Global COVID-19 Vaccine Inequity: Failures in the First Year of Distribution and Potential Solutions for the Future

Within the first year of distribution of vaccines against COVID-19, high-income countries (HICs) have achieved vaccination rates of 75-80%, whilst low-income countries (LICs) vaccinated <10%. This disparity in access has been one of the greatest failures of international cooperation during the SARS-CoV-2 pandemic. Global COVID-19 vaccine inequity affects us all, with ongoing risk of new variants emerging until global herd immunity is strengthened. The current model of global vaccine distribution is based on financial competition for limited vaccine supplies, resulting in HICs getting first access to vaccines, with LICs being forced to rely on voluntary donations through schemes like COVAX. Pharmaceutical companies own the intellectual property (IP) rights for COVID-19 vaccines, allowing them to control manufacturing, distribution, and pricing. However, the pharmaceutical industry did not develop these vaccines alone, with billions of dollars of public funding being instrumental in their discovery and development. Solutions to enable global equitable access already exist. The next step in scale up of manufacture and distribution worldwide is equitable knowledge sharing and technology transfer. The World Health Organization centralized technology transfer hub would facilitate international cooperation. Investments made into developing this infrastructure benefit the COVID-19 response whilst promoting future pandemic preparedness. Whilst globally there is majority support for waivers of IP to facilitate this next step, key opponents blocking this move include the UK and other European countries which host large domestic pharmaceutical industries. A nationalistic approach is not effective during a global pandemic. International cooperation is essential to achieve global goals against COVID-19.

University patenting and licensing practices in the United Kingdom during the first year of the COVID-19 pandemic.

Universities' decisions during technology transfer may affect affordability, accessibility, and availability of COVID-19 health technologies downstream. We investigated measures taken by the top 35 publicly funded UK universities to ensure global equitable access to COVID-19 health technologies between January and end of October 2020. We sent Freedom Of Information (FOI) requests and analysed universities' websites, to (i) assess institutional strategies on the patenting and licensing of COVID-19-related health technologies, (ii) identify all COVID-19-related health technologies licensed or patented and (iii) record whether universities engaged with the Open COVID pledge, COVID-19 Technology Access Pool (C-TAP), or Association of University Technology Managers (AUTM) COVID-19 licensing guidelines during the time period assessed. Except for the Universities of Oxford and Edinburgh, UK universities did not update their institutional strategies during the first year of the pandemic. Nine universities licensed 22 COVID-19 health technologies. Imperial College London disclosed ten patents relevant to COVID-19. No UK universities participated in the Open COVID Pledge or C-TAP, but discussions were ongoing in autumn 2020. The University of Bristol endorsed the AUTM guidelines. Despite important COVID-19 health technologies being developed by UK universities, our findings suggest minimal engagement with measures that may promote equitable access downstream. We suggest universities review their technology transfer policies and implement global equitable access strategies for COVID-19 health technologies. We furthermore propose that public and charitable funders can play a larger role in encouraging universities to adopt such practices by making access and transparency clauses a mandatory condition for receiving public funds for research.

Who funded the research behind the Oxford-AstraZeneca COVID-19 vaccine?

OBJECTIVES: The Oxford-AstraZeneca COVID-19 vaccine (ChAdOx1 nCoV-19, Vaxzevira or Covishield) builds on two decades of research and development (R&D) into chimpanzee adenovirus-vectored vaccine (ChAdOx) technology at the University of Oxford. This study aimed to approximate the funding for the R&D of ChAdOx and the Oxford-AstraZeneca vaccine and to assess the transparency of funding reporting mechanisms. METHODS: We conducted a scoping review and publication history analysis of the principal investigators to reconstruct R&D funding the ChAdOx technology. We matched award numbers with publicly accessible grant databases. We filed freedom of information (FOI) requests to the University of Oxford for the disclosure of all grants for ChAdOx R&D. RESULTS: We identified 100 peer-reviewed articles relevant to ChAdOx technology published between January 2002 and October 2020, extracting 577 mentions of funding bodies from acknowledgements. Government funders from overseas (including the European Union) were mentioned 158 times (27.4%), the UK government 147 (25.5%) and charitable funders 138 (23.9%). Grant award numbers were identified for 215 (37.3%) mentions; amounts were publicly available for 121 (21.0%). Based on the FOIs, until December 2019, the biggest funders of ChAdOx R&D were the European Commission (34.0%), Wellcome Trust (20.4%) and Coalition for Epidemic Preparedness Innovations (17.5%). Since January 2020, the UK government contributed 95.5% of funding identified. The total identified R&D funding was £104 226 076 reported in the FOIs and £228 466 771 reconstructed from the literature search. CONCLUSION: Our study approximates that public and charitable financing accounted for 97%-99% of identifiable funding for the ChAdOx vaccine technology research at the University of Oxford underlying the Oxford-AstraZeneca vaccine until autumn 2020. We encountered a lack of transparency in research funding reporting.

Making a COVID-19 vaccine that works for everyone: ensuring equity and inclusivity in clinical trials.

Coronavirus disease 2019 (COVID-19) mortality and morbidity have been shown to increase with deprivation and impact non-White ethnicities more severely. Despite the extra risk Black, Asian and Minority Ethnicity (BAME) groups face in the pandemic, our current medical research system seems to prioritise innovation aimed at people of European descent. We found significant difficulties in assessing baseline demographics in clinical trials for COVID-19 vaccines, displaying a lack of transparency in reporting. Further, we found that most of these trials take place in high-income countries, with only 25 of 219 trials (11.4%) taking place in lower middle- or low-income countries. Trials for the current best vaccine candidates (BNT162b2, ChadOx1, mRNA-173) recruited 80.0% White participants. Underrepresentation of BAME groups in medical research will perpetuate historical distrust in healthcare processes, and poses a risk of unknown differences in efficacy and safety of these vaccines by phenotype. Limiting trial demographics and settings will mean a lack of global applicability of the results of COVID-19 vaccine trials, which will slow progress towards ending the pandemic.

Missing clinical trial data: the evidence gap in primary data for potential COVID-19 drugs.

BACKGROUND: Several drugs are being repurposed for the treatment of the coronavirus disease 2019 (COVID-19) pandemic based on in vitro or early clinical findings. As these drugs are being used in varied regimens and dosages, it is important to enable synthesis of existing safety data from clinical trials. However, availability of safety information is limited by a lack of timely reporting of overall clinical trial results on public registries or through academic publication. We aimed to analyse the evidence gap in this data by conducting a rapid review of results posting on ClinicalTrials.gov and in academic publications to quantify the number of trials missing results for drugs potentially being repurposed for COVID-19. METHODS: ClinicalTrials.gov was searched for 19 drugs that have been identified as potential treatments for COVID-19. Relevant clinical trials for any prior indication were listed by identifier (NCT number) and checked for results and for timely result reporting (within 395 days of the primary completion date). Additionally, PubMed and Google Scholar were searched to identify publications of results not listed on the registry. A second, blinded search of 10% of trials was conducted to assess reviewer concordance. RESULTS: Of 3754 completed trials, 1516 (40.4%) did not post results on ClinicalTrials.gov or in the academic literature. Tabular results were available on ClinicalTrials.gov for 1172 (31.2%) completed trials. A further 1066 (28.4%) had published results in the academic literature, but did not report results on ClinicalTrials.gov . Key drugs missing clinical trial results include hydroxychloroquine (37.0% completed trials unreported), favipiravir (77.8%) and lopinavir (40.5%). CONCLUSIONS: There is an important evidence gap for the safety of drugs being repurposed for COVID-19. This uncertainty could cause unnecessary additional morbidity and mortality during the pandemic. We recommend caution in experimental drug use for non-severe disease and urge clinical trial sponsors to report missing results retrospectively.

Public Risk-Taking and Rewards During the COVID-19 Pandemic - A Case Study of Remdesivir in the Context of Global Health Equity.

Public investment, through both research grants and university funding, plays a crucial role in the research and development (R&D) of novel health technologies, including diagnostics, therapies, and vaccines, to address the coronavirus disease 2019 (COVID-19) pandemic. Using the example of remdesivir, one of the most promising COVID-19 treatments, this paper traces back public contributions to different stages of the innovation process. Applying the Risk-Reward Nexus framework to the R&D of remdesivir, we analyse the role of the public in risk-taking and reward and address inequities in the biomedical innovation system. We discuss the collective, cumulative and uncertain characteristics of innovation, highlighting the lack of transparency in the biomedical R&D system, the need for public investment in the innovation process, and the "time-lag" between risk-taking and reward. Despite the significant public transnational contributions to the R&D of remdesivir, the rewards are extracted by few actors and the return to the public in the form of equitable access and affordable pricing is limited. Beyond the necessity to treat remdesivir as a global public good, we argue that biomedical innovation needs to be viewed in the broader concept of public value to prevent the same equity issues currently seen in the COVID-19 pandemic. This requires the state to take a market-shaping rather than market-fixing role, thereby steering innovation, ensuring that patents do not hinder global equitable access and affordable pricing and safeguarding a global medicines supply.