Welcome.

Today we are going to speak about how science and technology

can be harnessed to improve the health of some of the poorest people in the world.

By the end of this session, you should be able to speak comfortably about: the needs

for drugs, diagnostics, and vaccines to address high-burden diseases

that affect the poor in low and middle-income countries.

The extent to which existing products meet those needs.

The potential of science and technology

to develop enhanced products to address high-burden and debilitating diseases.

And some of the key constraints to investments in such products.

As well as selected mechanisms to overcome these constraints and

encourage the development and uptake of enhanced diagnostics, vaccines and drugs.

Let's begin with some vignettes.

Juan lives in the highlands of Peru.

Juan is being treated for tuberculosis at a local clinic.

Juan has to take four drugs for two months, and then two drugs for

four months in order to cure his TB.

Juan is getting tired of taking so many pills for such a long time,

and some days Juan does not take his tuberculosis drugs.

Mei-Ling is four years old, and lives in the west of China.

Like so many children in her region, Mei-Ling is infected with hookworms.

The community has a deworming program, and

every six months Mei-Lling is given medicine to get rid of the worms.

This medicine is generally safe and effective.

However, it has to be given twice a year and

there are some indication that the hookworms are becoming resistant to it.

David is seven years old and lives in the eastern part of Kenya.

He had a high fever and chills and

his mother took him to the local health clinic.

The nurse examined David, decided he had malaria and

prescribed antimalarial medicine.

This was a new medicine, different from, and more expensive than

the one that used to be given because that one doesn't work any more in Kenya.

This was the third time in a year that David had malaria.

Now let's explore with the help of our students

some of the concepts brought up by these vignettes.

Let's begin by looking at what ideal forms of drugs, diagnostics, and

vaccines would be, if we were to better more effectively, more efficiently,

more affordably address high burden, communicable, and parasitic diseases.

As we do so,

lets keep in mind that many people who suffer from these diseases are poor.

They often live in tropical or sub-tropical environments, and

they often live in countries with weak health systems.

So, let me ask Emily,

if I might, what would an ideal vaccine for tuberculosis look like?

>> Well, we would want the vaccine to be heat stable and only need one dose, and

offer very good protection against tuberculosis throughout your entire life.

>> And TB of one form or many forms?

>> Of every form.

And Elizabeth, if I might,

what would an ideal form of a diagnostic be for tuberculosis?

>> An ideal diagnostic would be minimally invasive,

highly effective at detecting different forms of TB, and also

be effective in detecting TB that might be hidden, like latent TB or TB in children.

>> Okay, and and let me turn to Sherilyn, and say, Sherilyn, we know that

the standard course of therapy for drug susceptible tuberculosis is six months.

In a more ideal world, what would a ideal drug regimen for TB look like.

>> Yeah, it would be shorter than it is now, ideally, maybe one pill.

It would be cheap, and affordable, and have minimal side effects possibly.

And it would also be heat stable.

>> And probably even confer lifelong immunity of some kind, etc.

Indeed, it's important that diagnostics be specific,

sensitive, easy to use, and non-invasive.

Ideally in fact, diagnostics could be done quickly by relatively untrained workers,

and would rapidly produce easy to read results.

Of course they would also in the settings in which we want them to be used,

be easy to transport, heat stable, inexpensive, not require refrigeration.

And of course we could say, and we'll see in this graphic, very similar things about

the ideal state of vaccines, or the ideal state of drugs.

Wouldn't it be wonderful if we lived in a world where some of the important

health conditions affecting people, especially poor people in low and

middle-income countries, if we could have for

them vaccines that were affordable, safe and effective, required few doses,

conferred lifelong immunity, easy to transport and store, and heat stable.

Wouldn't it be wonderful as well if we had drugs as my students said that were

affordable, safe and effective, not easy for pathogens to become resistant to,

required only small doses over a limited period, were easy to store and

transport, were also heat stable.

And we're thinking also, of course, about delivery devices.

And there too, it would be wonderful if they were affordable, safe and

effective, not invasive, easy to transport, store, and heat stable.

For all of these in a more ideal state we would be looking at non-invasive,

affordable, relatively easy to use by even relatively untrained health workers

produce very quick results that both the workers and patients could understand.

That it would be easy to transport, easy to store, by and large for

all of these in a more ideal world, we'd love to see some similar characteristics.

Now let's talk however about the present state of affairs.

First it's important to understand that science and technology have been very

important to addressing a range of diseases and communicable diseases.

And if you look at the history of efforts, for example, to address smallpox or

onchocerciasis, you'll see that for

both of them along the route of global efforts to address these diseases,

there were important scientific and technical discoveries and developments

that allowed these diseases to be more effectively and efficiently addressed.

And in the case of smallpox, help to enable smallpox to be eradicated.

For smallpox, for example, the development of the bifurcated needle and

freeze-dried vaccine was very important.

For onchocerciasis, it was extremely important that they found

that a drug that was used to treat parasitic infection in animals

could in fact be used to treat or prevent onchocerciasis In humans.

And yet, even in a world where science and technology had been so valuable,

there's an enormous gap between the ideal state we'd like to see and

where we are today in terms of a number of important diseases,

especially diseases that affect.

Primarily, people in low and middle income countries.

For tuberculosis again, the standard course of therapy for drug susceptible

TB is six months long, and requires a lot of pills to be taken for a long time.

For malaria, there's an effective and

efficient drug called artemisinin that's given in combination with other drugs

in a manner that's called, artemisinin combinations therapy.

And yet, there's already resistance developing to artemisinin combination

therapy.

There aren't very many new drugs under development, and we're constantly at risk

of living in a world, where the malaria parasite becomes more, and more resistant

to the drugs that we have, and we won't be able to treat malaria effectively.

For the neglected tropical diseases, there are no vaccines,

though people are working on them.

And it's important, given the state of the drugs that we have, that people take them

several times, for example, per year.

And wouldn't it be wonderful instead, if we had a safe and effective vaccine for

some of these diseases.

And if they didn't have to take these drugs every year,

twice or three times a year for example, for 10, 15 or 20 years to try

to stop transmission of some of these neglected tropical diseases.

It's also important to note that the need for more ideal drugs,

diagnostics, vaccines, and delivery devices,

is also highlighted by the growing problem of drug resistance.

Vaccines prevent disease, and

keep us from using antibiotics, to which bacteria can become resistant.

In addition, we have substantial problems already of resistance with tuberculosis

as I mentioned, and a growing problem of resistance with malaria as well.

And we had historically substantial problems of resistance with malaria,

and the primary drugs that have been used traditionally to treat that malaria.

There also are only a few drugs that are effective now against some diseases, and

growing resistance to those drugs.

We're probably living in a world in which we urgently need to develop new drugs,

before some of the existing ones are really no longer effective.

So we need to ask ourselves therefore,

what are the constraints to meeting our ideals for these products?

And especially, these products as they might meet the needs for

better health of relatively poor people in low and middle income countries.

So let's turn to our students and see what thoughtful suggestions they have on this.

Emily, if I might, if you were the president of a major

pharmaceutical company, what would be your main goal in life?

>> Making a lot of profit.

>> Okay, making a lot of profit.

You would be paid by your shareholders to do what they call

increase shareholder value by making a lot of profit.

And let me ask you Elizabeth, if this were your goal,

then why would that maybe discourage you from investing in drugs, diagnostics, and

vaccines, that you might need, that the world might need to address some of

the health problems, especially of poor people in low and middle income countries?

>> Well, in order to make a lot of profit, I might decide to invest only

in drugs that treat high income countries' conditions,

especially conditions that might be chronic.

So they'd be forced to take the drug continuously.

>> And indeed what we see is a world in which there is a perception by many of

the private developers and manufacturers of these products, of a limited market

in low and middle income countries, for the goods that we would like to see.

We can see a number of key constraints in fact, as perception of the limited market,

high costs of research and development and the high opportunity cost.

If a pharmaceutical company might require $800 million, for example, to invest

in a vaccine to meet some of the health needs of poor people in poor countries.

And they don't think there may be the money to pay for

it at the cost they need to charge to recover their investment,

they are not going to manufacture that, or develop it.

They're much more likely to say, with this kind of opportunity cost,

let's invest in some of the drugs, for example, that Elizabeth has suggested.

The development and production of vaccines is also quite complicated,

and that itself has been a constraint to having more players in the vaccine market.

And at the same time we know that historically, though better now than

before, many important national research institutions have actually paid

relatively less attention to some of these diseases than they might.

Now in principle, we have to ask ourselves, are there measures that

countries or the global community together could take to address some of

these important constraints, to change the perceptions of the market?

And to make product developers, distributors, and sellers feel

like there are real prospects that they can get their return on investment,

if they develop the drugs, diagnostics, vaccines, delivery devices that we need to

improve the health, especially the health of poor people in some of these countries.

So let's look at another graphic that talks about some of the ways that

this might be done.

Some of the measures that might be taken can be classified as pull and

push mechanisms.

There are a number of so-called push mechanisms,

that have to do with lowering the costs to potential developers of these products.

Either by providing direct financing, by financing clinical trials at the expense,

for example, of the public, or of national research institutions.

Or perhaps by offering tax credits for research and development, so that

Elizabeth's company is willing to invest in the development of a new product for.

A government or a set of governments might offer her tax credits that would lower,

to her, the cost of that product development.

At the same time there's a number of interventions called pull interventions.

These lower the cost up front, and these, as you can see by the darkening colors,

actually try to incentivize you in the later stages of development.

One can, for example, encourage countries to uptake more, to take and use more

of a certain vaccine to help create the impression that there really is a larger

market, and there's money to pay for these vaccines, if companies would develop them.

One might offer prizes, I might say to Shalon, another who runs a company, and

other similar companies.

If you are able to develop a safe, effective and affordable drug against x or

y, let's say even tuberculosis, we're willing to give you a prize,

as high as $50 million, if you can do that in the next three or four years.

Patents are worth a lot of money.

And we might say to Emily, if your company can develop this,

we might be willing to give you or we would be willing to give you

a patent extension on one of the drugs from which you're now making good profit.

To help you offset the costs of developing this drug, for example, for which you

believe there is not a sufficient market or sufficient money to pay for the drug.

One can also get market assurances, promises, let's say,

from some of the better off countries, that they will help to pay for

some of these products if they're developed.

And also one might give tax credits for sales, for example, of vaccines.

Now, related to push mechanisms, a number of global health factors such as the Bill

and Melinda Gates Foundation, the U.S. government and the Canadian government,

has set up a program called Grand Challenges in Global Health.

And as part of this program, what they're doing is offering grants for, but

in a sense there are also prizes because people are proposing.

They're issuing broad-based tenders, and

they're encouraging scientists throughout the world to try to engage in research and

development that can help ultimately set the foundation for or

lead to more affordable, effective, safe, et cetera.

Drugs, diagnostics, and vaccines, like those that we're talking about.

And this graphic gives you some examples of some of the grants that have been

awarded historically by a number of these organizations in four areas.

One was discover new ways to achieve healthy birth, growth and development.

Another is to develop technologies that allow assessment of

multiple conditions and pathogens at the point of care.

Some of you may have been reading for example about the hope that one could

breath on a piece of paper, and that piece of paper might light up in different

colors,and eventually say to us whether or not we have one or more health conditions.

Create a full range of optimal,

bioavailable nutrients in a single staple plant species.

Some of you will be familiar with efforts, for example, to develop rice that's rich

in one micronutrient, or cassava, or potatoes that are rich in others,

and also efforts to improve delivery devices by for

example developing needle three delivery systems.

And this is a very very small sample

on a large number of rewards that have been given in the last decayed or so.

The scientist throughout the world to try to encourage them

to engage in research and development that might be needed to improved

the products that we have available.

Now, it’s also important to understand that Global Actors beginning

in 1997 created a new kind of organization called Public Private Partnerships for

Health or Product Development Partnerships, in the hopes that these

organizations could help also to overcome some of these market imperfections.

In the hopes that these organizations, which have largely been funded by

some private philanthropies and some high income country governments,

in the hopes that they could broker arrangements between the public sector,

research institutions, the private sector, and other important actors

to set a foundation for the more rapid development of some of these drugs,

diagnostics, and vaccines, than would otherwise be possible.

The first of these product development partnerships was created in 1997 and

is called the International AIDS Vaccine Initiative, but

today we see there's a large number of such partnerships and

they include the TB Alliance, whose goal is to enable the development of

more effective efficient drugs for tuberculosis.

The Medicines for Malaria Venture whose goal is to enable the development of

a safe and effective vaccine for malaria.

AERAS, whose goal is to encourage the development of a safe and

effective vaccine that coul hopefully find as many forms,

prevent as many forms of tuberculosis as possible.

And the foundation for innovative new diagnostics, which is largely focused on

the development of new diagnostics like those we discussed, that would be safe,

effective, efficient, and less invasive, produce more rapid results at

the point of care than some of the diagnostics that are available now.

Now, there has been some progress as a result of the efforts of the private

partnerships and product development partnerships, but

in some respects it's still early in their life cycle.

And it's going to be very important over the next five to ten years

to see the extend to, which they're able to encourage and

enable the development of the products that are needed.

Now, it's also important to understand that global, the global community has

gotten together not only to create product development partnerships,

but also to create a variety of new innovative financing mechanisms,

that would help to overcome the market constraints that we discussed, and one

such effort has been called the Advance Market Commitment or AMC for vaccines.

An Advance Market Commitment is a financing mechanism that aims to

encourage investment, and the development and manufacturing the vaccines,

that can be sold at affordable prices in low income countries.

The AMC that exists, was devised in 2005,

it was further refined over the period 2006 to 2009.

And then it started in 2009, it's housed at the GAVI Alliance,

what use to be called the Global Alliance for Vaccines and Immunization.

And it was initially funded by a group of high income countries

focusing on a pneumoccocal vaccine.

In a way the AMC can best be thought it was a fund that will make financing

available to vaccine manufacturers if they're able

under certain circumstances, to create the number of vaccines

needed by an agreed time to be sold at an agreed price.

This is meant to convince them that there really is a market,

and that there's really money to pay for

these vaccines, if they will only be able to make them available.

The manufacturers are pre-certified as technically competent,

they ensure that there are a number of manufacturers, so

no manufacturer can have a monopoly on the production of the vaccine.

And they agree in advance on the prices that will be paid for the vaccine.

The advanced market commitment was projected to save over 500,000

lives by 2015 And over 1.5 million lives by 2020.

The Gavi alliance had pledged to contribute $1.3

billion to this effort to 2015, with the hope of making

the vaccine available to nearly 60 different countries.

So it's important to understand that science and technology, have played and

continue to play an enormously important role in public health and global health.

Innovations in drugs, diagnostics in vaccines

have dramatically altered our ability to fight some health conditions.

And yet we also know that global markets don't work effectively or

efficiently to produce some of the drugs, diagnostics, vaccines or

delivery devices that we need to meet a number of the critical health conditions

that continue to plague people in low and middle income countries.

Thus the global community has gotten together, and

developed a range of efforts, like the grand challenges, product development and

partnerships, and innovative financing mechanisms to try to change the way in

which the market works and to try to enable development of needed products.

The next sessions would be our last one, and we'll speak about

the key global health challenges that we're likely to face in the next decade.

Science and Technology for Global Health

Essentials of Global Health

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