ClinicalTrials.gov and FDAAA for NIH Grantees

NIH Regional Seminar – October 2015

Rebecca J. Williams, Pharm.D., MPHAssistant Director, ClinicalTrials.govNational 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

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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

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How It’s Supposed to Work

5

Clinical Trials

Informed Decisions

Health Outcomes

JournalsFDA ReviewsSystematic Reviews

Meta-analyses

Guidelines

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

6

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. 7

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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• After a median of 51 months after study completion, a third of NIH-funded trials in the sample remained unpublished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 10

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Levels of Transparency

11Zarin DA, Tse T. Science. 2008.

About ClinicalTrials.gov

• Clinical studies registry and results database– Over 198,000 studies (trials & observational studies)– Studies with locations in all 50 states and 190 countries– Privately and publicly funded studies involving humans– Study information submitted by sponsors

• Web Site & registry launched in February 2000– Results database, in September 2008– Over 18,000 studies with results

• Database updated nightly• Usage

– 98 million page views per month– 64,000 visitors per day

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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

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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 VA-funded clinical trials

• U.S. National Cancer Institute (NCI) requires results reporting in a peer-reviewed scientific journal or ClinicalTrials.gov

15https://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!!16

https://clinicaltrials.gov/ct2/manage-recs/background#WhyRegister

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“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 ProposalGuide 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

18NIH 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 PolicyGuide 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

19NCI = 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 :1. Register the ACT in ClinicalTrials.gov no later than 21 days after enrollment of the first participant;

2. Update the ACT in ClinicalTrials.gov at least once every 12 months (Recruitment Status and Primary Completion Date within 30 days)

3. 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 circumstances20

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The Clinical Trial Lifecycle & ClinicalTrials.gov

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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 22

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

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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

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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 25

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)

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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 27

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/

• 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 compliance28

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.

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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.

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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

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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 32

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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

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 34

FDAAA Enforcement Provisions

• Notices of non-compliance• Civil monetary penalties (up to

$10,000/day)• Withholding of NIH grant funds

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Studies Evaluating Rates of Results Reporting

Prayle AP et al. BMJ. 2012: Anderson M et al. N Engl J Med. 2015.

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

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%

36* Methods for determining “subject to FDAAA” were different in each analysis and both had limitations

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.

The ClinicalTrials.gov Results Database

Results: NCT00137969

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Publication:

ClinicalTrials.gov:

Results: Participant Flow

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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 13

Lost to Follow-up 2 3

Death 0 3

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)

Completed Week 52(n=120) 71%

24 Withdrawals Total13 Adverse Events5 Patients’ Decision4 Physicians’ Decision2 Lost to Follow-up0 Death

49 Withdrawals Total19 Adverse Events11 Patients’ Decision13 Physicians’ Decision2 Lost to Follow-up0 Death

Period 1: 52 Weeks

Results: Baseline Characteristics

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  Placebo + Prednisone

Rituximab + Prednisone

Total

Number of Participants 88 169 257Age[units: years]Mean (Standard Deviation)

40.5 (12.8) 40.2 (11.4) 40.3 (11.9)

Gender[units: participants]

     

Female 82 152 234Male 6 17 23

Race[units: participants]

     

White 49 95 144African American 24 40 64Hispanic 8 24 32Asian/Pacific Islander 5 6 11Other 2 2 4

Disease duration[units: years]Mean (Standard Deviation)

8.7 (7.6) 8.5 (7.2) 8.6 (7.3)

Publication (“Table 1”) ClinicalTrials.govBaseline Measures

Adapted from Merrill JT et al. Arthrit Rheum 2010 and NCT00137969

Results: Outcome Measures

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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

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.govPrimary Outcome

Results: Adverse Events

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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   0/88 (0.00%)     1/169 (0.59%)  

Thrombocytopenia   0/88 (0.00%)     1/169 (0.59%)  

Cardiac disorders

Coronary artery disease …. … …

PublicationSerious Adverse Events

ClinicalTrials.gov

General Review Criteria

• Protocol and results must be clear and informative

• Review focuses on:– Logic and internal consistency– Apparent validity– Meaningful entries– Formatting

4444

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

4545

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

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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

Department and OMB Review

Final Rule Published in Federal Register 48

Overview of Rulemaking Process

Determining if a Trial is an ACT

• InterventionalStudy Type

• Other than FeasibilityStudy Phase

•Number of Arms > 2 OR•Single Arm Controlled = YesControlled

• Not Combination productIntervention Type

• YesStudies FDA-

Regulated Device?

• Facility Location in U.S. OR • Product Manufactured in U.S. OR• FDA IDE Number

FDA Jurisdiction

- OR-

Pediatric Postmarket Surveillance of a

Device?

• InterventionalStudy Type

• Other than Phase 1Study Phase

• Number of Arms > 2 OR• Single Arm Controlled = YesControlled

• YesStudies FDA-

Regulated Drug?

•Facility Location in U.S. OR•Product Manufactured in U.S. OR•FDA IND Number

FDA Jurisdiction

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Use registration data elements to determine if study meets definition of ACT

Devices Drugs (and Biologics)

NPRM: Section IV.B.2 and 4; IDE = Investigational Device Exemption; IND = Investigational New Drug application

-OR-

Results Submission Additional Issues Addressed in NPRM

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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.

50NPRM: Section III.C.5 to 8.

PRS Entry of NIH Grant Number

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PRS Tools

• Protocol Registration and Results System (PRS)– https://register.clinicaltrials.gov

• Main Menu – Record List– Column displays if a record has “Problems”– Allows investigators and administrators of

organizational accounts to identify potential problems with records, including potential FDAAA issues:• Late results - trials with certain characteristics that

reached Primary Completion Date more than one year ago and results are not posted on ClinicalTrials.gov

• Note: Report is for informational purposes only. The Responsible Party must determine if the trial is an “applicable clinical trial” subject to FDAAA requirements.

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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

* 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)

NumberMean

MedianLeast Squares

MeanGeometric Mean

Log Mean

(Circle One)

Not ApplicableStandard DeviationInter-Quartile Range

Full RangeStandard Error

95% Confidence Interval90% Confidence Interval

Geometric Coefficient of Variation

[*] Category Title

[*] Category Title

* Unit of Measure

Simple Results Templates:Basic Information Needed

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Results Data Preparation Checklists

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Recorded Presentations

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• Available at: http://clinicaltrials.gov/ct2/manage-recs/present

• Six presentations with audio and slides

General

1. Overview of ClinicalTrials.gov

2. 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

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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

60http://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.

61NIH 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 retention62

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– Proposed – 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

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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 64

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– Phone: 301-435-0949

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Select Publications

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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.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/RunningClinicalTrials/FDAsRoleClinicalTrials.govInformation/default.htm

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