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Office of Biostatistics Center of Drug Evaluation and Research, FDA

Presented at ASA Caucus of Academic Representatives

Ram Tiwari, Ph.D.Office of Biostatistics

Center for Drug Evaluation and ResearchU.S. Food and Drug Administration

Ram.tiwari@fda.hhs.gov

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Outline • FDA location and Organizational Charts • What FDA statisticians do - Review of Drug Products - Presentations at Advisory Committees - Write Guidance Documents for Industry - Regulatory Research and Professional Activities - Training, Communication and Outreach• Career Opportunities at FDA

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FDA White Oak Campus, Silver Spring, MD

OB/Building 21

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10 10 70 150 40 10

290 Statisticians at FDA and Growing!

New Center

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CDER ORGANIZATIONa condensed version

CDER

PharmaceuticalSciences

New DrugsSurveillance &Epidemiology

TranslationalSciences

ClinicalPharmacology Biostatistics

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CDER Office of BiostatisticsDirector: Robert T. O’Neill

DB1 Cardiovascular & Renal; Neurological; Psychiatric

DB2 Pulmonary & Allergy; Metabolism & Endocrine; Analgesics & Anesthetics

DB3 Gastrointestinal; Reproductive & Urologic; Dermatologic & Dental

DB4 Anti-Infective & Ophthalmology; Anti-Viral; Special Pathogen & Transplant

DB5 Oncology Biologics; Oncology Drugs; Imaging & Hematology

DB6 Generics; Pharmacology & Toxicology; Chemistry & Manufacturing; Special Projects

DB7 Quantitative Safety & Pharmacoepidemiology

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Typical Activities for an OB Statistician

• Review the statistical aspects of the drug development process

• Present at the advisory committee meeting

• Provide the statistical perspective to policy and guidance working groups

• Continue to develop professionally:– Conduct research on regulatory science

– Participate/ Present at Professional Meetings

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CDER Drug/Biologic Review Team

• Clinicians • Statisticians• Clinical Pharmacologists• Chemists• Pharmacologists /Toxicologists• Microbiologists• Safety Reviewer • Project Managers• Other Scientists, if needed

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Communication Dynamics between FDA and Industry

Project Manager

ClinicalStats

Micro

ClinPharm

Chem

Pharm/Tox

Regulatory Affairs

Project Team

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Types of Applications

• IND: Investigational New Drug Application• NDA: New Drug Application• BLA: Biologics License Application

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Statistical Review of NDA/BLA

• Review study protocol and conduct of trial and sponsor’s analyses

• Perform additional analyses, if necessary– Re-analyze the primary efficacy data– Conduct sensitivity analyses

• Review proposed label

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Advisory Committee Meetingshttp://www.fda.gov/AdvisoryCommittees/default.htm

http://www.fda.gov/ohrms/dockets/ac/acmenu.htm

• Typical issues at these meetings– Safety, efficacy, risk/benefits questions– Dosing concerns– Target population or labeling issues– Guidelines/Study/Protocol designs– Appeals of FDA decision

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CDER Special Government Employees(Partial List)

Victor De Gruttola Thomas FlemmingDavid Harrington Richard GelberJames H. Ware Daniel OakesLee-Jen Wei Stephen GeorgeMarvin Zelen Daniel GillenDianne Finkelstein Michael GinsworldDavid Schoenfield Robert HamerScott Evans Joan HsuPhillip Lavin Andrew LeonJanet Anderson James NeatonJohn C. Crawley David MeMetsLi Ming Dong Weichung ShihDianne Sisfo Thomas Ten HaveRobert Woolson Mary LindstromYing Lu Warren B. BilkerDaniel Sargent

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Guidance for Industry Adaptive Design Clinical Trials

DRAFT GUIDANCEThis guidance document is being distributed for comment purposes only.

Comments and suggestions regarding this draft document should be submitted within 90 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register.

For questions regarding this draft document contact Robert O’Neill or Sue-Jane Wang at 301-796-1700, Marc Walton at 301-796-2600 (CDER), or the Office of Communication, Outreach and Development (CBER) at 301-800-835-4709 or 301-827-1800. U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Biologics Evaluation and Research (CBER)

January 2010

Clinical/Medical

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Guidance for Industry Non-Inferiority Clinical Trials

DRAFT GUIDANCEThis guidance document is being distributed for comment purposes only.

Comments and suggestions regarding this draft document should be submitted within ___ days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register.

For questions regarding this draft document contact Robert O’Neill or Robert Temple (CDER) at 301-796-1700, or the Office of Communication

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Biologics Evaluation and Research (CBER)

January 2010

Clinical/Medical

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Guidance for Industry Multiple Endpoints in Clinical Trials

DRAFT GUIDANCEThis guidance document is being distributed for comment purposes only.

Comments and suggestions regarding this draft document should be submitted within ___ days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register.

For questions regarding this draft document contact Mohammad Huque, Robert O’Neill or Robert Temple (CDER) at 301-796-1700, or the Office of Communication

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Biologics Evaluation and Research (CBER)

January 2010

Clinical/Medical

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Work in Progress on Other TWO Guidance Documents

• Prevention and Treatment of Missing Data in Clinical Trials- National Academy of Sciences Report

• Meta-Analysis for Safety Evaluation

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Professional Meetings/ Research Activities

• 4th Annual FDA/DIA Statistics Forum • Midwest Biopharmaceutical Statistics Workshop • DIA Annual Meeting • ICSA 2010 • Applied Statistics Symposium • Joint Statistical Meetings 2010 • FDA/Industry Statistics Workshop

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The Critical Path to New Medical ProductsThe Critical Path to New Medical Products1. Better Evaluation Tools2. Streamlining Clinical Trials

– Adaptive Trial Designs– Non-inferiority Trials– Multiple Endpoints in Clinical Trials– Enriched Trial Designs

3. Harnessing Bioinformatics4. Moving Manufacturing into the 21st Century5. Developing Approaches to Address Urgent Public Health

Needs• Sentinel Initiative*

6. Specific At-Risk Populations -- Pediatrics

http://www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiativehttp://www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative

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Regulatory Science and Review Enhancement (RSR)

• CDER Regulatory Science and Review • Enhancement Program

– RSR MaPP– Overview of 2011 RSR Program

• RSR 2011 Cycle *Updated* (Deadline July 16, 2010)– Call for 2011 RSR Applications

– Guidelines for RSR 2011

– RSR 2011 Application Form

– Instructions for Completion, Approval and Submission of RSR Application Form

• RSR Presentations and Awardees (2007-2009)

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CDER Science Projects and Publications Databases

• The CDER Science Projects Database contains basic information about all CDER science and research projects and programs in a searchable format. The database was developed as an information and research management tool. It provides an opportunity for each investigator to clearly communicate the rationale, impact and relevance of their project/program to a broad audience.

• All CDER science projects and programs must have an entry in the Research Database. If your project is not in the database, please contact your Division Director. They can contact Jorge Urrutia.

• The CDER Publications Database captures publications and abstracts from the entire FDA. CDER publications resulting from research projects in CDER link back to the corresponding project description in the CDER Science Project Database.

• Please check that your publications are in the database by performing a Custom Search using your last name in the Author field. If some of your publications are missing, please click on Add Entry link on the Publications Database page to enter them, or email the citations to Tom Maudru.

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FDA Commissioner’s Fellowship Program

• Two-year Program, which provides an opportunity for health professionals and scientists to receive training and experience at the FDA.

• Designed to provide in-depth understanding of science behind regulatory review, drugs, devices, biologics and cosmetics

• OB Preceptor: Dr. Ram C. Tiwari, Associate Director• http://inside.fda.gov:9003/EmployeeResources/

EmploymentOpportunities/CommissionersFellowshipProgram/default.htm

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Internship Program

• Oak Ridge Institute for Science and Education (ORISE) Internship program

– The Office of Biostatistics has contracted with ORISE to administer a summer internship program to enable graduate students in statistics to work with some of our staff on important research projects.

• http://see.orau.org/

• Internships through CP and RSR Projects

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For More Information about Careers in Statistics at FDA:

•For Links to employment information: http://www.fda.gov/cder/Offices/Biostatistics/

http://www.fda.gov/jobs/positions08.html

•For U.S. Citizens: http://www.usajobs.opm.gov

•For U.S. Citizens and non-U.S. Citizens, both with and without green cards: Contact/send resumes to S. Edward Nevius, Deputy Director, FDA/CDER Office of Biostatistics: SEdward.Nevius@fda.hhs.gov

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Concluding Remarks

The Office of Biostatistics, CDER, would welcome academic institutions’ increased participation in:

• FDA Advisory Committees

• OB Ambassadors Program

• Commissioner’s Fellowship

•Internship Program

• Sabbatical/Visitors