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Thanks everybody for staying on the panel of this session of this two and a half day
meeting. Iím Joe Bresee from Flu Division of CDC and now weíre going to turn our attention
away from pushed mechanisms away from helping companies develop the technology to transfer
technology to overcoming some of the regulatory hurdles of developing sustainable vaccine
production in the country. We're going to turn our attention towards, for lack of a
better word, pulled mechanisms to developing the case for vaccination, to developing the
demand for the vaccination and to collecting the data to develop the argument that a vaccine
is actually needed in a country. I think that this is the yin and yang of vaccine production
or back sustainable vaccine supply and I think this is obviously a crucial part of it. We
have the fortune today of having two speakers and additional people in the room that have
actually done this before.
Fluís not the first vaccine down this pathway. There are other vaccines that have been introduced
in the last fifteen years that had a plan, a coordinated plan to bring the vaccine from
developed countries to developing countries. Our two speakers today represent two such
plans. Oneís called the Rotavirus ADIP Vaccine Program and one is called the New Pnuemo ADIP
and these programs were developed as a concept around 2002-2003, funded to accelerate the
vaccine introduction into the countries that could least afford lifesaving new vaccines.
So our first speaker, Dr Mark-Alain Widdowson, is the International Team Lead, in influenza
now, not rotavirus in the Influenza Division for all of our international activities. Heíll
give a talk on his previous life, working on rotavirus and give us a look at Rotavirus
Thanks everyone for allowing me to come to talk about the Rotavirus ADIP.
What I plan to do is give a brief overview. This is a big project with many partners including
several people in the room. Iím really going to focus on surveillance, and as Joe said
creating the demand for a vaccine in different countries and the approach that we took. Before
ADIP came along, what was the situation around the world? There was little sustained surveillance
anyway. Most of the studies have done in high income countries. The large capacity has been
limited for diagnosis and typing. Yet WHO had recognized the high global mortality during
the mid-1980s but the interest would rise still until the mid-1990s it still remained
largely the domain of biologists and had not been put in the public health perspective.
But there was approved rotavirus vaccine that had been established. This map shows rates
of rotavirus mortality in children under the age of 5 around the world. It can be seen
in the poorest parts of the world, Africa and Asia. Southern Asia particularly bore
the brunt of dire rotavirus mortality. This was really one of the driving forces for the
Today, as Joe introduced, itís an accelerated interactive plan, which was established in
2003 with a grant from the GAVI Alliance. It was a partnership with PATH, USCDC and
WHO. The main mission was to reduce childhood mortality, morbidity and viral disease by
accelerating availability of rotavirus vaccines that had started to be introduced in developed
countries and to accelerate the introduction into poorer countries. This is a graph initially
developed by Mckinsey and Corporation and the X axis shows the number of years from
availability of a commercial vaccine and its introduction around the world. On the Y axis
is the millions of doses. Next can be seen Hepatitus B took many years before many developing
countries with poor or middle income countries started to introduce these two vaccines. The
idea for rotavirus was to accelerate this process so that the number of doses globally
distributed and administered and in poorer countries was brought way forward by almost
This is shamefully lifted from a PATH presentation and basically outlines the paradigm here that
we start off with a safe effective vaccine or at least the principal of a safe and effective
vaccine, the strong disease evidence and then really to push and pull arms. One of which
is the available supply and the demand and the last few days have been focused on available
supply. What Iím going to talk a little bit more about is the demand and creating the
evidence base to stimulate that demand. There are many different bits to developing an evidence
base. Thereís cost effectiveness, economic models, impact models, logistics and then
of course actual policy part of persuading and advocacy efforts. Iím not going to go
into all of this because it would take me all morning. Iím really going to talk about
surveillance and how surveillance produced the dates that is required to go ahead and
move along that path and to creating a demand. So what was the objective of the expense?
One was to develop a global evidence base; to create data to that we could get global
mortality estimates developed a regional mortality estimates developed and also more importantly,
I think many countries sometimes look with some suspicion on to other countries data.
They would say ìwell thatís normal, they got rotavirus because that's the acts we know
we don't. They do.î so it was important to recognize the fact that you couldnít necessarily
translate data from one place to another. The second objective of surveillance was to
advocate to disseminate the data and to actually generate people in countries that would be
champions it would actually take ownership of the problem and usually theyíd be kind
of relatively high profile pediatricians or ministry of health officials that would then
be able to abdicate in their own settings for rotavirus vaccines. Lastly to create some
pre-introductory data sets for evaluation. The important thing about these networks is
that they are multi-partner networks. This is a list of people that were involved in
doing surveillance for rotavirus. Thatís clearly important.
Itís a network of networks if you will. Itís not only a network of sites but a network
of people coordinating these sites. That was important I think to get a overall buy in
to the whole global public health perspective into the paradigm of introducing rotavirus
vaccines. Really the engine for this was the genetic protocol which was largely developed
by Joe which was kind of a toolkit to see how countries go about hospital based surveillance.
So it was relatively straightforward in the sense that it was children under five. It
was ready to be simple data collection. One of the main outcomes was simply the percent
of children that had diarrhea that were positive for rotavirus. In some cases because the population
base and we could do a rate and then get some incidence rates, some guidelines on stream
typing and in some cases they would do outpatient visits as well, costs and also rates since
inception which for rotavirus vaccine was also another issue.
This slide basically shows the importance of different countries having different types
Some can do everything some canít. Some rusted away in a corner for a little bit. But the
little bit of technical support was that most countries would have the engines to be able
to generate some data. I think thatís important, you have countries that generally donít generate
data on a certain diseases then they suddenly start doing it, it causes a disproportionate
amount of impact, it perhaps puts neighboring countries to shame. So I think that itís
important that itís an all-inclusive model and no one that just focuses on certain easy-to-collaborate-with
This is a map from 2008, we had over fifty countries doing rotavirus surveillance. Some
of the early networks in Asia started off with Joe and Roger Glass in the back. These
were more bilateral networks that started working directly with academic institutions
and gradually as the program matured and as the reach of the surveillance went global,
WHO offices became clearly important and we had different colors relate to the regional
offices of WHO. The degree of support and interaction with WHO depended on the region.
In other regions we gave more support. Really the data that generates out of these surveillance
networks is really quite straightforward and this is to get a sense of the data that these
networks were generating. Here for instance we look at that age breakdown, so by age group
the percent positive for rotavirus.
Then we have a graph and we give these slides to our partner so that they would generate
the same type of data and same type of format. This is the cumulative distribution or cumulative
frequency of rotavirus outcomes. Then we look at seasonality. Then we might compare rotavirus
positives with rotavirus negatives idea saying that the rotavirus positives tend to be more
dehydrative than the rotavirus negatives and get some idea of the clinical presentation.
Of course we have some strain data which would say that the strain that you have circulating
in your country actually match very well to the strains that are in the vaccine or donít
match or at least give some information to make an informed decision.
This is the dissemination of the data. Here we have what the CDC wrote as an example.
PATH also had websites and newsletters. This was one that we generated: Rotavirus Severance
News. I think whatís important is to get this data out into the literature and there
were a variety of sequence of supplements and papers. This one, Rotavirus in Asia, focused
on Asia. Recently weíve come out of a global rotavirus surveillance that highlights a lot
of the data from these countries. There is a third rotavirus supplement coming out of
the second phase of Asia. Then we have these meetings every year to generate enthusiasm.
This table shows in a summary the kind of data that came out of this and this was in
supplements that came out a couple of months ago this goes by the region and gives a summary
of the percent positive and that's the fourth column along; the percent positive of rotavirus
among children entering hospitalization with diarrhea and you can see the range from 32%
I think cumulative weight of that evidence fed into a lot of the global disease mortality
estimates and Impact models and cost effectiveness models that were done for the global community
for the world which again drove the agenda for rotavirus introductions as well as creating
data for regions and countries to make their own decisions. This is one of Rogerís old
slides about different types of vaccines in the were in production or at least in developments
at the time and that the ADIP started and they were the two main ones, two Big Pharma
vaccines: Merck and GSK. China had also vaccine that it was using for national purposes. Then
there were other vaccine candidates that are being developed in India and Australia. There
was an NIH vaccine model that was farmed out to world manufacturers to create their own
kind of a homemade vaccine using different components of different rotavirus strains.
You can see from this map the lamb here, it was a lamb based vaccine in China. it's way
out ahead because China was using it for several years but the two Big Pharma candidates: the
cow and the human vaccine-because one was a cow based the other was a human rotavirus
strain based-are really ahead of these other strains. So a lot of the ADIP model was based
on the promise of these two Big Pharma vaccines with the future promise in the medium to long
term of other vaccine candidates maturing and going through licensure and recommendation.
The two concerns when the ADIP started was: one whether these new vaccines , even the
Big Pharma vaccines, were safe particularly in poorer settings where previous vaccines
had not been.
There were initial trials that were done in mid-income countries which basically established
the safety in those settings and lead to a limited recommendation by WHO for Europe and
the Americas but that were still doubts about what the vaccines would work effectively in
poorer settings. But then trials were initiated and coordinated largely by Cathy Nussel here
in the audience showed that these vaccines would work satisfactory in those settings
too it and WHO, last year, 2009 expanded their recommendations.
My last couple of slides really compares Flu and Rotavirus. This slide looks at the similarities.
Both of them have an available vaccine which is underused in poorer countries. Little is
known of the burden in developing countries, this was a case of Rotavirus before the ADIP,
though it may not be high. For Influenza I we really donít know enough about poorer
settings as has already been mentioned. The in-country perception is that it may not be
a big issue. Yet these are both viruses that ubiquitous and democratic, relatively straightforward
to collect specimens and diagnose, and both can be done with hospital based surveillance.
There are big differences too. Influenza affects all ages. One of the great things about Rotavirus
is that it was a simple; it was just children under five that was the real focus. The proportion
of illness among people who were hospitalized is likely less dramatic than it is for Rotavirus.
For Rotavirus almost half of children presenting for care for diarrhea was due to Rotavirus.
Thatís an impressive percent. Itís not quite so impressive for Influenza. The Influenza
can be difficult to determine because it is not always an influenza-like illness that
might cause the hospitalization or mortality. There are no detection aspects that Rotavirus
We have to rely on PCR for Flu at least to get reasonably sensitive estimates. Clearly
the current vaccines are yearly hit and miss; they may or may not be a match and it has
to be every year. Another thing that drove the ADIP was the promise that it was a subsidized
vaccine at the end of the process and GVAI subsidizes many countries for Rotavirus vaccines
and continues to. This is my last slide it says ìInfluenza ADIP?-Is it an Appropriate
Model or Notî I think that these are just a few things I just jotted down but I think,
as been said before, there should be a different focus for different countries. By no means
are all countires going to be giving seasonal vaccine to everybody in all ages every year.
We do need to determine the burden of Influenza, globally, through surveillance, perhaps using
vaccine probe studies to get by some of these issues that some of the disease is not obviously
attributable to respiratory illness or some outcomes are not obviously attributable to
Influenza and respiratory symptoms. For poorer countries we should we should be focusing
just on children and look at under five morbidity and mortality and letís see if a vaccine
there can help using novel vaccines and novel strategies. Live attenuated vaccines in young
children will have a broad, long lasting immunity to be sufficient to protect children for part
of the EPI schedule, it will protect up until the age of five. Universal vaccines, adjuvant
vaccines, these are all things. So I leave it with that and perhaps we can have a discussion
later on. Thank you very much.
Thanks very much Marc and like the other sessions what weíre going to do is go through to the
scheduled talks and then weíll open it up for the question and answers. I don't know
how to keep her talk up here actually is you're talk up on this computer.
So our next talk is by Dr. Lois Privor-Dumm, who is the Director of Alliances and Information
for the International Vaccine Access Center at Johns Hopkins. She will give us a talk
about the Pnuemo ADIP, the other ADIP that created a while back.
Thanks for the opportunity to come here and talk to you a little bit about the experience
with pneumococcal conjugate vaccines like Marc-Alain described, we are also an ADIP
sponsored by the GAVI Alliance and have gone through a very similar process. I'm not going
to touch too much on the surveillance aspects. There were a lot of challenges there for Pnuemo
just as there are for any vaccine. What Iím going to do is talk about some of the other
approaches that we took to generate demand for vaccines. OK so in order to do that I
think it's good to start with what was the environment when we started and why the demand
there wasnít in developing countries for pneumococcal vaccines. In 2003 when the group
was first put together there was an environment where there were pneumococcal vaccines which
were launched in 2000 in the US. No developing countries really had any intention at that
point of introducing the vaccine. I think the thought was that it was just too expensive
and that it would never come that there would never be enough supply. I don't know if any
of you remember in the end of the early years of pneumococcal vaccine there were also a
lot of supply issues. So there was no financing committed to the vaccines; they were considered
expensive, priced at around sixty dollars a dose. I think it was around fifty eight
dollars, somewhere around there.
There was no WHO recommendation and the developing country markets are largely driven by what
WHO says. They want to know that there is significant disease burden, that this makes
sense for the countries that they have a way to implement it.
The other major factor that we faced was that every country wants their own local data and
for pneumococcal disease, although there's been a number of studies, theyíre very limited
and many of the studies were not sufficient quality to be able to draw conclusions or
if they did draw conclusions it may have indicated that disease was not sufficient and the one
missing piece for us was this serotype data. So it wasn't enough to only have disease burden
to say how much pneumococcal disease was we really needed to know what the serotype distribution
was because the thoughts were that the existing vaccines was to seven valiant vaccine would
not sufficiently cover the serotypes in the country.
So in determining how to move forward we have to take a look at who are the stakeholders
and what type of solution space do we want to see? What is the answer? What do we need
to make happen to see pneumococcal vaccines reach the children that need it most? You
know the first thing we had to do was have industry thatís willing to supply. As I said
before it that the pneumococcal conjugate vaccine was in limited supply. It's a difficult
products to manufacture and develop and we needed to ensure that thereís more suppliers
out there and those that were willing to supply the product at reasonable prices. The next
thing that we had to make sure was that there were countries that were willing to introduce
and this was not an absolute given. Even though I think it was well understood that pneumococcal
disease was a problem they needed to be convinced that it would be worth the price that they
would have to pay and the perception was out there that the price would be a fairly high
Then finally we needed to donors in countries willing to pay and I put both donors and countries
here because in this case it is a shared burden. The cost of the vaccine is probably even at
the low cost going to be too high for most of the countries that weíre working in. So
it does require donor support, but one of the things that we wanted to see is that these
vaccines were not provided for free. There was a previous model and previous situation
with a vaccine where initially the vaccines were provided for free and the conclusion
was that that's not the best case because you don't get the commitment from the countries
and then the countries are saying ìwell what happens if donors stop paying? Iím not going
to put myself in this situation.î So that's what the situation that we were working towards.
So our group, the Pnuemo ADIP, worked in essentially three different areas as well as projects
administration, which is important for any product. So the first area is research and
surveillance and, as I described before, the main focus is to ensure that we have disease
burden, but not just at a global level but that we can describe it at the local level.
This was somewhat of a challenge. We also needed serotype data and serotype data again
at the local level; easier said than done. There was a major project that we worked on,
The Global Disease Burden Project, with our partners at it WHO. It was a WHO lead project.
We also worked with CDC on this project to be able to describe the burden of disease
for both pneumococcal disease and *** disease as well as the various syndromes. This was
brought down to a country level. Now one of the challenges here was that it was modeled
data so countries always wanted to hear about the studies that were done in their countries.
Many countries were not able to use their local data to determine disease and what we
had to do was go through a process to be able to educate the epidemiologists in the countries,
the decision makers, policymakers, etc. to explain why model data was preferred. We also
went through a global serotype project to be able to describe what's the likelihood
of a particular vaccine was to cover the majority of the diseased that existed in the country.
In the area of advocacy and communication this is a part that is often underestimated
by projects moving forward and something that we found to be very critical to generating
demand, not only in the countries but also convincing donors that is this important area
to support, and convincing suppliers that that the demand would be there when the product
actually reached the market. You know putting up those pieces together in coordinating it
is very challenging and the process of communication as well as developing advocates that are going
to be out there and moving the process forward was very critical. Vaccine access and implementation
was an area that was also seen is very important.
A lot of activities here involved forecasting and that's an activity not to be underestimated;
not only just generating the forecast but having the ability to take a look at what
is behind the forecast, what are the assumptions that have to happen. I actually came from
industry originally and was sitting on the other side of the table questioning ìWell
how what how would these how these numbers generated? You know what is the plan to actually
get there and why should I believe that these forecasts are going to actually materialize?î
So that's an important process to go through, the communication of what is the plan and
who is ultimately responsible for making sure that that plan is executed.
So some of the things that helped us in the process: we're having transparent assumptions,
having a lot of stakeholder input in recognizing that stakeholders come from various parts;
that it's not just the governments, not just donors, not just partners, but you need to
reach out to a number of different groups that also influence the whole process. Each
vaccine is going to be slightly different but there's civil society out there, thereís
the manufacturers and other groups as well as the media that want to be hearing about
how is this process going in constant communication is something that helps; as well as something
that provides input for you to be able to adjust your plans. We also made sure that
our messages were targeted towards the people that we were talking to. Down at the bottom,
this is unfortunately it's only a short fifteen minute talk; this is a lot of the work that
went into what we did to generate the demand for pneumococcal conjugant vaccines. We didn't
do it alone. We worked a lot with partners and I think partners are really critical in
The first group is Pace Pneumococcal Awareness Council of Experts. Theyíre a group of experts
around the world, many of them are pediatricians. Theyíre respected experts in their own countries
and this is a multi-country group that has come together to talk about the importance
of pneumococcal disease and advocate for the use of a vaccine. This kind of group does
a lot of different activities from holding conferences, to holding press conferences,
to writing op-eds. Many of the members will go and visit their political leaders and talk
to their political leaders and it's a coordinated way to get across that this disease is important
and that something needs to be done about it. The logo on the right is the all party
parliamentary group in the UK.
This is a group of parliamentarians from different political parties that again are coming together
and saying that we can't ignore the need for pneumococcal vaccines and this was a critical
tactic in helping ensure that there was donor funding. Showing that there were governments
out there that are willing to support these vaccines that place importance on it, and
say that is the right thing to do. It's something that has influence beyond just the UK; two
other donor governments as well as other developing country governments. Then the third group
Iíd like to highlight is also a coalition and this is a newer effort, one that we started
just last year and it involves over a hundred different coalition members coming together
to talk about pneumonia. One of the things that I want to talk about just for a couple
of minutes is that when we first started our project we started talking out about the pneumococcal
We soon found out that, although there were a lot of advocates that are very concerned
with the disease, we really to broaden the focus. A lot of the people that would support
the introduction of different interventions are not in the vaccine world at all or may
not be in the pneumococcal world at all. So we found that talking not only about pneumococcal
disease, you can't escape talking about that, but talking about that the broader problem
of child pneumonia and the broader problem of child survival was really critical. So
what this effort did was it joined together different groups. It joined together civil
society, it joined together various partners, country governments and a number of different
stakeholders around the world and we had activities in twenty-five different countries in the
first year to talk about the importance of pneumonia and the need to move forward to
do something about this disease. Now moving forward and doing something about
it was not only just introducing new vaccines but it was in ensuring that they were reaching
the children that needed it, ensuring that mothers were breastfeeding and that there
was good nutrition and ensuring that the systems were in place to make it happen. So finally,
where are we in 2010? We now have an advance market commitment. 1.5 billion coming from
six different donors, it was essentially matching support from the GAVI Alliance. This is something
that I think many people didnít believe would ever happen, but four manufacturers, including
both multinationals and emerging markets suppliers have now come to the table and said that they
are going to be providing pneumococcal conjugate vaccines. The other important part is that
we did the work to ensure that we're providing the vaccines that are needed by the country
and that are appropriate for the country.
There is a WHO recommendation on pneumococcal vaccines and a very strong recommendation.
Those recommendations hold a lot of weight, but a recommendation in itself is not enough
to make things happen. There also needs to be people down on the ground communicating
those recommendations and advocates really reinforcing those messages. So where we are
today is thirteen approvals from GAVI countries, so thirteen low income countries are planning
on introducing the vaccine within the next year or so and then twelve more that they're
awaiting approval. This is out of a total of 72. Our reference doesnít focus only on
low income countries, a lot of advocacy efforts are going towards middle income countries
as well as donor countries. We essentially from the approvals standpoint are focused
on the low income countries. The results I think a very clear. Its death diverted and
the deaths are in the millions. So that's pretty substantial. We're really proud of
what we have done. We havenít done it alone. I think the key is to do it with a lot of
different partners and I thank you for your attention.
Well thanks for those two great talks. I think we heard nicely two models of how we might
approach influenza and building the case for influenza vaccine. I think these two models,
these two programs have been wildly successful by any metric and I think have lots of lessons.
Iím going to take moderators prerogative before I open it up to general questions unanswered
to do two things. First thereís a couple of people here, Roger Glass and Kathy Neuzil
and others that worked on Rotavirus ADIP, and I would ask either of them that wants
to speak, if they have any comments, lessons learned, advice for the influenza crowd in
We owe a lot of debt in the rotavirus community to Doctor Glass, who really pushed rotavirus
and its importance before the rest of the world recognized that so I was hoping he'd
go first but weíll save the best for last on this one. Just to comment, having gone
from influenza to rotavirus and back to influenza, there actually are some other similarities
in addition to what Marc-Alain pointed out. This is true for Pnuemo as well. One is that
influenza causes a relatively non-specific clinical syndrome.
So when you get on the ground in terms of the building demand and on its own, you know
it's easy to recognize measles, it's relatively easy to recognize paralytic polio. A health
care provider and a parent can feel very good when they give a vaccine in and see that their
child does not get that disease. We're talking about syndromic illnesses now in these children:
acute respiratory disease, acute diarrheal disease, very common number one and two killers
of children in the world and so even if we implement pneumococcal and rotavirus vaccines
we will still have respiratory disease and diarrhea.
So it takes a much more specific and targeted demand generation and the show what percentage,
as you said Marc-Alain, of these broad categories of very serious diseases are caused. Also
I would say it's not just percentages, but it's absolute numbers and if you look at the
absolute numbers of flu, we believe that they are likely high, as Abdullah Brooks and others
are starting to show, in the developing world. In regard to financing, if we look at GAVI
who has been critically important we know for other vaccines, and certainly for pneumo
and rota, when they had their recent strategic planning for future vaccines, influenza was
not even on their list. So pandemic influenza people think about, but annual influenza and
the burden it causes and children in pregnant women and in other vulnerable groups is not
on people's radar screen yet.
Thanks Kathy. Roger?
Iíll make a couple of observations; one is that this whole program wouldnít have gotten
going without Bill Gatesí involvement. He saw the early disease burden from the 1993
World Development Report. He invested in the rota as the first vaccine he was interestedin,
along with pnuemo in the Children's Vaccine Program. He got the GAVI going and the ADIPs
going so without his strong support we never would have been here today. The second is
that the rotavirus surveillance started with precious little money and little attention
and so the surveillance was not ideal but it generated a whole group of people around
the world who could advocate for the program who were in centers of excellence in their
own capital cities and to do a lot to count that the disease burden in their own countries
and internalize and I think thatís a lesson for the flu folks to know exactly what's the
burden of flu and how to push for it. Third I would say that here we are eight years after
the ADIPs began, we started with over half a million deaths from rotavirus, we still
have over half a million deaths from rotavirus despite the fact the vaccines licensed in
over a hundred countries.
Why is that so? One is that despite the eight years, we have precious little data about
efficacy. I think Kathy Neuzil has done great things to push the efficacy data and the studies
in the developing countries. That said the efficacy of live world vaccines in poor developing
countries has been less than it's been in middle income countries. Thereís a research
agenda that we have to address to understand why that is so and to overcome it.
So one is to improve the efficacy, which remains, even though using vaccines that are half effective
could have a major impact on mortality. The second is the issue of cost. While the cost
in the middle income countries now and for GAVI is a tenth of what it is in the high
income countries, the tiered pricing, we still have a way to go to make them affordable in
the long term for the poor developing countries. We hope that by having local manufacturers
involved in vaccine production, we will have vaccines that are made at a target cost that
is less than a dollar or two dollars as opposed to that of prices even to the global health
So cost is one. Efficacy is the second. I would say that openness of data because we've
had data on the mediocre efficacy now for six years but it hasn't all been public. I
think that the US government is taking the position that efficacy data has to be in clinical
trial data and it has to be made public within nine months of completing the trial. That
hasn't been the case with some of the rotavirus vaccine studies even though they've been done
with public sector money. I think that change will be welcome to all. So the good news is
we have two vaccines and companies with vaccines that are working well and much of the world
and are licensed all over and we really have products and a lot to learn from their intervention.
The bad news is we still have 600,000 deaths a year and weíre about to hear the first
data on reduction in mortality and middle income countries.
Eighty five or so of the mortality for rotavirus is in those low income GAVI eligible countries
where the advocacy is likely to be substantially less and we still have a research agenda to
get more effective vaccines and more economical vaccines that can be sustainable for the long
run. So thanks very much.
Thanks very much Roger that was perfect.
By my watch Daniel we have about ten minutes for questions.
Yes and I have one.
Dr. Shapiro first, then Daniel.
This maybe is not a question for the folks here up on the dais but maybe of people who
were involved in discussions with GAVI about influenza vaccine. I think Rogerís right
in crediting Bill Gates and GAVI in introducing new vaccine. I don't think you can declare
success regarding Hepititus B or HIB or even activities with rota and pnuemo without the
support of GAVI. I know that there have been some previous discussions regarding influenza
with GAVI. I havenít been involved in them and don't know the results of those discussions
but I believe there was a discussion a year or two ago with GAVI board about having GAVI
support pandemic vaccines or pre-pandemic vaccines. I'm just curious if any of the people
the room here were involved in some of those discussions and what was the response from
GAVI. Why are they not supporting for example, establishing pre-pandemic vaccine stockpiles?
Was it the fact that it wasn't the age group that GAVI normally deals with? Was the data
that Dr Ruiz talks about-did they feel that it was not available. I was wondering if anybody
in the room was aware of those discussions and know the rationale behind the feedback
There were several options that were proposed to GAVI for involvement into pandemic preparedness.
Among the options proposed were participation in the financing of a stockpile but also financing
of increase of seasonal vaccine uptake in developing countries to push demand. GAVI
was not receptive to this idea. There were several reasons, as mentioned by Craig, among
those the fact that GAVI sees itself as being established in terms of childhood vaccination.
They didnít see influenza as one of most important disease as compared to rotavirus
and pnuemo. They also thought that in lieu of their constrained resources-indeed many
of us who are involved in GAVI currently into heavy pressure because of the financial crisis.
They are not able to fulfill their current commitments so therefore they didnít think
it was the time for them to engage in influenza and welcomes the participation of other stakeholders.
Thank you very much. Dan?
This is a question that reflects my ignorance of the ADIP process. I heard in terms of the
rotavirus that it was instrumental, the Bill and Melinda Gates Foundation interest in supporting
that. Process wise who is the funder who begins the process? Is there some institutional review
process or that how does one engage in initiation of an ADIP-like process for other vaccines.
I can try to answer this and then everyone else can correct me. In 2002-2003 GAVI issued
a call for proposals to establish a site for an ADIP and so the call was a public call.
A consortium of institutions applied for this and one award was given for pnuemo and one
for rota and so it was a very formal above board process and it turns out both successful
grantees were groups of institutions tied together that shared their particular skill
sets. Is there anything else anyone wants to add? It was normal funding opportunity
by GAVI. GAVI provided all the funds for the ADIPs initally.
Just to take it back further, I think Roger pointed out it was an initial grassroots effort
that brought it to the attention of GAVI I would say to get it to that funderís level.
Indeed thatís true.
I just want to
recap some of the points that were made. Marc-Alain very nicely illustrated some of the differences
in the challenges faced- letís say a pneumococcal vaccine or rota vaccine versus an influenza
vaccine and in the importance, I think everyone has already stated before of having good data.
I would argue that going forward in the absence of an ADIP, whether or not influenza needs
an ADIP to help bring this more to developing country demand.
I think that three things at least to me stand out. Three types of data stand out. One really
is not only data on disease burden but specifically the issue of the broader question of childhood
I do think that the developing countries, that is the question- that they do face that-that
they are making difficult choices about what cocktail of vaccines to introduce. Right now
I think there's general consensus that we don't have a complete understanding of all
etiologies behind childhood pneumonia. We can explain up to 50% on a good day, but
other 50% we cannot explain and I think we need better data, particularly that the contribution
of influenza to childhood pneumonia. So one is disease burden data, but syndromic data
tied to lab confirmed influenza. Second, we've discussed yesterday the importance of having
good post vaccine introduction surveillance. I think that's going to be crucial because
vaccines like this are introduced at a time, speaking as a pediatrician, at a time when
many other childhood diseases begin to manifest themselves importantly among those convulsive
It is important to have good quality data to robustly refute concerns about the safety
of the vaccine post-introduction, which can cause of donor support and other collaborative
support to weigh in if there's a perception that the vaccines somehow is making things
Third, I think Roger Glass and Kathy Neuzil, both pointed out today, and Kathy and I were
talking about that yesterday, there is a perception often that vaccines that are introduced appear
to have a different efficacy oftentimes substantially different efficacy in developing countries
versus in developed countries. Often people fall back to, forgive me, but hackneyed explanations
of differences in immune status and overall disease burden and so on.
A lot of this comes down to study design and having good carefully acquired data that really
are comparable and often this data is not comparable. I think it is important again
as we think of post vaccine introduction or even efficacy trials to pay attention, to
study design so that we really are comparing apples to apples.
When we look at efficacy in making sure we have common endpoints, common definitions,
so we really can compare what the efficacy is, keeping an eye on the ball and focusing
on the issue of childhood pneumonia so that we really can say ìyes we have comparable
or non-comparable impact on disease burden.î
Thank you. We have time for one more question.
Let me spend the last one minute and ask one question to either of our panelists or anybody
else in the audience who has an opinion, one of the issues that came up in both rota and
the pnuemo, as was mentioned, ADIPS, and a lot of things it is whether every country
needs their own data; because the answer to that really drives a lot of the resource utilization
for the ADIPs, how much money do they spend in countries, how much modeling do they do,
etc. For flu, in countries interested in influenza vaccine that are expanding or introducing,
do they need their own data? Can we use data from one country to estimate flu Burden in
another? Any opinions around the room, or maybe among the panelists first?
I could just comment. One of the things that we found is that the desire for countriesí
own data often slows down the process and I think one of the things that need to be
weighed is just that. Can you look to another country and make a decision that's that based
on a rational set of arguments and points? Or is it that the demand in your country may
be truly different? That was something that we struggled with quite a bit.
The whole purpose of the disease burden project was just that. It was to be able to summarize
the data that was going on in different countries because what countries had was very little
visibility to studies that were done in other areas. The other thing that we found in our
experience is that oftentimes there were studies that the various universities or various groups
that may not be directly involved in the government process that are not necessarily known and
having a group or somebody that is specifically asking questions to find out what data actually
exist is something that can be very helpful.
Just to say I think that for influenza perhaps is getting good quality data from science
that can do it well, at least in initial phase, and before over-stretching-we have the idea
of networks and I think these are important. But we'll also want to get the ball rolling
if weíre going to be looking at disease burden data and scientists who can get good quality
data is probably where all the effort should go. As the ball gets rolling then expand the
Thanks. I think we better move on now. Dan since you run the meeting, you can get last
We probably need to find the appropriate balance between country-specific data and learning
from the experiences of similar countries or other countries. Remember that when it
comes to national policies, you have to keep in mind who that the audience is and how receptive
they might or might not be too experiences from other countries.
Having worked in the former Soviet Union in the early 90ís, our experience was that there
was a lot of pushback in terms of the experiences in other countries are not applicable to the
specific countries we're working in. I think that you really need to, once again, do your
market analysis in terms of who's your audience and who are you trying to reach and in what
kinds of information are they going to need and work backwards from there. You may be
able to use data from other countries. You might need to make some effort at least to
get some relevant data from the country itself. Thank you very much and with that let's move
on. I thank the speakers for the wonderful talks to start the session.