1. FDAAA Clinical Trial Disclosure Briefing for GCP/QA SIAC
Barbara Godlew
President and Principal Analyst
The FAIRE Company, LLC
Maureen Strange
CTR Initiated Gatekeeper
Eli Lilly and Company

2. Food and Drug Administration Amendments Act of 2007 FDAAA (FDA3)
Objectives
Food and Drug Administration Amendments Act of 2007 FDAAA (FDA3)
Legislative objectives
Milestones, challenges and consternations (registry, results database)
Future

3. (1) Prescription and (2) medical device user fees
Food and Drug Administration Amendments Act of 2007­FDAAA (FDA3)—10 Acts
(1) Prescription and (2) medical device user fees
(3) Pediatric medical device safety, improvement
(4) Pediatric research equity
(5) Best pharmaceuticals for children
(6) Reagan-Udall Foundation
(7) Conflicts of interest
(8) Clinical trial databases
(9) Enhanced authorities of drug postmarket safety
(10) Other provisions

4. Clinical Trial Databases— Legislative Objectives
Register of all “applicable” clinical trials (excluding phase I) within 21 days FPFV
Drugs, biologics, and devices
Trials started after or are ongoing 27 Sept. ’07
Data elements similar, not identical to WHO
Disclose trial results of ongoing or new trials for approved drugs on public website
Expansion of ClinicalTrials.gov
Incremental results disclosure

5. Registry: Key Milestones
Trials in serious, life-threatening conditions
Ongoing trials: 27 Dec 2007
New trials: within 21 days of FPFV
All other applicable trials
Ongoing trials: 27 Sept 2008

6. Registry: Challenges Additional fields not mandated by law added
“Study design” expanded with creative license
Aligns to WHO and ICMJE elements
May populate tables for results database fields?
 workload exponentially for large pharmas
Must update legacy entries for ongoing trials
Register trials prior to FPFV for consideration by ICMJE journal

7. Registry: Consternations (1)
“New” definitions
Applicable clinical trial = “An applicable device clinical trial or an applicable drug clinical trial”
Applicable drug clinical trial
(I) IN GENERAL—a controlled clinical investigation, other than a phase I clinical investigation, of a drug subject to section 505 of the Federal Food, Drug, and Cosmetic Act or to section 351 of this Act.
‘‘(II) CLINICAL INVESTIGATION.—For…subclause (I), …‘clinical investigation’ has the meaning given…in section [21CFR] 312.3…
Are observational trials exempt?
Not according to ClinicalTrials.gov.
21CFR312.3 Clinical investigation: any experiment in which drug is administered or dispensed to, or used involving, 1 or more human subjects. For the purposes of this part, an experiment is any use of drug except for use of marketed drug in the course of medical practice.

8. Registry: Consternations (2)
“New” definitions
Completion date
FDAAA: date that the final subject was examined or received an intervention for the…primary outcome, whether the clinical trial concluded according to the pre-specified protocol or was terminated.
Industry: Last Patient Last Visit
Major deviation from current industry protocol

9. Registry: Consternations (3)
Public disclosure of responsible party by official title or toll-free number by which information may be accessed
States’ rights
Maine not pre-empted for 3 years
Others can still introduce legislation
Puts pharma employees at risk of harass-ment and harm from animal rights protest groups, disgrun-tled spouses, and others

10. Results Postings: Key Milestones (1)
Basic Results required by 27 Sept 2008
Demographic, baseline characteristics
Primary, secondary outcomes
Point of scientific contact
Contractual restrictions of investigators ability to discuss results

11. Results Postings: Key Milestones (2)
Serious Adverse Event, Frequent Adverse Event results rules expected by 27 Mar 2009
Risk communication experts will interpret SAE tables to enhance patient understanding and ensure tables are not misleading
Expanded Results rules expected by 27 Sept 2010
Lay and technical summary of results

12. Results Postings: Challenges
Potential quality assurance issues
ClinicalTrials.gov learning on the fly, but wants industry input
Technical summaries too technical?
Lay summaries potentially promotional?
Posting trials of unapproved drugs
Products not approved in US, but in ROW?
Must post all applicable trials in dossier 30 days after approval

13. Results Postings: Consternations
Possible requirement to post full protocol with results
Redactions?
Publications at risk
States’ rights
Maine not pre-empted for 3 years
Others can still introduce legislation

14. Other Noteworthy Items
Noncompliance has civil monetary penalties
Not more than $10,000 for all violations in a single proceeding
If not corrected within 30 days following notification, $10,000 per day thereafter until corrected
Noncompliance can result in IND/NDA nonapproval

15. Consolidated Time Table
Event
27 Dec 2007
Sponsor: Deadline to update new/ongoing trials in serious or life-threatening conditions posted to ClinicalTrials.gov; Certification document required for NDA submissions
NIH: Add FDA Links
27 Sept 2008
Sponsor: Post basic trial results on NIH website
Sponsor: Deadline to update ongoing trials in conditions not serious or life-threatening posted to ClinicalTrials.gov
27 Mar 2009
Sponsor: Post SAE/AE data to NIH website
HHS: Deadline for public meeting
27 Mar 2010
HHS: Enact expanded results regulations (lay summary, protocol, QA/QC procedures)

16. ClinicalTrials.gov staff members of DIA CTR/RD working group
Future
ClinicalTrials.gov staff members of DIA CTR/RD working group
Working together to find best practices, happy medium as allowed by law
NIH results database website to be established
Public meeting by 27 Mar 2009