Cloudy with a Chance of Prevention: Demand Forecasts and Assessments

New efforts are trying to gauge future demand for healthcare products, especially vaccines for neglected diseases

By Catherine Zandonella*

Preventive vaccines can alleviate needless suffering and deaths and save millions of dollars in health expenditures. For a variety of reasons, however, countries do not always rapidly adopt them. The reasons include inadequate health care infrastructure, country-level immunization policies, inability to pay, and individual and community attitudes towards the acceptance of the product.

As a result, the public health need for a vaccine is not the same as the demand. Need is determined through epidemiological estimates of the number of doses required to protect the at-risk population. Demand is a more complex concept that includes consideration of the country-specific issues mentioned above as well as vaccine characteristics, product availability, and funding. "Needs forecasting is extremely dangerous," says Stephen Jarrett, deputy director of UNICEF's vaccine supply division. "Anybody can come up with those figures; the real question is, what is the fundable forecast?"

The multinational pharmaceutical sector is experienced at estimating demand in resource-rich markets, but this expertise is not always applied to developing country markets, both because of the perceived lack of viable markets and the paucity of data to use in modeling.

Recently, public private partnerships (PPPs) and non-governmental organizations (NGOs) have stepped in to undertake demand assessments for vaccines and therapeutics as part of wider efforts to increase industry engagement in research and development (R&D) into diseases prevalent in developing countries. These organizations are developing the data sets and capacity needed to create demand forecasts with the goal of maximizing global access to these products.

To help with the task of creating these forecasts, PPPs and NGOs are seeking the advice of economists, industry forecasters, and consulting groups. IAVI, the Accelerated Development and Introduction Plans (ADIPs) for pneumococcal and rotavirus vaccines (PneumoADIP and RotaADIP, respectively) coordinated by the Global Alliance for Vaccines and Immunization, and the Program for Appropriate Technology in Health's (PATH's) Malaria Vaccine Initiative are each currently developing (or have recently conducted) strategic demand assessment research. And the Center for Global Development (CGD) is in the process of holding a series of stakeholder workshops over the course of this year to gain consensus on how best to share data, techniques, and principles for demand assessments of vaccines and other medicines.

Some of these assessments are for products already available, such as antiretroviral drugs, while others are for products like the preventive pneumococcal vaccine that are just beginning to be introduced. Still other assessments are for products such as an AIDS vaccine that are still very much in the R&D phase. The accuracy of the resulting forecast will necessarily depend on whether a product already exists, is just being introduced, or is still in development. There are outstanding questions about almost all of the determinants of demand for products farther from launch. In these instances, researchers must identify what they believe will be the main drivers of demand and envision plausible scenarios within which to frame and analyze potential demand.

Looking at the extremes of the spectrum, a short-range demand forecast might be based on previous consumption levels, how many people need the drug, how many new infections are expected, the price, how many doses can be purchased given available funding, and whether people come forward to be treated and remain on treatment. Since many of these parameters are not known for very long-range assessments, the endeavor is more about creating a set of demand scenarios, according to Wendy Woods of the Boston Consulting Group, which is working with IAVI to develop an AIDS vaccine demand assessment. "We never use the word forecast, " she says, "because frankly we don't think we can pinpoint scenarios for a product that will be launched years from now. "

An important impetus behind these demand forecasts and scenario specifications is having the conversation itself and taking into account the viewpoints of all constituents to consider the relevant issues. These constituents include national health officials, outreach organizations that understand the challenges of delivering vaccines and healthcare products, donor organizations that give grants for healthcare products or directly supply them, and developers or producers that research, develop, and/or manufacture the vaccines.

If demand forecasting and scenario building are done correctly they can act as tools that stakeholders can use to help make decisions. For example, country leaders and policymakers can evaluate required infrastructure investments, decide how to allocate funds for procurement, and potentially offset the costs of treating a disease through preventive efforts. Donors can map out multi-year finance strategies and ensure that funds are used appropriately. Outreach organizations can educate the community so that individuals are willing to come forward to be vaccinated, and PPPs can use the framework to undertake access planning.

Forecasts for existing products

Accurate forecasting for existing healthcare products is essential to ensure that appropriate quantities can be ordered from manufacturers, which in turn contract with downstream suppliers.

Inaccurate forecasts may result in oversupply, as was the case by the end of 2005 with the production of artemisinin-based combination therapies (ACTs) for the treatment of malaria. In response to estimates that demand would reach 50 million treatments, Novartis scaled up production of its ACT drug Coartem to 30 million treatments. This involved placing orders with downstream suppliers, including farmers who grow the agricultural product from which artemisinin is extracted. Real demand for Coartem, however, came in closer to 14 million treatments, resulting in an oversupply, says Hans Rietveld, global access and marketing director at Novartis' malaria initiative. "Long-term forecasts have proven to be very unreliable," says Rietveld, "because of uncertainties around the availability of donor funding and the absorption capacity of countries to implement new first-line drug policies. It is especially challenging for a product such as Coartem which originates as an agricultural compound and requires a 14-month production process."

In addition to helping manufacturers allocate resources, forecasts can reassure national decision makers about funding commitments and encourage policies that scale up adoption of available treatment or preventive interventions. Such forecasts may be helpful to national finance ministers, for example, who may be reluctant to make commitments even when donors pledge to provide funding for the first five years. "The finance ministers are worried about year six," says Jarrett.

Forecasts for emerging products

Demand forecasts for products that will be ready for introduction into developing markets in the near future can help developers/manufacturers decide to enter a market that they might not have previously considered. Without confidence in demand, vaccine developers and manufacturers may not attempt to market their products in developing nations. Even if they do, a lack of confidence may foster caution and production of fewer doses, which will then command higher prices. The result is a "vicious cycle" of demand uncertainty, inadequate supply, and high prices.

A credible demand forecast, however, could provide incentives for industry to enter markets in developing countries, which historically have implemented vaccinations 10-20 years after their introduction to wealthy nations. With this goal in mind, PneumoADIP created a near-term forecast based on the number of children that could be vaccinated in a few select countries using the existing public health infrastructure. While hundreds of millions of children are in need of pneumococcal vaccines in developing countries, PneumoADIP arrived at a demand forecast of about one to three million doses of the existing version of the vaccine that could be delivered over the next three years. "For the manufacturer, that was doable, whereas a needs forecast of 300 million doses was not," says Angeline Nanni, director of vaccine finance and supply for the PneumoADIP.

Starting small, Nanni hopes, will enable the demonstration of the health impact of a pneumococcal vaccine and lay the foundation for the introduction of future vaccines with broader serotype coverage. "If we can accomplish this," says Nanni, "we will have accelerated the introduction of a new vaccine in developing countries by 7-10 years and saved lives sooner."

Long-term vision

While demand forecasts clearly provide benefits for the introduction into developing markets of existing products like Coartem and emerging products like the pneumococcal vaccine, they can also benefit health care products that are in research or early development.

Demand forecasting and scenario building require epidemiological information as a starting point but additionally require identifying potential target populations, estimating the likelihood that each group will use the product based on its actual or likely characteristics, surveying the availability of funding and the projected or available amount of the product, and finally, calculating the number of doses needed at a given time and for a given country or region. In the case of scenario building, researchers must specify potential future states of the world to analyze how demand might change given a particular set of assumption about the future.

For these health care products, demand assessment and scenario building allow one to identify and pre-empt potential barriers to future demand. From the perspective of public-private partnerships like IAVI and PATH, the goals are to produce health technologies that are appropriate for their intended settings, promote policies that accelerate R&D, and maximize the breadth and speed of access to forthcoming vaccines and pharmaceuticals.

Demand scenario specification can be used to assist development of an 'access strategy' for new health care products. By identifying the most significant drivers of demand, these organizations can plan to influence these drivers to maximize access to new vaccines for those who need them most.

Through consultation with national stakeholders and individuals working in developing countries, demand scenario assessments can uncover potential social and psychological barriers to seeking or receiving a vaccine or other health intervention due to misinformation, cultural stigmas, or beliefs. Having revealed such issues, PPPs and outreach organizations can plan educational and social marketing interventions that might facilitate vaccine or pharmaceutical uptake.

Understanding the possible scenarios for the uptake of a new vaccine or other healthcare product can aid in advocacy as well. PPPs and NGOs can use the demand forecast to advocate about the need for the vaccine to policymakers and donors. "It allows us to talk about the level of investment required and the social impact the vaccine will have," says Patricia Roberts, senior officer for commercialization and corporate partnerships at PATH's Malaria Vaccine Initiative.

This is important for products that are already on the market, but even more important when considering long-range planning for products in early stages of development, such as an AIDS vaccine. "I don't think [a demand forecast] will give you particularly robust market values but I do think that it can help identify key drivers of demand," says Saul Walker, executive director for global public policy at the International Partnership for Microbicides.

Understanding key drivers of demand and possible future scenarios serves as a basis for program planning aimed at accelerating both the development and introduction of long-range vaccines because it will identify barriers to delivery and enable organizations to target needed areas, whether those be technical assistance, training, education, communication, or improving access to health care.

A developer perspective

For all these reasons, the efforts by PPPs and NGOs are promising. Forecasts and assessments for long-range products will contain more uncertainty than near-term ones but as vaccines move closer to market that variability will decrease. "Slowly we are closing the gap towards something that was shaky 10 years ago to a forecast that makes sense," says Rudi Daems, executive director of policy and corporate affairs at Chiron Vaccines. "This is credible, feasible, this is something that will match reality."

Understanding demand drivers in developing country markets can assist researchers in managing the portfolio of research projects. For example, if a robust demand assessment illustrated that demand would be high even for a vaccine with a low duration of protection in important markets, then this will have profound implications for decisions of those conducting and managing research.

A realistic estimate of future market may also spur producers/manufacturers to enter new markets and make investment decisions based on the size of the market opportunity. "One of the things that pharmaceutical companies cite as a reason for their reluctance to serve the developing country markets is the risk associated with poor demand forecasts," says Ruth Levine, director of programs and a senior fellow at the CGD.

Mark Feinberg, vice president for policy, public health and medical affairs at Merck Vaccines, thinks that vaccine demand scenario analyses conducted by PPPs and NGOs are useful in raising the level of discussion of how to implement vaccines in developing countries. "The demand assessment is an essential component of the development process. If these are done in an expert way, a transparent way, they can provide valuable information. They are not necessarily a substitute for an analysis that industry would develop itself, but they would benefit industry by gathering information on how product profiles would influence demand."

AIDS vaccine scenario building

For an AIDS vaccine, some of the specific variables will be the target population-which could be a certain age group or vulnerable populations such as intravenous drug users (IDUs) or commercial sex workers-and vaccine characteristics, including efficacy, number of inoculations needed to achieve protection, duration of protection, and price.

Three global demand assessments have been conducted for preventive AIDS vaccines, each with differing assumptions about the vaccine and its uptake. The latest, which was conducted by the WHO, UNAIDS, and IAVI, found that while the need was potentially 700 million doses, uptake of the vaccine would be only 20% for a vaccine with low- to moderate-efficacy and 40% for a highly effective vaccine. "A vaccine with low- to medium-efficacy will be acceptable in countries with high incidence and prevalence, and will be used to target specific populations," says Saladin Osmanov, coordinator of the joint WHO-UNAIDS HIV Vaccine Initiative.

How each country will adopt a preventive vaccine will hinge on the pattern of HIV incidence and prevalence in each country amongst many other factors. In Brazil the epidemic is concentrated in men who have sex with men and IDUs, so any vaccine would probably be deployed within such populations first. "To ensure that the vaccine has most effect," says Osmanov, "each country will have to develop its own vaccine strategy."

The WHO-UNAIDS-IAVI demand assessment was accomplished by staging workshops that brought together groups of stakeholders from various regions around the world. The stakeholders were asked, given a set of hypothetical vaccine characteristics, how widely they would adopt such a vaccine. With current vaccines now in clinical trials uncertainties exist around the level of efficacy, the number of doses required per course, the price, and the delivery cost. Demand will be sensitive to all of these factors.

IAVI is now taking a more in-depth look at demand assessments. In consultation with Boston Consulting Group IAVI is developing a flexible and dynamic framework that can be continually updated. "As the state of AIDS vaccine research progresses, data input quality will improve and, correspondingly, our understanding of the determinants of demand will evolve," says Gian Gandhi, manager of policy research and analysis at IAVI. "It is not a one-off answer or number that we want to generate but an ongoing process of scenario building and refinement."

The new effort will place a greater emphasis on how stakeholder preferences change in relation to the drivers of demand than did the WHO-UNAIDS-IAVI effort, which focused mainly on country needs. To better understand patterns of vaccine adoption across countries, IAVI will look at previous rollouts of vaccines such as for hepatitis B virus. The recently approved human papilloma virus (HPV) vaccine may also offer lessons on rolling out a vaccine targeted at adolescents and adults, assuming this would be the population in which an AIDS vaccine would be used. Another proxy measure of adoption might be the levels of coverage that have been achieved by countries involved in the WHO's 3 x 5 initiative. IAVI will also look at how well individual countries are able to deliver existing AIDS programs and whether any countries are conducting AIDS-related clinical trials since adoption is often quickest in regions where trials have been conducted.

By identifying the factors that influence introduction in each country IAVI hopes to learn which of these can be influenced to facilitate more rapid adoption. "We are using our best guesses for what a future vaccine will look like to predict how the world might respond to its availability," says Gandhi.

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*Catherine Zandonella, MPH, is a freelance writer whose work has appeared in Nature and New Scientist.