30 Oct, 09 | by BMJ
The H1N1 vaccination programme is underway in the UK and many other countries across the globe. In Sweden a million people have already been vaccinated. One swine flu vaccine manufacturer, GlaxoSmithKline, expects to produce 440 million doses over the next few months. With newspapers, television and the internet raising doubts about the safety of the vaccine, many doctors will be consulted by anxious patients wanting to know whether the vaccine is safe and effective.Yesterday, the Department of Health published a briefing for health professionals which responds to many of these concerns. This blog draws from this document and other sources such as the WHO, European Medicines Agency and BMJ Learning to provide answers to common questions that the public have on the H1N1 vaccine in the hope that they will be of some use during consultations. The answers are not meant to be exhaustive and many readers will have more up-to-date and comprehensive answers. If so please write them below to help other readers get the best information.
Is the vaccine safe?How can the swine flu vaccine be safe if the vaccine was only created a couple of months ago and there haven’t been any large scale clinical trials yet?
The problem is that large scale trials take months to conduct and would therefore only be published after the pandemic is over. To get around this problem the European Medicines Agency (EMEA) approves pandemic vaccines under the so called “mock-up dossier route“. The WHO Director of the Initiative for Vaccine Research, Dr Marie Kieny, explained the process during a press conference last month.
“Adjuvanted vaccines have been tested extensively at the time when all manufacturers were preparing vaccines for a potential H5N1 pandemic. In view of the potential gravity of an H5N1 vaccine, the European Regulatory Agency had designed a special process by which manufacturers would test extensively in clinical trials, prototypes of H5N1 vaccines, including with adjuvants, which submit all the safety data of clinical trials to the regulatory agency and obtain what is called a “mock-up registration”. So this is a registration for a prototype.”
For example, the Baxter mock-up licence was granted after data from five trials involving over 1300 people. A small trial of the H1N1 vaccine was undertaken to determine the immune response to the vaccine, and further trials are under way to monitor side effects as the vaccination programme gets under way.
Does the vaccine cause autism?
Concerns centre on Thimerosal which is added to vaccines to prevent contamination and keep the vaccine sterile. It is present in the GSK vaccine but not the one made by Baxter (Celvapan). It extends the time window in which the vaccine can be used to 24 hours after the adjuvant has been added (compared to just three hours in the case of Celvapan). Thimerosal contains mercury and there have been concerns that it may cause neurodevelopmental disorders including autism. According to Professor David Salisbury, the Department of Health’s director of immunisation speaking on the BMJ Learning Pandemic Flu podcast, large studies have been done to investigate this link, including two in the UK, which have not shown any association between Thimerosal and neurodevelopmental disorders. In addition, he says, in the United States autism continued to increase when thimerosal was removed from vaccines there. The Commission on Health Medicines in the UK state that the “balance of risks and benefits of thiomersal-containing vaccines is overwhelmingly positive.”
Is it safe in pregnancy?
H1N1 influenza has a higher prevalence in pregnant women than in the general public – around four times more common according to a study in The Lancet, which also highlighted an apparently higher mortality amongst this group.
Information on the possible harms of the vaccine is again based on assumptions from mock-up viruses and other inactivated virus vaccines. However, the Department of Health’s Clinical Professionals Brief on Swine Flu Vaccination recommends the Pandemrix vaccine for pregnant women. They quote the summary of product characteristics on the EMEA website:
“There are currently no data available on the use of Pandemrix in pregnancy. Data from pregnant women vaccinated with different inactivated non-adjuvanted seasonal vaccines do not suggest malformations or fetal or neonatal toxicity. Animal studies with Pandemrix do not indicate reproductive toxicity.”
Does it cause Guillain-Barré syndrome?
The H1N1 pandemic vaccination programme in 1976 led to a surge of cases of Guillain-Barré syndrome. Could the same happen this time around?
Professor Salisbury, speaking on the BMJ Learning Pandemic Flu podcast says: “The seasonal vaccine protects against Guillain-Barré. The situation is that there has been no robust evidence since 1976 between seasonal H1N1 vaccine and Guillain-Barré. There is good evidence that influenza itself is a risk for Guillain-Barré and we have got in place many different strands of surveillance that if there were a risk we would pick it up as early as possible.”
That evidence comes from a self-controlled case series using cases from the UK GP research database from 1990 to 2005.
“The relative incidence of Guillain-Barré syndrome within 90 days of vaccination was 0.76 (95% confidence interval: 0.41, 1.40). In contrast, the relative incidence of Guillain-Barré syndrome within 90 days of an influenza-like illness was 7.35 (95% confidence interval: 4.36, 12.38), with the greatest relative incidence (16.64, 95% confidence interval: 9.37, 29.54) within 30 days.”
Is it effective?
According to the EMEA, both vaccines have been shown to be effective in producing antibodies in mock-up and H1N1 versions.
“In the 61 subjects who received the marketed formulation Pandemrix, the vaccine was shown after the first dose to trigger immunity to a satisfactory level. The percentage of subjects who have a level of antibodies in their blood that is high enough to neutralise the H1N1 virus (seroprotection rate) was 100%.”
However, a recent editorial in BMJ Clinical Evidence cast doubt over the true effectiveness of flu vaccines. During a normal season flu period only a small proportion (around 11%) of those with influenza-like illness actually have influenza. In a pandemic this proportion may be expected to be higher, perhaps making the vaccine more effective at reducing the incidence of influenza-like illness. The effect of vaccination on mortality during seasonal flu outbreaks is unclear. Estimates range from a 48% drop in mortality to under 5%.
The true effectiveness of the H1N1 vaccine won’t be known until long after the pandemic has passed. In the meantime it’s up to patients, with the help of medical professionals, to decide whether it’s worth taking.
Tom Nolan is a trainee GP in London.