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Abstract
Advancements in research and development (R&D) have the potential to address pressing global health challenges. However, numerous barriers hinder innovation and access, particularly in areas of market failure, and there is an absence of a cohesive consensus on defining these various impediments. This paper presents a framework identifying the barriers that impede global health innovation and hinder equitable access to health technologies.
The framework presents clear typologies of barriers across global health R&D thematic areas. These include the market failures that require R&D incentives to stimulate innovation, how the complexity of product registration hinders access within specific regulatory domains and how health system implementation issues prevent affected populations from accessing the tools they require. Current and historical examples are provided for each end-point, and three case studies explore key barriers and how solutions have or may be applied.
This analysis contributes by adding to the body of knowledge on global health R&D and provides an analysis tool to policy-makers, researchers and stakeholders involved in addressing the barriers and promoting equitable access to healthcare innovations. The framework serves as a practical tool to guide future research, policy development and implementation efforts towards achieving sustainable global health outcomes.
- Vaccines
- Diagnostics and tools
- Health systems
- Health policy
- Public Health
Data availability statement
All data relevant to the study are included in the article or uploaded as supplimentary information.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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Summary box
There is no existing cohesive or commonly accepted characterisation of innovation and access to medicines issues.
This paper presents a framework identifying the simultaneous barriers that may prevent affected populations from using important health technologies.
The framework is intended for use as a problem-identification tool to assist in the deliberations of policy-makers, funders, product developers and other institutions contributing to the improvement of global health research and development.
Further work can help refine the framework for use as a practical tool including identifying and mapping proposed solutions and conducting analysis on how proposed solutions interact with identified barriers.
Introduction
Global health efforts around the provision of health technologies aim for affected populations to have access to quality-assured products that are effective, safe, affordable and available for all. Separate frames within global health research and development (R&D) are commonly used to analyse the barriers that prevent the equitable development, production and delivery of health technologies,1 where:
Innovation: Focuses on solving the market failure that exists as a result of the inability of affected populations and their health systems to incentivise the development, production and registration of the health technologies they need.
Access: Focuses on the ability of those affected to use existing products—with the criteria for access commonly broken down as availability, accessibility, affordability, acceptability and quality assurance.
Analysis within a single frame fails to properly account for the complex set of interactions that differentially affect innovation and access. Mechanisms or levers used to achieve positive outcomes when viewed within one frame may negatively affect outcomes in the other—and the benefits and burdens of each frame differ for individual stakeholders.2 3
What is clear and self-evident to specific stakeholders around their thematic area/s is not the case across the range of interdisciplinary global health R&D stakeholders. There is a need to create cohesive typologies of barriers, due to recent shocks in R&D ecosystems, such as COVID-19, which have highlighted previously unknown or underappreciated weaknesses and gaps. Social and political inputs have also improved or challenged global health R&D in ways that remain poorly understood or incorporated into existing analyses. These shifts include the ability of social media advocacy efforts to rapidly improve bedaquiline access outside of the traditional global health R&D policy process4; and the expansion of restrictive policies on contraceptive and abortion access across the USA, and for sexual and reproductive health and rights (SRHR) across Central and East Africa. Additional shifts in the global health R&D ecosystem—such as the gradual expansion of Public Development Partnerships into implementation, access and advocacy work as they adapt to new challenges5—can be highlighted by having clear typologies to assist in defining an organisation’s scope of work.
By using this framework as a problem identification tool, researchers and policy-makers can gain a deeper understanding of the complex dynamics and trade-offs involved across individual thematic areas, facilitating informed decision-making and the development of effective strategies to promote innovation while ensuring equitable access to healthcare technologies through the entire continuum of global health R&D.
This paper primarily focuses on the underlying market failures that inadequately incentivise private sector market-driven innovation and access to health technologies. The initial concept for the framework started with the market failures that drive unmet needs for neglected diseases and emerging infectious diseases, but the framework is more broadly applicable though not limited to orphan diseases, antimicrobial resistance, SRHR, non-communicable diseases and mobility and disability aids. The framework uses a broad definition of global health R&D and includes the product development lifecycle from basic research through phase III and extends to phase IV postmarketing surveillance and the ongoing delivery of health technologies.
Purpose
The framework aims to map the typologies of issues within innovation and access for global health R&D to assist in developing and applying a cohesive mix of effective and prioritised solutions. It should clarify the problem identification of issues that prevent global health R&D efforts from meeting the needs of those affected.
Typologies of market failure
The analysis in this paper aims to contribute to our understanding of health areas where the existing structure of incentives inadequately motivates private sector market-driven innovation and access. This creates R&D market failures,6 primarily the result of two different factors:
Market failure due to ‘time inconsistent incentives’: Where governments desire maximal private sector investments into the development of new products in the present, with the private sector assuming some or all of the costs and risks of investment, followed by a desire for minimal purchasing costs at the point of purchase. This is aided by the ‘dominant purchasing power’ of the purchasing government agencies as well as regulatory control, further disincentivising upfront investments into global health R&D from industry and the private sector.
Market failure for ‘global public goods’: Benefits and burden trade-off, where the benefits of investment are distributed to multiple countries, providing a disincentive for individual countries to bear the burden of unilaterally driving investments into health R&D.
The factors above are major drivers of unmet global health R&D needs, despite there being no universally accepted definitions of market failure in global health R&D, and competing claims about whether gaps in neglected disease R&D, for instance, result from market failure.
Using this framework
This tool is meant to be applied using the flow chart graphic (figure 1) and framework outcomes table (table 1). The framework should explore specific health R&D needs from multiple perspectives and allow users to identify the simultaneous barriers that prevent meeting those needs. Barriers identified using the framework may be removed, modified or introduced where changes in technology, economics, public policy or social determinants shift the landscape of global health R&D. The use of the framework should highlight that several interventions may be required to resolve needs, and that progress towards sustained access for health R&D is not linear. Any application of solutions or interventions needs to incorporate identifying and solving the multiple barriers and risks that exist, and analysis should continue after an initial barrier has been identified.
Innovation and access framework diagram. R&D, research and development.
Framework outcomes
The proposed problem-identification tool is designed to assist stakeholders in enhancing global health R&D outcomes. This framework contributes to academic policy and systems analysis by offering a methodical approach to identifying areas that require additional information and evidence, thus highlighting relative gaps in our understanding of global health R&D. The framework offers insights for government policy-makers, regulatory agencies and philanthropic funding organisations—clarifying the potential areas impacted by push and pull incentives and other mechanisms. Additionally, it catalyses civil-society advocacy engagement by pinpointing areas that hold potential for advocacy and lobbying efforts, thereby empowering them to drive positive change. It further aims to support government R&D agencies and pharmaceutical product developers in navigating the complex landscape of bringing innovative products to market and ensuring their widespread availability to those in need. By complementing existing integrated product and process development plans, this framework provides a roadmap for engagement by product developers. Importantly, this framework allows stakeholders to understand the broader perspectives and narrow technical areas of global health R&D, where their efforts end and others begin, and where they may best integrate their scope of work.
Existing frameworks
A review of existing literature analysing innovation and access issues within global health R&D was conducted using PubMed between March and April 2023. The review identified 23 articles (out of 128 articles) that included analysis exploring problems, solutions and contributing factors to innovation and access (see online supplemental resource). The resources identified included in part the analysis proposed in this framework but none did so in a comprehensive manner that incorporated problem identification across innovation and access issues.
Supplemental material
Definitions of a “clear market”
Private sector-driven R&D investment decisions are primarily determined by evaluations of a return on investment derived from NPV estimates.7 Where NPV equals the sum of all investment costs in development and the expected present value of future revenues. Estimates of NPV are:
Driven by patent exclusivity.
Include the role of risk.
Include discounting of future revenues and time value of money.
Include both real or perceived NPV and difficulties in forecasting.
In the context of this framework, definitions of a ‘clear market’ are limited to private sector-driven R&D investment decision-making being able to make reliable forecasts and estimates of NPV. A clear market here does not necessarily correlate with global health needs or priorities driven by global health responses.
Information asymmetries in global health R&D
Global health R&D stakeholders operate in environments with clear information asymmetries, which in turn can influence how effective efforts are in resolving global health needs. In addition to the pricing information asymmetries identified in the framework, there are distinct issues with information asymmetry when viewing global health R&D using the principal-agent theory.50 Where private-sector-supported product developers act as agents for health systems. The disconnect between the incentives and interests of private sector agents and the health systems of affected populations acting as the principal can be viewed as a root cause of much of the conflict over the benefits and burdens of innovation and access. Solutions and incentives working towards improving global health R&D need to account for this important disconnect.
Case studies
Case study 1: outcome A: feasibility, difficulties and progress for antibiotic R&D
Innovation for global health R&D has increasingly proven difficult as scientific progress has progressively resolved ‘low-hanging fruit’ and as the focus of R&D has shifted towards investments in more complex and difficult science.8 Scientific difficulties and feasibility limit progress in the development of new antibiotic classes, broad-spectrum vaccines, diagnostics and therapeutics, as well as R&D for rare genetic diseases.
In the case of the discovery of new antibiotic classes, there are a variety of difficulties in advancing basic research and antibiotic discovery that have created an early-stage R&D pipeline bottleneck.9 There is a need for new innovative methods for antibiotic screening, beyond the Waksman platform and the screening of actinomycetes that have in recent decades failed to produce new antibiotic candidates. Innovative approaches that have been proposed include screening underexplored classes of secondary metabolite producers such as Acidobacteria and the adaptation of existing technologies within new approaches.9
Besides revamping approaches to early-stage R&D, the existing incentive landscape for antibiotic development yields unfavourable or negative evaluations of net present value (NPV) for pharmaceutical companies. Given the billions of dollars in costs associated with drug development,10 and a limited commercial market in which to recoup costs and generate profit, there is limited pharmaceutical investment in antibiotic R&D.11 To overcome the challenges in developing new antibiotics, a combination of measures are needed beyond simply asking for ‘better science’—that appropriately incentivises private sector investments while balancing antibiotic stewardship. These could involve providing additional push incentives that offer milestone rewards for early-stage research, making participation in early-stage R&D more attractive to pharmaceutical developers. Milestone prizes of this nature may not incentivise product development through to delivery but would be targeted at improving the existing bottleneck. Progressing candidates through the problematic and riskier early /middle stages of product development could include creating market guarantees that solidify the NPV of antibiotic investment to promote pharmaceutical investment; improving the implementation of antibiotic stewardship to clarify how antibiotic use would operate once a product is approved; and expanding the scope of efforts like Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator and the European Commission’s Health Emergency Preparedness and Response initiative to include a greater emphasis on early-stage research.9
The technological barriers to scientific progress are not insurmountable and even as progress appears difficult at the moment, continued and incremental investments are needed to improve the scientific landscape over time and across different stages of the product development pipeline. This sentiment also ties into advocacy efforts aimed at adapting and improving domestic investments in the USA and EU to accelerate scientific, technological and industrial progress—a more self-interested justification to advocate for increased investments in R&D.12 13 There is also a justification for continued investment in R&D under the ‘hits-based’ giving approach favoured by philanthropic funders like Open Philanthropy.14 Efforts such as Open Philanthropy’s recently established global health R&D programme are a positive step towards resolving scientific difficulties; directing funding towards research with feasibility issues now but that require concerted effort and resources to produce a significant future benefit, even in situations where the probability of a payoff may be low.15
Case study 2: outcome B: priority review vouchers as incentives to solve neglected disease R&D market failure
Neglected tropical diseases R&D (NTD R&D) is a prime example of a global health need that requires additional R&D incentives to overcome market failures. Various push and pull incentives have been proposed and implemented, but there is limited literature available on the direction, depth and magnitude of effect of the various incentives that have been used.11 16–18 To effectively analyse the barriers and solutions for NTD R&D, it is crucial to understand how incentives drive innovation, the degree of innovation they stimulate and whether they positively impact a pharmaceutical developer’s assessment of NPV. Priority review vouchers (PRVs) have been used to promote NTD R&D, though there is limited proof that PRVs alone stimulate innovation.19 20
The ability of PRVs to improve assessments of NPV for pharmaceutical companies appears to have waned as the scarcity and value of PRVs have decreased. The sale price of a PRV has decreased to about US$100 million from a high of around US$300 million, corresponding to the expanding scope of the PRV programme and an increase in the number of target diseases that qualify for a PRV.21 Relative to the billions of dollars in estimated costs for drug development, any decrease in the sale price of a PRV is another reduction in the evaluation of NPV by pharmaceutical developers for NTD R&D.10
The degree of innovation a PRV is meant to stimulate is as important as the incentive provided by a PRV in increasing evaluations of NPV. The WHO R&D Blueprint’s product archetypes are one example of a proxy for the degree of innovation, where the registration of an existing product for a new target disease would rank lower than the development of a New Chemical Entity. PRVs appear to have stimulated a limited degree of innovation using such a gauge, as several have been issued for existing products that had not previously been Food and Drug Administration-registered for target disease use—such as the registration of benznidazole for Chagas.22
There are two distinct challenges to the implementation of PRVs as an incentive mechanism. First, there appears to be a limited ability to meaningfully improve NPV for pharmaceutical developers. Second, insufficient ability to encourage ‘blue sky’ innovation, which has meant more incremental improvements to global health R&D than may have been intended. The challenges faced in implementing incentives like PRVs extend to any intervention that aims to improve the environment of market failure and assessments of the NPV of investments in global health R&D. The inaccuracy of PRVs to achieve measurable progress for neglected disease R&D should be kept in mind with similar proposals like the transferable exclusivity voucher.23 24
Case study 3: multiple outcomes: vaccine inequality, COVID-19 and global health inequities
The inequities of COVID-19 vaccine distribution highlight the divide between the Global North and South. Vaccine inequality highlights how progress towards meeting global health R&D needs is not limited solely by innovation barriers but continues through our efforts to build and deploy equitable production, procurement and delivery systems. COVID-19 highlighted previously under-recognised gaps in vaccine access for marginalised populations globally, with procurement and delivery challenges, and issues with the transfer of vaccine production knowledge and technology. These challenges occurred in spite of or in parallel to COVAX, a global vaccine access initiative focused on preemptively securing vaccine access and distribution before the initial COVID-19 vaccines were approved.
Innovation-side global health R&D, in particular, is dominated almost entirely by Global North actors and discourse despite the efforts of the African Union and African CDC,25 and organisations such as the South Centre.26 Barriers such as resistance to North-South technology transfer reinforce the more existential issues of appropriate representation and participation in improving global health R&D.27 Key affected populations have little representation or participation in the governance and decision-making of procurement agencies and their mechanisms, with programmes reliant on donor leadership and priorities.28 Some important unanswered questions around equity and global health R&D include:
What would a more equitable R&D and procurement landscape look like?
How can the priorities and intended outcomes pursued by affected populations be better incorporated?
How can Global South efforts be bolstered at a policy, political and international level?
How can affected communities be engaged through the global health R&D process?
Are issues like the range of products and options available, and the upstream barriers and constraints, appropriately communicated to affected populations and health systems?
There are opportunities to incrementally improve equity and participation in global health research.29 Examples noted by others include:
Not excluding partners through rushed timelines or complex rules.
Encouraging cocreation with non-academic partners and end users.
Investing in equity.
There are also more implementation-focused avenues within existing global health structures to pursue new approaches and fill gaps—including the Gavi-MedAccess-GSK innovative funding agreement to guarantee RTS,S antigen production for the RTS,S/AS01e malaria vaccine ahead of WHO-Gavi policy and funding decisions,30 and GiveWell’s funding to PATH to improve the timing in which the newly approved malaria vaccine can benefit affected populations in Ghana, Kenya and Malawi.31 The post-COVID-19 negotiations on a pandemic treaty offer an opportunity for more sweeping improvements to global health inequalities, in fundamentally redesigning participation and equity, though it remains unanswered if stakeholders will be able to take advantage of this window.32
Conclusion
This framework has proposed a lens of analysis to identify and map the barriers that prevent global health R&D efforts from meeting the needs of affected populations. It is a single piece of a broader puzzle and process. Significant future work is required to improve how we investigate and understand innovation and access for global health R&D, and in how we design and deploy solutions and incentive mechanisms to solve the underlying market failures.
There are several limitations to this theoretical framework proposal. As a framework proposal, there is a finite level of practical application that can be included. In trying to synthesise analysis, the framework is inherently an oversimplification of a range of complex issues and is unable to include an in-depth analysis of all potential barriers.
Building on this framework may include improving our evidence base on the benefits and burdens of incentives and solutions, and how the existing application of solutions maps against barrier end-points identified in this framework. Further work could also focus on designing and implementing solutions that go beyond push-pull incentives—such as how to incorporate access language into grant funding and licensing contracts, or how delinkage approaches interact with the barrier endpoints. There is also limited evidence and research about the policy process for how we approach global health R&D—future work could focus on efforts such as mapping the workstreams of stakeholders against the barrier endpoints and identifying where gaps might exist across global efforts. These efforts would require a clear mapping and classification of barriers, provided by this framework, as an initial step.
Data availability statement
All data relevant to the study are included in the article or uploaded as supplimentary information.
Ethics statements
Patient consent for publication
Acknowledgments
The author would like to acknowledge the following for reviewing drafts of the framework and manuscript: Anna Doubell, Nick Chapman, Danny Edwards, Klara Henderson, Sanjana Mukherjee, George Rugarabamu and Claire Standley.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Handling editor Seye Abimbola
Twitter @mingyangong
Contributors MO conceived of the framework conceptualisation and methodology, and preparation and writing of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.