US Efforts in Vaccine Safety. Roger Baxter, MD California Immunization Coalition Summit 2011

Transcription

1 US Efforts in Vaccine Safety Roger Baxter, MD California Immunization Coalition Summit 2011

2 Conflicts of interest I receive research grants from Sanofi Pasteur, GSK, Merck, MedImmune, Novartis, Pfizer, and Protein Sciences

3 Vaccination scenarios A mother asks you to spread out her child s vaccines to decrease the likelihood of causing autism.

4 Vaccination scenarios Several parents refuse to let their child get the HPV vaccine because it is so dangerous, and they ve heard it causes MS, blood clots, and fainting. Not to mention that it encourages sexual activity.

5 Are vaccines safe? How are vaccines developed, and are they safe? What is done to ensure vaccine safety in the US?

6 Gillray, 1802 Anti-Vaccine Society

7 False scares UK, 1998: allegation of possible link between MMR and autism Immediate fall in rates of MMR Ireland, 2000: >1600 measles cases 350 hospitalized 3 deaths No confirmation of link Discredited results

8 Thimerosal scare timeline 1999: government report reveals that childhood vaccines might expose infants to more mercury than anyone had realized no evidence of harm Immediately, USDPH and ACIP call for a plan to eliminate or reduce as expeditiously as possible the mercury content of vaccines Public reaction is swift: thimerosal is unsafe

9 Thimerosal 2004: Institute of Medicine unanimous decision that thimerosal is not causally linked to autism 2009: Rejection by Special Masters that autistic children are entitled to benefits under the vaccine injury act.

10 But vaccines are not always safe

11 Cutter IPV Incident, 1955 Polio virus not killed in several vaccine lots Vaccine recipients infected with polio 149 vaccinated cases (6 deaths) Public confidence in vaccines shaken

12 Influenza Vaccine & Guillain-Barré Syndrome (GBS) Feb 1976: outbreak of Swine flu Mass vaccination campaign: 40 million vaccinated from Oct-Dec 1976 Over 500 GBS cases reported, 25 deaths Vaccination program suspended

13 Overall the benefits of vaccines far outweigh the risks

14 Vaccine Preventable Diseases US Disease Pre-vaccine Era* 2001 % change Measles 503, Diphtheria 175, Mumps 152, Pertussis 147,271 5, Rubella 47, Polio paralytic) 16, H.Influenzae type b 20, Tetanus 1, Cong. Rubella Synd Total 1,064,854 6, Vaccine Adverse Events 0 13,526 * Maximum cases reported in pre-vaccine era and year + Estimated because no national reporting existed in the prevaccine era

15 Need for Ongoing Vaccine Safety Program Public confidence in vaccine safety is critical Decreases in disease risks lead to increased attention on vaccine safety

16 Vaccine vs. Drug Safety Higher standard of safety Vaccinees are generally healthy and may be very young Vaccinations may be universally recommended or mandated Lower risk tolerance: Vaccine: less than 1/100,000 vs. drug: 1/1-1/1000

17 Vaccine pre-licensure studies 1st: Laboratory and animal studies Then: Human studies Phase I: gross toxicity (N: ~ 10) Phase II: dosing range/ reactogenicity (N: ) Phase III: efficacy (N: ,000)

18 Vaccine pre-licensure studies Advantages: Close, detailed follow-up Randomized blinded placebo-controlled design Disadvantages: Rare or delayed reactions are difficult to detect Often cannot study subpopulations

19 Post-Licensure Surveillance Passive surveillance VAERS Active surveillance Phase IV trials (N =10,000-50,000) Mandated by FDA Many done at the KP Vaccine Study Center Large-linked databases Up to > 100,000 vaccinees

20 CDC s Immunization Safety Office (ISO) Vaccine Safety surveillance Research on vaccine safety

21 ISO Key Components Vaccine Adverse Event Reporting System (VAERS) Clinical Immunization Safety Assessment Network (CISA) Vaccine Safety Datalink project (VSD)

22 VAERS - Passive Surveillance FDA/CDC collaboration since 1990 Reports of suspected VAEs from physicians, patients, etc. Web-based reporting and public access to data (

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24 VAERS - Strengths National in scope Timely Relatively inexpensive/cost-effective Generation of hypotheses ( signals )

25 VAERS - Weaknesses Underreporting Biased reporting (lawyers, news events) Mix of causal and coincidental events Inadequate report quality Lack of denominators and control group Generally unable to address causality

26 CISA Clinical Immunization Safety Assessment Network

27 CISA National network of six medical research centers with expertise in immunization safety Established in 2001 Goal: to improve the scientific understanding of vaccine safety at the individual level.

28 CISA Network Sites Kaiser Permanente Vaccine Study Center Boston Medical Center Columbia University Medical Center Stanford University Johns Hopkins University Vanderbilt University

29 CISA Goals To study the basis of adverse events following immunization (AEFI) To study risk factors associated with developing an AEFI To provide clinicians with evidence-based guidelines and consultation for Evaluating AEFIs Vaccination or revaccination in risk groups

30 CISA Current Activities Evaluation of individual patients with serious or unusual AEs Vaccination in children with metabolic (and mitochondrial) disorders Hypersensitivity management Vaccination/Revaccination protocols Live vaccines in DiGeorge Syndrome Revaccination of GBS patients

31 CISA Vaccine Safety Fellowship Sponsored at CDC Current Fellow is at KPVSC: Ali Rowhani-Rahbar, MD, PhD

32 How to get in touch with CISA Call me: Or or

33 VSD Vaccine Safety Datalink Collaboration between CDC and 10 managed care organizations Enrollment of over 9.5 million 3.1% of the American population

34 Vaccine Safety Datalink Sites Group Health Cooperative Northwest Kaiser Permanente No. CA Kaiser Permanente So. CA Kaiser Permanente Health Partners Kaiser Permanente Colorado Marshfield Clinic CDC Harvard Pilgrim Kaiser Georgia Kaiser Hawaii

35 VSD Distributed Data Model

36 VSD Priorities Evaluate safety of: newly licensed vaccines new recommendations for existing vaccines vaccines in high-risk populations Develop new methodologies for vaccine safety assessment Test hypotheses suggested by signals from VAERS

37 Rapid Cycle Analysis (RCA) Ongoing surveillance of multiple vaccines Weekly updates of data Example Increased likelihood of febrile seizure 7-10 days after MMRV compared with MMR+V Klein NP, Fireman B, Baxter R., et al. Measles-mumps-rubellavaricella combination vaccine and the risk of febrile seizures. Pediatrics;126:e1-8

38 Seizures within 42 days of Vaccine, Months of Age Rate per 100K Doses Days Since Vaccine MMRV MMR+V MMR VZV

39 Other RCA Studies Menactra Rotateq Tdap Flu vaccines HPV

40 VSD Studies To Evaluate Safety of Newly Licensed Vaccines Meningococcal Conjugate (Menactra ) Rotavirus (Rotateq ) Tdap (ADACEL and BOOSTRIX ) HPV (Gardasil ) Cervarix Herpes zoster (Zostavax ) Prevnar13

41 Investigation of vaccine adverse event associations Guillain Barré Syndrome following any vaccine Safety of repeated influenza vaccine administration Rheumatoid arthritis and various vaccines

42 Vaccine Safety In Special Populations High-risk newborns Pregnancy Genetic risk factors Travelers Metabolic and mitochondrial disorders Persons with history of GBS

43 New Research Methodologies for Vaccine Safety Studies Pioneered by KP Vaccine Study Center Case-centered analyses Exact Sequential analysis Outcomes-bases surveillance

44 VSD - Strengths Large sample size Electronic medical records data available for epidemiology studies Can calculate incidence rates and attributable risks Relatively quick and timely

45 VSD - Limitations Dynamic cohorts loss to follow up Expensive Not large enough for some hypotheses Difficult to study VAEs with delayed or insidious onset MCO members generally well-vaccinated so can be difficult to find unbiased controls

46 New systems for detecting vaccine AEs FDA Mini-sentinel Sentinel initiative PRISM Kaiser CESR

47 Conclusions There are many organizations involved in keeping vaccines safe. Hopefully this will reassure people that

48 about vaccine safety!

49 Extra slides

50 From: Chen et al. Vaccine 1994; 12(6):