ClinicalTrials.gov Does this project include one or more applicable clinical trials that must be registered in ClinicalTrials.gov under FDAAA? Yes No If yes, provide the ClinicalTrials.gov Identifier, NCT Number (e.g., NCT00654321) for those trials.

After the Trial “Completes” (NIH/FDA Certifications may still apply) Definitions Primary Completion Date - PCD (FDAAA 801) “The date that the final subject was examined or received an intervention for the purposes of final collection of data for the primary outcome, whether the clinical trial concluded according to the prespecified protocol or was terminated.” Study Completion Date (last subject, last visit) Final date on which data were collected See ClinicalTrials.gov Protocol Data Element Definitions: http://prsinfo.clinicaltrials.gov/definitions.html

After the Trial “Completes” (cont.) Submit Summary Results (FDAAA 801) Which Trials? ACTs of FDA-approved or -cleared drugs, biologics, & devices; Initiated on or after 9/27/07 or “ongoing” as of 12/26/07 When to Submit? < 1 year after PCD (or < 30 days of approval or clearance) Delays possible Seeking approval of a new use (if Sponsor = manufacturer) Extensions for “good cause” Pending publication is not considered “good cause” ACT = applicable clinical trial PCD = primary completion date

After the Trial “Completes” (cont.) Submit Summary Results Scientific Information (“per arm”)* Participant Flow Baseline Characteristics Primary and Secondary Outcome Measures Statistical analyses, as appropriate Adverse Events – Serious and “Other” Administrative Information Results Point of Contact Certain Agreements (related to investigator’s right to publish, if not an employee of sponsor) *ClinicalTrials.gov Results Data Element Definitions at http://prsinfo.clinicaltrials.gov/results_definitions.html 33 33

FDAAA Results Clarifications Summary results at the end of the trial No interim or “real-time” reporting No participant-level reporting Summary results submission not required for: Registered non-ACTs (e.g., observational, Phase 1) Trials completed by 12/26/07 Relationship to publication (ICMJE) Submitting summary results to ClinicalTrials.gov will not interfere with publication* (But, failing to register the trial will!) *http://www.icmje.org/publishing_10register.html

FDAAA Enforcement Provisions Notices of non-compliance Civil monetary penalties (up to $10,000/day) Withholding of NIH grant funds

Studies Evaluating Rates of Results Reporting Prayle et al. (2012) Anderson et al. (2015) Anderson et al. (2015) – subsample Sample Trials likely to be subject to FDAAA* completed 1/1/2009 – 12/31/2009 (analyzed Jan 2011) Trials likely to be subject to FDAAA* completed 1/1/2008 – 8/31/2012 (analyzed Sep 2013) Main sample + assessment of approval status of product in trial Trials in Sample 738 13,327 205 Study Follow-up after PCD Up to 2 years By 12 months Up to 5 years Overall Rate of Results Reporting All Trials 22% 13.4% 38.3% -- Industry 40% 17.0% 41.5% 79 – 80% NIH 8% 8.1% 38.9% 49 – 50% Other 7% 5.7% 27.7% 42- 45% * Methods for determining “subject to FDAAA” were different in each analysis and both had limitations Prayle AP et al. BMJ. 2012: Anderson M et al. N Engl J Med. 2015.

Zarin DA et al. N Engl J Med 2015. DOI: 10.1056/NEJMc1505965 Trials by 80 Sponsors Estimated to Be Subject to Proposed Results Reporting. Figure 1. Trials by 80 Sponsors Estimated to Be Subject to Proposed Results Reporting. Each bar represents an academic medical center or other nonprofit organization with 10 or more registered trials in the sample, arranged according to the total percentage of registered trials sponsored by that organization and estimated to be subject to at least one of the two proposed results-reporting requirements. Algorithms involving ClinicalTrials.gov data elements (http://prsinfo.clinicaltrials.gov/definitions.html) were used to estimate trials subject to each proposal. For the Food and Drug Administration Amendments Act of 2007 (FDAAA) Notice of Proposed Rulemaking (NPRM), the algorithm and data elements were an “Interventional” Study Type; a Study Phase other than “0” or “1,” at least one Intervention Type as “Drug,” “Biologic” (or “Genetic”), or “Device” (or “Radiation”); at least one Facility Country as “United States” or Investigational New Drug Application (IND) or Investigational Device Exemption (IDE) Status as “Yes” (not available publicly); and a Primary Completion Date (if missing, Study Completion Date) as “January 2008” or later. For the draft National Institutes of Health (NIH) policy, the algorithm and data elements were an “Interventional” Study Type and at least one NIH Institute or Center as Collaborator. Zarin DA et al. N Engl J Med 2015. DOI: 10.1056/NEJMc1505965

The ClinicalTrials.gov Results Database

Results: NCT00137969 ClinicalTrials.gov: Publication:

Results: Participant Flow Adapted from Merrill JT et al. Arthrit Rheum 2010 and NCT00137969 Publication (CONSORT Flow Diagram) ClinicalTrials.gov Patients Randomized 2:1 (n=257) Completed Week 52 (n=64) 73% Rituximab + Prednisone (n=169) Placebo + Prednisone (n=88) (n=120) 71% 24 Withdrawals Total 13 Adverse Events 5 Patients’ Decision 4 Physicians’ Decision 2 Lost to Follow-up 0 Death 49 Withdrawals Total 19 Adverse Events 11 Patients’ Decision 13 Physicians’ Decision 3 Lost to Follow-up 3 Death Period 1: 52 Weeks Placebo + Prednisone Rituximab + Prednisone STARTED 88 169 COMPLETED 64 120 NOT COMPLETED 24 49 Adverse Event 13 19 Patients’ Decision 5 11 Physicians’ Decision 4 Lost to Follow-up 2 3 Death

Results: Baseline Characteristics Publication (“Table 1”) ClinicalTrials.gov Baseline Measures Adapted from Merrill JT et al. Arthrit Rheum 2010 and NCT00137969   Placebo + Prednisone Rituximab + Prednisone Total Number of Participants 88 169 257 Age [units: years] Mean (Standard Deviation) 40.5 (12.8) 40.2 (11.4) 40.3 (11.9) Gender [units: participants] Female 82 152 234 Male 6 17 23 Race White 49 95 144 African American 24 40 64 Hispanic 8 32 Asian/Pacific Islander 5 11 Other 2 4 Disease duration 8.7 (7.6) 8.5 (7.2) 8.6 (7.3)

Results: Outcome Measures Publication “At week 52, no difference was noted in major clinical responses or partial clinical responses between the placebo group (15.9% had a major clinical response …) and the rituximab group (12.4% had a major clinical response …)” Figure 2A. Proportion of patients experiencing a major clinical response (MCR) … at 52 weeks Adapted from Merrill JT et al. Arthrit Rheum 2010 and NCT00137969 Measured Values ClinicalTrials.gov Primary Outcome Measure Title Participants Achieving Either a Major Clinical Response (MCR) or Partial Clinical Response (PCR) Defined by British Isles Lupus Assessment Group (BILAG) Scores Over the 52-week Treatment Period Measure Description The BILAG Index is used for measuring clinical disease activity in Systemic Lupus … Time Frame Baseline to 52 weeks Placebo + Prednisone Rituximab + Prednisone Number of Participants Analyzed 88 169 [units: participants] MCR (excluding PCR) 14 21 PCR 11 29 Nonclinical Response 63 119

Results: Adverse Events Publication Serious Adverse Events ClinicalTrials.gov Placebo + Prednisone Rituximab + Prednisone Total # participants affected/at risk 32/88 (36.36%) 68/169 (40.24%) Blood and lymphatic disorders Neutropenia 0/88 (0.00%) 6/169 (3.55%)   Pancytopenia   1/88 (1.14%)   1/169 (0.59%)   Haemolytic Anaemia   0/88 (0.00%)     1/169 (0.59%)   Lymphophenia Thrombocytopenia Cardiac disorders Coronary artery disease …. …

General Review Criteria Protocol and results must be clear and informative Review focuses on: Logic and internal consistency Apparent validity Meaningful entries Formatting 44

Experience with Results Database Entering results is similar to the process of preparing a journal article Data provider must be familiar with the study design and data analysis Typically, the investigator and/or a statistician will need to be involved 45

ClinicalTrials.gov Practical Considerations

FDAAA - Next Steps HHS published proposed rule for clinical trial registration and results submission under FDAAA. Public comment period ended March 2015 Comments now under review. Draft policy requiring all NIH clinical trial grantees to register and report results published in NOT-OD-15-019 at: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-019.html

Overview of Rulemaking Process Food and Drug Administration Amendments Act of 2007 Announcement in Department’s Unified Agenda of Regulatory Action Agency Develops Draft Notice of Proposed Rulemaking (NPRM) Department and OMB Review NPRM Published in Federal Register Public Comment Period (typically 60 – 90 days) Agency Responds to Comments/ Develops Final Rule Final Rule Published in Federal Register 48

Determining if a Trial is an ACT Use registration data elements to determine if study meets definition of ACT Devices Drugs (and Biologics) Study Type Interventional Study Phase Other than Feasibility Controlled Number of Arms > 2 OR Single Arm Controlled = Yes Intervention Type Not Combination product Studies FDA-Regulated Device? Yes FDA Jurisdiction Facility Location in U.S. OR Product Manufactured in U.S. OR FDA IDE Number - OR- Pediatric Postmarket Surveillance of a Device? Study Type Interventional Study Phase Other than Phase 1 Controlled Number of Arms > 2 OR Single Arm Controlled = Yes Studies FDA- Regulated Drug? Yes FDA Jurisdiction Facility Location in U.S. OR Product Manufactured in U.S. OR FDA IND Number -OR- NPRM: Section IV.B.2 and 4; IDE = Investigational Device Exemption; IND = Investigational New Drug application

Results Submission Additional Issues Addressed in NPRM 50 Topic Addressed NPRM Proposal EXTEND RESULTS SUBMISSION DEADLINE? Extend the deadline for submitting results from 12 to 18 mos. NO. Little support from industry or patient groups NARRATIVE SUMMARIES? Include technical and lay summaries if Secretary determines can be included without being misleading or promotional. DEFERS DECISION. Invites additional public comment PROTOCOLS? Require submission of the full protocol or such information as may be necessary to help to evaluate the results of the trial. DEFERS DECISION. Invites additional public comment. RESULTS FOR UNAPPROVED PRODUCTS? Require results for trials of drugs and devices that have not been approved by FDA? If so, deadline for submitting those results. YES. Due within 12 months of completion date. May delay for up to 2 years w/ certification. NPRM: Section III.C.5 to 8.

PRS Entry of NIH Grant Number

PRS Tools Protocol Registration and Results System (PRS) https://register.clinicaltrials.gov NEW – Planning Report Supports planning for when study records posted on ClinicalTrials.gov need to be updated and when results may need to be submitted Tool to identify probable Applicable Clinical Trials May be downloaded into a spreadsheet Use with the Record List and Problems column on the home page to identify records that may need attention Note: Report is for informational purposes only. The Responsible Party must determine if the trial is an “applicable clinical trial” subject to FDAAA requirements.

ClinicalTrials.gov PRS Resources Protocol Registration and Results System (PRS) https://register.clinicaltrials.gov General Data element definitions Review criteria Recorded presentations: http://clinicaltrials.gov/ct2/manage-recs/present Results Submission Simple results templates Results data preparation checklists Example records using common study designs (e.g., parallel, cross-over, factorial, dose escalation) Help [PRS Main Menu and data entry screens] PRS staff: register@clinicaltrials.gov Submit Studies > Support Materials: http://www.clinicaltrials.gov/ct2/manage-recs/resources

Simple Results Templates: Basic Information Needed * Outcome Measure Type (Circle One) Primary Secondary Other Pre-specified Post-Hoc Safety Issue? (Circle One) Yes No * Outcome Measure Title Outcome Measure Description * Outcome Measure Time Frame * Arm/Group Title Arm/Group Description * Number of Participants Analyzed Analysis Population Description * Measure Type * Measure of Dispersion/Precision (Circle One) Number Mean Median Least Squares Mean Geometric Mean Log Mean Not Applicable Standard Deviation Inter-Quartile Range Full Range Standard Error 95% Confidence Interval 90% Confidence Interval Geometric Coefficient of Variation [*] Category Title * Unit of Measure Updated with newer version of template

Results Data Preparation Checklists

Recorded Presentations Available at: http://clinicaltrials.gov/ct2/manage-recs/present Six presentations with audio and slides General Overview of ClinicalTrials.gov Key FDAAA Issues Results 3. Participant Flow Module 4. Baseline Characteristics Module 5. Outcome Measures and Statistical Analyses Module 6. Adverse Event Module

Contact Us! If submitting results for the first time, we strongly encourage people to contact us before they begin. Our well-trained staff can provide 1-on-1 assistance with any results submission. Email us at: register@clinicaltrials.gov

NIH OER Resources and Tips

NIH OER Resources “What NIH Grantees Need to Know about FDAAA” http://grants.nih.gov/ClinicalTrials_fdaaa/ Step-by-step guidance Flowcharts for ascertaining ACTs and RP “At-a-glance” requirements FAQs for NIH Grantees

Tips: Take a Team Approach Be aware of your Institution’s approach/SOP Work as a team to identify ACTs and RPs Sponsored research office, PI, Counsel Work across institutions Take actions early to clarify roles and responsibilities NIH’s role Resources Cannot make determinations or register/report results on behalf of Grantee or RP http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-147.html

Tips: Plan Ahead Are the costs (including staff time) of … reporting … in ClinicalTrials.gov allowable charges on an NIH grant? Given the nature of this requirement and that the project staff will generally be in the best position to submit and maintain these data, the costs of FDAAA compliance will generally be allowable as direct charges to NIH supported grants. While it is expected that these costs will be covered by the funds provided with the grant, administrative supplements could also be considered. NIH Grants FAQs: http://grants.nih.gov/Clinicaltrials_fdaaa/faq.htm

Tips: Manage Risk Wisely Grantee Institutions as Sponsors Do you have standard operating procedures? Including process for when key staff leave the institution Training Monitor compliance How will you ensure trials are registered and results reported? (Some institutions require NCT Number for IRB approval) Use personnel appropriately to fulfill FDAAA Not necessary to have PI designated as RP in order for him/her to enter data Plan for registration and results reporting early in the trial development process Implement appropriate record retention

Tips: Understand FDAAA Responsible Party must register and submit results for applicable clinical trials (ACTs) Informed Consent Updates throughout trial lifecycle Certifications of Compliance Be attentive to rulemaking and potential NIH policy Last estimated date for publication was May 2016, but not yet sent to OMB for review Draft policy requiring all NIH clinical trial grantees to register and report results published in NOT-OD-15-019 http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-019.html

Tips: Create culture of disclosure The NIH encourages registration and results reporting for all NIH-supported clinical trials, regardless of whether or not they are subject to FDAAA FDA Compliance Program 7348.810: Sponsors, Contract Research Organizations, and Monitors* Instructs FDA staff to identify SOPs and determine if studies were registered on ClinicalTrials.gov appropriately *http://www.fda.gov/ICECI/ComplianceManuals/ComplianceProgramManual/default.htm

NIH Grants Contact Information Division of Grants Policy: E-Mail: GrantsPolicy@mail.nih.gov Phone: 301-435-0949 Division of Grants Compliance & Oversight: E-Mail: GrantsCompliance@mail.nih.gov

Select Publications Available at: http://www.clinicaltrials.gov/ct2/resources/pubs Zarin DA, Tse T, Ross JS. Trial-results reporting and academic medical centers. N Engl J Med. 2015 May 20. Zarin DA, Tse T, Williams RJ, Califf RM, Ide NC. The ClinicalTrials.gov results database – update and key issues. N Engl J Med 2011;852-860. Tse T, Williams RJ, Zarin DA. Reporting basic results in ClinicalTrials.gov. Chest 2009;136:295-303.

Additional Resources Contact us: register@clinicaltrials Additional Resources Contact us: register@clinicaltrials.gov ClinicalTrials.gov information (Submit Studies page): http://clinicaltrials.gov/ct2/manage-recs Office of Extramural Research (OER) http://grants.nih.gov/Clinicaltrials_fdaaa/ Food and Drug Administration (FDA) http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTria ls/FDAsRoleClinicalTrials.govInformation/default.htm