To attain and sustain universal health coverage, we must harness the power of healthcare innovation. But it’s hard to do so when in many settings, these innovations do not align with local priorities. Many countries around the world still lack effective solutions to fight a plethora of diseases, leading to an often disproportionate health and economic burden on the poorest and most vulnerable communities. Some of the most cost-effective interventions available (e.g. Haemophilus influenzae type b (Hib) conjugate vaccines), go vastly underused for a multitude of reasons, including unaddressed research gaps to support decisions about value in local settings. As a result, globally there remains a substantial but otherwise avoidable disease burden that yields considerable suffering.
Research and development (R&D) is likely to have the most impact when it aligns with the a country’s priorities, which can help avoid a mismatch between the characteristics of new technologies and those features that are considered important to drive local uptake. In this blog we explore how country priorities and technical innovation can go hand in hand – creating potential for a “win-win” scenario. We outline the importance of evidence-based approaches in achieving this, and emphasize the role of early stage health technology assessments.
For product developers, the mismatch between new technology and local priorities and engagement, can waste time and resources and significantly reduce the potential for increased returns, as, for example, when manufacturers don’t see an adequate return on their investment in particular jurisdictions. For countries left without the appropriate health intervention to meet their needs, this can also be costly, both in terms of health and economic outcomes. In 1998, GlaxoSmithKline’s (formerly SmithKline-Beecham) LYMERix was marketed as the world's first vaccine to prevent Lyme disease, but poor sales lead to its withdrawal from the market in 2002. Though there are several perceived factors associated with its discontinuation, a vague target population played a part in its downfall. Better insight into a country’s priorities could help manufacturers determine an appropriate target population for a product to maximise its uptake.
So, what exactly are these priorities? Unsurprisingly, they depend on the context in question. In the case of vaccines, decision-makers confront multiple considerations when implementing vaccination policy, including, among others, disease burden, equity, cost, coverage, availability of vaccine supply, and programmatic considerations. In reality, some factors will be more important than others. For instance, in a country with a large community health volunteer work force, ease of administration may be a crucial factor behind a vaccine introduction decision. Yet there is no explicit methodological approach for communicating country decision-making criteria to manufacturers in order to inform the R&D agenda.
Making novel use of existing tools to “bridge the gap”
A recent publication that some of us co-authored (“‘It takes two to tango’: Bridging the gap between country need and vaccine product innovation”) discusses a proof-of-concept pilot study conducted by Thailand’s Health Intervention and Technology Assessment Program, the National University of Singapore, and the World Health Organization, that tested an approach in Thailand to reduce the disconnect between manufacturers and country decision-makers (Thailand was one of four countries studied). Capacity-led Assessment for Prioritisation on Immunisation (CAPACITI), originally named Total Systems Effectiveness (TSE) at the time of the study, aims to characterise preferred vaccine product attributes (e.g., number of doses, efficacy, duration of protection, vaccine schedule) from a country perspective to inform the research and development of upcoming and existing vaccines.
While the CAPACITI approach might seem novel, in reality it pulls together existing concepts such as “early health technology assessment (HTA)” and multiple-criteria decision analysis (MCDA). Early HTA involves systematically assessing the value of vaccine candidates in the pipeline, whereas traditional HTA evaluates existing products on the market. Typically, economic analysis is incorporated as an integral part of HTA. Quantitative MCDA evaluates decision alternatives and, as the name might suggest, it can formally capture multiple dimensions of value (including cost-effectiveness) in one single metric. In MCDA methodology, quantitative weights are explicitly allocated to different criteria to represent the relative importance of each criteria to stakeholders. It is used as a tool to help navigate trade-offs through quantifying stakeholders' priorities.
The study used an Excel-based model to analyse the trade-offs of multiple criteria using five hypothetical rotavirus vaccine products. During a consultation with stakeholders including representatives from the Ministry of Public Health, academia, and industry, their perspectives on the criteria for vaccine introduction decisions were elicited (safety, health impact, budget impact, delivery cost, and cost-effectiveness), with the stakeholders nominating their top criteria through an open-ended questionnaire. We inputted Thailand-specific data gathered from government databases, published studies, key informant interviews, and grey literature into the model.
We then used sensitivity analysis to identify which vaccine characteristics could influence the ranking of vaccine products against the five decision criteria. Within this proof-of-concept exercise we were able to identify preferred vaccine attributes of pipeline products that were important to the Thai stakeholders consulted. Given an array of vaccine characteristics (relative risk of intussusception, number of doses, vaccine efficacy, duration of protection, and commodity cost), the rankings of individual vaccines could shift depending on whether likely input values were used, or scenarios were chosen that reflected a “best-case” situation (see Table 1). We believed that such information would be key to steering future product development in order to maximise public health gains whilst simultaneously benefiting manufacturers by de-risking investment.
Table 1. Sensitivity analysis to identify significant vaccine characteristics for making a hypothetical rotavirus vaccine product (RVV-2) the highest ranked vaccine out of five alternatives.
There were limitations to the approach used. For instance, the model used in the Thailand pilot was data-intensive, raising questions around the applicability of the methods to settings grappling with data challenges. This shortcoming has been important in the further development of CAPACITI, which now seeks to support a more flexible approach.
Early HTA and COVID-19
As COVID-19 ravages the world, it is hard to escape discussions of an upcoming COVID-19 vaccine. With as of yet no highly effective treatment for COVID-19, much rests on the development of a COVID-19 vaccine, and, as importantly, on selecting and rolling out a vaccine appropriately, as there may be multiple vaccines available and decision-makers face complicated implementation decisions. A previous CGD blog discusses how early HTA can help countries prepare for a COVID-19 vaccine becoming available, arguing that early HTA can accelerate vaccine utilisation by communicating to manufacturers those vaccine attributes that are preferred in a given setting. Additionally, the authors maintain that early HTA can support implementation planning (e.g. determining priority groups) and price negotiations in the context of COVID-19 and beyond. The CAPACITI experience highlighted that, unlike Thailand, many countries across the world lack HTA mechanisms for reimbursement decisions. Before early HTA can be used to inform research and development, efforts are first needed to sensitise users and practitioners to HTA approaches more generally, and build capacity for evidence-informed decision making in these settings.
For increased vaccine coverage and uptake, decision-makers and manufacturers need to both shoulder the burden and work collaboratively; as the paper puts it, “it takes two to tango.” Whilst the concept of CAPACITI is still in its development phase, the pilot study demonstrates its potential to help bridge the gap between country demand and vaccine research and development.
Many thanks to Saudamini Dabak and Chris Painter for supporting the writing of this blog.