Response to Meningococcal Gold Rush III Claims

MEDIA STATEMENT

4 September 2006

Ministry of Health responds to claims made by Ron Law and Barbara Sumner Burstyn in Meningococcal Gold Rush III:post-MeNZB Vaccine Update

The article quotes Meningococcal B Immunisation Programme Director Dr Jane O’Hallahan referring to the programme as a 'calculated gamble'. What was meant by this?
These words have been taken out of context. Dr Jane O’Hallahan was giving a presentation, near the end of the immunisation programme, and was referring to the fact that there are always unknowns and always risks in everything that is done. The presentation covered the careful calculation of risks and how you ensure successful immunisation by working through risks.

Did the studies meet ethics committee requirements?
The Ministry of Health ensured all the official research for the Meningococcal B Immunisation Programme met the appropriate ethics committee requirements. All ethics committees operate independent of the programme.

What is the Principal Investigator's role?
The role of the Principal Investigator is to conduct the clinical trials according to GCP guidelines, that is, Good Clinical Practice. The Principal Investigator performed this role according to the correct procedure, having had access at the appropriate times to the information required to do so.

Was the Principal Investigator, Professor Diana Lennon, denied access to data?
The University of Auckland’s Dean of Medical and Health Sciences Professor Iain Martin is satisfied that the Principal Investigator had access to the full paper-based datasets required to describe and submit for publication the full primary studies.

Was there a change in research agreement in breach of ethics committee approval?
All aspects of the Ministry of Health contracting for research to do with the Meningococcal B Immunisation Programme has been carefully planned and implemented to ensure it meets ethics committee requirements.

Did Wellington Medical School undertake work on MeNZB™ effectiveness?
This claim is incorrect. Wellington Medical School have undertaken no work regarding the MeNZB™ vaccine effectiveness. Statistical modelling has been undertaken by Victoria University for vaccine effectiveness estimates. Victoria University is independent of all parties involved in the Meningococcal B Immunisation Programme.

Did the Ministry of Health can a MeNZB™effectiveness study?
The Auckland case control study, one of a number of methods used to assess the vaccine’s effectiveness, was halted under independent international scientific advice. This was because there were insufficient numbers of young children contracting meningococcal disease after the high uptake of vaccine in Auckland therefore any results from the study would have been statistically unreliable.

It is also claimed that a two-fold not four-fold rise in serum bacterial antibodies (SBA) was used.
This claim is incorrect. The surrogate for protection for all trials was a four-fold rise in SBA.

What about the fourth dose and decay in antibodies?
It is not expected that this vaccine will give life-long protection. It was implemented to control an epidemic. It is expected that protection will last a number of years. Antibodies drop off for all age groups but that does not mean the person is unprotected.
The 4th dose was introduced for younger infants because in the clinical trials a lower proportion of infants compared to older age groups achieved a four-fold rise in serum bacterial antibodies (SBAs) after three doses. Giving these youngest infants a 4th dose at 10 months of age meant the same proportion as older children achieve a four-fold rise in titres. The Ministry will continue to monitor disease trends and at this stage no other age group requires a 4th dose.

It is claimed that there is leaked Ministry of Health data showing the vaccine could not be credited with the drop in disease.
This claim is incorrect. The Ministry has no such data. As stated before, all indications are that the vaccine has accelerated a 76 per cent drop in cases. Effectiveness assessments are currently undergoing independent scientific review.

The facts about MeNZB™

What is meningococcal disease?
Meningococcal disease is a bacterial infection. It causes severe illnesses including meningitis (an infection of membranes that cover the brain) and septicaemia (a serious infection in the blood). There are several strains of bacteria which cause meningococcal disease including A, B and C. MeNZB™ vaccine was developed to protect against the strain of meningococcal B causing the New Zealand epidemic.

What proportion of New Zealanders in the eligible age group have received the MeNZB™vaccine?
As at 2 July 2006, 87 per cent of all those eligible for the vaccine had completed their first dose, with 80 per cent having completed all three doses.

Does the MeNZB™vaccine work?
Yes. Preliminary results from an independent study confirm that the vaccine is 80 per cent effective.
The initial impact of the vaccine has seen a critical reduction in the number of epidemic strain Meningococcal B cases since the immunisation programme began. In the northern region, where the programme started, cases of the epidemic strain fell by 76 per cent between 2003 and 2005. In Maori and Pacific communities, with the highest rates of the disease, cases fell by 90 per cent and 70 per cent respectively. For further information on the reduction in epidemic strain Meningococcal B cases please see the attached graphs:

How many meningococcal disease deaths have there been this year?
We have had six deaths from meningococcal disease so far this year. Three could not have been prevented by the vaccine programme as they were outside the age range for vaccine and of the three, only one was epidemic strain.
There were three deaths in under 20-year-olds, the age group eligible for vaccination. For one the strain cannot be confirmed. One was epidemic strain but in a child so young they were only partially vaccinated. The third death, the most recent, was also epidemic strain but fully vaccinated.

How many epidemic strain Meningococcal B confirmed cases have occurred in under 20-year-olds?
In the five years before the introduction of the vaccine there was an average of 213 cases and seven deaths per year in under 20 year olds from the epidemic strain. In 2005 there were 82 epidemic strain cases and one death in this age group. In 2006, to date there have been 28 cases and two deaths.

How many vaccine breakthroughs have there been since the programme started?
A vaccine breakthrough is an individual who has become sick from the epidemic strain up to 28 days or more after the third dose. It is believed that it takes up to 28 days after the third dose for the vaccine to confer immunity. There have been 24 vaccine breakthroughs since the programme started in July 2004. Of these 24 vaccine breakthroughs, two were in infants who were overdue for their fourth dose.

When is the MeNZB™ vaccine given?
It is recommended that babies begin their MeNZB™ vaccinations at six weeks of age, followed by a second dose at 13 weeks or three months, a third dose at 21 weeks or five months and a fourth dose at 43 weeks or 10 months. For all other ages, three doses should be given at six-weekly intervals.

How was the vaccine developed and tested?

- New Zealand has had an epidemic of group B meningococcal disease since 1991. The MeNZB™ vaccine was developed to target the particular strain of bacteria that was causing the epidemic. Other meningococcal B vaccines that are available do not give protection from this particular bacterium.

- MeNZB™ was manufactured by Chiron Corporation (now Novartis Vaccines) and was based on a vaccine that was developed and tested by the Norwegian Institute of Public Health (NIPH) in the 1990s for another strain of group B meningococcal disease. Millions of doses of similar vaccines have been given around the world but because it was a new vaccine, MeNZB™ underwent a clinical trial before it could be used.

- There was considerable bridging data available about the parent vaccine and other similar group B meningococcal vaccines, which enabled the clinical trial of MeNZB™ to be condensed to about three years while still meeting the usual standards of safety and efficacy.

- A similar approach was used in the United Kingdom to introduce a group C meningococcal disease vaccine in 1999. Further back in 1981, the United States licensed a meningococcal A/C polysaccharide vaccine based on safety and immunogenicity data. In 2005, the US also licensed a tetravalent polysaccharide-protein conjugate vaccine (Manactra) on the basis of safety and immunogenicity results i.e. antibodies.

- Auckland University conducted the trials. Trials began in 2002, with the final trial completed in October 2004. Participants were mainly being recruited from the Counties Manukau area of Auckland because this area contains children who are most at risk from meningococcal disease. Principal Investigator Professor Diana Lennon oversaw all trials and worked closely with the Institute of Environmental Science and Research (ESR) Ltd, Chiron Corporation (now Novartis Vaccines) and the Ministry of Health.

- Clinical trials tested MeNZB™ for safety, tolerability and the required concentration of each dose. Each participant received three vaccinations six weeks apart and had a blood test about four weeks after each vaccination. The blood is tested to find out if the vaccine produces protective antibodies and increased immunity to the meningococcal bacterium.

- International guidelines for clinical trials were followed. A regional ethics and safety committee and the Standing Committee on Therapeutic Trials (SCOTT) approved each trial before it started. Auckland University staff explained the trial process to all participants and their families before they consented to participate. Medical teams closely monitored all participants. Participants were not exposed to meningococcal disease any more than the general population. The research and study design was peer reviewed by clinical and vaccine experts around the world to ensure all international standards of procedures were being met.

- Clinical trials showed the vaccine was safe and protective. No serious adverse events were attributed to the vaccine.

Who has the trial data and how is it accessed?
The trial data is held by the Institute of Environmental Science and Research Ltd (ESR) on behalf of the Ministry of Health. Researchers who wish to do further analysis using the data must submit a proposal to the Ministry. If accepted, the analysis is done by ESR and Chiron (now Novartis Vaccines). Researchers do not have access to the raw data but will have access to the results.

Is the MeNZB™vaccine safe?
Yes.There are no live meningococcal bacteria in MeNZB™ vaccine and it is not possible to catch the disease, or to become a carrier of the disease, from the vaccine. The vaccine has been manufactured to international standards. Extensive safety data collected during the programme was reviewed by an Independent Safety Monitoring Board (ISMB). The ISMB has stated that based on the data it has seen, it has no concerns regarding the safety of the MeNZB™ vaccine. Serious side effects are very rare however some people experience a mild temporary reaction such as redness at the site of the injection, a headache, nausea, a slight fever, feeling unwell, drowsy or irritable.

Key milestones of the Meningococcal Vaccine Strategy
1991 New Zealand's group B meningococcal disease epidemic begins.
1992 The Institute of Environmental Science and Research (ESR) identifies a single substrain defines strain of bacterium starting to cause an increase in notified cases of meningococcal disease.
March 1997 New Zealand Government approves an initial $6 million towards prevention of meningococcal disease.
August 1997 Auckland Healthcare Services undertakes feasibility study of a New Zealand vaccine clinical trial.
September 1998 The Ministry of Health meets with vaccine manufacturers and national and international advisors at the World Health Organization to discuss developing a strain-specific vaccine for New Zealand.
January 2000 Findings released of a three-year research project into risk factors of meningococcal disease; research influences government policy including health education and housing.
December 2000 Requests for proposals sent to four collaborations of vaccine manufacturers.
February 2001 Chiron Vaccines, working with the Norwegian Institute of Public Health, is selected as preferred providers.
July 2001 The Ministry of Health and Chiron Corporation sign a contract to develop a vaccine.
2001 Worst year of the epidemic to date; 650 cases and 26 deaths.
January 2002 Health Minister Annette King announces funding of $100 million plus towards the Meningococcal Vaccine Strategy project.
May 2002 Funding of $200 million over five years allocated to the Meningococcal Vaccine Strategy.
First phase of clinical trials begins in Auckland under the direction of the University of Auckland; 75 adults are involved in this phase.
October 2002 Second phase of clinical trials begins; 600 children aged 8-12 years are involved in the first trial of this phase.
December 2002 Ministry of Health announces delay to the expected launch of the proposed nationwide immunisation programme due to additional time needed to upscale the vaccine to produce the large volumes required.
February 2003 Clinical trials involving 320 toddlers aged 16-24 months begins.
May 2003 Clinical trials involving 320 infants aged 6-8 months begins.
August 2003 Results of clinical trials of adults announced at Paediatric Society of New Zealand annual conference; results indicate the vaccine is safe and produces protective antibodies.
January 2004 Clinical trials involving about 400 infants aged 6-10 weeks begins.
March 2004 Results of clinical trials involving toddlers aged 16-24 months announced at WHO/UNICEF Workshop on the expanded programme on Immunisation in the Pacific in Auckland; results continue to be encouraging.
July 2004 MeNZB™ is licensed for use in those aged over six months.
The Meningococcal B Immunisation Programme begins in the Counties Manukau area of Auckland.
October 2004 All clinical trials completed.
February 2005 The licence is extended down to cover the delivery of the MeNZB™ vaccine to six-week-old babies.
July 2005 The programme is underway nationwide.
May 2006 The Government announces a further $22 million to extend the immunisation programme.
The Independent Safety Monitoring Board (ISMB) states that based on the data it has seen, it has no concerns regarding the safety of the MeNZB™ vaccine.
June 2006 The Meningococcal B Immunisation Programme ends. The MeNZB™ vaccine will still be available until 31 December 2006 for all those aged under 20, to allow them to complete their vaccinations. For babies and children aged six weeks to five years the vaccine will continue to be available until 2009. New babies need four doses of the vaccine for the best possible protection against the epidemic strain of the disease. Babies should get the MeNZB™vaccine at the same time as their scheduled childhood immunisations.

ENDS

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