Vaccine Safety: Its everyone s business! PHO Rounds: Nov 19, 2013

Transcription

1 Vaccine Safety: Its everyone s business! PHO Rounds: Nov 19, 2013 Tara Harris, Nurse Consultant Shelley Deeks, Medical Director Immunization and Vaccine Preventable Diseases 1

2 Learning objectives 1. Describe AEFIs reported in Ontario following administration of vaccines in Demonstrate the value of AEFI surveillance with respect to monitoring vaccine safety and building confidence in immunization programs in Ontario. 2

3 Why is this important? Public confidence in vaccine safety is critical and key to success of programs Higher standard of safety is expected of vaccines Lower risk tolerance = need to search for rare reactions Vaccinees generally healthy (vs. ill for drugs) Decrease in disease risks and increased attention on vaccine risks Vaccination universally recommended and subject to mandatory choice 3

4 Where do Canadian parents go for information? If you were looking for the most reliable and trustworthy information on vaccines, where would you look or who would you talk to? N=1,737 Available at: 4

5 What do Canadian parents think? Available at: 5

6 Is there a perfect vaccine? NO Vaccines should cause no adverse reactions and completely prevent the infection that they target Current technology does not allow for such perfection. Key is to minimize adverse events and ensure safe use of vaccines Adverse events are monitored 6

7 BUT: they are getting safer all the time Vaccines given to today s children are safer than the vaccines given to their parents Oral polio vaccine replaced with inactivated polio vaccine in 1998 Whole cell pertussis vaccine replaced with acellular pertussis vaccine in 1997/8 Available at 7

8 Types of vaccine safety issues Not all safety issues are related to the vaccine per se Vaccine administration errors Storage and handling Administration Adverse events following immunization (AEFI) Temporal associations Causal associations 8

9 Background Monitoring vaccine safety: Post licensure Identify signals of possible adverse events that may warrant further study or affect current immunization program Rare reactions not detected during pre-licensure studies Increases in known reactions Events associated with a specific lot Risk factors or pre-existing conditions that may promote reactions 9

10 Background Post marketing safety surveillance Shared responsibility Health Canada Regulatory oversight Lot release program Review Yearly Biologic Product Report Post-marketing surveillance of efficacy and adverse events Industry 10

11 Background Objectives of AEFI surveillance in Ontario To identify and investigate serious or unexpected occurrences of AEFI, particularly for new vaccines To detect and investigate safety signals (e.g., lot-specific problems) To estimate provincial rates of reported AEFIs by vaccine To report to stakeholders on the safety of publicly funded vaccines in Ontario To maintain public confidence in vaccine programs 11

12 Background Roles and responsibilities in routine AEFI surveillance Immunization provider Public health units Public Health Ontario Public Health Agency of Canada WHO/ Uppsala Monitoring Centre Inform and counsel re: risks/benefits Recognize and report AEFIs Manage AEFIs Case assessment & management Reporting of AEFIs (iphis) MOH Recommendation Provincial surveillance Case / cluster management advice Signal detection National AEFI database Signal detection Causality assessment Global AEFI database Signal detection Expert advisory Group Public health action Mills A. (CDC Public Health Image Library), Reproduced with permission. Microsoft Images, Reproduced with permission. 12

13 Annual Report on Vaccine Safety in Ontario Objective: To summarize AEFIs reported in Ontario following vaccines administered in 2012 First comprehensive vaccine safety assessment in Ontario Complete description of provincial AEFI surveillance system and discussion of its limitations Recommendations for improved data, surveillance processes Public health unit (PHU) and public dissemination Microsoft Images, Reproduced with permission. 13

14 Methods Weekly review & follow-up of AEFI reports throughout 2012 Data clean-up initiative (Feb.-March 2013) targeting missing/incomplete information for selected iphis fields All reports of AEFIs with a vaccine administration date from January 1 to December 31, 2012 extracted from iphis on May 6, 2013 Active immunizing agents only Publicly funded and non-publicly funded vaccines 14

15 Analysis limited to reports classified as Confirmed only Methods Any reported event listed in sections 5.0 (Clinical Evidence) in a vaccine recipient which follows immunization which cannot be clearly attributed to other causes. A causal relationship with the administration of the vaccine does not need to be proven. 1 Each AEFI report represents One or more vaccines One vaccine recipient One or more adverse events Infectious Diseases Protocol, Appendix B: Provincial Case Definitions for Reportable Diseases. Disease: Adverse Events Following Immunization (AEFIs) [Internet]. Toronto: Ministry of Health & Long-Term Care; 2013 [updated Jan.1, 2013; cited May 22, 2013]. Available from: 15

16 Methods Reports defined as serious 2 if the AEFI resulted in death; was life threatening; required in-patient hospitalization of 24 hours or more or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; causes congenital anomaly/birth defect; or, any other important medical event that may have jeopardized the patient or may have required intervention to prevent one of the outcomes above Important medical events anaphylaxis, Guillain Barré Syndrome, Bell s palsy, paralysis (other than Bell s palsy), seizure, meningitis, encephalopathy / encephalitis, intussusception and thrombocytopenia 2. Definition and Application of Terms for Vaccine Pharmacovigilance. Report of CIOMS/WHO Working Group on Vaccine Pharmacovigilance [Internet]. Geneva: Council for International Organizations of Medical Sciences; 2012 [updated 2012; cited May 22, 2013]. Available from: 16

17 Methods Enhancement of AEFI surveillance in Ontario Ontario AEFI Reporting Form (New) AEFI Appendix B (Revised) Vaccine Safety Surveillance Working Group (VSSWG) Education and training Periodic data quality reviews Enhanced signal detection Annual Provincial AEFI Surveillance Report iphis application (Updated) iphis User Guide (Revised) 17

18 Methods Notes on interpretation AEFI reported in iphis are temporally associated and are not necessarily causally linked to vaccine Assessment is based upon iphis data only and not comprehensive chart review Reporting rate estimates are presented for comparison to other passive safety surveillance systems and monitoring reporting trends over time; should not be interpreted as incidence rates Trends in reported AEFI are influenced by changes to the publicly funded program istock, Reproduced with permission. 18

19 Results 631 confirmed AEFI following vaccines administered in million doses of publicly funded vaccine distributed AEFIs reported in Ontario following vaccines administered in 2012, by classification status (N=765). Overall number and % confirmed increased compared to 2010/2011 Wide variation in reporting by HU 17.5% (134) 82.5% (631) CONFIRMED DOES NOT MEET DEFINITION 19

20 Results AEFI reporting rate in 2012 was 4.7 per population Annual reporting rate 30.6% in 2012 compared to 2010 / 2011 Most frequent reporting sources Physicians 38% Health care professionals 21% Family members 17% 20

21 Results Total confirmed AEFI reports following vaccines administered and publicly funded vaccine distribution 1 by month in Ontario, ,000, ,500,000 Number of reports ,000,000 1,500,000 1,000,000 Doses distributed ,000 0 JAN FEB MAR APR MAY JUN JUL AUG SEP OCT NOV DEC Month reports Vaccine dose distribution Notes: Includes net vaccine distribution from Ontario Government Pharmacy & Medical Supply Service (OGPMSS) (i.e., publicly funded vaccine doses) only. Counts include all confirmed AEFIs reported in

22 Results AEFI reports by age and sex Distribution of AEFI reports by age weighted toward younger ages 31.7% of reports under 7 years of age Overall, females outnumbered males slightly more than 2:1 (67.4% reports female) 22

23 Results Age and sex distribution of confirmed AEFI reported following vaccines administered in Number of reports FEMALE MALE 20 0 < Age (years) 23

24 Results Health care utilization Medical consultation (76%), emergency room visit (18%), hospital admission (4%) Majority recovered at the time of the AEFI report (65%); 20% not yet recovered; 3% residual effects (12% unknown outcome) Risk factor information completed in 19.2% of reports Chronic illness/underlying medical condition (67.6%), Other (22.3%), Immunization program error (5.8%) 24

25 Results AEFI reports by agent Majority of AEFI reports associated with one agent (84.0%) Most frequently reported agents Influenza 28.7% DTaP-IPV-Hib 9.0% Tdap 9.7% DTaP-IPV 8.4% Highest reporting rates (per doses distributed) DTaP-IPV HPV BCG 82.6 HB 21.1 Rabies

26 Results AEFI reports by event Majority of reports associated with one adverse event category (73.5%) Injection site reactions most frequently reported (45.0% of all reports) Rash, allergic skin reactions also commonly reported (21.7% and 20.8% respectively) Other severe/unusual events selected in 19.5% of all reports 26

27 Results Serious AEFI 56 serious AEFI (8.9% of all reports) Most hospital admissions (79.2%) among those <18 years of age Including 11 detected and investigated by IMPACT Most frequently reported medically important events Anaphylaxis (46.2%), convulsions/ seizures (30.1%), Bell s palsy (7.7%), Encephalitis/encephalopathy (5.1%), GBS (2.6%) No reports of death temporally associated with receipt of vaccine in

28 Results Anaphylaxis 18 reports temporally associated with 20 agents 8 influenza 1 HB + Men-C-ACYW 3 HPV4 1 MMRV + DTaP-IPV 2 HB 1 HA-Typh-I 2 Tdap All assessed using the Brighton Collaboration case definition 6 (33.3%) met the Brighton case definition of anaphylaxis 9 (50.0%) reports did not meet the Brighton case definition based on information contained in the report 3 (16.7%) reports did not contain enough information to complete an assessment 28

29 DISCUSSION istock, Reproduced with permission. 29

30 Discussion Reporting rate (4.7 per population) Increase between 2011 and 2012 Enhanced surveillance follow-up activities Increased awareness of AEFI surveillance New programs (e.g. rotavirus) Ontario reporting rate is lower compared to other jurisdictions with passive AEFI surveillance systems National reporting rate estimated at 9.4 per population; Ontario represents approximately 23% of all AEFI reports vs. 39% of national population Other countries (10.4 and 8.5 per population, Australia and the US respectively) 30

31 Discussion Distribution of AEFI by sex Various by age Over-representation of females in adult age groups consistent with other passive vaccine safety surveillance systems Why? Higher vaccine uptake among females Higher proportion of females are HCWs targeted for specific vaccines Differences in health-seeking behaviours 31

32 Discussion Case classification Increasing proportion of cases classified as Confirmed ( 10% in 2012) Decreasing use of other case classifications (e.g., Person Under Investigation and Does Not Meet ) Active follow-up throughout 2012 and data clean-up initiative Misclassification issue identified in early 2012 and validated by the HPV4 AEFI assessment AEFI case definitions clarified in revised Appendix B 32

33 Discussion AEFI by event type High burden of injection site reactions among AEFI reports Pain/redness/swelling <4 days 9.7% Pain/redness/swelling lasting 4 days 19.3% Changes as of Jan.1, 2013 Pain/redness/swelling <4 days discontinued Pain/redness/swelling lasting <4 days further differentiated (4-10 & >10 days) Rationale: Relatively common event, not considered a contraindication to further immunization Continued monitoring in subsequent reports to determine if further changes are necessary 33

34 Discussion Serious AEFI Proportion of AEFI that were serious (8.9%) similar to previous analyses (HPV4 AEFI 7.5%) Somewhat similar to other passive vaccine safety surveillance systems Australia 7% United States (VAERS) 13% Standard definitions used (World Health Organization), however application varies Outcome data missing / incomplete (i.e. persistent/significant sequelae) Inclusion of important medical events is jurisdiction-specific 34

35 Discussion Anaphylaxis Relatively low proportion of anaphylaxis reports (33%) met Brighton case definition; possibly related to 1. Misclassification 2. Missing or incomplete information 3. Altered progression of event due to administration of epinephrine Continued uptake of revised AEFI surveillance definitions and guidelines will improve data quality Guided reporting tools available to improve AEFI investigation and reporting for complex events 35

36 Limitations Discussion Under-reporting, inconsistent quality and completeness of reports, and reporting bias Key missing/incomplete fields: dose number, time to onset and duration of the event, complete description of the reaction (case notes), treatment, and outcome Lack of population-based denominator to calculated incidence rates (total population or doses distributed used as proxy) Limited analysis on trends over time. AEFI surveillance changes implemented Jan.1,

37 Conclusions Vaccines are safe and continually monitored Annual reporting an important part of provincial vaccine safety surveillance Data provides reassurance regarding safety of vaccines used in Ontario Types of events broadly consistent with safety profile of many vaccines istock, Reproduced with permission. 37

38 Conclusions (2) AEFI reports increased in 2012 but are still lower than other jurisdictions AEFI by vaccine mainly driven by volume of distribution Revised case definitions will help characterize specific events over time Ongoing monitoring will further establish the safety profile of vaccines used in Ontario istock, Reproduced with permission. 38

39 Recommendations Annual report Continue annual assessment of AEFIs iphis data extraction date of May 1 for AEFIs reported during previous calendar year Annual data cleaning process to ensure data consistency and comparability Knowledge translation plan Dissemination of annual report to public health units, health professionals and members of the public Produce additional KT products to assist with communication regarding vaccine safety messages Microsoft Images, Reproduced with permission. istock, Reproduced with permission. 39

40 Recommendations Anaphylaxis reporting Implement a guided reporting tool for health units to use Improve provincial assessment and classification using standard, internationally accepted criteria Increase AEFI reporting Further explore possible explanations for underreporting of AEFI Recommend strategies to improve reporting rates in Ontario istock, Reproduced with permission. 40

41 Acknowledgements Kenny Wong Jill Fediurek Margaret McIntyre Michelle Uy Laurie Stanford Sarah Wilson Natasha Crowcroft Public health unit staff Microsoft Images, Reproduced with permission. 41