Review of CBER's Current and Planned Post-marketing Safety Practices

Transcription

1 Review of CBER's Current and Planned Post-marketing Safety Practices Robert Ball MD, MPH, ScM Director, Office of Biostatistics and Epidemiology (OBE), Center for Biologics Evaluation and Research (CBER), FDA May 2,

2 Agenda Background on Office of Biostatistics and Epidemiology (OBE), CBER Charge to committee Discussion of charge 2

3 OBE Organizational Structure Office of the Director Division of Biostatistics Risk Assessment Staff Associate Director For Research Staff Division of Epidemiology Vaccine Evaluation Branch Therapeutics Evaluation Branch Analytical Epidemiology Branch Pharmacovigilance Branch Pre-licensure Review Post- and Pre-licensure Review (some post-licensure) 3

4 Functions of the Office of Biostatistics & Epidemiology Division of Biostatistics Review of clinical study and bioassay data and statistical analyses Methods Development Division of Epidemiology Review adverse event reports, pharmacovigilance plans, study protocols Conducts surveillance and epidemiological studies Risk Assessment Staff Conducts quantitative benefit risk assessments & modeling Simulation modeling and quantitative analyses Research Team Genomics Evaluation Team for Safety Epidemiology Team Biostatistics Team Administrative staff Special support for contracting, IPA s and research fellows 4

5 OBE Staffing Substantial growth since 2007 FDAAA FTE s & ~5 fellows FTEs plus ~20 fellows, IPA s, and computational science support contractors Increased staffing across the board, plus - Analytical Epidemiology Branch - Research Team 5

6 Biological Products Regulated by CBER Vaccines (preventive and therapeutic) Blood, blood components and derivatives Allergenics Cell and Gene Therapies Tissues Xenotransplantation Products Related Devices (including certain IVDs) 6

7 Volume and Variety of CBER Marketed Medical Products Vaccines (20%) Immune globulins Therapeutics (80%) (No. Products > 300) Hematopoietic stem cells Fibrin sealants Antivenins Therapeutic vaccines Factor replacement Volume expanders Alpha 1 anti trypsin inhibitor C1 esterase inhibitor Thrombin and anti thrombin Fibrinogen concentrate 7

8 Charge to the FDA Science Board The FDA Science Board is charged with conducting a review of CBER's current and planned post-marketing safety practices. Review objectives include: Processes and analysis tools FDA/CBER uses for identifying safety signals for CBER regulated products in FDA spontaneous reporting systems, especially the Vaccine Adverse Event Reporting System (VAERS) and the Adverse Event Reporting System (AERS). Approaches FDA/CBER is taking to improve the use of population-based healthcare databases for both safety surveillance and hypothesis testing studies, including the FDA/CBER s mini-sentinel projects, PRISM and BloodScan; collaborative activities with other government agencies including CMS and CDC; and special studies with private health care providers. Efforts to use genomic and other omic data from the post-marketing period to improve the safety of CBER regulated products, especially vaccines. Efforts to develop and evaluate novel methodological approaches in the post-marketing safety areas outlined above. 8

9 Vision for Post-Market Safety Monitoring All patients biologic product exposures and health outcomes are immediately and continuously accessible in automated database(s) allowing optimal detection and analysis of potential problems in biologics safety We will use many sources of data - Spontaneous reports - Healthcare databases - Electronic medical records - Public health databases - Intrinsic properties of biologic products Automated signal generation from all sources will be seamlessly integrated with signal validation 9

10 Spontaneous Reporting Systems Goals - Improved efficiency and validity of inferences Three pronged approach - Statistical datamining - Artificial intelligence approaches - Incorporation of external information about intrinsic properties of biologic products Ball R, Botsis T. Can network analysis improve pattern recognition among adverse events following immunization reported to VAERS? Clinical Pharmacology & Therapeutics 90:271-8, doi: /clpt Epub 2011 Jun

11 Developing New Biologic Product Safety Surveillance Infrastructure and Capabilities CBER helping to build mini-sentinel infrastructure and safety surveillance methods - Post-licensure Rapid Immunization Safety Monitoring (PRISM) and active surveillance - Blood Safety Continuous Active-surveillance Network (Blood-SCAN) - creating an inpatient surveillance system for blood safety CBER Post-marketing Safety Collaborations - Centers for Medicaid & Medicare Services (CMS) - Department of Defense - Department of Veterans Affairs - Indian Health Service - Vaccine Safety Datalink (managed by CDC) - International collaborations (WHO, regulatory and public health agencies worldwide) 11

12 Rapid Assessment of Vaccine Safety Developed a novel approach to near real-time safety surveillance adjusting for delay in claims in collaboration with CMS season: monitored safety of seasonal and H1N1 pandemic influenza vaccines - Approximately 45 million CMS beneficiaries and more than 3 million H1N1 pandemic vaccinations monitored Monitoring of GBS after seasonal influenza vaccine now routine 12

13 How Might Genomics Improve Product Safety? Identify variable efficacy Discover safety biomarkers Distinguish adverse events from adverse effects Improve signal detection Elucidate mechanisms Inform rational product design 13

14 OBE has created a multidisciplinary team to apply human genomics approaches to biologics safety Overall plan is to work collaboratively with CBER product offices, and partner / leverage government omics resources at CDC, NIH, academia, and industry - Research, Education, Policy, - Focus on vaccines Sponsor epidemiological studies of potential genetic risk factors for vaccine adverse effects - MMR vaccine and idiopathic thrombocytopenic purpura - MMR vaccine and febrile seizures (with CDC) Simulation of genetic data sets to explore methods development - Population-based vs personalized vaccination? 14

15 Charge to the FDA Science Board The FDA Science Board is charged with conducting a review of CBER's current and planned post-marketing safety practices. Review objectives include: Processes and analysis tools FDA/CBER uses for identifying safety signals for CBER regulated products in FDA spontaneous reporting systems, especially the Vaccine Adverse Event Reporting System (VAERS) and the Adverse Event Reporting System (AERS). Approaches FDA/CBER is taking to improve the use of population-based healthcare databases for both safety surveillance and hypothesis testing studies, including the FDA/CBER s mini-sentinel projects, PRISM and BloodScan; collaborative activities with other government agencies including CMS and CDC; and special studies with private health care providers. Efforts to use genomic and other omic data from the post-marketing period to improve the safety of CBER regulated products, especially vaccines. Efforts to develop and evaluate novel methodological approaches in the post-marketing safety areas outlined above. 15