What We’re Hearing: Potential Pull Mechanism Use Cases for High-Value Global Health Innovation

At CGD, we’ve long argued that pull mechanisms—while no panacea—are underused relative to their potential role in helping drive global health innovation. Previous CGD efforts have explored potential applications for pneumococcal vaccines, TB treatments, and, most recently, tools like vaccines and therapies to fight the COVID pandemic. But we think there’s still untapped potential out there—so last October we asked our readers to weigh in on promising opportunities for pull mechanisms to help drive high-value global health innovation.

We started with a wide-net horizon scanning exercise, consulting the literature and soliciting expert opinion among international bodies/funders, biomedical researchers, philanthropists, and economists, among others. Ultimately, we’ll zero in on three specific use cases that could serve as promising avenues for exploration and investment, with a particular focus on the US government’s potential participation (stay tuned!). For now, we’re pleased to offer a sneak peek: our interim findings, with great gratitude to the 25+ individuals and groups who took the time for a conversation.

Big Picture: Global Health Still Needs Biomedical Innovation

Stakeholders across disease areas, organizations, and disciplinary perspectives agreed on one high-level message: despite recent biomedical innovations and significant progress addressing the global disease burden, we still need new tools to effectively address our most pressing global health challenges.

At a high level, COVID-19 has brought increased attention to the potential of innovation and related issues—manufacturing capacity, incentives, regulatory environments, and research pipelines—but it has also sucked the oxygen from other global health priorities. The situation is complex. Some health areas, such as HIV, have seen consistently large investments in research and development (R&D) which may now be at risk; others, like neglected tropical diseases (NTDs) and pandemic readiness, consistently fail to attract significant commercial interest. Then there are non-communicable diseases, like cancer and diabetes, where effective therapies exist but remain unaffordable and/or otherwise inaccessible to most in low-and middle-income countries (LMICs), and where new, better adapted interventions may be needed to ensure access for all.

On the Agenda: Promising and Necessary Innovations for Global Health

New and better antimicrobials are high on many stakeholders’ agendas as they are needed to address antimicrobial resistance (AMR), fight long-time global health scourges (TB), and prepare for the next pandemic. The need for greater innovation in the antimicrobial R&D pipeline is clear and well-documented (see, for example, here, here, and here). New drugs are necessary to counter a broad range of pathogens (including viruses, fungi, and protozoans—not  just bacteria). The social value of effective, multipurpose antimicrobials can be enormous; consider, for example, a counterfactual where effective multi-use antivirals were approved and stockpiled in January 2020.

But treatments for pathogenic diseases are only as useful as the diagnostic tools that catch such diseases. Better, faster, and more accessible diagnostic tools across health areas—both infectious and noncommunicable—formed another common thread across stakeholder conversations. Standard of care for TB, for example, involves a blood, sputum, or skin test, all of which require either sending results to a lab or multiple visits to a healthcare facility. A rapid point-of-care diagnostic for tuberculosis could be a gamechanger, as the diagnostic gap for TB is currently quite significant. Ensuring people who have active TB infections receive a timely diagnosis and access to treatment is also important for curbing drug-resistant TB. Other promising examples include a rapid diagnostic for childhood pneumonia and a multi-pathogen diagnostic platform.

Some health areas where investments have been consistently lacking include NTDs (they’re called “neglected” for a reason!). Developing a single-dose cure for African sleeping sickness or an effective treatment for leishmaniasis, for example, could generate enormous social returns. Innovations in TB prevention, diagnosis, and treatment are also sorely lacking; relative to HIV and malaria, there is also no comparable effort to develop a vaccine for TB. In the reproductive and sexual health space, non-hormonal and male contraceptives could be transformative, if drug developers made the requisite investment.

At the other end of the R&D pipeline, access remains a persistent challenge. NCD diagnostics and therapeutics such as insulin, dialysis, and cancer care, for example, are available to most people across Europe and North America (with the partial exception of the United States) but inaccessible and unaffordable to many LMIC populations. Mental and neurological disorders comprise another area of huge unmet need; diagnostic services and access to medicines for anxiety and depressive disorders, for example, remain limited outside of HICs. The innovation agenda here for such issues is two-fold: both to make existing products more accessible in LMICs, and to develop new and more affordable/appropriate approaches for care in LMIC settings.

At the frontier, many pointed to digital tools, digital health, and patient-led care as promising avenues to help streamline service delivery and improve access. A greater range of self-testing tools—now common for COVID-19, but also viable for HIV and hepatitis C, for example—could similarly transform the service delivery landscape. Some also highlighted multipurpose tools, like broad spectrum antimicrobials, pan-influenza or -coronavirus vaccines, or new applications for the mRNA vaccine platform and monoclonal antibodies, as potential game changers.

One note of caution: we want to be clear that these are not necessarily the most important innovations, nor the highest priority health challenges. Our search and analytic approach were not powered to make definitive judgments of that sort—merely to source promising innovations that might be both viable and valuable.

Beyond Innovation Gaps and Toward the Application of Pull Mechanisms

Our conversations suggested a wide range of familiarity with and enthusiasm for pull mechanisms as a tool to drive global health innovation. Global health stakeholders were most familiar with advance market commitments (AMCs, e.g., by Gavi for pneumococcal disease) and volume guarantees (e.g., Bill & Melinda Gates Foundation for contraceptive implants), but had mixed perceptions of their effectiveness. Many seemed more receptive to “non-traditional” pull mechanisms, including prizes, priority review vouchers, subscription models, milestone payments, and advance purchase agreements, especially if complemented by targeted “push” investments upstream. Enthusiasm was generally highest for health areas perceived as global public goods with high relevance even in high-income countries—antimicrobials, pandemic preparedness and response, and diagnostics/surveillance—and lower for those perceived as primarily relevant to LMICs, like NTDs—where many stakeholders appeared to favor a continued push/grant funding approach.

Regardless, any pull mechanisms must be highly context-specific, supported by an enabling ecosystem, and carefully designed to avoid perverse unintended outcomes. Our conversations highlighted several top-of-mind design considerations:

• How do we ensure access considerations are incorporated early in the R&D pipeline, and directly addressed within any pull mechanism design?

• Are health systems ready and fit-for-purpose to deploy the targeted innovation? And if not, can investments in system strengthening/adaptation now ensure appropriate and timely regulatory review plus readiness upon regulatory approval?

• How does pull mechanism design reflect the stage of development within the R&D pipeline? Should pull mechanisms be used to drive drug discovery–and if so, how? Or exclusively used for later-stage commercial development? How does the pull mechanism fit within the entire R&D pipeline–from drug discovery to clinical development and commercial deployment?

• How do we design evaluation/assessment criteria against the target product profile (TPP) that are sufficiently clear/predictable to drive investments, but also sufficiently adaptable/flexible to accommodate an ever-shifting innovation landscape?

• How do we ensure direct and meaningful participation from affected communities and the health workforce in product specification–which is essential to ensure the innovation actually responds to local needs?

• How do we set and design the incentive level? How do we balance the risk of “over-paying” against the risk of innovation failure/benefit of the target innovation–and how should “over-payment” be defined in context? Would required remuneration be lower/different for different kinds of innovators (e.g., SMEs versus “big pharma”), or LMIC-based companies versus those based in HICs?

What’s Next

We’re now entering the final phase of this initiative, where we’ll build out investment cases for pull mechanisms to drive three promising innovations—with a particular focus on the potential role of the US government. Our selection is not a competition for the three “best” innovations, but instead aims to reflect a range of potential designs/health areas while also considering feasibility and potential social value. In the coming months, we will also share a more detailed read-out from the horizon scanning exercise related to the broader innovation landscape.

Stay tuned!

We are grateful for the contributions and suggestions of stakeholders consulted for this work. All consulted organizations will be acknowledged in the final report.