Swine flu story Mikko Pohjola, THL. Contents Introductory overview Step by step walk-through of the case –Swine flu (AH1N1 influenza) –Beginning of the.

Swine flu storyMikko Pohjola, THL

Contents• Introductory overview• Step by step walk-through of the case

– Swine flu (AH1N1 influenza)– Beginning of the pandemic– Preparedness in Finland– Vaccination campaign– Public doubts

• THL-GSK connections? Exaggerated risk? Vaccine efficacy? Counter-campaigning– Narcolepsy cases– Public discussions vs. experts– Halting of vaccination campaign– Pandemrix vs. narcolepsy elsewhere?– THL narcolepsy study– Publication of results and apologies– Public rage

• Sacking of the guilty? Vaccine testing? Actions of S&H Ministry, THL, doctors?, Spoiled vaccine batche(es)?

– EMA statement on connections between Pandemrix and narcolepsy– Re-occurence of swine flu and new vaccinations– Further vaccine/narcolepsy studies in Finland and elsewhere – Participation and openness in the swine flu – narcolepsy assessment

Introductory overview

• Swine flu vaccinations and narcolepsy in Finland– Effects and side-effects?– Vaccination campaign vs. threat?

• Big thanks to Otto Hänninen, THL– Many of the slides are translations from his recent

presentation on the topic in Finnish

The threat in summer 2009

• mortality 0,6% of those infected

• Infects 5-15% of poulationhttp://fi.wikipedia.org/wiki/Vuoden_2009_sikainfluenssapandemia

• I.e. ca. 500.000 with swine flu (according to10%) and 3.000 deaths

ca. 100 nm

Global situation 2009

WHO pandemic-alert:

4 - 27.4.2009

5 - 29.5.2009

6 - 11.6.2009

(6 is the highest alert level)

4 5 6

2009

Narcolepsy incidence in Finland

0

20

40

60

80

100

120

2006 2007 2008 2009 2010

Vuosi

Nar

kole

psi

atap

auks

ia S

uo

mes

sa

Age-stratified narcolepsy incidence in Finland

0

5

10

15

20

25

30

35

0-4 5-9 10-14

15-19

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80-

2006

2007

2008

2009

2010

Narcolepsy (ICD-10 G47.4)

• Wikipedia:– a chronic sleep disorder, or dyssomnia, characterized

by excessive daytime sleepiness (EDS) in which a person experiences extreme fatigue and possibly falls asleep at inappropriate times, such as while at work or at school.

– Another problem that some narcoleptics experience is cataplexy, a sudden muscular weakness brought on by strong emotions (though many people experience cataplexy without having an emotional trigger).

– ”numbness attack”

Narcolepsy

• International background incidence in whole population 0.05% (1/2000), in Finland 0,026% (1/4000)

• Normally ca. 60 incidences/year in Finland

• Genetic factors important, but no deterministic inheritability

• Some possible triggers: infections (streptococcus, virus), allergic reactions, autoimmune diseases, brain damage, hypothyreosis, psychological traumas

www.thl.fi > sikainfluenssahttp://www.thl.fi/thl-client/pdfs/f890b9f3-9922-4efe-889b-157fe2e03aa4

Asiantuntijat, Suomen unitutkimusseura ja Suomen Lastenneurologiyhdistys suosittelijoina:

• LT Päivi Olsén, Oulun yliopistollisen sairaalan lastenneurologian yksiköstä,

• dosentti Christer Hublin, Työterveyslaitoksen Aivot ja työ tutkimuskeskuksesta,

• dosentti Sari-Leena Himanen, Päijät-Hämeen sairaanhoitopiirin Kliinisen neurofysiologian yksiköstä,

• dosentti Turkka Kirjavainen Helsingin yliopistollisen keskussairaalan Naisten- ja lastentautien tulosyksiköstä,

• dosentti Markku Partinen Helsingin uniklinikalta ja • lääketieteen tohtori Outi Saarenpää-Heikkilä Tampereen

yliopistollisen sairaalan lastenneurologian yksiköstä.

Sosiaali- ja terveysministeriön edustajana ryhmässä toimi lääkintöneuvos Merja Saarinen 31.12.2010 asti.

THLdosentti Terhi Kilven THL:n Rokotusten ja immuunisuojan

osastolta, lääketieteen tohtori Hanna Nohynekin THL:n

Rokotusohjelmayksiköstäfilosofian tohtori Jukka Jokisen THL:n Rokotetutkimusyksiköstä, tutkimusprofessori Ilkka Julkusen THL:n Virusinfektioyksiköstä tutkimusprofessori Outi Vaaralan THL:n Immuunivasteyksiköstä.

A committee was set on 13.10.2010to study the possible connection betweenPandemrix vaccine and narcolepsy

Narcolepsy cases 2010

• 33 females, 24 males, in total 57 patients

• Average age 12 years, median 11 years, range 4-37 years

• 3 cases above 19 years of age

• Symptoms appeared on average 52 days (0 days -8 months) after swine flu vaccination

Narcolepsy in other countries

Iceland: icreased narcolepsy incidence also among non-vaccinated

Epidemiology

• Retrospective cohort study

• Follow-up (mainly) 1.1.2009-16.8.2010– (publicity and potential diagnose sensitivity)

• Incidences in age group 4-19 years / follow-up time

• 9.2 fold risk (95% CI 4.5 - 21.4)

Swine flu vaccines

• Three vaccine groups– Split virus containing vaccines (80M vaccinated, 29M

of them children)– Whole virus containing vaccines– Adjuvant containing vaccines

• Pandemrix: Nordic countries, Great Britain, Ireland, Germany, France, the Netherlands, and Spain

• Focetria: mainly in Italy, the Netherlands, and Greece• GlaxoSmithKline’s Arepanrix (used in Canada) has

exactly same composition as Pandemrix

Pandemrix side-effects (NIPH, Norway)• Normal side-effects in 1 out of 10 of those vaccinated (10%)• · Headache• · Tiredness• · Pain, redness, swelling, or hardness around the injection area• · Fever• · Pain in muscles or joints.

• Other common side-effects in 1-10 out of every 100 vaccinated (1-10%)• · Heat, itching, or bruises around the injection area• · Increased sweating, shaking, flu-like symptoms• · Swollen lymph-nodes in the neck, armpit, or groin

• Less common side-effects in 1-10 of every 1,000 vaccinated (>1‰)• · Tingling or numbness in the hands or feet• · Drowsiness• · Dizziness• · Diarrhoea, vomiting, stomach pains, or nausea• · Itching or a rash• · Feeling generally unwell• · Sleeplessness

Vaccine batches

• 28 production batches to Finland, in total 5.286.000 dosages

• Vaccines from nine different batches used for those who came down with narcolepsy within the age range 5-19 years

– Over 500.000 5-19 year olds vaccinated with vaccines from these batches

• Some vaccines to both Finland and Sweden from same batches; distribution of narcolepsy cases does not indicate batch specificity

Vaccination campaign in Finland• Aim: prevention of deaths and severe swine flu cases• Vaccination order:

1. Infection patients, personnel treating infection patients and service personnel in pharmacies

2. Pregnant women3. Risk groups (6 months – 64 years of age)

(sydänsairaus tai keuhkosairaus, aineenvaihduntasairaus, krooninen maksan tai munuaisten vajaatoiminta, vastustuskykyä heikentävä tauti tai hoito, krooninen neurologinen sairaus tai hermolihastauti)

4. Healthy children of age 6-35 months5. Healthy children and young people of age 3-24 years, and those

currently in military service6. Risk groups of age 65 years and older7. Others

Vaccinations

0

50 000

100 000

150 000

200 000

250 000

300 000

350 000

400 000

450 000

0-4 5-9 10-14

15-19

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80-

Ikäryhmä

Väe

stö

mää

rä i

käry

hm

ittä

in

Rokottamatta

Rokotetut

Swine flu cases in Finland 2009-2010

• In total 7669 pandemic influenza A(H1N1) 2009 –virus induced infections confirmed between 10.5.2009−8.3.2010.

• 44 deaths– median 56 years (1-88

years)– 4 children– 26 men– 40 with a primary disease– 3 vaccinated (1 child)

Vaccine efficacy?

• Did the vaccination campaign subdue the epidemic or was it already subsiding by itself?

• Herd immunity?

Side effects of vaccination campaigns

• Polio vaccination campaign in 1985 (94% of whole population of Finland)

– 9 children diagnozed with Guillain-Barré syndrome• paralysis of the lower body

Kinnunen et al., 1998

Discussion

• Swine flu case as a decision analysis problem?– Exercise part 1: plan a DA study

• Swine flu case as a risk management problem?– Exercise part 2: analyze RM in the case and propose

and discuss alternative approach(es)

• Is this feasible? Comprehensible?

Swine flu and narcolepsy – assessment: openness and participation

Different aspects on the media content

• What is discussed? Contents, discourses, meanings.

• Who talks? Whose point of view is presented? How are issues framed? Interaction settings?

• How do people talk? Argumentation, rhetoric methods, use of language, prejudices...

• E.g. How is swine flu or authority, citizen or expert knowledge constructed? What meanings are communicated? In what ways?

Important aspects in narcolepsy news

(rough order of occurrence)

• Emphasis on threat and fear

• Taking over the problem

• Reporting about the spread of swine flu

• Preparedness and prevention

• Survival and protection

• Emphasising familiarity and safety

• Impacts of swine flu

• Criticising authorities

• Advice about what should (have been) done

• Emphasising the responsibility of authorities

Swine flu – narcolepsy assessment: role of participation?

• How could other people than experts have been participated in the narcolepsy assessment?

• How should other people participate?

• What additional value would this bring in?

The five dimensions of openness:

• Scope of participation, referring to who are allowed to participate in the process.

• Access to information, referring to what information regarding the issue at hand is made available to participants.

• Timing of openness, referring to when participants are invited or allowed to participate.

• Scope of contribution, referring to which aspects of the issue at hand participants are invited or allowed to contribute to.

• Impact of contribution, referring to what extent are participant contributions allowed to have influence on the outcomes, i.e. how much weight is given to participant contributions.

Development of narcolepsy assessment

• Spring 2010 Neurologists surprised about # of new narcolepsy cases.

• June 2010 Neurologists contact THL about their findings. • 18.8.2010 The MPA (Sweden) investigates reports of narcolepsy in

patients vaccinated with Pandemrix MPA [1] • 18.8.2010 Expert: Unlikely that H1N1 vaccine and narcolepsy have

connection YLE [2] • 18.8.2010 THL will study the connection. Vaccine and narcolepsy

experts will meet in the afternoon to design the study. YLE • 19.8.2010 The study has been started. It will last for months. THL

[3] • 24.8.2010 THL recommends to stop Pandemrix vaccination. THL [4] • 27.8.2010 European Medicines Agency starts review of Pandemrix

EMA [5] YLE [6] • 23.9.2010 EMA: Evidence insufficient to determine causal link.

Pandemrix benefits larger than risks. EMA [7]

Development of narcolepsy assessment (2/2)

• 8.9.2010 Swedish study shows no connection between vaccination and narcolepsy MTV3 [8]

• 17.11.2010 Ties Between Big Pharma and THL Draw Complaints YLE [9]

• 30.1.2011 Swine flu faccination to children maybe a mistake YLE [10]

• 31.1.2011 First assessment report published by THL [11] • 1.2.2011 THL: Pandemrix vaccine increased the risk of

narcolepsy YLE [12] • 18.2.2011 EMA: Causal relationship not established EMA [13] • August 2011: Final assessment report will be published by

THL

The five dimensions of openness:

• Scope of participation, referring to who are allowed to participate in the process.

• Access to information, referring to what information regarding the issue at hand is made available to participants.

• Timing of openness, referring to when participants are invited or allowed to participate.

• Scope of contribution, referring to which aspects of the issue at hand participants are invited or allowed to contribute to.

• Impact of contribution, referring to what extent are participant contributions allowed to have influence on the outcomes, i.e. how much weight is given to participant contributions.