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Lessons Learnt from Influenza A(H1N1) Vaccines Benefit-Risk Monitoring Encepp Plenary Meeting

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Lessons Learnt from Influenza A(H1N1) Vaccines Benefit-Risk Monitoring Encepp Plenary Meeting Lessons learnt from Influenza A(H1N1) vaccines benefit-risk monitoring ENCePP Plenary meeting Xavier Kurz 8 June 2010 An agency of the European Union ContentsContents 1. Safety database at time of authorisation 2. Mechanisms for vaccine safety surveillance 3. What worked well 4. Areas for improvement of vaccine vigilance system 5. On-going work 2 1. Safety database at time of authorisation Pandemrix • H5N1 vaccine: 6,100 subjects – 300 children 3-9 years, 5,071 adults 18-60 years, 729 elderly >60 years • H1N1 vaccine: 130 adults 18-60 years Focetria • H5N1 vaccine: 1,496 subjects – 145 children 6-35 months, 96 children 3-8 years, 93 children 9-17 years, 989 adults 18-60 years, 173 elderly >60 years • H1N1 vaccine: none Celvapan • H5N1 vaccine: 836 subjects – 556 adults 18-60 years, 280 elderly > 60 years • H1N1 vaccine: none Safety profiles observed with H5N1 vaccines expected to be generally applicable to A/H1N13 vaccines. Limited data in children and pregnant women. European Strategy published on 5 November 2009 http://www.emea.europa.eu/pdfs/human/pandemicinfluenza/european_strategy.pdf or: EMEA website Æ Pandemic influenza website Æ Latest news 4 2. Vaccine safety surveillance Marketing Authorisation Holders • Monthly simplified Periodic Safety Update Reports (s-PSUR) • Summary of important information from spontaneous reports and analysis of safety issues in populations at risk • PASS of 9,000 subjects for each vaccine stratified by age • As soon as vaccination starts • Pregnancy registries • Creation or collaboration with existing pregnancy registries • Rare disorders (eg. Guillain-Barré syndrome) and populations at risks • Active surveillance • Effectiveness studies 5 • Collaboration between ECDC (I-MOVE consortium), EMA and MAHs Vaccine safety surveillance EMA and Member States • Strenghtening of the spontaneous reporting system • list of Adverse Events of Special Interest (AESIs) • standardised list of data to collect (eg batch number) • weekly distribution of EudraVigilance reaction monitoring report • observed-to-expected analyses • Procedures for rapid assessment and decision-making • e.g. variation of product information for high fever after 2nd dose • Collection of EU-wide information • vaccination policies • exposure data • background rates on adverse events of special interest • Collaboration with research projects relevant for A/H1N1 vaccine B/R monitoring 6 • 43 projects, 8 multicountry, 35 national (14 countries) Vaccine safety surveillance EMA and Member States • Establishment of Pandemic Pharmacovigilance Rapid Response Expert Group (PREG) • Weekly teleconferences, more if needed • Analysis of emerging safety issues and recommendations • Rapid response to concerns raised by Member States • Weekly Pandemic Pharmacovigilance Updates published on EMA website • Exposure data • Overall benefit-risk evaluation • List of most frequent reactions per system organ class • Review of all fatal cases • Safety updates: new safety concerns, PREG conclusions 7 3. What worked well 1. Spontaneous reports – only source of data on vaccine safety until 01/10 Pandemic A/H1N1 influenza vaccines: Reports of ADRs Eudravigilance (EEA; up to 23 May 2010) 16,000 14,359 14,554 14,015 14,000 14,642 12,705 13,130 14,456 12,377 13,725 14,243 13,354 12,000 11,649 12,915 11,126 12,057 10,000 Celvapan: 557 8,745 Celvapan: 8,000 Focetria: 3,096 6,000 5,301 6,101 3,882 Pandemrix: 10,014 4,000 2,644 2,381 2,000 1,469 800 523 408 320 328 210 215 224 371 290 228 116 97 98 88 Number of case reports received 0 3- 9- 16- 23- 6- 13- 20- 27- 3- 10- 17- 24- 10- 24- 08- 21- 05- 20- 02- Dec-Dec- Dec-Dec- Jan- Jan- Jan- Jan- Feb- Feb- Feb- Feb- Mar- Mar- Apr- Apr-May-May- Jun- 09 09 09 09 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 Date of update publication New cases since last report Total rec eived over time 8 Ad-hoc weekly EMA survey of EEA members. CAP vaccines: Estimated exposure to pandemic A/H1N1 influenza vaccines (EEA, up to 25 Apr 2010) 40,000,000 35,000,000 Celvapan:Celvapan 0.6 m. 30,000,000 Focetria:Focetria 6.5 m. 25,000,000 Pandemrix: 30.7 m. 20,000,000 15,000,000 10,000,000 Estimated exposure 5,000,000 0 3- 9- 16- 23- 6- 13- 20- 27- 3- 10- 17- 24- 10- 24- 08- 21- 05- Dec- Dec- Dec- Dec- Jan- Jan- Jan- Jan- Feb- Feb- Feb- Feb- Mar- Mar- Apr- Apr- May- 09 09 09 09 10 10 10 10 10 10 10 10 10 10 10 10 10 Date of update publication 9 Reported vaccine reactions by SOC: Pandemrix PANDEMRIX: Number of patients who experienced one or more reactions for each System Organ Class (up to 23 May 2010, EEA) Number of patients 0 1,000 2,000 3,000 4,000 5,000 6,000 7,000 8,000 General disorders and administration site conditions Nervous system disorders Gastrointestinal disorders Musculoskeletal disorders Skin and subcutaneous disorders Respiratory disorders Psychiatric disorders Infections Vascular disorders Cardiac disorders Investigations Immune system disorders Metabolism and nutrition disorders Eye disorders Blood and lymphatic system disorders Injury and procedural complications Ear and labyrinth disorders System Organ Class Organ System Pregnancy and perinatal conditions Renal and urinary disorders Reproductive and breast disorders Surgical and medical procedures Hepatobiliary disorders Social circumstances Neoplasms benign, malignant and unspecified Endocrine disorders Congenital and genetic disorders 10 Reported vaccine reactions by SOC: Focetria FOCETRIA: Number of patients who experienced one or more reactions for each System Organ Class (up to 23 May 2010, EEA) Number of patients 0 200 400 600 800 1,000 1,200 1,400 1,600 General disorders and administration site conditions Nervous system disorders Musculoskeletal disorders Gastrointestinal disorders Skin and subcutaneous disorders Respiratory disorders Infections Injury and procedural complications Cardiac disorders Pregnancy and perinatal conditions Vascular disorders Ear and labyrinth disorders Psychiatric disorders Eye disorders Investigations Blood and lymphatic system disorders Metabolism and nutrition disorders System Organ Class Immune system disorders Surgical and medical procedures Reproductive and breast disorders Renal and urinary disorders Congenital and genetic disorders Hepatobiliary disorders Neoplasms benign, malignant and unspecified Endocrine disorders 11 Social circumstances Reported vaccine reactions by SOC: Celvapan CELVAPAN: Number of patients who experienced one or more reactions for each System Organ Class (up to 23 May 2010, EEA) Number of patients 0 50 100 150 200 250 300 Nervous system disorders General disorders and administration site conditions Gastrointestinal disorders Skin and subcutaneous disorders Respiratory disorders Musculoskeletal disorders Vascular disorders Immune system disorders Eye disorders Injury and procedural complications Infections Ear and labyrinth disorders Cardiac disorders Investigations Psychiatric disorders Blood and lymphatic system disorders Metabolism and nutrition disorders System Organ Class Organ System Pregnancy and perinatal conditions Renal and urinary disorders Reproductive and breast disorders Congenital and genetic disorders Endocrine disorders Hepatobiliary disorders Neoplasms benign, malignant and unspecified Social circumstances 12 Surgical and medical procedures Adverse events of special interest (EEA+non-EEA) 30/05/2010 Validation on-going Pandemrix Total Total paediatric Anaphylactic reaction (narrow SMQ) 329 54 - anaphylactic shock 45 10 - anaphylactoid shock 1 0 Angioedema (narrow SMQ) 550 185 Convulsions (narrow SMQ) 312 199 Demyelination (narrow SMQ, excl GBS) 76 3 - multiple sclerosis 14 1 - multiple sclerosis relapse 19 0 GBS/MS (incl. PT Nerve root lesion); partly validated 75 6 Noninfectious encephalitis (narrow SMQ, excl ADEM) 21 2 Vasculitis (narrow SMQ) 34 8 Facial palsy (PT) 56 Neuritis (PT) 25 0 13 Adverse events of special interest (EEA+non-EEA) 30/05/2010 Focetria Validation on-going Total Total paediatric Anaphylactic reaction (narrow SMQ) 23 4 - anaphylactic shock 5 1 - anaphylactoid shock 0 0 Angioedema (narrow SMQ) 151 24 Convulsions (narrow SMQ) 55 29 Demyelination (narrow SMQ, excl GBS) 16 0 - multiple sclerosis 1 0 - multiple sclerosis relapse 3 0 GBS/MS (incl. PT Nerve root lesion); partly validated 32 0 Noninfectious encephalitis (narrow SMQ, excl ADEM) 81 Vasculitis (narrow SMQ) 15 1 Facial palsy (PT) 20 2 Neuritis14 (PT) 40 Adverse events of special interest Adverse(EEA+non-EEA) events 30/05/2010 of special interest (EEA+non-EEA) Validation on-going Celvapan Total Total paediatric Anaphylactic reaction (narrow SMQ) 23 4 - anaphylactic shock 1 1 - anaphylactoid shock 0 0 Angioedema (narrow SMQ) 56 17 Convulsions (narrow SMQ) 12 4 Demyelination (narrow SMQ, excl GBS) 20 - multiple sclerosis 1 0 - multiple sclerosis relapse 0 0 GBS/MS (incl. PT Nerve root lesion); partly validated 20 Noninfectious encephalitis (narrow SMQ, excl ADEM) 10 Vasculitis (narrow SMQ) 41 Facial palsy (PT) 10 Neuritis (PT) 10 15 Reaction reports in Pregnancy SOC (EEA+non-EEA) 30/05/10 Celvapan Focetria Pandemrix Abortion not specified/spontaneous 1 5 74 Amniotic fluid and cavity disorders 1 1 Failed labour 2 Foetal (growth) complication 2 4 Foetal presentation abnormalities 1 Premature/small for date baby 3 4 4 Haemorrhagic complications 2 3 Pre-eclampia, pregnancy-induced HT 2 Premature/threatened labour 1 5 6 Maternal complications/ectopic pregnancy 3 6 Placenta abnormalities 4 1 Intra-uterine death, stillbirth 27 34 Umbilical cord complications 3 1 Unintended16 pregnancies 3 Reports of fatal cases (EEA+non-EEA)
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