DARM DA study exercise Group 1

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Background

The 2009 flu pandemic was an outbreak of a new strain of H1N1 influenza virus, usually referred to as "swine flu". First described in April 2009, the influenza A(H1N1)v virus was a new virus subtype of influenza affecting humans, which contains segments of genes from pig, bird and human influenza viruses in a combination that had never been observed before anywhere in the world. A(H1N1)v virus is the result of a combination of two swine influenza viruses that contained genes of avian and human origin (ECDPC 2011). Unlike most strains of influenza, H1N1 does not disproportionately infect adults older than 60 years; this was an unusual and characteristic feature of the H1N1 pandemic (Writing Committee of the WHO 2010).

The outbreak began in the state of Veracruz, Mexico, with evidence that there had been an ongoing epidemic for months before it was officially recognized as such (McNeil 2009). The Mexican government closed most of Mexico City's public and private facilities in an attempt to contain the spread of the virus; however, it continued to spread globally, and clinics in some areas were overwhelmed by infected people. In June, the World Health Organization (WHO) and US Centers for Disease Control (CDC) stopped counting cases and declared the outbreak a pandemic (WHO/Chan 2009).

The pandemic began to taper off in November 2009 (McKay 2009), and by May 2010, the number of cases was in steep decline (WHO 2010). On 10 August 2010 the World Health Organization announced the end of the H1N1 pandemic (Helsingin Sanomat 2010). According to the WHO statistics from July 2010, the virus had killed more than 18,000 people since it appeared in April 2009 (redOrbit 2010), approximately 4% of the 250,000 to 500,000 annual influenza deaths (WHO 2009).

Now the H1N1 influenza virus has moved into the post-pandemic period. However, localized outbreaks of various magnitudes are likely to continue. Influenza outbreaks, including those primarily caused by the H1N1 virus, show an intensity similar to that seen during seasonal epidemics. Recently published studies indicate that 20–40% of populations in some areas have been infected by the H1N1 virus and thus have some level of protective immunity. Many countries report good vaccination coverage, especially in high-risk groups, and this coverage further increases community-wide immunity (WHO 2010b).

In Finland the first laboratory confirmed cases of influenza A(H1N1) was discovered on May 2009. At that time the spread of influenza A(H1N1) to Finland was expected as the virus has spread widely around the world (THL 2009a). The first death in Finland associated with the A(H1N1)v influenza virus was confirmed in on October 2009. As of 26 October 2009, there had been 522 confirmed cases of influenza A(H1N1)v in Finland. In the same time the epidemic had continued its spread throughout Europe (THL 2009b).

The Ministry of Social Affairs and Health (MSAH) and the National Institute for Health and Welfare (THL) both recommended the vaccine, especially to the priority groups (health care professionals) and risk groups (pregnant women and persons aged from 6 months to 64 years belonging to a risk group due to another illness), to prevent the spread and severe complications of the illness (THL 2009b). The MSAH asked the THL to give opinion about getting vaccines. As the THL saw it, vaccinations were well reasoned in that situation. It was made sure via procurement that vaccines would be received as fast as possible. Order for vaccines was placed at the end of April 2009 right after the news from new epidemic had spread (THL 2010).

Vaccinations of health care personnel against influenza A(H1N1)v were initiated all over the country during autumn. The plan was to start vaccinating pregnant women after health care personnel. After this, local authorities began vaccinating risk groups, according to the stated schedule. The proposal for the order of vaccination in Finland was approved by the Government in September 2009. The order was determined on medical grounds. Finland was among the first countries in Europe to receive the vaccine (THL 2009b).

The influenza vaccine being used in Finland was approved by the European Medicines Agency (EMEA), and it was also recommended by the World Health Organisation. The vaccine contained an adjuvant, a substance that enhances the immune response so less extract of the virus is needed in each dose. This immune response-enhancing substance had been thoroughly reviewed and tested even before it was considered for use in vaccines. The pandemic influenza vaccine had not been used in practice, but previous vaccines had provided data and knowledge on the behaviour of parts of it and other closely related vaccines. THL announced that the vaccine might cause side effects similar to seasonal flu vaccines, like a sore arm from the shot, headache, muscles aches, joint pains and mild fever. The vaccine effectiveness was expected to be good, about 90 percent (THL 2009b).

Since August 2010, following widespread use of vaccines against influenza (H1N1) 2009, cases of narcolepsy, especially in children and adolescents, have been reported from at least 12 countries. Narcolepsy is a rare sleep disorder that causes a person to fall asleep suddenly and unexpectedly. The rates reported from Sweden, Finland and Iceland have been notably higher than those from other countries (WHO 2011) .In Finland during 2009–2010, 60 children and adolescents aged 4–19 years were diagnosed with narcolepsy. This number is based on patient data collected from hospitals discharge registers and primary health care on all identified narcolepsy cases and an independent assessment of the patient records by an expert panel of neurologists and sleep researchers. When combining this information to pandemic vaccination data obtained from primary health care, it was noted that 52 persons, i.e. nearly 90 % of the cases, had received Pandemrix vaccine, when the vaccination coverage of that particular age group was 70 %. According to these preliminary results, which still need to be confirmed, the risk of narcolepsy in the age group of 4–19 years was 9-fold among those Pandemrix-vaccinated in comparison with those unvaccinated in the same age group, corresponding to a risk of about 1 case of narcolepsy per 12,000 vaccinated in this age group. The increase was most marked among those 5–15-years of age. No cases were observed in children less than 4 years of age. Among persons over 19 years of age the incidence of narcolepsy has not increased and there is no sign that the vaccine had had an effect on the risk for falling ill with narcolepsy. Overall, the observed association between the vaccine and narcolepsy in the age group of 4–19 years is so evident that it is unlikely that some underlying or so-called confounding factor could alone completely explain it (THL 2011).

Narcolepsy is a condition that has a strong genetic linkage. Of the cases of narcolepsy tested so far in Finland (n=22), diagnosed during 2009-2010, all have the same genotype. It is considered most likely that the Pandemrix vaccine increased the risk of narcolepsy in a joint effect in those genetically disposed with some other, still unknown, genetic and/or environmental factor (WHO 2011).

In those countries which used similar pandemic vaccines in 2009-2010, an increased incidence of narcolepsy in children and adolescents has been observed only in Finland, Sweden and Iceland. In contrast to Finland, increased numbers of narcolepsy have been observed also among unvaccinated children and adolescents in Iceland. In Norway, United Kingdom, Germany and Canada, an estimated total of 3,5 million 4–19 year old children and adolescents have been vaccinated with the same vaccine as in Finland with no sign of an increase in narcolepsy (THL 2011).

In Finland, Pandemrix-vaccinations were halted as a precautionary action in August 2010 due to narcolepsy suspicions. European drug authority (EMEA) still recommends Pandemrix vaccinations. (THL 2010)

The association between narcolepsy and Pandemrix vaccine requires much further investigation (THL 2011).

Scope

Purpose

Purpose of this DA study is to evaluate the impact of vaccination in Finland.

Questions addressed in the study are

• was the decision to vaccinate everybody the right one?
• would it have been better if vaccinations were not done?

Boundaries

• Spatial and temporal boundaries of the study: assessment from Finland, from June 2009 to March 2011
• Actions of Ministry of Social Affairs and Health and National Institute for Health and Welfare

Scenarios

Approach chosen in Finland was to vaccinate the whole population. There are at least 2 scenarios related to vaccination policies which could have been chosen instead:

1. vaccinate only the priority group [health care workers] and risk group [pregnant women, children below age two or five, diabetics, people with asthma or other chronic lung diseases, neurological and neuromuscular disorders,heart diseases, kidney diseases and suppressed immune systems (HIV)]

Possible outcome:

• complications still possible (some people may have undiagnosed diseases)
• reduced cost of vaccination
• reduced side effect (limited to only the risk group)
• reduction in disease development and possibly death.
• easy management of those vaccinated
• vaccination is too late to have any actual effect on the epidemic

2. No vaccination

Possible outcome:

• spreading of swine flu 2009 pandemic leading to high amount of H1N1 cases, deaths
• H1N1 fades away with minor impacts
• some children are not affected by possible life-long side effects of Pandemrix (narcolepsy)
• resistance for future outbreaks of H1N1 remains weak in Finland

Intended users

• Ministry of Social and Health Affairs of Finland and all opasnet users.

Participants

• Anna Kokkonen, Jukka-Pekka Männikkö, Oluyemi Toyinbo, the media, research groups, health practitioners, ministry of health and social welfare.

Definition

Add a legend for your diagram.

Decision variables

Vaccination coverage variables:

• everyone is vaccinated
• risk group and priority group are vaccinated
• no-one is vaccinated

Indicators

• For decision to vaccinate everybody we will measure amount of swine flu cases, complications and complications due to swine flu vaccination by the number of these in Finland.

• For scenario not to vaccinate anyone we will measure amount of swine flu cases and complications due to swine flu vaccination by the number of these in Mexico.

• Effect of swine flu vaccination on the 2009 pandemic can be evaluated by comparing swine flu cases to the amount of people vaccinated, remembering there is an approximately 2 weeks lag before the vaccination was done. By this evaluation, it is possible to estimate what would have happened without the vaccinations. For example a simple trend analysis reveals that the amount of confirmed new swine flu cases is already trending down before vaccination started. This does not mean the vaccination would have been futile since it contributes to resistance against future outbreaks.

• All impacts will be converted to DALY's.

Other variables

• population of Finland and Mexico
• vaccination coverage
• sensivity and spesificity of detecting H1N1
• age and life expactancy
• health status
• DALY weights

• Actions by the pharmaceutical companies to get the vaccines ready in time
• Approval of the vaccines by international authorities
• Skills and education of the health care personell in Finland
• Willingness of the population to take vaccines
• Personal hygiene affecting spread of the virus
• Actions taken outside of Finland to contain spread of the epidemic

Calculation

Information needed for the decisions:

Before the decision:

• Estimations about the spreading speed of the epidemic
• Estimations about the danger level posed to subjects
• Estimations about the effectiveness of the vaccine
• Estimations about the side-effect rates
• Uncertainties related to above estimates (which are likely to be large)
• Real time surveillance of new H1N1 (suspected) cases in Finland

After the decision:

• After the actions have been taken, statistics about possible side effects
• Estimates about effects of the vaccination on spreading of the virus

Analyses

DALYs are calculated

DALY = YLL + YLD

YLL=Years of life lost

YLD=Years lived with disability

YLD = number of cases x severity weight x duration of disease

We would calculate DALYs for decision to vaccinate everyone taking into account things like:

• 7828 swine flu cases in Finland during 2009-2010 and 8 deaths due to swine flu
• 60 narcolepsy cases in Finland and from those 52 vaccinated (90% narcolepsy cases received vaccination)
• average age of narcolepsy cases 12 years
• vaccination coverage (in total 50 %, children 4-19 years old 70 %)
• population of Finland 5 375 276 (at the end of 2010)
• life expactancy for Finnish men 77 years and for women 83 years

We would calculate DALYs for decision not to vaccinate anyone based on similar information (than above) of Mexico.

After calculating DALYs we would compare them and assess which decision where better one.

Results

Despite of the narcolepsy risk we would expect that decision to vaccinate all would give a better outcome than decision not to vaccinate anyone. That is based on our expectation that DALYs would be lower for decision to vaccinate the whole population than not vaccinate anyone.

References

Chan M. 2009. World now at the start of 2009 influenza pandemic. World Health Organization. [1]. Published 11.6.2009

Centers for Disease Control and Prevention (CDCP). 2009. Updated Interim Recommendations for the Use of Antiviral Medications in the Treatment and Prevention of Influenza for the 2009–2010 Season. H1N1 Flu. [2]. Published 7.12.2009

Bronze, MS. H1N1 Influenza (Swine Flu). eMedicine. Medscape. [3]. Published 13.11.2009

Helsingin Sanomat. 2010. WHO julisti: Sikainfluenssa on ohi. Published 10.8.2010 [4]

McKay B. (2010-03-02). The Flu Season That Fizzled. The Wall Street Journal. [5]. Published 2.3.2010

McNeil DG. 2009. In New Theory, Swine Flu Started in Asia, Not Mexico". The New York Times. [6]. Published 23.6.2009

National Institute for Health and Welfare (THL). 2009a. Ministry of Social Affairs and Health: Two cases of influenza A(H1N1) confirmed in Finland. Published 12.5.2009 [7]

National Institute for Health and Welfare (THL). 2009b. THL and MSAH: Influenza A(H1N1)v epidemic about to start, first death in Finland confirmed. Published 27.10.2009 [8]

National Institute for Health and Welfare (THL). 2010. Pandemiarokotehankinnasta piti päättää nopeasti. Published 19.11.2010 [9]

National Institute of Health and Welfare (THL). 2011. Interim Report of the National Narcolepsy Task Force, 31 January 2011. Published 31.3.2011.

RedOrbit. 2010. H1N1 Still A Pandemic, Says WHO. 2010. [10]. Published 20.7.2010

WHO. 2009. Influenza (Seasonal). April 2009. [11]. Retrieved 2010-02-13.

WHO. 2010a. Global Update on 2009 H1N1. Global Intensity Map, Week 17 (April 26, 2010-May 2, 2010). [12]

WHO 2010b. H1N1 in post-pandemic period. Director-General's opening statement at virtual press conference. Published 10.8.2010 [13]

WHO. 2011. Statement on narcolepsy and vaccination. Published 8.2.2011. [14]

Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza. 2010. Clinical Aspects of Pandemic 2009 Influenza A (H1N1) Virus Infection. The New England Journal of Medicine 362: 1708–19 [15]