European Medicines Agency recommends restricting use of Pandemrix

July 21, 2011:

EMA recommends restricting use in persons under 20 years of age Pandemrix to be used only in the absence of seasonal trivalent influenza vaccines, following link to very rare cases of narcolepsy in young people. Overall benefit-risk remains positive.

Read more about the EMA recommendation....

Read comment from ECDC about EMA recommendation....

 

No substantial link between swine flu vaccine and Guillain-Barré syndrome, confirm experts

July 13, 2011:

 

 

BMJ Press release for media

Research: Guillain-Barré syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccine: multinational case-control study in Europe
Read full article...

 

Editorial: Safety of adjuvanted pandemic influenza A (H1N1) 2009 vaccines
Read full editorial...

 

Adjuvanted vaccines used during the 2009 swine flu pandemic did not increase the risk of Guillain-Barré syndrome substantially, if at all, finds a large Europe-wide study published on bmj.com today. An adjuvant is a substance added to a vaccine to stimulate the immune system to respond to the vaccine.
The study provides reassurance about potential risks of adjuvanted pandemic influenza vaccines. It also exemplifies the use of a newly available infrastructure in Europe, which may help to provide reliable risk assessments related to future concerns.
Guillain-Barré syndrome is a rare disorder in which a person's own immune system damages the nerve cells, causing muscle weakness and sometimes paralysis.
In 1976, a vaccine used during a US flu pandemic was linked with the syndrome and vaccination was stopped abruptly. Since then, studies have shown no or only slight increases in risk but, to date, the role of flu vaccines as a trigger in Guillain-Barré syndrome remains controversial.
Therefore, the European Centre for Disease Prevention and Control (ECDC) requested and funded a consortium of European researchers (VAESCO) to estimate the risk of Guillain-Barré syndrome following pandemic influenza A (H1N1) 2009 vaccination.
The study published in BMJ today was carried out in a population of 50 million people across five European countries which vaccinated people during the 2009 swine flu pandemic. A total of 104 cases of Guillain-Barré syndrome (and its variant Miller Fisher syndrome) were matched to one or more controls.
After adjusting for recognised risk factors, such as influenza-like illness or upper respiratory tract infection, and seasonal influenza vaccination, the researchers could find no association between pandemic flu vaccination and Guillain-Barré syndrome. The consistent pattern across countries also provides reassurance about the findings, they add.
However, they point out that they cannot rule out the possibility of a small increased risk remaining.
Based on these results, they estimate this risk to be less than three excess cases of Guillain-Barré syndrome for every million individuals protected by the vaccination.
They conclude: ?This study provides reassurance that adjuvanted pandemic influenza A (H1N1) 2009 vaccines did not increase the risk of Guillain-Barré syndrome substantially, if at all.? They also say that larger studies, using different techniques to minimise bias, are currently underway that will give a clearer picture of the link between flu vaccines and Guillain-Barré syndrome.
This view is supported in an accompanying editorial by US researchers, who say the risk of Guillain-Barré syndrome, if any, is considerably smaller than that seen with the 1976 swine flu vaccines. They add that safety findings on adjuvanted flu vaccines are important if such vaccines become more common in future, whether in seasonal flu vaccines or for the next pandemic.


VAESCO provided interim results on the possible association between Pandemrix and narcolepsy to ECDC and EMA

July 11, 2011:

VAESCO produced prelilminary results on the possible association between the specific monovalent pandemic vaccine Pandemrix® and narcolepsy on request of the European Centre for Disease Preventiion and Control (ECDC). These results were supplied to the European Medicines Agency (EMA) for the expert meeting on 12 July 2011 and the PhWP and CHMP meetings 18 July 2011. Data collection of the multi-national (including DK, FI, FR, IT, NL, NO, SE, UK) case control study is ongoing. Therefore the results provided to ECDC and EMA should be regarded as interim.   

WHO Global Advisory Committee on Vaccine Safety (GACVS): statement on narcolepsy and vaccination

April 21, 2011:

WHO's Global Advisory Committee on Vaccine Safety (GACVS) reviewed the available data from Finland on 4 February 2011 and the new data from Sweden on 18 April 2011. GACVS agrees in the recent statement on narcolepsy and vaccination that further investigation is warranted concerning narcolepsy and vaccination against influenza (H1N1) 2009 with Pandemrix and other pandemic H1N1 vaccines. An increased risk of narcolepsy has not been observed in association with the use of any vaccines whether against influenza or other diseases in the past. Even at this stage, it does not appear that narcolepsy following vaccination against pandemic influenza is a general worldwide phenomenon, as no excess of narcolepsy has been reported from several other European states where Pandemrix was used, or from Canada where a pandemic vaccine similar to pandemrix was used. This complicates interpretation of the findings in Finland and Sweden. It seems likely that some as yet unidentified additional factor was operating in Sweden and Finland. The findings from the VAESCO project and further investigations in Finland and Sweden, may help clarify the determinants of any increased risk of narcolepsy, which currently appears to be restricted to the months following vaccination and by age group and country.

GACVS will continue to monitor the situation closely and updates will be provided as further information becomes available and is assessed.

European Medicines Agency recommends interim measures for Pandemrix

April 15, 2011: Updated prescribing advice highlights preliminary results from epidemiological studies on narcolepsy; further research needed

In a press release, The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the product information for Pandemrix should be amended to advise prescribers to take into account preliminary results from epidemiological studies on Pandemrix and narcolepsy, and to perform an individual benefit-risk assessment when considering the use of Pandemrix in children and adolescents. This is an interim measure pending the outcome of the European review, expected to conclude in July 2011.

The CHMP reviewed all available data, including new findings from Sweden and France on the suspected link between narcolepsy in children and adolescents and Pandemrix. The CHMP concluded that, following the earlier results of an epidemiological study from Finland, the new evidence strengthened the signal in children and adolescents, but that the data had methodological limitations. The relationship between Pandemrix and narcolepsy is still under investigation.

The risk for narcolepsy after vaccination with Pandemrix in Sweden: A first and preliminary report, by the Swedish Medical Products Agency

March 28, 2011:

The current report from the Swedish Medical Products Agency presents results from a Swedish registry study, based on a 5.3 million population, comparing the risk of narcolepsy in vaccinated versus unvaccinated individuals from October 2009 through December 2010.

However, due to inherent methodological limitations the final interpretation of the study results, in particular for the understanding of a presumed causal relationship, needs to be supported by further investigations and extended observation time.

18.02.2011

EMA reviewed data from Finland

Today the EMA published a report on the review of further data from Finland on the suspected link between narcolepsy in children and adolescents and Pandemrix. The interim report from the Finnish National Institute for Health and Welfare is available at their website.

EMA concludes that further investigations are needed to clarify the available observations. The final results of the VAESCO background rate and case control study will be available in June 2010.

08.02.2011

WHO recommends further investigation

WHO Global Advisory Committee on Vaccine Safety recommends further investigations prior to drawing conclusions on the potential association between narcolepsy and pandemic influenza vaccines as communicated in the press release today.

01.02.2011

Finland communicates first results of national cohort study

Narcolepsy is a highly unusual event. It was never described before in association with immunization.
In Finland, one of the few countries in Europe were this is a public concern, a national cohort study was conducted in addition to the VAESCO case control study (see below). First results from the Finnish study will be communicated today.

The results of the VAESCO case control study will be available in Mai 2011.

15.12.2010

Narcolepsy background rates and case control study

A contract with ECDC is signed to investigate the incidence rate of narcolepsy in multiple European Countries. This will elucidate the incidence of the disease before, during and after the H1N1 pandemic and the immunization campaign in different European countries. Thus, it will show whether there are changes of disease frequency over time.

In addition, a case control study is conducted to determine the potential association between narcolepsy and H1N1 virus, immunization with seasonal or pandemic influenza vaccine, or other potential risk factors. The case control design allows for detailed analysis of various potential risk factors and crystallize their respective individual or combined effects.

Further investigation into the disease itself including genetic and molecular studies by European specialist networks will be needed to determine how potential risk factors may induce - or uncover pre-existing - disease.

01.01.2008

Start of VAESCO Project
Contracts with ECDC were signed in the last days of December 2007. The project commences.

01.12.2010

GBS case control study finalized

The case control study investigating the potential association of GBS and infuenza disease, immunization or other risk factors is finalized. The results of the study highlight the importance of looking at both the wild type disease and the immunization as potential risk factors. They will be published in a scientific journal.

01.09.2010

A new safety signal to be addressed

In August 2010 a cluster of narcolepy cases was reported each in Sweden and Finland. Further investigations are needed. We are looking into the need for hypothesis testing with ECD and await national and Pharmacovilance Working Party and CHMP decisions. The VAESCO network would have the capacity to conduct a European Study large enough to investigate the asociation of the narcolepsy with or without cataplexy in Europe.

01.07.2010

Time for quality control

After the challanging times during the Pandemic it is now time for quality control. Until the end of the year, the centers will validate the background rates to determine the prdictive values and adjust background rates accordingly.

In prepration of the next EVSD study, we are developing template protols for the various designs.

01.09.2010

A new safety signal to be addressed

In August 2010 a cluster of narcolepy cases was reported each in Sweden and Finland. Further investigations are needed. We are looking into the need for hypothesis testing with ECD and await national and Pharmacovilance Working Party and CHMP decisions. The VAESCO network would have the capacity to conduct a European Study large enough to investigate the asociation of the narcolepsy with or without cataplexy in Europe.

01.07.2010

Time for quality control

After the challanging times during the Pandemic it is now time for quality control. Until the end of the year, the centers will validate the background rates to determine the prdictive values and adjust background rates accordingly.

In prepration of the next EVSD study, we are developing template protols for the various designs.

30.06.2010

The first year of VAESCO II successfully completed

All deliverables including the final report on all studies were submitted to ECDC according to schedule.

The case control study will be closed in August and the Self controlled case series will run until Novermeber 2010. A report on the final results will be available in December 2010.

18.02.2010

Interim results of association studies available

The interim results of the case control and self controlled case series are available and were discussed at the in person meeting in London February 18, 2010.

In summary, the established infrastructure is working, the data are trusted, the results look promissing. Some country data are still expected to be transmitted to the central datamanagement group in Rotterdam.

24.12.2009

First background rate results available
The first results of the background rate study are available and discussed with the participants and ECDC.

01.12.2009

Infrastructure for data sharing in place
The distributed data model software "Jerboa" developed by the EMC, Rotterdam for drug safety studies is adapüted for vaccine safety studies and distributed to the participating centers.

01.11.2009

The Network of databases is ready

Finland, Norway, Sweden, Denmark, UK, Netherlands, Spain, and Italy are ready to contribute to the Background rate study.

Finland, Norway, Sweden, Denmark, UK, Netherlands, France, and Germany are ready to contribute to the self controlled case series.

Norway, Sweden, Denmark, UK, Netherlands, and France are ready to contribute to the self controlled case series.

01.10.2009

Study protocols ready
The study protocol to determine the background rates of multiple adverse events of special interest to the EMA and FDA is developed and submitted to national review boards.

In addition, the protocols to investigate the association between H1N1 immunization and Guillain-Barré Syndrome by a self controlled case series and a case control design are agreed on.

In addition to the above studies related to pandemic influenza vaccine, a comparative approach to pooled versus meta-analysis of thrombocytopenia associated to MMR vaccine is being started.

18.09.2009

VAESCO II launch meeting
September 15-16, 2009 we held the VAESCO and EVSD launch meeting with over 20 participants. For 2 days the progress of building the network and common methodologies were discussed and approved.

05.07.2009

Start of VAESCO II
Following an interim phase between the projects, the VAESCO Consortium was awarded a second competitiv grant.

The project is now generally being agreed on.

The inclusion of an H1N1 package is being explored.

07.06.2008

During June 5/6, the VAESCO Steering Committee has met in Helsinki to discuss the draft documents of each Work package.

The progress is generally according to schedule. The meeting was fruitful and generated useful feedback for the work packages.

29.01.2008

Launch Conference Call
The Steering Committee meets to discuss the Project Plan and agree on the next steps.

End of the VAESCO agreements

March 15, 2012:

The VAESCO Narcolepsy project agreement ended  March 15, 2012. 

 

Lessons learned exercise

March 15, 2012:

2.1 Lessons learned exercise - overarching goal

The objective of the Lessons learned exercise of the VAESCO II project – lessons learned from the first two years of enhanced monitoring of vaccine safety in Europe is to identify overall organizational and methodological strengths and limitations in the project established so far and advise ECDC about future strategic directions regarding development of a sustainable structure for active vaccine safety monitoring and assessment  and identify where and what type of capacity building is needed.

The results from this lessons learned process will be used by ECDC in further efforts to develop a sustainable organization and funding of post-marketing safety monitoring of vaccines in the EU involving stakeholders such as Member States, the European Medicines Agency, the European Commission and if needed the European Parliament

 

Conclusion

VAESCO has provided important benefits to the EU, EMA, ECDC, and public health and regulatory agencies in the participating countries.  In addition, its scientific contributions have implications beyond the EU (including the US in particular adjuvanted vaccines) since vaccines produced in Europe are exported worldwide.

The network became quickly productive during an intense emergency response environment despite limited resources and disparate data capabilities of participating countries.  In moving forward, many constructive suggestions have been offered by the participating investigators and the leads of specific projects.  Ultimately, some fundamental decisions need to be made about if and how to move forward toward a sustainable vaccine safety monitoring and assessment network in the European Community. Chief among these, a commitment from the EC is necessary to move forward and to determine the purpose, governance, and sources of sustained funding.

Read the report about the lessons learned from the VAESCO project...

 

 

 

Narcolepsy in association with pandemic influenza vaccination – a multi-country European epidemiological investigation

September 20, 2012:

This report summarises the results from two epidemiological studies to investigate a possible association between an unexpected increase in narcolepsy cases following the use of the influenza A(H1N1)pdm09 vaccines. The studies were conducted by the Vaccine Adverse Event Surveillance and Communication (VAESCO) Consortium under the auspices of ECDC and undertaken in Denmark, Finland, France, Italy, the Netherlands, Norway, Sweden and the United Kingdom.

Read more in the results section...