Ray Kennedy

Is there a more effective way of getting a (better) malaria vaccine?

World Malaria Day is next week! To celebrate the 

 made in the last decade towards eradicating malaria, join our 

We finally have a 35% effective malaria vaccine

. Last year, the world’s first malaria vaccine, Monsquirix/RTS,S, was recommended by European drugs regulators

 (though there are still some concerns about the safety of the vaccine

) and initial studies of cost-effectiveness have shown positive results, though it is slightly less cost-effective than insecticide treated bednets

. The vaccine has been developed under a product development partnership between the Bill and Melinda Gates Foundation and GSK. In exchange for funding support, GSK have made strong commitments to make the vaccine available at an affordable price

Discovering a new vaccine is excellent news. But we should still question our approach to vaccine development. Is the way we currently fund vaccine and drug research for developing countries working as well as it should? Are we missing out on opportunities? Can we make progress faster?

Because the speed at which we develop a vaccine matters.

Just speeding up the discovery of a vaccine by a single year and the adoption of this vaccine in poor countries by two years, could save many lives4. One analysis suggested that spending $3bn to achieve this would only cost $80 - $90 per additional life year saved

So when we think about developing a malaria vaccine 

we should remember that there are big payoffs if we can speed up the process.

One of the ways we can divide different funding efforts is between push and pull funding mechanisms.

 funding mechanisms pay for or subsidise 

 (like paying a team of researchers to do research). 

 or outcomes, for instance, by paying a prize for successfully developing a drug, or guaranteeing a future price at which a profit can be made

In the case of the malaria vaccine, the Gates Foundation pursued a ‘push’ funding approach.

A big downside with push-funding approaches is that they can dis-incentivise other organisations to develop vaccine candidates. In this case, anyone else developing a malaria vaccine would end up competing with a vaccine which will be sold at close to marginal cost

Regrettably the RTS,S vaccine offers only modest protection from malaria

: it is about 35% effective, meaning that Mosquirix reduces the number of cases of clinical malaria in children by about 35% over a two year period. This is very low when other highly effective vaccines for children such as 

But there are many of other malaria vaccine candidates being investigated

 - although they are probably receiving much less funding to do so

. So it is perfectly possible there are other more effective vaccines than RTS,S waiting to be developed - and putting money behind just one vaccine, may have slowed or stalled their progress. This is because there is another way of developing vaccines (and indeed other products): 

recreate the market incentives that help develop drugs in richer countries

. Donors make legally binding pledges to subsidise vaccines which meet certain requirements. But crucially they aren’t tied to any particular manufacturer. This means that donor organisations don’t have to pay if development is unsuccessful, and they don’t have the difficult decision of assessing which pharmaceutical company has the most promising vaccine prospect. This decision is instead left to pharma companies themselves- who are better placed to evaluate the prospect of success.

This approach was used to develop vaccines for pneumococcal diseases common in the developing world. A collection of governments alongside the Gates Foundation committed $1.5bn as a top-up subsidy for manufacturers if they agreed to develop and supply vaccines at a low price

How can we do better in the case of malaria?

Would this approach have worked better in the case of malaria? Would it have found a quicker solution?

Ultimately these are very difficult questions to answer. But these issues of skewed funding incentives were well known over a decade ago

There can be downsides to an AMC approach. Critics allege that the AMC could have negotiated a price closer to the cost of production and that other push funding efforts have had more success in negotiating a low price

. The fact that drug companies have voluntarily lowered the ‘tail price’

 under the AMC suggests it was set too high originally. Some see the AMC as overly generous to existing large developed country pharmaceutical companies

almost all the organisations and people involved in vaccine or drug development have strong incentives to prefer push funding

. Donors might prefer giving money to support local companies and research outfits. Activist organisations may strongly dislike the idea that private companies can make big profits from pull funding (although they can lose money from unsuccessful research efforts). Drug companies- and also academics- may prefer a guaranteed flow of money for research rather than it being tied to results.

We still have not seen another Advance Market Commitment comparable to that launched for pneumococcal vaccines that was first announced back in 2007. And there are many diseases other than malaria that could benefit from new efforts to develop vaccines or new drugs against them.

even while we celebrate a new tool against malaria, we should still stop to consider whether there is a better way to get to effective vaccines

Where should we donate to do the most good? - Essay Competition Winner

Where should we donate to do the most good?' What is the most effective, scalable, evidence-based, but currently underfunded global health intervention that is already being implemented or could be implemented soon?

In 2004, a World Bank report stated that deaths from malaria could be “all but eliminated” using then available treatment interventions (World Bank, 2004). But ten years later, malaria still kills over 500,000 people every year (World Health Organization, 2014).

One estimate suggested that if use of all the proven effective childhood preventive and treatment interventions were to rise from current levels to 99 % (95% for breastfeeding), the number of under-five deaths worldwide could fall by 63% (Jones, Steketee, Black, Bhutta, & Morris, 2003).

We invest billions of dollars in finding the next vaccine, the next drug, the next possible intervention. But not nearly so much in improving the delivery of interventions we already know work well. These are primarily not scientific or technological challenges. They are challenges of implementation, of delivery.

So what is an example of a delivery intervention we should be trying?

 is a social enterprise founded in 2012. Its key innovation is to use simple vaccine reminder bracelets which are worn by children from birth to age four years old.

Vaccines are highly effective, scalable and have one of the best evidence bases of any intervention in health (according to 

). The number one risk factor in infectious disease is failure to vaccinate (McHugh, Guarecuco, Langer, & Jaklenec, 2015). Yet an estimated one in five children in the world do not receive full or timely immunisation. Vaccines are one of our best weapons against poverty and ill health, yet we aren’t getting them to 

Failure to provide reminders and the forgetfulness of caregivers are key reasons for missed vaccinations across a wide range of contexts (Patel & Pandit, 2011)(Wakadha et al., 2013)(Wilson, 2000)(Quaiyum et al., 2011). Mothers may be illiterate and struggle to understand routine immunisation cards.

 is worn by the child and uses symbols for each disease which are ‘punched out’ when a vaccine has been delivered. The bracelet has been implemented in an initial 6 month pilot study in rural Peru and Ecuador. A bracelet costs $0.10 to produce. Initial results are positive. 91% of mothers said the bracelets helped remind them of vaccination visits. 90% said they would continue to use the bracelets in the future if possible. 87% said they would recommend the bracelets to other mothers. The next step of the innovation is to run a larger 1 year study with 5,000 mothers and babies. Further information is at 

Could this be a viable, practical solution for the challenge of vaccine delivery? Perhaps. We need to test it. Adapt it. Iterate. But this is the sort of innovation needed to get to the 20% of unvaccinated children who are hard to reach.

In Bangladesh, relatively simple innovations such as adding the phone number of vaccinators to immunisation cards helped increase immunisation coverage by 15% in a single year (Save the Children, 2012). Bangladesh is one of the poorest countries in the world but its national immunisation coverage rate (measured using DPT3 rate) is 95% (WHO & UNICEF, 2014). This should be achievable for all countries if the right focus is placed on delivery and experimentation.

The beauty of this Alma Sana vaccine bracelet is that it has the potential to improve service delivery of all childhood vaccinations- an enormous potential impact at a very low cost. Vaccinations are already seen as a ‘best buy’ in public health and highly cost-effective (World Health Organization, UNICEF, & World Bank, 2009).

When considering whether to fund an innovation, we should think about both the impact it could have and the likelihood of achieving that impact. At this stage we cannot say for certain whether the vaccine bracelets will be effective at increasing immunisation rates despite early positive indications. But for approximately $1m this intervention will be rigorously trialled in three different countries to establish whether it works. Given the very low intervention cost even a small improvement in vaccination rates is highly likely to be cost-effective.

Giving What We Can rightly has a focus on what areas are underfunded. As an organisation that can only realistically hope to direct or steer a minority of philanthropic donations this is an absolutely appropriate goal. But Giving What We Can should also consider its comparative advantage when compared to other funding organisations.

Facing a choice between donating to two equally effective organisations, GWWC donors should choose the more obscure, the smaller, less well-known alternative. They are less likely to get the money some other way. Alma Sana is a small social enterprise that has to date received a small grant from the Gates Foundation and some money from a crowdfunding campaign. I do not know their internal financial picture, but it seems unlikely that they currently have the money to fund worldwide trials and they certainly do not have the resources to scale this intervention nationally should it prove successful.

This is where Giving What We Can donors should put their money. Not in the ‘sexy’ development of new drugs, or in the already well-funded, tried and tested rollout of malaria bednets. But in the vital, dull yet risky work of optimising the delivery of proven interventions to make sure they reach everyone who needs them. Alma Sana is an excellent example of the sort of service delivery innovation that is so badly needed.

Jones, G., Steketee, R. W., Black, R. E., Bhutta, Z. A., & Morris, S. S. (2003). 

How many child deaths can we prevent this year? Lancet (London, England), 362(9377), 65–71.

McHugh, K. J., Guarecuco, R., Langer, R., & Jaklenec, A. (2015). 

Single-injection vaccines: Progress, challenges, and opportunities. Journal of Controlled Release : Official Journal of the Controlled Release Society.

Why infants miss vaccination during routine immunization sessions? Study in a rural area of Anand District, Gujarat. Indian Journal of Public Health, 55(4), 321–3.

Quaiyum, M. A., Gazi, R., Khan, A. I., Uddin, J., Islam, M., Ahmed, F., & Saha, N. C. (2011). 

Programmatic aspects of dropouts in child vaccination in Bangladesh: findings from a prospective study. Asia-Pacific Journal of Public Health / Asia-Pacific Academic Consortium for Public Health, 23(2), 141–50.

Immunisation for All: No Child Left Behind.

Wakadha, H., Chandir, S., Were, E. V., Rubin, A., Obor, D., Levine, O. S., … Feikin, D. R. (2013). 

The feasibility of using mobile-phone based SMS reminders and conditional cash transfers to improve timely immunization in rural Kenya. Vaccine, 31(6), 987–93.

WHO, & UNICEF. (2014). Bangladesh: WHO and UNICEF estimates of immunisation coverage: 2014 revision. Retrieved August 31, 2015, from 

http://www.who.int/immunization/monitoring_surveillance/data/bgd.pdfWilson

Factors influencing the immunization status of children in a rural setting. Journal of Pediatric Health Care : Official Publication of National Association of Pediatric Nurse Associates & Practitioners, 14(3), 117–21.

Ray Kennedy

Articles

Is there a more effective way of getting a (better) malaria vaccine?

Where should we donate to do the most good? - Essay Competition Winner