Cost-benefit analysis of a potential hepatitis C vaccine: a modelling study
Farah Houdroge, Phillip Luong, Jessica Zuk, Chris Seaman, Kelly Maynard, Heidi Drummer, Paul Zimmer-Harwood, Circe McDonald and Nick Scott (July 2, 2026), BMC Infectious Diseases, “Cost-benefit analysis of a potential hepatitis C vaccine: a modelling study“
Falling prices and wider availability of curative direct-acting antivirals, alongside global elimination commitments centred on treatment scale-up, have made the value of a hepatitis C vaccine unclear. We estimated the health impact and benefit-cost ratio of a hypothetical vaccine using a dynamic compartmental model of transmission, disease progression, and the care cascade, calibrated to 116 countries and stratified by age, sex, injecting drug use, and incarceration status. Five delivery scenarios were projected for 2026–2050, ranging from vaccinating people who inject drugs at existing testing coverage through progressively broader strategies adding scale-up campaigns, prison programs, school-based vaccination, and an adult catch-up campaign, each compared with a counterfactual offering equivalent testing and treatment but no vaccine. The vaccine was assumed to raise spontaneous clearance to 80% for a mean of five years. Across scenarios, vaccination averted 1.13–8.76 million infections and 2,490–24,100 deaths. Targeting people who inject drugs at existing coverage, via scale-up, and in prisons yielded benefit-cost ratios of 2.86, 3.24, and 2.20; adding school-based vaccination exceeded 1 only with a long duration of protection, while general adult vaccination remained below 1 throughout. A hepatitis C vaccine is likely to deliver a positive return on investment when directed at populations at highest risk of infection.
Motivations and experiences in controlled human infection trials vs. phase I clinical trials: a survey study
Victor M Cnossen, Olivia A. C Lamers, Rogier P van Leeuwen, Paul Zimmer-Harwood, Meta Roestenberg, Ingrid M. C Kamerling, and Marie-Astrid Hoogerwerf (June 23, 2026), BMC Med Ethics, “Motivations and experiences in controlled human infection trials vs. phase I clinical trials: a survey study”
Controlled human infection (CHI) trials deliberately expose healthy volunteers to a pathogen and share design features with phase I clinical trials, yet participant motivations and experiences across the two remain poorly characterized. This two-centre, cross-sectional survey compared 70 CHI and 98 phase I participants using a previously developed questionnaire covering motivation, decision-making, and ethical views. While the overall distribution of motivational factors was similar, reimbursement was the single most important motivator far more often for phase I participants, whereas CHI participants more frequently cited altruistic drivers such as contributing to science, suggesting CHI trials attract a more altruistically motivated population. CHI participants reported more severe symptoms and weighed symptom burden heavily in their decision to participate, reflecting a conscious risk-benefit assessment. Views on core ethical principles—reimbursement fairness, risk-benefit balance, and the right to withdraw—were comparable between groups. Findings indicate CHI participation is a well-informed choice and should inform future trial design.
The WHO pandemic agreement—securing Africa’s leadership in a fragmenting global order
Nelson Aghogho Evaborhene, Jessica Oga, Yusuff Adebayo Adebisi, Echezona Ejike Udokanma, Newton Runyowa, Zacharia Kafuko, Shashika Bandara, and Chizaram Onyeaghala (February 26, 2026), BMJ Global Health, “The WHO pandemic agreement—securing Africa’s leadership in a fragmenting global order“
In May 2025, the World Health Assembly adopted the historic WHO Pandemic Agreement, aimed at strengthening global pandemic preparedness and equity. This legally binding treaty emerged from years of negotiation shaped by the COVID-19 pandemic’s stark inequities—particularly those experienced by African nations. While the treaty introduces important innovations, notably the Pathogen Access and Benefit-Sharing system, significant challenges remain. Ambiguities in equity commitments, geopolitical fragmentation and rising nationalism threaten effective implementation. For Africa, realising the treaty’s promise requires robust legal frameworks, enhanced manufacturing and regulatory capacities and sustainable financing mechanisms that reduce donor dependency. This analysis critically examines the treaty’s provisions and political economy, emphasising the need for enforceable obligations, continental leadership and multi-sectoral accountability. We propose the establishment of a Pandemic Peer Review Mechanism to embed political accountability at national and regional levels. Only through coordinated African leadership, institutional investment and global solidarity can the Pandemic Agreement deliver equitable health outcomes in a fracturing global order.
Equitable partnerships to advance early-phase trials in sub-Saharan Africa
Katherine E. Stott, Anthony E. Chirwa, Christine Cole, Kondwani Jambo, Neil French, David G. Lalloo, Marc Henrion, Richard FitzGerald, Zacharia Kafuko, Henry C. Mwandumba, Stephen B. Gordon, and Brian Ngwira (February 11, 2026), Nature Health, “Equitable partnerships to advance early-phase trials in sub-Saharan Africa”
Early-phase trials (phases 1 and 2) are pivotal in shaping decisions regarding the progression of investigational medicinal products to market, through the generation of key safety, pharmacometric, immunogenicity and early efficacy data. Historically, just 10% of investigational medicinal products obtain eventual approval for marketing, and approximately 40% fail to progress from phase 1 to phase 2. It is essential that data obtained in early-phase trials are relevant to key populations, to mitigate this attrition risk. Sub-Saharan Africa bears the greatest human disease burden per population globally. Despite this, fewer than 3% of clinical trials are conducted in Africa, and the vast majority that are undertaken are phase 3 trials; phase 1 trials are the least developed in the region. A clear tension exists between perceived industry profitability and the inequities that arise from underinvestment in sub-Saharan Africa. Nevertheless, the rationale for enhancing early-phase trial capacity in sub-Saharan Africa is ethical, pharmacological and economic, and the mechanisms for achieving the same are within reach.
Targets of protective immunity and opportunities in hepatitis C virus vaccine development
Seung Bum Park, Paul Zimmer-Harwood, and T. Jake Liang (September 12, 2025), Nature Reviews Immunology, “Targets of protective immunity and opportunities in hepatitis C virus vaccine development”
Hepatitis C virus (HCV) remains a serious global health burden that affects nearly 50 million people worldwide. Despite the availability of highly effective direct-acting antiviral drugs, the lack of an effective HCV vaccine hinders control and elimination worldwide, wherein new infections and overall prevalence remain high. HCV vaccine development faces challenges, including high genetic diversity of the virus, unclear correlates of protective immunity, and a lack of robust in vivo models for vaccine testing. Despite these obstacles, the landscape of HCV vaccine development is rapidly evolving. Innovative strategies, including subunit, virus-like particle, viral vector, DNA and RNA vaccines, show promising results, and controlled human infection models offer a unique, albeit ethically complex, opportunity to accelerate vaccine development. Collaborative efforts among academia, industry, governmental agencies, and regulatory bodies are crucial for optimizing vaccine strategies, overcoming current challenges, and effecting advances towards global HCV elimination through vaccination.
Pursuing fair and just compensation for research participants: An open letter to the research ethics community
Roberto Abadie, Emily Anderson, Jake Eberts, Holly Fernandez Lynch, Jill Fisher, Luke Gelinas, Emily Largent, and Lindsay McNair (May 23, 2025), The American Journal of Bioethics, “Pursuing Fair and Just Compensation for Research Participants: An Open Letter the Research Ethics Community”
A cornerstone of modern research ethics oversight is the avoidance of undue influence on potential research participants to enroll in studies. Yet little guidance is given as to what influence is “undue.” Concerns over undue influence often arise in discussions of payment to research participants, and many research ethics oversight bodies default to “payment conservatism,” preferring minimal compensation to participants (or none at all) out of an abundance of caution. This practice, however, is unfair and does not convincingly protect against harm or undue influence. Sixty-four experts from fields including philosophy, law, medicine, policy, public health, patient advocacy, and research ethics offer this open letter to highlight the growing recognition of the pitfalls of excessive concern over payment to research participants.
Biosecurity considerations of controlled human infection model studies
Madeleine Eaton, Enlli Lewis, Ryan Duncombe, Lin Bowker-Lonnecker, Vinoy Vijayan, Bright Adorbley, Sriram Kumar, Bilal Ahmed Khan, Muhammad Zohaib, and Euzebiusz Jamrozik (February 28, 2025), Preprint, “Biosecurity considerations of controlled human infection model studies”
Controlled human infection model (CHIM) studies involve the deliberate exposure of healthy volunteers to pathogens under controlled conditions and can offer valuable insights for vaccine development and infectious disease research. While these studies have a strong safety record and are increasingly deployed worldwide, their associated biosecurity risks remain underexplored. This paper examines three key CHIM study biosecurity risk areas: onward transmission of pathogens, information hazards, and challenge agent manufacturing risks. We propose risk mitigation strategies to enhance biosecurity without compromising the role of these studies in advancing infectious disease research and vaccine development.
An analysis of controlled human infection studies registered on ClinicalTrials.gov
Danny Toomey, Jupiter Adams-Phipps, James Wilkinson, John Pietro, Jake Littman, Steffen Kamenicek, Daniel Kaufman, Joshua Osowicki, Meta Roestenberg, Ian J. Saldanha, and Euzebiusz Jamrozik (February 10, 2025), BMJ Open, “An analysis of controlled human infection studies registered on ClinicalTrials.gov”
Controlled human infection studies (CHIS) involve intentional exposure of human volunteers to infectious agents. A previous systematic review found that adverse event (AE) reporting across CHIS is inconsistent,
which makes data aggregation and reuse difficult. We hypothesised that data may be more easily aggregated using a clinical trial registry such as ClinicalTrals.gov, the largest publicly accessible registry of clinical trial data. The objectives of the current analysis were to (1) evaluate the use of ClinicalTrials.gov for CHIS data reporting and (2) compare CHIS clinical trial participant flow and AE reporting in ClinicalTrials.gov with the same data in corresponding published articles.
Ethics & utility of controlled human infection studies (CHIS) in low- & middle-income countries
Jake Daniel Eberts, Nir Eyal, and Sayantan Banerjee (October 30, 2024), Indian Journal of Medical Research, “Ethics & Utility of controlled human infection studies (CHIS) in low- & middle-income countries”
In 2023, the Indian Council of Medical Research (ICMR) released the draft guidelines for controlled human infection studies (CHIS). While they have become more common in the past decades, the guidelines drew criticism from some activists and experts as premature. While we agree with some of the critiques put forth, we also believe that the guidelines fail to account for the full spectrum of scientific benefits from CHIS. While the exact mechanism of how India should best prepare for CHIS are outside the scope of this paper, we argue the the successful use of malaria CHIS in low- and middle-income countries (LMICs) with less robust scientific, medical, and ethics infrastructure provides evidence that some CHIS could still be conducted ethically in India and similar countries with due caution and preparation.
Ethical acceptability of human challenge trials: Consultation with the US public and with research personnel
James William Benjamin Elsey, David Manheim, Abigail Marsh, Virginia Schmit and David Moss (October 22, 2024), PLOS ONE, “Ethical acceptability of human challenge trials: Consultation with the US public and with research personnel”
Human challenge trials (HCTs) may accelerate the development of treatments and vaccines, and deliver novel insights into the course and consequences of infection. However, HCTs are contentious because they involve purposely exposing volunteers to infection. Consultation with the public and other stakeholders is essential for understanding how HCTs can be most ethically and acceptably pursued. Previous research has found public support for COVID-19 HCTs, but little research has considered public attitudes towards HCTs in principle and the various factors making a trial more or less acceptable. Empirical data on the attitudes of research personnel is also missing. An online survey covering overarching support/opposition towards HCTs, as well as factors of importance for deciding whether or not an HCT is ethically acceptable gathered the responses of 1,500 participants. The general public, in particular, appear relatively unconcerned about participants’ motivations, and favor higher payment in accordance with risk. This study adds to a growing body of public consultation surrounding HCTs, demonstrating high levels of support for their use in principle–not just in relation to COVID-19. The importance attributed to various ethically-relevant factors can help in designing HCTs with high public acceptance.
Standardizing controlled human infection publication
Jupiter Adams-Phipps and Dan Toomey (March 2023, preprint), “Standardizing Controlled Human Infection Study Reporting Discussion and Guidelines.”
This paper discusses the challenges of conducting research on challenge studies stemming in part from the wide variance in terminology used to describe these studies. The authors proposed the adoption of “Controlled Human Infection Study”. The paper also highlights the lack of standardized reporting of adverse events among challenge study participants, making trends in safety and breakdowns of risk by disease, among other useful information, functionally impossible to determine.
Doing more to honor volunteers in medical research
Stephanie A. Kraft, Abie Rohrig, Anthony Williams, and Seem K. Shah (January 2023), “Better recognition for research participants: what society should learn from covid-19,” BMJ 380: e071178.
Society has significant obligations to medical research volunteers, who “enable advances in science and medicine related to a wide range of conditions and diseases, thereby contributing to the public good.”. It is universally agreed that studies and researchers ought to “respect” volunteers, but “respect” is often construed very narrowly, focusing mainly on respect for individual autonomy and the nonviolation of their civil and legal rights. This paper argues that there are many ways that respect for volunteers can and should be further expanded, from measures such as guaranteeing medical care and compensation in the case of study-related injury in the United States (where there is no law requiring such a guarantee) to improving the public recognition of volunteers and their contributions to modern medicine.
Altruism in those willing to volunteer for Covid-19 challenge studies
Abigail A. Marsh, Monica Magalhaes, Matthew Peeler, Sophie M. Rose, Thomas C. Darton, Nir Eyal, Josh Morrison, Seema K. Shah, and Virginia Schmit (November 2022), “Characterizing altruistic motivation in potential volunteers for SARS-CoV-2 challenge trials,” PLOS ONE 17(11): e0275823.
This study compared 1Day Sooner volunteer survey results against a control, gaining insight into the motives of tens of thousands who signed up with us during the pandemic. The sample from 1Day Sooner’s nearly 40,000 volunteers showed higher levels of altruistic thinking, and notably, did not have deficits in risk assessment or reasoning — they were altruistic, but not reckless, contrary to some concerns expressed during the pandemic.
40 years of challenge studies and zero deaths
Jupiter Adams-Phipps, Danny Toomey, Witold Więcek, Virginia Schmit, James Wilkinson, Keller Scholl, Euzebiusz Jamrozik, Joshua Osowicki, Meta Roestenberg, David Manheim (October 2022), “A Systematic Review of Human Challenge Trials, Designs, and Safety,” Clinical Infectious Diseases: ciac820.
1Day Sooner researchers and other scientists conducted a systematic review of published human challenge trials from 1980 to 2021 in Clinical Infectious Diseases. In total, over 15,000 participants took part in hundreds of different studies involving over two dozen pathogens, including Influenza, Plasmodium (malaria), SARS-CoV-2, Rubella, and E. coli. No deaths were reported. 10,016 volunteers were in studies that reported severe adverse effects (SAEs); only 23 SAEs occurred. The authors conclude it was unlikely that any of the 23 were even life-threatening, “because the events were primarily brief hospitalizations for observation or supportive care requiring noninvasive interventions or falling under the broad category of ‘other serious (important medical events)’ in the FDA definition of SAEs.”
Covid-19 volunteer risk modeling
David Manheim, Witold Wiȩcek, Virginia Schmit, Josh Morrison, and the 1Day Sooner Research Team (May 2021), “Exploring Risks of Human Challenge Trials For COVID-19,” Risk Analysis 41(5): 710–20.
1Day Sooner introduced an interactive model in Risk Analysis for exploring some risks of a SARS-COV-2 dosing study, a prerequisite for any COVID- 19 challenge trials. The risk estimates were based on a Bayesian evidence synthesis model which can incorporate new data on infection fatality rates (IFRs) to patients, and infer rates of hospitalization. Using young, healthy volunteers, the chances of a study resulting in a fatality were extremely low. The model is available under an open license along with the data and source code on GitHub.
How and when should challenge studies be used for Covid-19?
Linh Chi Nguyen, Christopher W. Bakerlee, T. Greg McKelvey, Sophie M. Rose, Alexander J. Norman, Nicholas Joseph, David Manheim, Michael R McLaren, Steven Jiang, Conor F. Barnes, Megan Kinniment, Derek Foster, Thomas C. Darton, and Josh Morrison (February 2021; orig. published July 2020), “Evaluating Use Cases for Human Challenge Trials in Accelerating SARS-CoV-2 Vaccine Development,” Clinical Infectious Diseases 72(4): 710–715.
First published in the summer of 2020, this paper discusses three potential use cases of human challenge trials in the Covid-19 pandemic: for evaluating efficacy, converging on correlates of protection, and improving understanding of pathogenesis and the human immune response. Complex ethical issues involved in infecting volunteers with a novel disease for which there is no cure, but ultimately, the potential benefits are substantial enough to warrant serious consideration.