Covid vaccine coverage in middle and lower income countries, and preparations for future pandemics

 Vaccine rollout to lower and middle income countries left something to be desired.  Some of that has to do with initial distribution when vaccines were scarce, and some has to do with vaccine hesitancy in poor as well as rich countries.  Here are two related views in Science and Nature.

The global plan for COVID-19 vaccine fairness fell short. Will next time be different?  BY GRETCHEN VOGEL, Science, 13 DEC 2022 

"On 8 December, the board of Gavi, the Vaccine Alliance—a key partner in the project—voted “in principle” to phase out much of its support for COVID-19 vaccines in middle-income countries starting in 2024, and to incorporate COVID-19 vaccinations into its regular vaccine programs for the poorest countries—if they still want them.

"The decision isn’t final, but critics of COVAX—many from poorer countries—would not mourn its demise. The effort has delivered some 1.84 billion vaccine doses to 146 countries, but many, if not most, arrived too late to have a big impact. “COVAX was completely useless for developing countries,” says Claudia Patricia Vaca González, an expert on access to medicines at the National University of Colombia, Bogotá. “It was a failure and we should admit it,” says Christian Happi, a molecular biologist at Redeemer’s University in Ede, Nigeria.

"Others have a more positive take. “Gavi and COVAX were in my mind transformational and inspirational in their aims,” says Lawrence Gostin, an expert on global health law at Georgetown University. “It got a lot of shots in a lot of arms.” Still, “I totally understand Gavi’s reasoning,” Gostin adds. Demand for COVID-19 vaccines dropped sharply after the pandemic ebbed, and Gavi wants to refocus on campaigns that have lagged during the crisis, including vaccination against the cancer-causing human papillomavirus, and ensuring no child fails to receive routine childhood vaccinations.

...

"Making vaccines where they are needed is the way forward, says Gostin, who thinks it’s unrealistic to expect wealthy countries not to put their own populations first. “Vaccine nationalism is a fact of life.” Vaca González agrees. She says COVAX’s basic premise—buying vaccines developed in wealthy countries from large pharmaceutical firms—was flawed from the start: “That was the original sin of COVAX.”

*********

Even after COVID, the world’s vaccine strategy is failing. Without a global, publicly funded strategy, the market will fail to deliver vaccines to stop pandemics before they surge. By Seth Berkley, Nature, 13 December 2022.

"Despite rallying to produce billions of doses of vaccines in the face of COVID-19, when it comes to developing vaccines to prevent a disease in the first place, the world is still asleep at the wheel. There is still no incentive for markets to deliver vaccines that can prevent outbreaks, even when the technology is available. If we can’t even have vaccines ready for known severe threats such as Ebola, then what hope is there for future unknown pandemic threats?

...

"The World Health Organization keeps a list of nine priority pathogens with pandemic potential, including severe acute respiratory syndrome (SARS) and Ebola, as well as ‘disease X’, which represents a possible, as-yet-undiscovered pathogen. All nine deserve a full effort: development of several candidate vaccines through the animal-model and early clinical testing stages; vialed and quality-tested vaccines that are ready for immediate testing in an outbreak; and stockpiling of enough doses to control the disease if the vaccine is shown to be efficacious. For disease X, a set of viral vectors and messenger RNA delivery systems should be ready to carry the sequences of whichever antigens prove effective against the disease, and the manufacturing and clinical trials should be worked through as far as possible. By doing much of the preclinical and clinical work in advance, we can have doses as close to ready as possible when we need them.

...

"A key first step is the establishment of an adequate, publicly subsidized market. This will enable a coordinated global strategy with the support of G20 governments to drive the research, development and flexible small-scale manufacturing needed to produce vaccines to prevent epidemics, even if, as we hope, they will not be needed."

Preparing for a drug-resistant bacteria pandemic---vaccines and challenge trials

 Axel Ockenfels recently alerted me that "The German National Academy of Sciences Leopoldina has established a working group to analyze the economic causes of the problem of global increase in pathogens resistant to antimicrobial agents, and develop better incentives for developing antibiotics and possible solutions. "

I sent him some quick thoughts, as follows:

"one direction that seems potentially worth exploring is vaccines for bacteria pathogens.  Most of our vaccines are antiviral, but there are some vaccines against bacterial infection, even though we mostly deal with bacteria through post-infection antibiotics.  But antibiotic discovery has lots of problems, both economic and technical. And it appears that vaccine technology has advanced a lot, given the speed with which Covid vaccines were developed.  So I wonder if it wouldn’t make sense to start now to develop vaccines against some of the bacteria that we think might be candidates for developing antibody resistance, so that when those variants show up, we’ll be able to protect lots of people from getting infected by vaccinating them. 

 And challenge trials would be very useful for that, since pre-pandemic it’s hard to do conventional trials of a vaccine against a disease that most people don’t get. Challenge trials wouldn’t necessarily be very hazardous if the relevant bacteria aren’t yet highly antibiotic resistant, since the diseases would be curable… (The assumption here is that a vaccine against say, conventional tetanus, would also be protective against antibiotic-resistant tetanus, which might be true since the evolutionary pressure to evade a new vaccine is likely very different from the long evolutionary path that leads to resistance to an existing antibiotic..)"

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Earlier posts, on antibiotics here, and vaccine challenge trials.

Challenge trials for future Covid vaccines are still needed, by Stanley Plotkin and Josh Morrison

 Covid is still with us, new vaccines are needed and will likely continue to be needed into the forseeable future, and the case for human challenge trials to speed selection among promising candidates is stronger than ever.  Two veteran advocates make the case:

Human Challenge Trials Hold Promise for Next-Generation COVID Vaccines— These investigations could accelerate effective development of a pan-coronavirus vaccine as well by Stanley Plotkin, MD, and Josh Morrison, JD November 7, 2022

"Two years ago, the prospect of deliberately infecting fully informed volunteers with COVID-19 to aid in vaccine research and development was controversial. We and many others argued that the risks were justifiable, and the reservations of some bioethicists did not deter nearly 40,000 people from over 160 countries from expressing interest in volunteering for these investigations, called human challenge trials. Yet in the end, while they have been extensively pursued in the U.K.*, there were no such studies in the U.S.

"We have made great strides against COVID-19 illness in the form of vaccination and treatments, but there are still thousands of deaths in the U.S. every week.

...

"The White House hosted a summit on the issue in July, showcasing the myriad ways researchers are going about developing new vaccines. There are hundreds of candidates in early stages around the world, but the resources devoted to COVID-19 vaccine research are a fraction of what they were 2 years ago. Human challenge trials can greatly speed the selection of the most promising in this field of candidates, providing scientific and economic benefits over uniform reliance on large field studies.

...

"The use of human challenge trials offers the greatest promise for testing intranasal vaccines for their ability to reduce infection and transmission. In the case of a live attenuated vaccine, something as simple as regular nasal swabbing can reveal just how much of the live virus is present in the nose over time -- and how much would spread when a patient sneezes, for example.

...

"There are obviously risks to COVID-19 challenge studies, and it was on these grounds that initial proposals for such research faced opposition. However, the risk of death is now lower than it was early on in the pandemic given better immune protection garnered from both vaccination and natural exposure, and various treatments options further reduce the risk.

Of course, long-COVID still looms large, but this risk can also be managed by selecting trial participants at lower risk of serious illness, as more severe COVID-19 illness is correlated with lingering post-COVID symptoms. Ultimately, if COVID-19 becomes endemic, long-COVID may well be a threat to everyone, whether or not they sign up for a challenge trial -- all the more reason we must act quickly to develop vaccines that stop transmission.

"We believe that volunteers are perfectly capable of considering these risks rationally. Those who decide to make a potential sacrifice for the good of humanity should be lauded, not dismissed as naive. (Notably, a study of the nearly 40,000-strong prospective volunteers organized by 1Day Sooner showed that their risk tolerance was the same as a control group, and they were driven primarily by altruistic motivations.)"

"Stanley Plotkin, MD, is professor emeritus in pediatrics at the University of Pennsylvania, a veteran vaccinologist, and a board member of 1Day Sooner, an organization that advocates on behalf of challenge trial volunteers. Josh Morrison, JD, is co-founder and president of 1Day Sooner, and a founder of Waitlist Zero and the Rikers Debate Project."

********

Earlier:

Monday, June 20, 2022

Report of a SARS-CoV-2 human challenge trial. In Britain.

* Josh Morrison writes:

there are four COVID challenge studies announced or underway in the UK, though only imperial [the study above] has published results. Besides the imperial one, there’s an Oxford reinfection study, 

https://www.ox.ac.uk/news/2021-04-19-human-challenge-trial-launches-study-immune-response-covid-19 (interestingly the talk one of our staff saw indicated they were having a difficult time getting any infections in previously infected people even when using doses 1,000 times higher than the infectious imperial dose).

 

There has also been an Imperial delta study that’s recruiting now — 

https://www.imperial.ac.uk/infectious-disease/research/human-challenge/covhic002/register-your-interest/

 

And HVIVO has announced an omicron challenge study, though I’m not sure that will happen. 

https://investors.vaxart.com/news-releases/news-release-details/vaxart-announces-agreement-hvivo-develop-worlds-first-human

Josh Morrison profiled in Vox

 Josh Morrison, the founder of WaitlistZero and 1DaySooner, is an unusually energetic and effective effective altruist.   

Here's a profile in Vox:

Josh Morrison took risks for science, and he thinks you can, too. From kidney donations to human challenge trials for Covid-19 vaccines, Josh Morrison shows the vast good any individual can do. By Muizz Akhtar

"Morrison first became familiar with this kind of direct public health participation when he read about kidney donations in the New Yorker when he was a law student in 2009. In the piece, people explained why they gave their kidneys to strangers in need — though there was slight risk to donors, the reward and benefit for the recipients was more than worth it. Two years later, he donated a kidney himself.

...

“The basic logic of my work in general is to try to use a sort of identity politics to get better political decision-making,” Morrison told me. “So with kidney donation, the theory is if kidney donors are more empowered in the political system as a sort of identity group, then the system will treat donors better and that will mean more people donate.”

HT: Frank McCormick

**********

I've mentioned Josh Morrison in many of my posts...

Challenge trials in Britain and (not) in the U.S.

 The NY Times has an excellent piece on Covid vaccine challenge trials, and the different traditions (and repugnance) in Britain and the U.S.

Britain Infected Volunteers With Covid. Why Won’t the U.S.? By Kate Murphy

"In an age of masking, compulsive hand sanitizing and plexiglass dividers, it seems inconceivable that for more than 40 years people enthusiastically signed up — and were often put on a waiting list — to have respiratory viruses, including coronaviruses, dripped into their noses.

"They were volunteers at the Common Cold Unit, set up in 1946 by the British government’s Medical Research Council.

...

"the Common Cold Unit established and refined a model for so-called human challenge studies that paved the way for the first Covid-19 human challenge study just completed in Britain, where young, healthy and unvaccinated volunteers were infected while researchers carefully monitored how their bodies responded.

"Then, as now, there were those who decried deliberately infecting or “challenging” healthy volunteers with disease-causing pathogens. It violates the medical principle of “do no harm.” The trade-off is a unique opportunity to discover the causes, transmission and progression of an illness, as well as the ability to more rapidly test the effectiveness of proposed treatments.

...

"“The key benefit of human challenge studies is that they are controlled — everyone gets the same virus, the same amount and they are in the same environment,” said Dr. Christopher Chiu, professor of infectious diseases at Imperial College London and chief investigator in Britain’s Covid challenge study.

...

"In the United States, the regulatory hurdles to conduct challenge studies mean there are precious few, mostly for finding better treatments for malaria, cholera and influenza. Ethicists and regulators are more comfortable approving clinical trials where subjects are given a treatment, say a drug or vaccine, to see if it helps improve a condition volunteers already have, or could prevent them from developing later.

...

"Dr. Fauci’s office said the institute has no plans to fund Covid-19 human challenge trials in the future. Many bioethicists support that decision. “We don’t ask people to sacrifice themselves for the good of society,” said Jeffrey Kahn, director of the Johns Hopkins Berman Institute of Bioethics. “In the U.S., we are very much about protecting individual rights and individual life and health and liberty, while in more communal societies it’s about the greater good.”

"But Josh Morrison, a co-founder of 1Day Sooner, which advocates on behalf of more than 40,000 would-be human challenge volunteers, argues it should be his and other people’s right to take risks for the greater good. “Most people aren’t going to want to be in a Covid challenge study, and that’s totally fine, but they shouldn’t project their own choices on other people,” he said."

HT: Axel Ockenfels

Participating in a Covid challenge trial: a participant's experience

 The WSJ's Jenny Strasburg has another story on British challenge trials of Covid-19:

Researchers Infect Volunteers With Coronavirus, Hoping to Conquer Covid-19. So-called challenge trials have long been used to study infections, but so far only the U.K. is doing them for Covid-19   By Jenny Strasburg

"On March 8, 23-year-old Jacob Hopkins, a U.K. university student, watched researchers enter his quarantine room’s airlocked entrance at London’s Royal Free Hospital. They wheeled a cart carrying a big red box, like a picnic cooler, labeled “biohazard.”

...

"A few days after the virus was dripped into his nose, he was shivering with a mild case of Covid-19, with the antiviral remdesivir pumped through a thin tube inserted into his arm. He spent 19 days in quarantine and said he felt fully recuperated a month later. He will ultimately be paid about £6,000, equivalent to $8,300, for that time, a year of follow-up tests and phone calls, and a parallel study he agreed to. Trial payments are based on U.K. living wages and go through ethical review."

...

"All volunteers are 18 to 30 years old and screened for known risk factors. They are isolated in quarantine suites with full-time medical care and specialized air systems to contain the virus. Researchers hope to publish peer-reviewed initial findings from the first phase of the challenge trials by this autumn.

...

"Researchers hope trial data will shed light on the durability of immune protection and how Covid-19 affects breathing, heart function, smell and concentration even before symptoms show. They say the model could test new vaccines and treatments head-to-head, eliminating weaker candidates before expensive, large-scale trials. Transmission data could help authorities prioritize who gets booster doses.

************

As an observer of repugnant/controversial transactions, I've been following the challenge trial discussion, including in particular about appropriate payments for participants.  There's a part of the medical ethics literature that worries that payments to volunteers might be 'coercive,' particularly to poor volunteers, and that payments should therefore be as small as possible, e.g. minimum wage payments for time spent, and that some things (such as risk) should not be compensated. My colleagues and I have been among those pointing out that there can also be ethical (as well as practical) issues involved in paying too little (or in providing too little post-trial medical care and insurance).

Here are some earlier posts focusing on articles I've coauthored about compensation for participation in challenge trials:

Thursday, October 29, 2020

Paying participants in challenge trials of Covid-19 vaccines, by Ambuehl, Ockenfels, and Roth

"we note that increasing hourly pay by a risk-compensation percentage as proposed in the target article provides compensation proportional to risk only if the risk increases proportionally with the number of hours worked. (Some risky tasks take little time; imagine challenge trials to test bulletproof vests.) "

Sunday, November 1, 2020

What do we know about the effects of payments to participants in challenge trials for vaccines, and other public spirited activities?

Monday, February 22, 2021

Ethical Payment in Human Infection Challenge Studies in the American Journal of Bioethics

Monday, March 1, 2021

Compensating challenge vaccine trial participants: further discussion in the American Journal of Bioethics

Australia and England swap millions of vaccine doses

Barter can increase efficiency. The Financial Times has the story:

Australia strikes deal to ‘swap’ 4m vaccine doses with UK  by William Langley and Oliver Barnes 

"The UK will send 4m Covid-19 vaccine doses to Australia in a swap deal aimed at accelerating Canberra’s stuttering rollout and bolstering British supplies later in the year when ministers are pushing for a booster campaign. 

"The first batch of 292,000 BioNTech/Pfizer doses will arrive in Australia in the coming days, with the remainder due by the end of the month, Prime Minister Scott Morrison said on Friday. 

"Australia will return an equivalent 4m doses before the end of the year, according to the UK health department.

"The deal is designed to speed up Australia’s vaccination rollout, which has been one of the slowest in the world, and Morrison said it would allow the government to bring forward its prospective reopening date.

"It reflects the UK’s calculation that it does not currently need all its stockpiled doses, which expire in a matter of months if not used, while allowing London to boost supplies later this year in anticipation of a broad booster campaign and the vaccination of 12 to 15-year-olds."

Challenge trials for Covid-19 Delta variant

 Before the development of the first Covid vaccines, there was a good deal of discussion about the appropriateness of testing vaccines with human challenge trials, i.e. with tests in which volunteers were deliberately exposed to Covid so that the vaccine effectiveness could be more readily assessed.  Now, with the Delta variant spreading, those issues are once again live.

Only England has authorized challenge trials. Here's a story from the WSJ:

Researchers Ready Lab-Grown Covid-19 Delta Variant for Human Trials. U.K. company is growing the highly contagious variant under tight lab controls for use in challenge studies  By Jenny Strasburg

"While the rest of the world is trying to stamp out the Covid-19 Delta variant, British researchers are making progress growing a carefully controlled batch in a lab that they hope to use to infect volunteers in studies.

"The effort marks a new phase in the U.K.’s human challenge trials, the only Covid-19 studies in the world intentionally exposing participants to the virus with the goal of developing new vaccines and treatments. 

...

"Two Covid challenge trials sponsored by Imperial College London and the University of Oxford started earlier this year in the U.K. They so far have exposed more than 40 healthy, young volunteers under isolated medical supervision to the original Wuhan strain that circulated widely in 2020.

"Since then, the highly transmissible Delta variant has come to dominate infections globally, rendering vaccines less effective and boosting case numbers across the U.K., U.S. and elsewhere. Delta’s fast rise led researchers and U.K. challenge-trial partner hVivo Services Ltd. to focus on trying to grow the variant in the lab.

...

"It took U.K. researchers and government advisers almost a year to plan and gain approval from a U.K. ethics committee and medicines regulators to start the controversial challenge trials for which the Delta strain could eventually be used. The government provided funding; so did the London-based Wellcome Trust, a large healthcare-focused charitable foundation.

...

"The challenge trials faced pushback from some U.K. academics and foreign researchers, as well as from some government officials, who considered them unsafe or otherwise unethical, people involved in the process say. Delays have caused friction among partners. hVivo, part of London-listed pharma-services company Open Orphan ORPH 3.08% PLC, had hoped to use the Covid-19 challenge-trial model by now to test antivirals and other products for drug companies, executives have told industry peers. A U.K. government spokesman said the pace of the challenge studies has reflected appropriate caution, and the trials have been safe.

"Challenge trials have been used for decades to study viruses and other pathogens by deliberately exposing volunteers and studying the body’s response. While scientists in the U.S. and Europe also pushed to do Covid-19 challenge studies, only the U.K. has moved forward."

**************

Other posts about challenge trials.

Marketplace for supplies to produce vaccines: COVAX

 Scott Kominers sends me the following link, of a marketplace intended to notify vaccine makers of supplies that may be available:

The COVAX Marketplace

"The COVAX Marketplace aims to accelerate the global production of COVID-19 vaccine doses for COVAX by matching existing suppliers of critical inputs with vaccine manufacturers who urgently need them to produce vaccines for fair and equitable distribution through COVAX

...

"The COVAX Marketplace is a key deliverable of the COVAX Manufacturing Task Force. It aims to respond quickly to immediate market needs and bottlenecks and improve the free flow of critical COVID-19 vaccine supplies by:

– Providing suppliers with a platform to allocate and reallocate unused materials.

– Mobilising idle stock from vaccines and candidates that fail prior to gaining regulatory approval – as well as from those that might scale down their production in the future.

– Mobilising potential surplus stock from manufacturers with non-vaccine activities.

...

"The initial version of the Marketplace will include COVAX vaccine manufacturers and suppliers of the key materials that have been identified as being most urgently needed.

"Participants in the COVAX Marketplace will be able to offer and request any materials required for vaccine production through the Marketplace, but it will initially focus on six categories of supplies that have been identified as critical: bioreactor bags, single use assemblies, cell culture media, filters, lipids, vials, and stoppers.

...

"Matches negotiate and conclude the transaction between themselves, independently of the Marketplace. Pairs notify CEPI on successful closure."

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Other posts on supply chains.

Are incentives for vaccination coercive, exploitative, or otherwise unethical? Persad and Emanuel think not, in JAMA

 Many jurisdictions and venues are now offering incentives for people to be vaccinated against Covid-19.  It will not surprise the readers of this blog to learn that some people have found incentives for vaccination to be repugnant, and perhaps to be immoral and unethical coercion or exploitation.  Here's an article rebutting those concerns, in JAMA

Ethical Considerations of Offering Benefits to COVID-19 Vaccine Recipients  by Govind Persad, JD, PhD1; Ezekiel J. Emanuel, MD, PhD, JAMA. Published online July 1, 2021. doi:10.1001/jama.2021.11045

"Entry into a million-dollar lottery for getting vaccinated against COVID-19 is Ohio’s offer to adults. Teens who get vaccinated receive a lottery ticket for state college tuition, room, board, and more. Other states are offering gift cards. Now many employers are offering rewards for COVID-19 vaccination. Businesses ranging from Krispy Kreme and Sam Adams beer to the Cincinnati Reds have announced discounts or prizes for vaccinated individuals. Are these benefit programs ethical? Are they useful? Are they better than mandates?

...

"The ethical case for instituting vaccine benefit programs is justified by 2 widely recognized values: (1) reducing overall harm from COVID-19 and (2) protecting disadvantaged individuals.1 If benefit programs increase vaccine uptake, they directly protect recipients. By reducing transmission, increased uptake also protects the population, including ineligible children and adults, unvaccinated adults, and individuals with conditions reducing vaccine efficacy (Table). Because transmission has been higher and outcomes worse in less-advantaged communities, stemming transmission especially protects those in disadvantaged communities. In addition, costs, such as time off work for getting a vaccine or dealing with vaccine-related adverse effects, finding daycare for children, and transportation to a vaccine site, hamper access for poorer and marginalized people. Benefit programs, especially in the form of guaranteed cash payments, could improve access and increase uptake by offsetting these costs."

Covid and COVAX, lessons being learned for the next pandemic

 From the Lancet:

A beautiful idea: how COVAX has fallen short by Ann Danaiya Usher, June 19, 2021DOI:https://doi.org/10.1016/S0140-6736(21)01367-2

"At the pledging summit for COVAX on June 2, 2021, hosted by Japan, Gavi finally reached its US$8·3 billion ask for the procurement and delivery of vaccines for the 92 eligible low-income and middle-income countries (LMICs) this year. However, even with full financing, the COVAX roll-out has moved much more slowly than that in high-income countries (HICs). Speaker after speaker at the summit lamented the gross inequity in access to vaccines. “Today, ten countries have administered 75% of all COVID-19 vaccines, but, in poor countries, health workers and people with underlying conditions cannot access them. This is not only manifestly unjust, it is also self-defeating”, UN secretary general António Guterres told the gathering. “COVAX has delivered over 72 million doses to 125 countries. But that is far less than 172 million it should have delivered by now.” Of the 2·1 billion COVID-19 vaccine doses administered worldwide so far, COVAX has been responsible for less than 4%.

...

"COVAX, managed by Gavi, along with the Coalition for Epidemic Preparedness Innovations and WHO, was designed to stand on two legs: one for HICs, which would pay for their own vaccines, and the other for 92 lower-income countries, whose doses would be financed by donor aid.

"In the so-called self-financing leg of COVAX, HICs were asked to pay upfront by mid-September, 2020, for the option to buy vaccines for their own populations. The UK, for example, paid £71 million for 27 million doses from COVAX, and Canada paid CA$220 million for 15 million doses. Australia, New Zealand, Norway, and South Korea also bought vaccine options from COVAX as self-financing countries.

"In the other leg of COVAX, vaccines for lower-income countries would be financed with donor grants through an Advance Market Commitment (AMC). The poorest of the 92 countries would receive them at no cost. Team Europe (led by Germany) and the USA have together provided US$5 billion to the COVAX AMC, Japan has given US$1 billion, and the UK, US$735 million. Most of these funds have been pledged only in the past few months.

"The grand idea of COVAX was that the combination of these two funding streams—the self-financed part and the aid-financed AMC—would give the facility the means to invest in research and development of several promising vaccine candidates. Additionally, as a pooled procurement mechanism, COVAX would have the financial muscle as a buyer to drive down prices for all participants. Once any of the COVAX portfolio vaccines had successfully undergone clinical trials and proved themselves to be both safe and effective, both self-financing and AMC countries would be allocated vaccines at the same rate, proportional to their total population size.

...

"Everyone knew that rich countries would enter into bilateral vaccine deals, Yamey said. But it was hoped that they would also buy into COVAX as insurance in case some vaccine candidates did not prove successful. Most of them did not. In the end, “three dozen countries bypassed COVAX and made huge deals directly with manufacturers. They were very lucky that the vaccines worked out. And since they cleared the shelves, there were not enough doses left for COVAX”, he said.

...

"The report of the Independent Panel for Pandemic Preparedness and Response also pointed to the harm caused by the slow mobilisation of resources for COVAX: “Had COVAX had sufficient and readily available early funding it would have been better able to secure enough immediate supply to meet its aims”, it states.

...

"The original notion of a global vaccine hub more or less collapsed, and COVAX ended up using a traditional aid-financed approach, which has left lower-income countries wholly at the mercy of wealthy nations and profit-driven companies.

“It is still this model of seeing how much money you can bring in and then seeing what you can negotiate with industry based on that money”, said Elder. “The promise of COVAX from the beginning that it would be the most attractive buyer for industry because it represented the ‘global need’ obviously did not pan out.” For any future iterations of COVAX, Taylor has argued that since national leaders have a responsibility to protect their own populations, vaccine nationalism is inevitable and this should be integrated into the design from the start.

"Several global health experts point to the failure to recognise supply constraints as a major obstacle to global vaccination and emphasise diversifying and scaling up manufacturing from the beginning. This lack of recognition was a serious flaw in the COVAX design, said Gostin. “Supply shortages should have been anticipated and ramping up supplies should have been baked into the design of COVAX from the start.”

Covid vaccine congestion in France looks familiar

France is some weeks behind the U.S. in delivering vaccines, but the script will look familiar to Americans.

The  Financial Times has the story:

France finally gets its Covid vaccination act together. The country’s inoculation drive has picked up speed after a slow start. by David Keohane 

"All it took to get my first dose of the Covid-19 vaccine in France was a five-hour round trip and two days and eight hours of incessant refreshing at my computer. 

...

""Until May 12, younger people in France weren’t allowed to book a vaccination unless they suffered from an underlying health condition which pushed them up the queue. 

"Since then anyone can book as long as the dose is set to go begging in the following 24 hours."

Vaccinating the whole world quickly turns out to be hard

 As Covid vaccines became available, rich countries that had made early, advanced purchases at high prices had contracts that delivered available doses early, while countries and organizations that had made later purchases at lower prices had "best effort" contracts that allowed delivery dates to slip as supply chain problems developed.  The consequences were greatest for the poorest countries, despite efforts to speed vaccination worldwide.

The WSJ has the story:

Why a Grand Plan to Vaccinate the World Against Covid Unraveled. The multibillion-dollar Covax program was supposed to be a model for vaccinating humanity, but has hit problem after problem By Gabriele Steinhauser, Drew Hinshaw and Betsy McKay

"The Covax program, conceived in early 2020 as a kind of Operation Warp Speed for the globe, was supposed to be a model for how to vaccinate humanity, starting with those who needed it the most. The plan was scheduled to have the developing world’s entire healthcare workforce immunized by now.

"Instead, the idealistic undertaking to inoculate nearly a billion people collided with reality, foiled by a basic instinct for nations to put their own populations first, and a shortage of manufacturing capacity around the world.

"Dr. Berkley and a small crew of global health experts spent months trying to recruit much of the world into buying their vaccines from one common pool, rich and poor countries alike. While they were hammering out the details and raising money, nations that could afford it rushed to secure their own shots first.

...

"Most of the world’s poorest nations were left highly dependent on a single vaccine, produced by a single manufacturer in a single country. In a cruel twist, that supplier—the Serum Institute of India—ended up engulfed by the world’s worst Covid-19 outbreak.

...

"Dr. Berkley, the chief executive of Gavi, the Vaccine Alliance, a public-private partnership that secures childhood immunizations for the world’s poorest countries and is the central organization behind Covax, said the facility did its best to navigate a hypercompetitive vaccine market. “We hear a lot of criticism, and the truth is, we’ve tried to do something that we think is the right thing,” he said. “Hindsight’s 2020. Should we have not invested in India? Well, that was the fastest way to get there.”

...

"Covax started shipping Covid-19 vaccines within three months of the world’s richest countries administering their first shots—lightning speed, compared with the five to 10 years it often takes for new immunizations to reach the developing world.

"Yet now it is running out of vaccines just when Covid-19 cases are escalating across countries it was meant to protect: the low- and middle-income states of Latin America and South Asia. The program has shipped 72 million shots, far short of the 238 million it had targeted by the end of May. That’s 4% of the total 1.7 billion vaccines shipped world-wide.

"Some 20 million of Covax’s shots have come from India, which was due to ship 140 million by the end of the month but stopped exporting them as it works to inoculate the country’s 1.3 billion citizens

...

"Wealthy countries, including ones that had promised to fund Covax, were buying their own doses first. In late May, the U.K. had sealed its own agreement with AstraZeneca, for 100 million doses. The U.S., without a commitment to Covax, had signed up for 300 million from AstraZeneca, pledging up to $1.2 billion.

"In June, the European Union, worried that its own countries would start competing for limited supply, stepped in to buy shots for its 450 million citizens. As part of its deal with member states, the EU blocked governments from joining any parallel vaccine purchasing programs. That meant France and Germany were now effectively barred from buying doses from the pool they had championed.

...

"By late December, after months of haggling over prices, Covax had 2 billion doses lined up, enough to vaccinate some 20% of the population in over 100 countries. Yet most were soft agreements with no clear delivery dates or involved drugmakers whose shots hadn’t yet panned out. As Europe and the U.S. began to vaccinate, Covax’s only completed purchases were with AstraZeneca and the Serum Institute.

...

"On Feb. 15, the WHO approved the AstraZeneca shot for emergency use, six weeks after it was cleared in the U.K. That allowed Covax to make its first shipment to a developing country, Ghana, weeks after Serum began exporting shots to other countries.

"Three days later, the U.S., now under President Biden, announced a $2 billion contribution to Covax, with another $2 billion planned through 2022. The EU upped its commitment to 1 billion euro.

"By then, there were scant vaccines available to buy. This month, Covax reached a deal with Moderna for 500 million doses, of which 466 million won’t be delivered until 2022."

Payments for Covid vaccine

 The NY Times has the story:

Pakistan’s Private Vaccine Sales Highlight Rich-Poor Divide.  An inoculation push, plagued with limited supplies and red tape, makes doses available to those who can pay for them. In a country with a struggling economy, most can’t.  By Salman Masood

"Access to the coronavirus vaccine has thrown a stark light on global inequality. The United States and other rich countries have bought up most of the world’s vaccine supplies to protect their own people, leaving millions of doses stockpiled and in some places unused. Less developed countries scramble over what’s left.

"To speed up vaccinations, some countries have allowed doses to be sold privately. But those campaigns have been troubled by supply issues and by complaints that they simply reflect the global disparities.

...

"“The Pakistani example is a microcosm of what has gone wrong with the global response — where wealth alone has primarily shaped who gets access,” Zain Rizvi, an expert on medicine access at Public Citizen, a Washington, D.C., advocacy group, said in an email.

...

India sells vaccines to private hospitals, though they are scrambling to find supplies now that the pandemic there is so serious. Kenya authorized private sales, then blocked them over fears that counterfeit vaccines would be sold. In the United States, some well-connected companies, like Bloomberg, have secured doses for employees.

...

"Pakistan says the private program could make more free shots available to low-income people. By purchasing doses of the Russian-made Sputnik 5 vaccine, the country’s wealthy wouldn’t need to get the free doses, which are made by Sinopharm of China. Some people would prefer to get inoculated at a private hospital because they are widely believed to be comparatively better organized and more efficient than overwhelmed government facilities.

Vaccine shortages are more about congested supply chains than about patent protection: Alex Tabarrok at MR

 Alex Tabarrok has a nice post at Marginal Revolution about the actual problems in worldwide vaccine supply, involving congested supply chains much more than protected intellectual property.

Patents are Not the Problem! by  Alex Tabarrok May 6, 2021 

Challenge trial for Covid-19 reinfection, in Britain.

A second round of (controvesial) challenge trials is being conducted in England, this one designed to assess how susceptible are people to reinfection with Covid-19, after recovering from it once.

The WSJ has the story 

Covid-19 ‘Challenge Trial’ Will Purposely Reinfect Adults. Dozens of quarantined volunteers in U.K. to receive coronavirus in study focused on reinfection  By Jenny Strasburg

"University of Oxford scientists plan to reinfect dozens of adult volunteers with the coronavirus in the second U.K. clinical trial to study deliberate Covid-19 infection in quarantine—this time among people who have already recovered from the virus.

"Such “human challenge” trials are controversial because they involve intentionally infecting healthy humans, and the U.K. is the only country so far conducting them with Covid-19, researchers said.

...

"The first Covid-19 challenge study, led by Imperial College London infectious-disease researchers, started in March with a handful of volunteers isolated inside London’s Royal Free Hospital, part of the state-funded National Health Service. That study received a pledge of more than $45 million from the U.K. government.

...

"the U.S. and other countries have steered clear of purposely infecting healthy people with the coronavirus. Critics argue the risks aren’t justified, given the broad presence of naturally circulating virus and the success of vaccines already available.

...

"Challenge-trial proponents argue there is no substitute for the precision of controlled studies. They have been used for decades to study diseases including typhoid, malaria and tuberculosis and to develop vaccines. With Covid-19, Prof. McShane told journalists in a briefing last week, “We don’t know whether someone has not been infected because they haven’t been exposed or [because] they have protective immunity.” Controlling exposure will help with those questions, she said.

...

"Volunteers will be tracked for a year. They will be paid around £5,000, equivalent to $6,917, for their time in quarantine and for follow-ups, Prof. McShane said."

*************

Related posts here:  https://marketdesigner.blogspot.com/search/label/challenge 

Congestion in vaccine delivery: uncancelled extra appointments

 In school choice, the reason universal enrollment systems that give each child one assignment are so desirable is that if children are accepted by multiple schools, it often takes time (e.g. the first week of the school term) to sort out which children are going where, and to free up the unclaimed spaces.

The same thing is happening with decentralized appointments for Covid vaccines. The WSJ has the story:

Got Your Covid-19 Vaccine? Now Cancel Your Extra Appointments.  Pharmacies and community clinics say uncanceled appointments lead to no-shows, adding to their already heavy workload   By Jaewon Kang and Sharon Terlep

"Pharmacies and health officials are making a plea to Americans who received their Covid-19 vaccines: Cancel the other shots you booked.

"As vaccine eligibility expands and more places offer shots, many people are signing up for multiple appointments and not backing out of the ones they don’t need. The resulting influx of no-shows is forcing vaccine providers, from pharmacies to community clinics, to find last-minute replacements so doses aren’t wasted.

...

"Appointments remain tough to score in many parts of the country even though the overall supply of vaccines and the pace of inoculation are improving. Some people are making multiple bookings in hopes of getting vaccinated sooner or sometimes because they don’t receive or see confirmation emails, according to pharmacies and community vaccination sites. Others receive shots at pop-up vaccination events before scheduled appointments and don’t notify providers.

"The U.S. lacks a concrete system of tracking wasted doses. Generally, local and state officials say that demand is high enough that no-shows aren’t leading to tossed vaccines, though vaccine providers say they sometimes fail to find takers for all the doses they have thawed in time to use them all safely."

***********

Previous post:

Monday, February 15, 2021

Multiple queues for Covid vaccines, as pharmacies join the supply chain

Allocating leftover vaccine before it spoils

 The NY Times has the story:

Hunting for a Leftover Vaccine? This Site Will Match You With a Clinic.  More than half a million people have signed up for Dr. B, a service that promises to match them with clinics struggling to equitably dole out extra doses before they expire.   By Katie Thomas

"a New York-based start-up is aiming to add some order to the rush for leftover doses. Dr. B, as the company is known, is matching vaccine providers who find themselves with extra vaccines to people who are willing to get one at a moment’s notice.

"Since the service began last month, more than 500,000 people have submitted a host of personal information to sign up for the service, which is free to join and is also free to providers. Two vaccine sites have begun testing the program, and the company said about 200 other providers had applied to participate.

...

"The company’s database sorts people by local rules about vaccine priority, giving providers better odds of administering their leftover shots to those in the greatest need.

"For many providers, that orderly procedure would be a welcome change from the haphazard systems they are using now. At some pharmacies and supermarket chains, workers have resorted to combing the shopping aisles to find people willing to get a last-minute vaccine. At other locations, vaccine hopefuls wait in line at the end of every shift, which could pose an infection risk, particularly to the most vulnerable."

Coordinating vaccine delivery is hard (California/Blue Cross version)

 The Mercury News has the story:

Santa Clara County will not participate in state’s Blue Shield-run vaccine program  by Maggie Angst

"Santa Clara County said late Monday it won’t take part in the state’s new centralized vaccine distribution system run by Blue Shield — a potentially huge blow to Gov. Gavin Newsom’s highly-touted plan.

"County Executive Jeff Smith said the county would not sign a contract with Blue Shield allowing the health insurance company to take over vaccine distribution in the county, claiming the new oversight wouldn’t do anything to improve vaccination speed or efficiency.

...

"According to officials from Blue Shield and the state, only one county of 58 in the entire state — Kern County — has signed a contract with Blue Shield.

“I think everyone sees it as a solution looking for a problem,” Smith said. “We’re talking about adding bureaucracies rather than vaccinating people.”

Vaccine supply and delivery in Germany: I'm interviewed in Zeit

 Here's an interview in the German newspaper Zeit, in which I was asked in early February about the vaccine rollout here and there. (Google translate is pretty readable, although some of the Q&A is a bit garbled by the translation from English to German and re-translation back into English...)

"Die Welt kann es sich leisten, einiges zu bezahlen" Alvin Roth weiß, wie man begehrte Güter effizient verteilt. Er hat den Nobelpreis dafür bekommen. Ein Gespräch über knappen Impfstoff und wie er vermehrt werden kann.  Interview: Lisa Nienhaus

Google Translate: "The world can afford to pay a lot" Alvin Roth knows how to efficiently distribute desirable goods. He got the Nobel Prize for it. A conversation about scarce vaccine and how it can be propagated. Interview: Lisa Nienhaus February 15, 2021,

The interview starts off talking about congestion, and line jumping, and the tradeoffs between speed and fairness (and how it's really costly to allow some vaccine to expire unused in the name of fairness).  It then turns to shortages of vaccine in the near term:

ZEIT ONLINE: Attempts are being made to build new production facilities. But in Germany we are - to be honest - pretty late.

Roth: But now is not the time to give up. Everything we build now may help us in August. Even if Germany is running late, there is still time to expand production facilities. Especially since these systems would certainly not have to be destroyed after Covid. Being able to produce mRNA vaccines oneself is also a good thing in the future. Vaccine production is not that complicated. You can build production facilities anywhere. And you should too.

ZEIT ONLINE: It's not happening on a large scale yet. What to do?

Roth: Laws are really useful for that. Pfizer / BioNTech and Moderna could be forced to license the production technology to other German pharmaceutical companies.

ZEIT ONLINE: That sounds radical.

Roth: I only think it's logical. If you had a pharmaceutical company, you'd think, "I'm paid by the dose. I've got enough capacity to ship to the whole world in the next year and a half. Why should I hurry?" There is no need to set up production facilities just to supply the world in six months instead of 18. It doesn't make any difference from a business perspective. But for the German or American government, these two options are by no means equivalent. It is important that we vaccinate quickly. We need a lot more production capacity than the pharmaceutical companies think it makes sense.

ZEIT ONLINE: Economists rarely suggest such a strong market intervention. And that also applies to companies that we must first be grateful to because they show us a way out of lockdown.

Roth: It's a global pandemic. It is economically necessary to think about how to avert the damage to the economy. But of course you have to pay the manufacturers. Many forget that.

ZEIT ONLINE: How fair the companies think that probably depends on how much you pay them.

Roth: Yes. But the world can afford to pay a lot. Because the world economy is currently largely at a standstill. We have a multi-trillion dollar economy. Paying a billion to save a trillion is good business.

ZEIT ONLINE: Why is that not happening so far?

Roth: The pharmaceutical companies themselves don't think that way at the moment. But we need the vaccine now. And it's very expensive for the world to shut down its economy like that. If you lose a few percentage points of GDP growth in Germany, that's a huge number. And there is almost no amount to pay to license the vaccine that is not worth it.