FDA AA - Title VIII

Clinical Trial Databases

Friday, 30 November 2007

MBC

Sarah Doyle LarsonProgram Manager,

Biomedical Regulatory Affairs Compliance

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Agenda Title VIII Overview

Timelines Clinical Trial Registry Clinical Trial Results Database Other Provisions

Other Non-FDA Influences to Consider State of Maine WHO ICMJE Trade Associations International Regulations and Standards

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What is Title VIII?

Definitions Registry = Protocol parameters for ongoing trials Results Database = Results data from completed trials

Title VIII Mandates the expansion of www.ClinicalTrials.gov to form a Clinical Trials Registry and Results Database Broader scope of trials that must be registered Increases the amount of data elements required in each posting Requires submission of clinical trial results data Penalties for noncompliance Several “other” requirements Implementation is a “phased” approach

Timelines for complying range from Dec. 26, 2007 to Sep. 27, 2010

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FDA/NIH Implementation Timeline1

Sept 272007

CongressCongressPassesPassesLawLaw

90 Days (12/26/07)Linking to FDA and

NIH information

Expanded registry data elements

Expanded registry scope

2008 2009 2010

1 Year (9/27/08)Basic results

reporting

Expanded registry scope

18 months (3/27/09)Public meeting to discuss expanded registry and results database

Adverse events (if by rulemaking)

3 years (9/27/2010)Expansion of

registry and results database by rulemaking

2 Years (9/27/09)

Adverse events (if by default)

1Timeline provided by Terry Toigo, Director, FDA Office of Special Health Issues, 27 Nov 2007

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Clinical Trial Registry

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Expanded Registry Data Bank – 26 Dec 2007

Scope of trials expanded beyond FDAMA §113 Drug/Biologics: All controlled clinical investigations, other than Ph. 1

Devices: All controlled trials with health outcomes; excludes small feasibility studies; includes pediatric postmarket surveillance

Additional Information Required: Some previously optional fields are now mandatory New data elements Links to “results” information to be provided by FDA / NIH

Maintaining Postings: Updates – at least once/every 12 months Recruitment Status – w/in 30 days of change

Penalties for Noncompliance and Public Notices NIH Implementation & Compliance: 90 Days (26 Dec 2007)

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Newly initiated applicable trials: register by later of: 26 Dec 2007 -OR- 21 days > 1st pt enrolled

“Ongoing” applicable trials as of 27 Sep 2007 that are not “completed” by 26 Dec 2007 … if SLT = “yes”, update posting to include all req’d fields by:

26 Dec 2007 if SLT = “no”, update posting to include all req’d fields by:

27 Sep 2008

Notes regarding NIH “posting” dates: Drugs OR approved/cleared Devices

w/in 30 days of receipt

Devices not previously approved/cleared “held” for release until approved; then released w/in 30 days of approval

Expanded Registry Data Bank – When to Register?

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Clinical Trial Results Data BankResults LinksBasic ResultsExpanded Results Data Bank

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Scope: Approved Drug, Biologics, Devices CTs that form basis for efficacy claim or CTs conducted > approval

FDA Information to be posted (Links): Advisory Committee Meetings FDA assessment of results for pediatric trials (Sec 505A/B) FDA public health advisories FDA drug “action package” for approval documents FDA device PMA or 510(k) summary of safety/efficacy

NIH Information to be posted (Links): Medline citations Label

Implementation Timeline: “Beginning” 26 Dec 2007 Responsibility of FDA/NIH For applicable trials ongoing as of 27 Sep 2007, link 30 days >

approval and w/in 30 days of results becoming public For other trials posted prior to 27 Sep 2007: as available

Results Data Bank “Links” – 26 Dec 2007

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Scope: Approved Drugs, Biologics, Devices Includes applicable trials completed per protocol & terminated trials

Information to be posted: Demographics & baseline characteristics of patient sample Primary & Secondary Outcomes Point of Contact Certain Agreements

Implementation Timeline: 27 Sep 2008 In general, submit w/in 12 mos of completion date (estimated or actual)

Completion Date = LPLV Delayed submission w/ certification:

Initial approval: Submit results w/in 30 days of initial approval/clearance New use: Submit results w/in 30 days of

Approval/clearance of new use Issuance of letter by FDA (e.g. complete response, not approving/clearing, not

approvable) Withdrawal w/out resubmission after 210 days Limit if no action: 2 years

Results Data Bank “Basic Results”– 27 Sep 2008

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Public meeting to be held by 27 Mar 2009 Rulemaking for AE Reporting by 27 Mar 2009

(or default provision will apply on 27 Sep 2009)

Rulemaking for Expansion of Data Bank by 27 Sep 2010: Scope:

Trials w/ completion date on or > Sept 1997 for approved products May include unapproved products (whether approval was sought or not)

Information and format to be posted: Non-technical & technical summaries of results (non promotional) Protocol or other info needed to “evaluate” completeness of results “Other categories as determined to be appropriate” by FDA

Results Submittal Timeline – extend from 12 mos to 18 mos? How to address trials where results were posted < data bank “Expansion”?

Implement QC Procedures Consider WHO Data Set

Results Data Bank “Expanded Data Bank”

27 Sep 2010

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Other Provisions

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Certification w/ all submission - 27 Dec 2007

State Preemption – 27 Dec 2010

Modify ICF

Public Notice of Noncompliance; Penalties Guidance to be issued re: how requirements apply to a

pediatric postmarket surveillance Voluntary submissions acceptable QC Pilot Program

confirm completeness, accuracy, and ensure non-promotional

Consult w/ experts on risk communication Waiver process for “extraordinary circumstances” when

protecting public health or national security

Other Provisions in Title VIII

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Other non-FDA influences to consider

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US States: Maine - passed March 2007; FDAAA preemption effective 27 Sep 2010 Other State activity in 2007

WHO: Policy: registration & results of ALL human subject trials WHO Primary Registers WHO data elements

ICMJE – WHO data elements Require prospective registration of “any research project that prospectively

assigns human subjects to intervention or comparison groups to study the cause-and-effect relationship between a medical intervention and a health outcome”

As of July 2008, will no longer exclude Phase I Ingelfinger Rule / Post results abstract <300 words if pub is pending

Trade Associations PhRMA - joint position statement Jan 2005 BIO - Principles on Clinical Trials Advamed

Other Considerations

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Varying International Standards Mandatory

Israel (clinicaltrials.gov) Italy (local language; country specific EUDRACT posting) South Africa (country specific) Taiwan

Proposed France (local language; requirements similar to Italy)

Voluntary Australia (country specific website) China (country specific website) Germany India (country specific website) Japan (country specific website) Netherlands Spain UK (country specific website)

Local IRB/EC requirements

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Summary New FDAAA requirements begin 26 Dec 2007 and will

continue through 27 Sep 2010 FDA / NIH is still in the process of implementing … Stay

tuned! http://www.clinicaltrials.gov http://prsinfo.clinicaltrials.gov

In some cases, the NIH’s timeline for implementation allows little time to update internal SOPs and/or to complete tasks as required.

Rulemaking! Lack of harmonization between FDAAA and other

“influences”

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Questions?

Sarah.Larson@Genzyme.com