Developments at Dadhaleh Institute

Retraction of two high-profile papers raise concerns about research integrity

Chronology of events On May 1, the NEJM published a study that suggested that two types of [ ... ]

Last week also saw the Gates Foundation and Gavi, the Vaccine Alliance doubling their funding to the Indian Serum Institute in order to provide up to 200 million doses of a future COVID-19 vaccine to low- and middle-income countries. The partnership includes 16 of the leading pharmaceutical companies that are developing Coronavirus vaccines, as the increased likely that more than one vaccine may be available as early as next year would allow for a rapid scaling up of production and distribution capacities. The additional funds will allow the Serum Institute to boost manufacturing of the vaccine candidates that are being developed by AstraZeneca and Novavax for delivery under the COVAX Facility as early as the first half of 2021. An analysis by DW outlines the enormous manufacturing capacity of the Serum Institute that have made it the largest vaccine manufacturer by volume in the world at over 1.5 billion doses a year. While 33 COVID-19 vaccine candidates are currently in clinical trials, the Serum Institute has already produced two million doses of the Oxford-AstraZeneca ‘Covishield’ vaccine candidate for use in testing, including State 3 Clinical Trials in India, the U.S., Brazil and South Africa. Should the clinical trials indicate that the vaccine candidate is both safe and effective, the Serum Institute has indicated it could scale up production to 10 million doses a month, as economies of scale would bring the cost down to under US$13 a dose.

The U.S. FDA last month approved an Emergency Use Authorization for Remdesivir, an experimental broad-spectrum antiviral. Initially developed by Gilead Sciences for the treatment of Ebola virus and despite mixed clinical findings, Remdesivir has since been approved to treat severe cases of COVID-19 in hospitalized patients. An article in BMJ, however, reports on major shortages, in part due to limited supply and its steep price. While Gilead claims it has temporarily licensed the production of the antiviral on a non-cost basis to nine generic manufacturers, as Gilead’s CEO blames the shortages on global supply chain disruptions. Critics, however, argue that countries not covered by Gilead’s licence would still have to procure Remdesivir directly from Gilead at themselves at US$2,340-3,120 for one course of treatment. Supply issues are also exacerbated by advanced economies placing advance purchase commitments that limit access in lower income countries, as the authors of the BMJ paper urge greater compulsory licensing. The former head of the CDC also urged local, regional and national authorities to accelerate preparation to ensure efficient vaccine distribution.

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Astra Zeneca and Oxford University resumed clinical trials for AZD1222, considered among the most promising COVID-19 vaccine candidate. The Phase 3 human trials for the experimental vaccine were briefly put on hold after one participant was hospitalized with neurological symptoms. Health experts noted that it was standard procedure to halt trials in the case of an adverse event and commended the quick stoppage of the trials. Following established safety protocols, the research team was able to confirm that the symptoms were consistent with transverse myelitis that was not related to the vaccine. The participant recovered in a few days, and no other trial participants reported any notable symptoms.

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The GAVI Vaccine Alliance announced a landmark collaboration last month that aims to expand existing vaccine capacity so that production can begin as soon as a COVID-19 vaccine is approved, which could be as early as 2021. The partnership includes the Gates Foundation, the Coalition for Epidemic Preparedness Innovations as well as the Serum Institute of India (SII), the world leading vaccine manufacturer. The former would provide US$150 million in initial funding to support vaccine production for low- and middle-income countries who are often relegated to the back of the line for new therapeutics or vaccines. As part of the agreement, SII would develop candidate vaccines that are licensed to the WHO prequalification, at a capped price of US$3 per dose. The development would be part of the COVAX Facility, a collaboration between the WHO, Gavi, and CEPI to share the risks of vaccine development, invest in manufacturing, and pool purchasing power to deliver vaccines equally among all countries. The advance marketing commitment part of the COVAX Facility provides vaccine purchase funding for 92 low- and middle-income countries.

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Over 150 efforts are currently underway around the world to develop COVID-19 vaccines and therapeutics, according to the WHO, with 23 vaccine candidates currently in human trials. Most of these studies are in Phase 1 trials that typically include a small number of healthy people where the goal is to determine safety and whether an immune response is observed. A small number of Phase 2 trials are also underway that include a larger and more diverse population, while none of the vaccine candidates have entered Phase 3 trials that focus on balancing efficacy (i.e. vaccine dosage to elicit immune response against SARS-Cov-2) and safety (i.e. minimizing adverse side effects). A number of papers over the past week reported on promising developments in three leading vaccine trials currently underway in the U.S., the U.K. and China.
A paper in the New England Journal of Medicine last week shows encouraging interim results for Moderna’s mRNA-1273 that targets the “spike” protein used by SARS-Cov-2 to enter cells. The Phase 1 clinical trials conducted by the U.S. National Institutes of Health confirmed that 45 health adults who received two doses of the vaccine 28 days apart had higher levels of antibodies than those who had recovered from being infected by COVID-19 (with the peak in antibody production coming only after the second dose). Moderna will begin Phase 2 trials on July 27, while mRNA-1273 is also expected to be the first vaccine candidate to enter Phase 3 efficacy trials later this year, with efforts underway to recruit over 30,000 people.
The Lancet this week also published encouraging results for another leading vaccine candidate from the U.K., AZD1222, developed by Oxford University and AstraZeneca. The interim findings show the vaccine continues to induce antibody and T-Cell immune responses up to day 56 of the ongoing Phase 1/2 trials that involve 1,077 health adults. A sub-group study of 10 patients receiving a second dose showed an even greater immune response to SARS-Cov-2. While no major adverse events were observed, 60% of patients did report mild side effects (fever, headaches, muscle aches, and injection site reactions) compared to the control group, a meningitis vaccine. AZD1222 is expected to advance to Phase 2 trials this month of a diverse patient population.
A research team from China also published results in the Lancet this week on Phase 2 trials for a vaccine candidate developed by CanSino. The latest findings validate previous Phase 1 data that show the vaccine induces an immune response to SARS-Cov-2, but that the neutralizing antibody response is not as strong in some key demographics, including people over the age of 55.
While these early results are promising, Merck’s CEO in the Harvard Business Review claimed it would be a “great disservice” to raise hopes that a vaccine would be available to the public by the end of the year. Novel vaccines often take years or decades to develop, due to established research protocols to ensure safety and efficacy. Vaccines also present unique manufacturing and distribution challenges that often limit production capacity while requiring complex logistical efforts. This is further strained by the global demand for a COVID-19 vaccine, as civil society groups have urged the international community to establish vaccine distribution agreements to prevent hoarding by wealthier countries.
The WHOhas confirmed that 165 countries representing 60% of the world’s population have engaged in COVAX, the COVID-19 vaccine global access facility that is designed to promote rapid, fair and equitable access. As part of the mechanism, 75 countries would finance the vaccines using domestic budgets, while partnering with up to 90 lower income countries that would be supported through voluntary donations to the COVAX Advance Market Commitment coordinated by GAVI. Other regions like PAHO announced parallel pooled procurement plans to ensure countries receive vaccines at subsidized, affordable prices.

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Chronology of events

On May 1, the NEJM published a study that suggested that two types of blood pressure medications (angiotensin-converting–enzyme inhibitors and angiotensin-receptor blockers) were not associated with worse outcomes in patients with COVID-19, while noting ACE inhibitors in particular had significantly protective effects on mortality.

On May 22, the Lancet published an article by the same authors that found that chloroquine and hydroxychloroquine, explored as potential therapies for COVID-19, did not correspond with improved outcomes and may be associated with higher mortality by up to 30%.

Over the following week, a number of high-profile clinical trials were halted or suspended as a result of the Lancet paper. That included the multi-country Solidarity Trial that was being coordinated by the WHO.

On May 28, more than 180 scientists submitted an open letter to the Lancet editor and study authors outlining questions about the statistical analysis and a lack of transparency in the underlying data, including contributing countries or hospitals.

On June 2, the editors of the NEJM and Lancet issued respective “Expressions of Concern” over methodological and data integrity questions related to the two publications, while the WHO resumed the relevant arm of the Solidarity Trial. Two days later, the co-authors retracted both papers from the NEJM and Lancet, as the journal editors indicated that they would undertake an internal audit of their procedures.

What are the issues?

Data Integrity

Much of the controversy has been around the quality and nature of the large proprietary collection of electronic health records analysed and provided by Surgisphere, a private medical data provider based in the U.S. The primary author of both papers claimed that an independent audit of the data was requested by Medical Technology and Practice Patterns Institute, but were told by the medical data research institute that Surgisphere would not share the underlying data due to “agreements with its clients and the fact that the documents contain confidential information,” It should be noted that Surgisphere Chief Executive was a co-author on the papers. According to a statement on the Surgisphere company website, its data registry was based on electronic health records from customers of its machine learning program and data analytics platform producing data that allows researchers to study “real-world, real-time patient encounters.”

Methodological integrity

The high-profile retractions and pulled pre-print raise broader questions about working with large datasets that researchers are not able to validate, and particularly about how such work could pass peer review at prestigious medical journals.While it is not uncommon for studies to use large datasets without external scrutiny of the raw data, but it is far more uncommon for high-impact journals like the Lancet. While its editor and the NEJM claim the review process was confidential, both journals claim the papers had “external peer review, statistical review, as well as scientific and manuscript editing.” How such a comprehensive dataset could have been gathered from hospitals around the world in the middle of a pandemic is a question that researchers, journals and peer reviewers should have raised.

Adverse Impacts

Although the retrospective analysis was not a randomized control trial, it received a lot of attention given its publication in a high-impact journal and purported scale of almost 100,000 patient records from 671 hospitals around the world between December 2019 and April 2020. Even if the results were correct, however, experts suggest such observational data, with its inherent weaknesses, should not be used to stop trials that could provide definitive and actionable answers. Among the major adverse impacts of the published Lancet study has been suspension of several well-designed clinical trials. One of the major concerns is that the publicity around the Lancet findings have made it harder to conduct trials or recruit patients, as the retraction won’t receive as much attention as the original study. In retrospect, researchers and decision makers may have placed too much reliance on the study, particularly as there had been prior queries about the methods of analysis and some of the results did not fit with what is known about other risk factors. The Annals of Internal Medicine, for example, maintained an ongoing and regularly updated review that summarised data from randomised trials and from observational studies. The journal did not include the Lancet study in their review or conclusion that “at this time, there is insufficient and often conflicting evidence on the benefits and harms of using chloroquine or hydroxychloroquine to treat COVID-19” that currently make it “impossible to determine the balance of benefits to harms.”

Ensuring research integrity during a pandemic

Scientific publication must above all be rigorous and honest. The retractions raise larger issues of reproducibility and scientific integrity, particularly when using big databases to draw conclusions, an approach that has been gaining rigor in the era of big data. While big databases have opened new lines of inquiry, there are also major issues as experts warn conducting studies properly is far more difficult and require a thorough understanding of underlying data to ensure the methods are rigorous and outcomes reasonable. There have been calls from scientists for independent auditing of data by journals and possibly regulatory bodies like the FDA which has extensive experience of auditing clinical data.

Part of the challenge has been pace. Unlike prior pandemics like SARS and Ebola, the COVID-19 pandemic has led to substantially more scientific publications, most notably pre-prints that are often not peer-reviewed. The rapidly increasing number of publications and urgency to quickly understand the virus present significant challenges in ensuring that research is conducted according to methods and standards of research integrity. This includes, for example, underlying models used to plan pandemic response and predict future outbreak trajectories that are often “poorly reported, at high risk of bias, and reported performance that are optimistic.” Serological tests that have received accelerated approval raise similar concerns, as claims by manufacturers around specificity and sensitivity often lack published data, presenting challenges as countries use testing to determine how to ease lockdowns.

Related papers

Top journals raise concerns about data in two studies related to COVID-19 (STAT)
High-profile coronavirus retractions raise concerns about data oversight (Nature)
Jeffrey Aronson: When I Use a Word . . . Retraction (BMJ Opinion)
After retractions of two Covid-19 papers, scientists ask what went wrong (STAT)
Will the pandemic permanently alter scientific publishing? (Nature)

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Updates on COVID-19 clinical trials

The pace of research and development for treatments and vaccines for the novel Coronavirus has intensified, with dozens of clinical trials underway around the world. Several papers were published over the weekend with preliminary findings on the two largest studies that were both stopped for different reasons.

In the New England Journal of Medicine, researchers reported on a randomized double-blind study for remdesivir by the U.S. CDC that was stopped prematurely due to positive preliminary results. For patients hospitalised with COVID-19, the antiretroviral appears to reduce the recovery time (by four days) and mortality (from 12% to 7%), while presenting no additional adverse events. While this is promising, the results appear to be worse for visible minorities (a group that has been disproportionately impacted by the pandemic). Researchers have also been surprised that patients treated sooner after symptom onset may not have markedly better outcomes than those treated later in the course of disease.
A paper in the Lancet, meanwhile, presents on the WHO Global COVID-19 Solidarity Trail on chloroquine and hydroxychloroquine. Based on the advice of the WHO Executive Group – comprised of experts from ten countries involved in the trial – the observational study was stopped as preliminary findings suggest the possibility of higher mortality rates. The WHO Chief Scientist committed to a comprehensive analysis of all emerging clinical trial data globally to consider benefit and harm, acknowledging that unlike randomized controlled trials, observational studies have been known to yield misleading results. Expertshave also critiqued the failure of the study to adequately adjust for the fact that many of the patients in the trial are more likely to be severely ill and already at increased risk of death.

Ethics of controlled Coronavirus infection

An article in Science this week also expresses concern in the growing trend of researchers pursuing, and thousands of people expressing interest in participating in, controlled human infection (CHI) studies, i.e. deliberately exposing healthy people to COVID-19 to study infection and treatment efficacy. The authors present an ethical framework for CHIs that emphasizes “social value” as fundamental in justifying these studies. The proposed Ethical Framework for SARS-CoV-2 CHI considers six additional criteria, including: Reasonable Risk-Benefit Profile, Context-Specific Stakeholder Engagement, Suitable Site Selection, Fair Participant Selection, Robust Informed Consent, and Proportionate Payment.

Everyone in the (patent) pool

More than 100 former heads of government and leading scientists have urged all COVID-19 related research and intellectual property to be shared freely, and for the equitable distribution of vaccines. An editorial this week in Nature laments that the growing concern of “techno-protectionism” necessitates such a letter, while highlighting the remarkable speed of advancements as a result of global consortia of researchers (“Work that would normally have taken months, possibly years, is completed in weeks”). The Nature article focuses particularly on the patent pool model that is was popularized by the UNITAID Medicines Patent Pool that was successful in bringing antiretrovirals to market.

The World Health Assembly Resolution last week made explicit reference to IP rights flexibilities with respect to R&D, manufacturing and distribution of COVID-19 vaccines. Support was not unanimous, however, as some countries (notably the U.S. and the U.K) and research consortia (including the Coalition for Epidemic Preparedness Innovations) expressed their preference for conventional models where vaccine developers retain the IP rights that they may sub-license and their determined price. An article in the Harvard Business Review drew attention to the dangers of this form of ‘vaccine nationalism’, particularly as the underlying research thus far has been pooled and governments around the world have shouldered much of the risk in funding the vaccine effort.

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Global Map of COVID-19 Innovations

StartupBlink in collaboration with Health Innovation Exchange (a UNAIDS initiative) and the Moscow Agency of Innovations launched a Coronavirus Innovation Map this week. The platform aims to connect innovators with venture capital and government officials in order to support the response to COVID-19 and address its impacts across five categories: prevention, diagnosis, treatment, information and life and business adaptation. Over 500 innovations are currently on the visual database, and the Health Innovation Exchange has committed to producing a report on shortlisted innovations to share with country partners.

Local Challenges, Local Solutions: African Innovators and COVID-19

Among the WHO reforms in 2018 were three key priorities: increasing capacity around digital health, recruiting diverse and younger leaders, and seeking local solutions to local challenges. This past week, the WHO AFRO Regional Office hosted an inaugural virtual event at the intersection of all three: showcasing solutions by young African innovators that have been implemented to address local challenges in responding to the pandemic. From the 350 innovators in attendance, the virtual event highlighted eight projects, including interactive public transport contact tracing apps, mobile testing booths and low-cost critical care beds. The event builds on a ‘Hackathon’ the WHO AFRO Region hosted in April to develop scalable solutions that align with one of the priority areas, providing seed funding to three projects.

Ten actions to boost local manufacturing in developing countries

Record demand globally for medical supplies like PPEs, diagnostics and treatments for COVID-19 has disproportionately affected affordability and access in developing countries. While local and regional production has gained more prominence, producers and investors in developing countries often face unique challenges. The UNCTAD highlights at least five: lack of capital, technical and resource capacity; low quality and regulatory standards; weak enabling policy frameworks; small markets and unstable demand; and poor physical infrastructure. In order to increase coordination and cooperation with existing initiatives (e.g. WHO voluntary technology pool and ACT Accelerator Global Response Framework) and partner agencies (e.g. The Global Fund, UNICEF, UNIDO, and UNAIDS), the UCTAD proposes the following ten actions to boost medicine production capacity in developing countries:

Investment in skills development to ensure GMP-compliant production
Sharing COVID-19-related technologies to enable affordable mass production
Target impact investors to access necessary capital
Build partnerships to initiate “lighthouse” projects on low-hanging fruit
Improve investment incentives to increase local firms’ sustainability
Use streamlined regulation to facilitate investment
Invest in infrastructure
Emphasize the regional approach to reduce costs
Seek funding from official development assistance
Ensure sustainability of efforts despite an unpredictable market

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WHO to create a COVID-19 Intellectual Property Pool

The WHO embraced a proposal by Costa Rica to develop a voluntary mechanism that would pool patents and regulatory testing data to develop drugs, vaccines and diagnostics for COVID-19. Modelled after the Medicines Patent Pool by UNITAID for HIV/AIDS medical products, the COVID IP Pool would serve as a repository that target governments, industry, universities and non-profit organizations in order to ensure equitable access to resulting medical products, something that the Access to COVID-19 Tools (ACT) Accelerator announced last month does not sufficiently address.

The WHO has until May 29 to finalize the framework for the voluntary pool. The US has expressed reservations, while it has been accused of “pandemic chauvinism” because it refused to attend the launch of the WHO ACT Accelerator and is alleged to have offered to buy a German vaccine developer, while the CEO of Sanofi said that the U.S. may get priority access to COVID-19 vaccine, even though the company is headquartered in France.

Covid-19 has exposed the limits of the pharmaceutical market model

As the global search for Coronavirus treatments and vaccines intensify, two articles this week highlight the limitations of the existing drug development models. Health Policy Watch featured an interview with the Director General of a trade association representing the leading pharmaceutical companies. Among the “old-new tensions between profit and public needs” that were discussed was the “concern” by the pharmaceutical industry that the newly adopted World Health Assembly resolution referenced WTO flexibilities that allow countries to override patents to ensure access to vaccines, therapeutics and diagnostics.

The STAT article, meanwhile, points to failures of the existing market model that do not sufficiently incentivize investment into new treatments and vaccines for neglected diseases and pandemic preparedness despite warnings. Building on an extensive body of research, the author advocates for a new economic model of drug development that does not rely on market mechanisms. That would include more open and transparent research and development practices that address the “rapid global expansion of intellectual property” as well as more expansive government initiatives to address collective challenges (particularly given the significant role of government-funded research).

The 15 drugs being tested to treat COVID-19 and how they work

Even under the most optimistic projections, developing new treatments and vaccines for COVID-19 will require far greater time and resources than would be required for repurposed existing therapeutic compounds. An article in Nature this week provides an overview of the 15 leading candidates of existing drugs that are being studied as treatments for COVID-19. These can be divided into two categories: those that target the viral replication cycle, and those that aim to control the symptoms of the disease. They include:

Chloroquine/hydroxychloroquine (primarily used to treat malaria)
Lpinavir and ritonavir (HIV/AIDS)
Nafamostat and camostat (pancreatitis)
Famotidine (heartburn)
Umifenovir (influenza virus A and B)
Nitazoxanide (anti-infective)
Ivermectin (anti-parasitic)
Corticosteroids (cytokine storm, acute respiratory distress syndrome)
Tocilizumab and sarilumab (cytokine storm, ARDS)
Bevacizumab (oncology)
Fluvoxamine (antidepressant)

Contact tracing apps: balancing privacy and public health

Traditional public health contact tracing systems require significant time and resources, as one projection by Johns Hopkins University estimates a workforce of 100,000-300,000 would be needed to contain COVID-19 in the U.S. alone at a cost of $12 billion. As a result, health systems are increasingly turning to mobile contact tracing apps that are pitched as a way to reduce these costs by automating the process of logging people’s contacts should they became infected in the future. Despite their promise, there are outstanding challenges, including marginalizing vulnerable populations that may not have smartphones.

There are also privacy concerns that has led civil liberties advocates to raise warnings about potential abuses, including by authoritarian countries during and after the pandemic. The CSIS also urges policy makers that digital tools such as contact tracing apps are not “silver bullet” substitutes for investment in fundamental pandemic response capabilities. That message was echoed by health authorities in Iceland, where Rakning-19 yielded very little benefit compared to traditional public health systems, despite its high uptake of 40% of the population.

Machine learning applications

In Nature Machine Intelligence, authors report on machine learning tools applying pattern classification to identify three biomarkers associated with COVID-19 mortalities.

Another paper in Nature examine real-time tracking of self-reported symptoms to predict potential cases of COVID-19. The smartphone app allowed the authors to develop a model that was 80% accurate and showed that loss of smell and taste were additional symptoms indicative of COVID-19. While this study used simple statistical regression analysis, another paper in pre-print used machine learning algorithms on a smaller Brazilian dataset that achieved better performance of 92% specificity and 95% sensitivity.

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Soaring drug prices could bar access to future coronavirus treatments (Guardian)
- COVID-19 exposes drug supply gaps as Canada explores local ‘Made in Canada’ solutions (CTV News)
To deliver a COVID-19 vaccine equitably, we must start planning now (Devex)
- U.S. taxpayer funding contributed to research for a remdesivir patent that will likely remain inaccessible to many people due to the $4,500 price tag by Gilead (STAT)
Protect against market exclusivity in the fight against COVID-19 (Nature Medicine)
- Compulsory Licensing: A Cure for Distributing the Cure? (CSIS)
Mobile apps that allow real-time tracking of self-reported symptoms are effective in predicting infections, according to a new study in Nature Medicine
- COVID-19 and digital inequalities: Reciprocal impacts and mitigation strategies (Computers in Human Behavior)

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World leaders pledge $8 billion for research into vaccine and therapies as well as equitable and timely distribution (Coronavirus Global Response Summit)

The absence of the U.S., India and Russia points to possible fractures in global health diplomacy (Washington Post)

Vaccine could be available as early as 9-24 months (Gates Foundation)

A vaccine likely won’t be available until the end of 2021 due to Phase 2 and 3 clinical trials to ensure safety and efficacy, according to the chair of the WHO Global Outbreak Alert and Response Network (CNBC)

Nature: Multiple vaccines are in competition: how will scientists choose the best?

Rapid review for the anti-coronavirus effect of remdesivir (Drug Discoveries & Therapeutics)

Video: How does Gilead’s drug remdesivir work against coronavirus? (STAT)

Gilead to charge up to US$4,500 for experimental COVID-19 treatment remdesivir (Institute for Clinical and Economic Research)

WHO to engage U.S. and Gilead as data on safety and efficacy emerge to ensure wider availability of remdesivir (CNBC)

GAVI Vaccine Alliance proposes an Advanced Market Commitment program for COVID-19 vaccine (GAVI)

Internet of Things has been deployed in innovative ways to provide information and monitoring during the COVID-19 epidemic, including automated and transparent treatment (Journal of Diabetes & Metabolic Syndrome)

Emerging technologies to combat COVID-19 pandemic (J of Clinical and Experimental Hepatology)

Going Viral: how to boost the spread of coronavirus science on social media (Nature)

COVID-19 has reinforced the importance of preprints as a means for rapid research dissemination (Nature Biotechnology)

Tool: Google releases an AI-powered COVID-19 Research Explorer to assist researchers with complex queries

UK researchers create antibody test claiming 100% sensitivity, 99.8% specificity and results in 35 minutes (UK Standard)

U.S. Food and Drug Administration tighten standards for antibody testing following false specificity and sensitivity claims (WSJ)

Ethical and practical challenges of COVID-19 human vaccine trials (STAT)

Human Challenge Studies to Accelerate Coronavirus Vaccine Licensure (Journal of Infections Diseases)

WHO to issue ethical guidelines this month to inform human challenge trials amidst reports of deliberate infection of healthy human volunteers to test vaccine candidates (SCMP)

Frontier technologies for COVID-19 need better governance (WEF)

Unproven herbal remedy, ‘Madagascar Tonic’, touted by some African governments despite warnings from health officials (Globe & Mail; The Economist)

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The Gates Foundation announced an additional 150 Million USD commitment to fund and ensure equitable access to drugs, diagnostics and vaccines, while calling on world leaders to unite in a global response to COVID-19 to ensure equitable access.

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Last week also saw the Gates Foundation and Gavi, the Vaccine Alliance doubling their funding to the Indian Serum Institute in order to provide up to 200 million doses of a future COVID-19 vaccine to low- and middle-income countries. The partnership includes 16 of the leading pharmaceutical companies that are developing Coronavirus vaccines, as the increased likely that more than one vaccine may be available as early as next year would allow for a rapid scaling up of production and distribution capacities. The additional funds will allow the Serum Institute to boost manufacturing of the vaccine candidates that are being developed by AstraZeneca and Novavax for delivery under the COVAX Facility as early as the first half of 2021. An analysis by DW outlines the enormous manufacturing capacity of the Serum Institute that have made it the largest vaccine manufacturer by volume in the world at over 1.5 billion doses a year. While 33 COVID-19 vaccine candidates are currently in clinical trials, the Serum Institute has already produced two million doses of the Oxford-AstraZeneca ‘Covishield’ vaccine candidate for use in testing, including State 3 Clinical Trials in India, the U.S., Brazil and South Africa. Should the clinical trials indicate that the vaccine candidate is both safe and effective, the Serum Institute has indicated it could scale up production to 10 million doses a month, as economies of scale would bring the cost down to under US$13 a dose.

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