BIO Ventures for Global Health

Purpose: This paper formulates a new theoretical framework to address the principal-agent problem in representative democracy through a dynamic voting mechanism. Based on Rousseau’s concept of the general will and contemporary analyses of corporate influence in politics, I build a rigorous mathematical model that enables voters to maintain continuous oversight over their elected representatives. Design/methodology/approach: I developed a rigorous mathematical model integrating an anonymous blockchain-based voting system. This system allows voters or voter groups to continuously monitor their representatives while preserving their privacy through zero-knowledge proofs. The model uses game theory and extends Condorcet’s Jury Theorem to analyze voter behavior under dynamic oversight conditions. Findings: The results show that such a system can encourage a more responsible form of representative democracy while maintaining electoral stability. Detailed implementation architectures show that the model is not only theoretically rigorous but also practically feasible through advanced cryptographic tools. Practical implications: The proposed architecture enables real-time voter engagement without compromising privacy, providing a blueprint for secure, transparent, and scalable voting systems applicable in modern democratic systems. Originality/value: This research combines political theory, cryptographic system design, and social choice theory to propose a new paradigm for democratic governance. The integration of zero-knowledge proofs with dynamic feedback mechanisms offers a scalable solution to fundamental challenges of voter privacy and election integrity, with far-reaching implications for democratic theory and its practical application.

Abstract Background: To address the need for a skilled workforce in breast cancer (BC) pathology in sub-Saharan Africa (SSA), we implemented an education program to train laboratory technicians in manual immunohistochemistry (IHC). Methods:A cross-sectional quality improvement education project was developed. Interactive webinars were held every six months with didactics and presentations from African experts with experience in IHC. We conducted knowledge assessments and surveys on current practice, equipment, and human resources. A digital mentorship platform (DMP) was created for discussions, sharing SOPs, and networking. For one year (2022-2023), we followed developments in pathology capacity, practice changes, and educational needs. Results: 266 participants from 10 SSA countries attended the first webinar, a series of six lectures on IHC theory, methods, and practice. 95 participants from nine SSA countries provided a baseline assessment of pathology capacity and feedback. Mean knowledge increased by 17.4% (from 41.8% pre-webinar to 59.2% post, p=<0.0001). Self-reported confidence in topics increased by 11.3% (mean 3.36 pre- to 3.74 post, p=0.1). Over six months, recordings were accessed 412 times. After six months, the second webinar had 93 participants from eight SSA countries. Membership in the DMP increased from 64 to 172; recordings were viewed 412 times in six months; and 113 participants from nine SSA countries completed surveys. Among 74 respondents who perform IHC, 43.5% reported moderate or significant positive practice changes such as improved antigen retrieval techniques and optimization of preanalytical variables. The majority (52.7%, n=39) reported the quality of slides had moderately or significantly improved. After one year, a third webinar had 98 participants from eight SSA countries. Thirty-eight completed surveys, DMP membership increased to 199, and 1 reported launching IHC in a lab in Nigeria. Conclusions: Our program 1) reached hundreds of participants and provided a baseline assessment of pathology capacity across nine SSA countries; 2) created a novel mechanism to build pathology capacity and assess progress with this cohort; and 3) improved practices and the preparation of slides for the majority performing manual IHC. After one year, interest was sustained. Tracking impact on diagnosis and treatment of BC in the region is needed long-term.

Understanding past successes in reaching unvaccinated or "zero-dose" children can help inform strategies for improving childhood immunization in other settings. Drawing from positive outlier methods, we developed a novel approach for identifying potential exemplars in reducing zero-dose children. Focusing on 2000-2019, we assessed changes in the percentage of under-one children with no doses of the diphtheria-tetanus-pertussis vaccine (no-DTP) across two geographic dimensions in 56 low- or lower-middle-income countries: (1) national levels; (2) subnational gaps, as defined as the difference between the 5th and 95th percentiles of no-DTP prevalence across second administrative units. Countries with the largest reductions for both metrics were considered positive outliers or potential 'exemplars', demonstrating exception progress in reducing national no-DTP prevalence and subnational inequalities. Last, so-called "neighborhood analyses" were conducted for the Gavi Learning Hub countries (Nigeria, Mali, Uganda, and Bangladesh), comparing them with countries that had similar no-DTP measures in 2000 but different trajectories through 2019. From 2000 to 2019, the Democratic Republic of the Congo, Ethiopia, and India had the largest absolute decreases for the two no-DTP dimensions-national prevalence and subnational gaps-while Bangladesh and Burundi registered the largest relative reductions for each no-DTP metric. Neighborhood analyses highlighted possible opportunities for cross-country learning among Gavi Learning Hub countries and potential exemplars in reducing zero-dose children. Identifying where exceptional progress has occurred is the first step toward better understanding how such gains could be achieved elsewhere. Further examination of how countries have successfully reduced levels of zero-dose children-especially across variable contexts and different drivers of inequality-could support faster, sustainable advances toward greater vaccination equity worldwide.

As COVID-19 strained health systems around the world, many countries developed or adapted digital health tools to detect and respond to the novel coronavirus. We identified transferable lessons from an assessment of implementation factors that led to the rapid launch and scale-up of eight digital tools in low- and middle-income countries during the COVID-19 pandemic. These lessons should inform the development of digital health tools to support public health objectives such as the Sustainable Development Goals. Using the mHealth Assessment and Planning for Scale Toolkit, we assessed the implementation of eight digital tools through desk research and stakeholder interviews. Three core lessons emerged from our findings: (1) user-centered design is key to the widespread adoption of digital tools; (2) strong, country-led partnerships are essential for scaling up and sustaining digital tools; and (3) using adaptable digital tools enables implementers to focus on the content of the solution rather than the technology. Lessons learned from implementing and adapting digital tools quickly during the COVID-19 pandemic can inform the use of digital tools for additional health applications, such as bolstering primary health care, reaching vulnerable and marginalized populations, and empowering health workers with the real-time information necessary to optimize their work and improve the health of their target populations. Future efforts should focus on robust monitoring and evaluation of digital tools and sustainable financing models.

Data silos are proliferating while research and development activity explode following genetic and immunological advances for many clinically described disorders with previously unknown etiologies. The latter event has inspired optimism in the patient, clinical, and research communities that disease-specific treatments are on the way. However, we fear the tendency of various stakeholders to balkanize databases in proprietary formats, driven by current economic and academic incentives, will inevitably fragment the expanding knowledge base and undermine current and future research efforts to develop much-needed treatments. The proliferation of proprietary databases, compounded by a paucity of meaningful outcome measures and/or good natural history data, slows our ability to generate scalable solutions to benefit chronically underserved patient populations in ways that would translate to more common diseases. The current research and development landscape sets too many projects up for unnecessary failure, particularly in the rare disease sphere, and does a grave disservice to highly vulnerable patients. This system also encourages the collection of redundant data in uncoordinated parallel studies and registries to ultimately delay or deny potential treatments for ostensibly tractable diseases; it also promotes the waste of precious time, energy, and resources. Groups at the National Institutes of Health and Food and Drug Administration have started programs to address these issues. However, we and many others feel there should be significantly more discussion of how to coordinate and scale registry efforts. Such discourse aims to reduce needless complexity and duplication of efforts, as well as promote a pre-competitive knowledge ecosystem for rare disease drug development that cultivates and accelerates innovation.

PURPOSE Cancer now kills more Africans than malaria. Without intervention, the number of cancer deaths in Africa is projected to double by 2040. BIO Ventures for Global Health (BVGH) launched the African Access Initiative (AAI) to address Africa’s cancer crisis by establishing sustainable access to cancer medicines. Through AAI, BVGH and the Ahmadu Bello University Teaching Hospital (ABUTH) are piloting a first-of-its-kind program focused on improving Nigeria’s access to affordable, gold-standard cancer drugs manufactured by multinational pharmaceutical companies. METHODS BVGH, the Federal Ministry of Health, and Nigerian oncologists held a stakeholder meeting to prioritize cancers and their associated drugs. After the meeting, pharmaceutical companies were invited to submit proposals outlining the terms by which the prioritized drugs could be made available. In parallel, Nigeria’s regulatory agency, the National Agency for Food and Drug Administration and Control, was engaged to discuss expediting its review and approval of priority drugs. RESULTS Forty-one priority cancer drugs covering 8 of Nigeria’s most prevalent cancers were selected for this program. Requests for proposals were sent to 14 multinational pharmaceutical companies. Companies responded with deeply discounted access prices, the majority of which were more affordable than cancer drugs available through ABUTH’s current procurement structure. On the basis of the companies’ proposed prices, BVGH crafted a budgeting tool tailored to the cancer treatment protocols offered at ABUTH. Using this tool, ABUTH, together with 7 northern Nigerian teaching hospitals and under the leadership of Ahmadu Bello University, calculated the number of patients they could treat and drug quantities they could purchase with their current budget. The relevant funds will be placed in an externally managed escrow account to ensure oversight of the drug procurement process. BVGH is working with the pharmaceutical companies and National Agency for Food and Drug Administration and Control to hasten approval of priority drugs. CONCLUSION The AAI drug access model is not donation based. Instead, it is an innovative, demand-driven program that is uniquely positioned to ensure affordable and sustainable access to cancer drugs in Africa.

PURPOSE Cancer now kills more Africans than malaria. Despite this statistic, Africans remain drastically underrepresented in cancer clinical trials. BIO Ventures for Global Health (BVGH) launched the African Consortium for Cancer Clinical Trials to foster cancer clinical trials involving African populations by assessing, profiling, and building clinical trial capacity in African hospitals. METHODS BVGH developed a checklist tool for hospitals to self-assess their current clinical trial capabilities and compare these capabilities with those that are essential for performing trials at international standards. The checklist evaluates a site’s metrics across 6 categories: clinical trial experience, regulatory processes, staffing, cancer diagnostic and treatment capabilities and equipment, pharmacy management, and research management systems. The checklist was distributed widely across Africa. Any interested site, regardless of its ability to treat patients with cancer, was invited to complete the self-assessment. RESULTS To date, BVGH has received checklists from 40 institutes, of which, 34 offer cancer treatment services. These institutes are distributed across 16 countries and are composed of public and private hospitals, universities, and nonprofit research institutes. Of the sites assessed, more than 85% had performed a clinical trial in the past, with drug studies being the most commonly performed trial. Sites frequently had research coordinators, nurses, and data managers on staff, whereas biostatisticians, database programmers, and epidemiologists were the most commonly unavailable personnel. Whereas the majority of the sites’ laboratories were accredited, fewer than half had the equipment needed for clinical research. More than 70% of the sites had the necessary pharmacy infrastructure, whereas 60% had the requisite research management systems. CONCLUSION With Africa’s cancer mortality rate predicted to double by 2040, more cancer clinical trials must be performed in Africa. Our assessments reveal African institutes’ common areas of strength, as well as opportunities for improvement. Of importance, our results demonstrate that Africa can perform cancer clinical trials.

IntroductionThe recent failure of several late‐stage Alzheimer's disease (AD) clinical trials focused on amyloid beta (Aβ) highlights the challenges of finding effective disease‐modifying therapeutics. Despite major advances in our understanding of the genetic risk factors of disease and the development of clinical biomarkers, and that not all Aβ‐based approaches are equivalent, these failures may engender skepticism regarding the value of the AD pipeline.MethodsTo investigate these concerns, we compiled a database of current Phase 2 and 3 trials based on disease‐modifying targets through a query of the National Institutes of Health's ClinicalTrials.gov. We then assessed the financial value of the pipeline. Financial modeling utilized risk‐adjusted net present value (rNPV) measurements and included sensitivity analyses to help inform the drug development process.ResultsResults indicate that the preponderance of current Phase 3 trials were indeed targeting Aβ, with only 15% addressing other targets. In contrast, the pipeline of Phase 2 trials was more diverse. The estimated rNPV of Phase 2 and 3 therapeutics was estimated to be $338 billion over 10 years. This figure increased to a theoretical cumulative value of $788 billion when incorporating the assumption that diagnostics will be developed to identify individuals at high risk for developing AD. Results from model sensitivity analyses showed that speed of market penetration and patient access contributed the most weight to financial value. In contrast, decreasing drug development costs had minimal impact on rNPV.DiscussionThese findings argue in favor of conducting thorough biomarker‐driven Phase 2 proof of concept studies to avoid prematurely advancing assets into Phase 3. Insights from these analyses are also discussed in the context of the financial ecosystem needed to maintain a healthy AD pipeline.