By Lois Privor-Dumm and Bruce Lee
You are having 100 guests for an outdoor picnic and need to make the decision: do you buy big bottles of soda (potentially messier but less expensive), smaller bottles (potentially more convenient but also more expensive), individual cans, or a compromise between the two? Your decision will depend on several factors including available refrigerator space, price, convenience, expected number of guests, and probability of leftover soda. You may also consider the servers (adult or child), the risks (e.g. mess, amount consumed) availability (will there be enough, is there a need to ration?), and waste produced (e.g., aluminum cans versus plastic bottles).
Sound familiar? It’s a very similar decision process for vaccines – which must consider the price to the country, if there is enough storage space, how difficult is it to transport all of the required product to where it needs to be, how much wastage will there be, if is there enough for everyone, and what is the risk that some containers will remain unopened?*
Looking at shelves in a grocery store, it is clear marketers understand the dynamics of these everyday decisions. Companies like Coca-Cola fully research how consumers make decisions and weigh trade-offs of price, size, and convenience. They vary offerings by region and by store, limiting choice in some places and providing every option under the sun in others.
Interestingly enough, where the stakes are very high – in vaccines – there doesn’t seem to be the same level of consideration. No one gets sick if a bottle of Coke is not available. We wish the same were true with a vaccine. Yet countries, donors, and manufacturers often do not fully weigh the consequences of container choice on cost, availability, likelihood of usage, and safety.
IVAC’s new report, Coverage, Cost and Safety Impacts of Primary Container Choice, details these tradeoffs and calls on the public health community to take a more data-oriented approach to supporting decisions for each individual vaccine. The report uses various scenarios run on the Highly Extensible Resource for Modeling Supply Chains (HERMES) model of the Benin vaccine supply chain built by the HERMES Logistics Modeling Team, working with colleagues from the Logivac Project and Benin. The HERMES Benin model allowed us to change the size of a vaccine container and simulate the resulting effects (e.g., cost per dose delivered and vaccine availability). The effects depend on a number of factors, including other vaccines in the supply chain, current constraints, and wastage policies (e.g., is a vaccine vial opened or not depending on number of children in a session).
We also considered what could happen at particular locations and clinics...not just at the country or global level. This is important since country-wide measures of routine vaccine coverage may be misleading. Often, country-wide routine vaccine coverage is high (>90%) even when coverage in remote areas (where vaccines are needed most urgently) remains low. Remote areas also may be very difficult to reach, have limited refrigerator space to store vaccines, and offer poor access to health care, all resulting in limited vaccine availability and high disease risk. At the same time, fewer children may show up to be vaccinated on a particular day, making healthcare workers loath to open a vial if they want to avoid wasting unused doses and country policies may compel them to do so. There is also an additional scenario to be considered for countries or even communities that are risk averse. Some product presentations inherently carry with them an increased risk for contamination (particularly multi-dose vials if not handled appropriately) or error (e.g, when a lyophilized vaccine is reconstituted with product other than diluent), or even contain a preservative that may be perceived to have safety issues (as is the case with thiomersal in some high- and middle-income countries). In this scenario, containers not requiring preservative or single-use presentations may be preferred, even when space is limited and/or cost may be higher.
At a global level we must start looking at the unique characteristics of each new antigen, providing guidance well in advance of product introductions, and looking across a range of scenarios. Although it is tempting for the manufacturer to limit the number of product presentations, building a case based on simulation experiments from a variety of countries, considering implications on coverage, cost, safety, and feasibility could help manufacturers better understand the investments needed and the “cost” of getting it wrong. Furthermore, the global community can better appreciate why certain costs may be higher for some populations and evaluate the need for more specific guidance on individual vaccines across a variety of scenarios. Container choice is not as straight forward as looking at price, wastage, and space. When humans are involved and there are imperfect choices, we should be approaching the decision with a framework that considers global, local, and manufacturing implications to make better-informed choices for every product introduced.
A number of efforts are underway that have improved forecasting and enabled a more systematic view of cold chain space. Now is the time to invest in ensuring we understand the full picture of cost per dose delivered, availability, and safety for each individual product and scenario to make better informed decisions.
*When there is a mismatch between number of doses in a vial or container and expected session size (e.g. the health worker sees two children per day and has a 10-dose vial of vaccine) and there is concern about wastage or availability of vaccine for future sessions, some health workers may not open the vial and vaccinate those children that particular day. The multi-dose vial policy, which enables the vaccine to remain opened for a designated period of time, can help mitigate wastage concerns, but it isn’t always followed, and not all vaccines are eligible.
Lois Privor-Dumm, MIBS, is Director of Policy, Advocacy & Communications and Bruce Lee, MD, MBA, is Director of Operations Research at IVAC.
By Dr. Dagna Constenla and Samantha Clark
For many people throughout the world, the bite of a mosquito is nothing more than a common annoyance. But for individuals living in dengue endemic countries such an annoyance can quickly turn into a life threatening condition. Patients who get sick with dengue fever often experience excruciating headaches, skin rash, and debilitating muscle and joint pains. In severe cases, it can lead to circulatory failure, shock, coma, and death. Though early and effective treatment can ease symptoms, there is no specific cure available for dengue. Efforts to control dengue through preventing mosquito bites and breeding have proven to be largely ineffective due to the mosquito’s tendency to feed throughout the day and ability to breed in even small bits of stagnant water.
The good news is a vaccine is forthcoming. After more than 60 years, the development of dengue vaccines has accelerated dramatically. Today, several vaccines are in various stages of advanced development, with clinical trials currently underway on five candidate vaccines. While it is difficult to predict the introduction date of a new dengue vaccine, it is expected that one will be available by 2017.
Unlike a new iteration of an existing vaccine, this is uncharted territory. Even if a dengue vaccine is successfully developed, a number of issues remain. How do we predict its use? Its costs? Its cost-effectiveness and affordability? How will countries introduce it?
Perhaps the greatest challenge facing countries will be how to finance the addition of a dengue vaccine to the national vaccine schedule. Vaccine price, availability of funding, and ability to negotiate pricing will all play a critical role in the ability of a country to finance a dengue vaccine. In the Americas, one of the regions where dengue is endemic, a key mechanism for introducing new vaccines has been PAHO’s Revolving Fund. This, along with other options such as pooled procurement, regional and domestic taxes, and low interest multilateral loans are all potential sources of funding.
These and other funding topics will be on the agenda at a workshop starting today and hosted by IVAC, a core partner in the Dengue Vaccine Initiative, in partnership with the International Vaccine Institute, the Sabin Vaccine Institute and the Pan-American Health Organization. The dengue finance workshop will bring together more than 30 experts from the Latin America and Caribbean region, including academics, representatives from bilateral organizations, international public health agencies, nonprofit organizations, international financial institutions, and government agencies. They will convene in Washington, D.C. on July 22-23, 2013 to discuss the challenge of vaccine finance in countries throughout the region.
This workshop will be critical to laying the groundwork for countries to establish a viable financing plan that can be immediately implemented following the introduction of a dengue vaccine. Stay tuned to the IVAC website for more information following the workshop.
Dagna Constenla, PhD, is the Director of Economics & Finance at IVAC. Samantha Clark is a Health Economist at IVAC.
By Dr. Samba Sow
Dr. Samba Sow is Director General of the Center for Vaccine Development – Mali (CVD Mali) and a Professor of Medicine at the University of Maryland School of Medicine. This blog is cross-posted from Lancet Global Health.
Scientific research, by definition, is about process. Scientists must follow carefully developed guidelines and established protocols to make sure research is conducted validly, accurately, and ethically. As any field researcher knows, meticulous attention to detail is challenging at the best of times, when obstacles like staff turnover, equipment shortages or delays, power outages, strikes, security concerns, and disruptive rumours are not out of the ordinary. But these “everyday” logistical challenges of doing research are further compounded when political instability surrounds your research site.
In the past year, my colleagues and I at Center for Vaccine Development (CVD) Mali faced immeasurable challenges in keeping research efforts going when the insurgency that has afflicted our country for decades began moving southward and threatening the capital city of Bamako, where our research centre is located. Read the full blog at the Lancet Global Health.
By Dr. Kate O'Brien
While the political turmoil and violence in Mali occupied headlines earlier this year, we here at IVAC were acutely aware of the situation as we worried daily about our partners there, including Dr. Samba Sow and his team at Center for Vaccine Development (CVD) in Bamako, who lead the Mali site of our Pneumonia Etiology Research for Child Health (PERCH) project. Earlier this month, our team had a chance to return to Mali, now that the situation in the capital has stabilized. We were impressed at CVD’s ability to keep the PERCH project – not to mention their work on the Global Enterics Multi-center Study (GEMS), MenAfriVac, and a few other randomized vaccine trials – up and running during the crisis, and to make the right choices to safely balance the security of their staff and care for patients while maintaining the integrity of the research. The trip got me reflecting on the broader efforts around pneumonia prevention, and three things struck me as worth sharing.
Kate O'Brien with members of IVAC's PERCH team and CVD-Mali in Bamako.
First, in spite of the progress on PCV, our work is not done on squelching the burden of pneumonia and the problem is not being fully met with the resources needed to tackle it. Much time and many resources are being allocated to global mortality estimates, including for pneumonia, and there is evidence that this burden of mortality has fallen meaningfully over the past decade. Credible disease burden efforts have an important place in the global health landscape and deserve to be done, and done properly, but they are, and will always be, a monitoring and planning tool. They only reflect the progress; they are not the progress itself. These estimates are fully dependent on sound, high-quality fieldwork on pneumonia burden, and the consequent efforts and research on protection, prevention, and treatment of pneumonia. There is too little funding for strategic fieldwork on pneumonia. Being in Bamako, in the hospital, in the clinic, and most importantly visiting communities and households of families who are affected by pneumonia, reminded me that this is where progress is made and this is where we must invest and innovate.
Second, we have to focus on what will meaningfully make changes in the burden of and mortality from pneumonia. We still don’t have tools that can readily differentiate the children with true pneumonia from those with other lower respiratory diseases that require a different treatment. Families still don’t have the basic understanding of signs of respiratory disease for which they should readily seek care. And hospitals and clinics remain crowded, under-resourced, and fragile with treatment approaches that too often are unable to support children through their illness. This is why children die from pneumonia, still.
CVD-Mali staff demonstrate procedures as Kate O'Brien and other PERCH team members observe.
Third, there are field research sites that have built expertise, infrastructure, and experience to tackle the important unknowns, but they are fragile and will not remain unless investments are made. In spite of the constraints, there is research of the highest quality ongoing in places where child mortality from pneumonia is highest, including in Mali. It is outstanding how the CVD-Mali team managed to keep all of its critical research projects up and running not only through the day-to-day challenges, but also through the political challenges of this past year. It was a great honor to learn from them, to work on solving challenges at the site, and to renew our understanding of where focus and effort is needed to make reductions of pneumonia and diarrhea a reality on the ground, and not just in our computer algorithms and spreadsheets.
Kate O’Brien, MD, MPH, is Acting Executive Director of IVAC. A pediatric infectious disease physician, epidemiologist, and vaccinologist, she previously served as Deputy Director of IVAC. She also serves as Associate Director of the Center for American Indian Health.
By Dr. Kate O’Brien
This week scientists came together to declare that we will eradicate polio in 5 years. It’s an achievable goal, and admittedly an aspirational one. But, if we as a global community leverage proven strategies and follow through on commitments made, it will be met. It is amazing to think that this goal, which just two decades ago seemed impossible to many, is now firmly in our sights. It also gives me confidence that we can reach other goals, such as reducing preventable childhood deaths to a degree that any such death is seen as a shocking, rare event rather than predictable and intractable. This challenge, which the global health community laid out in last year’s Promise Renewed initiative may seem daunting, given that despite recent declines, 6.9 million children died in 2011. However, when you consider that worldwide polio cases have dropped by 99% since the Global Polio Eradication Initiative began in 1988, it is clear these problems are surmountable. Like polio eradication, we need a concrete approach to tackling the leading child killers, and we made a big step forward with today’s launch of the Integrated Global Action Plan for Prevention and Control of Pneumonia and Diarrhoea (GAPPD). Released by WHO and UNICEF, GAPPD clearly outlines the steps we must take to eliminate the two leading killers of young children in 20 years.
The Integrated Global Action Plan for Pneumonia and Diarrhoea (GAPPD)
Most of my professional life has been spent assessing and applying interventions to reduce pneumonia and diarrhea, both in the United States among American Indian communities and around the world in the communities where most child deaths still occur. I’ve seen the burden of these diseases in the numbers we calculate and on the faces of the patients I’ve treated. I’ve also seen that we have the tools we need to stop children from dying or suffering from severe pneumonia and diarrhea. When I worked in Haiti, the ward was full of children, over a third of whom would die in those beds. Nearly all of the illnesses these children had were fully preventable, mostly through the use of vaccines but also through other simple, sensible interventions. The interventions we have work, and the task we have is to figure out how to use them most effectively, to know if what we are doing is working, and to make adjustments in optimizing their impact. This feedback loop can only be put in place when we can measure the impact of what we’re doing. We may not be able to measure with absolute precision, but with enough precision to know if our time and treasure is being wisely spent.
We know what we need to do to tackle pneumonia and diarrhea, and establishing clear evidence on the burden of disease and on interventions that work creates the platform from which we can prioritize our efforts. A new series published in the Lancet today in conjunction with GAPPD provides updated evidence on this front. One of the papers, led by faculty in our Department of International Health at Johns Hopkins provides updated mortality estimates for pneumonia and diarrhea – together responsible for more than 2 million child deaths in 2011.
We also have a clear understanding of which interventions work, and we know that many of them overlap. As my colleague Bob Black pointed out in the Lancet series launch, while diarrhea and pneumonia have very different symptoms and causes, several risk factors for the two diseases are the same, including under-nutrition, suboptimal breastfeeding, and zinc deficiency, meaning that they can be effectively prevented and treated as part of a coordinated program. We also know that vaccination campaigns will play an important role. A second paper in the Lancet evaluated 15 key interventions using the Lives Saved Tool. It found that nearly one third of severe diarrhea episodes could be prevented by widespread vaccination against rotavirus and cholera, while up to two thirds of pneumonia deaths could be prevented by implementation of pneumococcal and Haemophilus influenzae type b vaccines. With ambitious scale-up – 80% coverage or more – the authors estimated all 15 interventions could effectively eliminate (95% prevented) diarrheal deaths and prevent around two-thirds of pneumonia deaths by 2025. All this at a total cost of just USD6.7 billion.
GAPPD and the Lancet series reflect years of work toward a consensus among all stakeholders that we must target our efforts on proven interventions, and we must work together in an integrated way. Many of the interventions for childhood diseases overlap, and can be delivered more efficiently if all parties work together. This integration will not only result in better care for each child, it is also crucial in resource-poor settings, where countries simply cannot afford to maintain siloed efforts and where partnering countries and organizations are increasingly demanding more impact for their investments.
We have the evidence, and our marching orders are clear. With polio eradication beckoning our efforts, it is the time to leverage this energy, know-how, and confidence by fulfilling our promises and advocating for all stakeholders – donors, governments, civil society, and other leaders – to fulfill theirs. We can all take inspiration and insight from polio eradication efforts and make the end of preventable pneumonia and diarrhea deaths a reality.
Kate O’Brien, MD, MPH is Acting Executive Director of IVAC. A pediatric infectious disease physician, epidemiologist, and vaccinologist, she previously served as Deputy Director of IVAC. She also serves as Associate Director of the Center for American Indian Health.