Why is the vaccine rollout slow and what we could do

A lack of imagination is holding us back

In New York 1947, 5 million people were vaccinated in 2 weeks

Like many, I have been puzzled by the seemingly slow vaccine rollout in the UK, US and many other countries. I do not automatically assume incompetence or bad actors. At first, I do not even automatically assume the vaccine roll out is slow. I thought I should investigate further. But slow it seems to be, although not everywhere.

Screenshot 2021-01-13 at 21.13.15.png

Israel is at 4-5x the pace of the UK and close to 10x the pace of the US. The United Arab Emirates is almost 3x the pace of the UK. Although the UK and US are doing better than Germany and France.

Screenshot 2021-01-13 at 21.14.31.png

How are we doing relative to history? We have built things fast in history (see Patrick Collinson list end). For instance:

On 24 June 1948, the Soviet Union initiated a blockade of Berlin. Two days later, the Berlin Airlift commenced. Over the following 463 days, the US, the UK, and France flew 277,000 flights with 300 aircraft to deliver the supplies required to support 2.2 million Berlin residents. On average, a supply aircraft landed every 2 minutes for 14 months.

I found a recent NYT article on how New York ran a vaccination programme in 1947 (link end). I went to the orginal review of the programme by Dr. Weinstein.

5 million people were vaccinated in 2 weeks and 6.35 million in less than a month.

The original article in the American Journal of Public Health (1947) is available here to review (link end)

Dr Weinsten writes:

Vaccination stations were set up in all police precincts, in addition to Health Department buildings and municipal hospitals and clinics. There was a total of 179 city installations being used for vaccination. Practically every hospital in the city setup a special clinic where vaccinations were given to all who applied, free of charge. The vaccine was furnished by the Health Department and was administered by doctors on the hospital staff. Many community organizations setup local centers staffed by volunteer physicians and clerks. 

Labour and industry cooperated by establishing vaccination stations in factories offices and union headquarters. In some cases their own positions did the vaccinating and others it was performed by health Department personnel. The station is maintained by the city remain open from 9 am until 10 pm including Saturdays and Sundays on April 26 those at the police print sinks were discontinued and on May 3 all other stations were closed. 

(The vaccination plan was drafted after 4 April).

The NYT article and a quick glance at other commentators have suggested these reasons for being slower today:

  • Regulation. This is at a city level vs centralised. But also the bureaucracy around registering volunteers.

  • Logistic delays. This is in getting vaccines to doctors. And quality control testing that is required (although that is partly regulation). 

  • Priortisation schedules. A complex process behind evaluating which batches go where. Essentially trying to get priority cohorts covered first.

  • Manufacturing Capacity. These are delays in glass vials, fill/finish capacity in specialised glass rather than pure vaccine supply.

  • A lack of trust in government. This supposedly means problems with vaccine hesitancy.

  • A lack of public health infrastructure.

Now while there seem to be elements of truth to those causal ideas many of them do not seem to hold up to the challenges in 1947. Health infrastructure today is more sophisticated and more plentiful both in absolute and per capita basis. The regulatory and logistical burden can part explain the gap and for instance the UK has much more vaccine than it has been able to administer but we certainly have capacity to do and I think we have both state and private capacity.

My theory is that we lack imagination. Or more precisely, the people in leadership positions either lack imagination or are too risk adverse in outlining a more ambitious plan.

Rather than saying why, we should be saying why not?

Rather than  a focus on errors of commission - taking a bad action - like lack of paper work for a volunteer - we ignore the errors of omission - simply taking good decisions.

What would that mean in practice? Applying 3 minutes of imagination time, I come up with the below. I am sure a group of school children allowed to use their imagaination could do better in a day.

  • Why not co-opt all police stations, fire stations and like?

  • Why not co-opt every pharmacy of size, and the expertise of the pharmacists, both public and private? Not only community pharmacies. (Sun newspaper claims offers from the private sector were shunned, although it’s not obvious if this has now been taken up - I’m unsure why they can not have been involved from the start)

  • Why not set up temporary open air type vaccination stations in our major parks in our cities?

  • Why not co-opt major business head quarters and industrial parks or gyms or leisure centres or restaurant chains.

  • Why not drive-ins?

  • Why not co-opt schools and all the places we use for polling?

  • Why not convince the logistics experts of Amazon and the like to take a sabbactical and help run our services (and give them so authority to have things done)

Countries probably don’t even have to be as extreme to have better roll outs. They could copy Israel (which also has an over 60 and key worker prioritisation list).

“In Israel our paramedics or nurses are able to travel with a set of 50 to a very distant point without wasting one single shot."

The country has 335 "drive-through" vaccination centres which operate extended hours.

At one, in the northern city of Haifa, doctor and recipient Natalie Roynik was in, jabbed and out in minutes without leaving the driving seat. (From Sky news)

And

Distributing the jabs quickly is crucial, and this is one area where the eagerness among Israelis to get vaccinated is accelerating the effort. Interest is so high that every day, queues of younger people hoping for leftover doses form in front of inoculation stations. WhatsApp groups filled with people contacting each other to secure these doses have also appeared.

And copy our past in terms of public information roll outs and co-opting private/public spaces to help. I know the UK is rolling outmass vaccination centres and using its health infrastructure, but we simply seem slow and it doesn’t necessarily seem a lack of resources. And while we can laud the Israeli use of digital health, New York City 1947 didn’t need digitisation.

There are legitimate debates around state capacity and if the right amount of investment has been made in the right areas.

However, my sense is this is not so much a state capacity problem in tangible infrastructure but a deficit within intangible capacity. In this case the imagination to dream more ambitiously and then the know how and social capital to make it happen.

The silver linings...Israel could be fully vaccinated in 3 months. 

The UK could take anywhere between 6 months to 12 months depending on how the roll out pace continues. 

I sincerely wish we could replicate some of the speed of the past.

https://www.thesun.co.uk/news/13661315/high-street-pharmacies-1m-covid-jabs-snubbed-vaccinate/

NYT article on 1947 vaccination.

The original article in the American Journal of Public Health (1947) is available here to review

Patrick Collison list of fast building.

COVID, why so many are mostly wrong, or only a little correct.

Summary: Vaccines are likely to give protection for at least c. 12 months and likely to reduce transmission rates, but vaccine hesitancy, mutation and maybe some amount of re-infection will mean that the virus stays with us permanently like influenza does. However like ‘flu we will find this disease manageable. We may also never know for sure why certain groups (eg men) suffer higher mortality. 

The medium to long term speculative thoughts is that this crisis will spur more innovation and creativity across several domains.

This is because many may conclude it is human innovation that has saved us and will save us. Similar thinking may be applied to climate challenges (I expect Bill Gates will double down on this in his next book). I also think - while with much pain- the creative arts will also react with more creativity, although extremely crimped near term, as people will have to find new ways of reaching audiences/consumers.

This is a long form read over why so many people are fairly wrong (or only a little correct) about COVID and why the information seems so confusing. I will attempt to touch on:

  • Predicting vaccines

  • Immunity and immune memory

  • Cross-protection

  • Different strains

  • Different genetics

  • Super-spreaders

  • Cultural differences

  • Data reporting differences

  • Complexity models

  • Re-infection

  • Narrow vs broad thinking (fox vs hedgehog)

  • Ideology

Back in August 2020, I made the point estimate judgement of an 80% chance of a vaccine by the end of 2020. Significantly above some observers estimates (although a good number of healthcare investors were making similar judgments).  I noted some of my thinking in my August blog.

What’s useful to note is why many expert observers were more pessimistic. I can summarise that those group were focused on past experiences, focused on the risks (which were clear) and anchored on previous examples. They were not willing to place faith in mRNA technology that had not produced commercial vaccine before even if much of the theory is well established.

Source: Google Finance

Source: Google Finance


Stock market prices embody future expectations that people with money (not reputation or press articles) buy and sell at. It’s very difficult typically to be ahead of this collective wisdom of the crowd. Still with in a stock price reveals a signal that can be interpreted.

If you look at Moderna’s (one of the vaccine makers) stock price - which embody many factors including politics, interests rates, etc - there was much of a run up from March to early November before the positive pivotal data in November. There are still future unknown events to come eg launch and distribution, but looking back one can suggest that investors with money were not super surprised by early November as much had already been “priced in” over March to October.


Mostly investors do not bet directly on a question such as “will there be a COVID vaccine in 2020?” But indirectly on stocks or other assets and prices which lead to money win/loss outcomes. These investors were suggesting through the Moderna stock price signal that there was a decent expectation of some success here.


I won’t rehash all the many science and socio-political points that went into my August forecast but suffice to say there are a number of people who do make and essentially bet behind these predictions.

Cross-immunity, herd-immunity, re-infection, strains, genetics and why everyone is only a little bit right.


Mostly - with rare exceptions - media articles will take a single look at a narrow domain question and present evidence in favour of a certain answer. Sometimes coloured by an ideology. (Even studies tend to look at a narrow question).


For example, if by ideas, you strongly favour individual choices you may balk at the idea of government imposed lockdowns and so you are drawn to articles suggesting Sweden or a “herd immunity” process as a way of proceeding without lockdowns. The actual data from Sweden does not matter too much - especially when you can find media articles to support your inclination.

Another example is re-infection. There are cases of re-infection, but it seems from what we know re-infection is rare but it can and does make article headlines.

[A distant simplistic parallel that people might understand is that you can get chickenpox twice (or rather, shingles after chickenpox) but it is rare.]


Still depending if you have an idea already about what we should be doing then a case of re-infection or an article about it can be used to support that view.

So you can put all of these statements together which have a little bit of truth to them.

  • There are asymptomatic carriers of COVID.

  • You can gain (some amount of) cross-protection for some (unknown) amount of time by exposure to other coronaviruses including the common cold. 

  • This level of protection will vary with strain, genetics, immune responses and memory - which in turn vary with factors such as age.

  • Different strains can act with different people’s genetics to cause varying levels of severity of disease.

  • Different people’s immune system will “remember” the virus differently (age, strain etc. variant)


All of this becomes confusing because we would like a simple answer of do I get cross-protection or not? Not the complex answer of it dependant strain, time and genetics (and perhaps environment)  and will not be static.

And from some of these simple parameters that can change we can have events such as “super-spreaders” where one person or one event (eg a sports or a night club evening) seem to cause many infections. The interplay of all those infection factors can produce those results. Or not.

In that sense - a distant parallel is with weather forecasting.  We can put together large trends to fairly accurate assess total infection cases in regions over  a few weeks or days, but predictions at the single person or event level are much more uncertain.

Other factors which interplay are cultural differences and reporting data differences. Certainly, if you have ever travelled through Japan then the cultural differences in hygiene and also in the populations general adherence to rules from authority (also see China, Taiwan) are very different from England or the US.

As an aside, I do think the politics of mask wearing especially in the early days of the pandemic in Europe and the US were surprising to me - although not in hindsight. There was (and is) a strand of thought as to how so simple an intervention could have an impact. A walk through a poorer country or even a more mixed one like South Africa would not scorn “simple” interventions so heavily (access to proper toilets and hygiene make huge impacts). I do think - again with hindsight - it is surprising that more weight was not given to first principles - in that we knew the virus was carried in aerosol droplets (and like colds, flus) and so the physical methods of transmission could well be interrupted by barriers like masks.

Putting this all together what does this mean? In my view, vaccines are likely to give protection for at least c. 12 months and likely to reduce transmission rates, but vaccine hesitancy, mutation and maybe some amount of re-infection will mean that the virus stays with us permanently like influenza does. However like ‘flu we will find this disease manageable. We may also never know for sure why certain groups (eg men) suffer higher mortality. 

The medium to long term speculative thoughts is that this crisis will spur more innovation and creativity across several domains.

This is because many will conclude it is human innovation that has saved us and will save us. Similar thinking may be applied to climate challenges (I expect Bill Gates will double down on this in his next book). I also think - while with much pain- the creative arts will also react with more creativity, although extremely crimped near term, as people will have to find new ways of reaching audiences/consumers.

Here are a mix of random thoughts and questions that I considered when thinking about COVID:

Where did SARS-CoV-2 come from?

Some uncertainty, but seems very likely that it came from animals (zoonotic, maybe bats) and crossed into humans. Evidence that is was present in China in November 2019 (as early as 17 Nov) and maybe earlier. Open question. We don’t know if the virus mutated in animals and then crossed to humans. Or crossed to humans and then mutated and crossed human-to—human.

Definitely seems NOT lab made (IMO).

https://www.nature.com/articles/s41591-020-0820-9

https://www.scmp.com/news/china/society/article/3074991/coronavirus-chinas-first-confirmed-covid-19-case-traced-back

Why have certain regions (Taiwan, South Korea, Singapore, Hong Kong) handled the pandemic better than others (Italy, Spain, all of Europe, US….)?

…Same for sectors and businesses ?

The high-performers had:

-Very prepared systems

-Responsive public health authorities

-Responsive general public

-Responsive private companies (at the request of the public health authorities)

But, they had very prepared systems + public because:

-They had dealt with the trauma and cost of SARS-classic

The actions were/included:

-Early responses (masks, restrictions)

-High testing (fast deployment + development of tests)

-Strict isolate, contact, trace protocols

-Travel bans and similar

-Tracking of quarantined people

There is a 124 point list of what Taiwan did:

https://www.vox.com/future-perfect/2020/3/10/21171722/taiwan-coronavirus-china-social-distancing-quarantine

https://jamanetwork.com/journals/jama/fullarticle/2762689

…Same for sectors and businesses ?

Some sectors/businesses:

-had more awareness on what exponential growth can look like (tech), and/or, 

-had more respect for the seriousness that China were taking (and put weight on that signal)

-more redundancy built into their supply chains (typically, as product considered critical, eg insulins, other must-have pharmaceuticals)

-more cash on balance sheets to deal with emergencies (typically these were maybe ear marked for litigation or other catastrophic events)

-ability to remote work

-business models that are resilient to COVID (eg. Video conference calls)

This has lead to:

(Parts of) Tech + Health + Utilities > most business

Big business > small business


Within countries / regions 

Some regions influenced by:

-understanding of exponential growth (Tech community in San Francisco)

-population density

-culture

-strains

-maybe weather?


Open Question: Why are death rates different across European regions, Asia etc ? Also, knows as heterogeneity.

We don’t know. 

We do know:

-Data is patchy

-Testing criteria are different

-Testing efficacy varies

-Older people, men, people with underlying diseases (eg heart problems) are more at risk

(But even here, there are regional differences with US rates of hospitalisation in the young much higher than in other regions).

-Different strains

-Different genetics

-Different cross protection

No one has a model that explains these intersecting factors.

One tentative suggestion is the difference in “viral load” or dosage of virus you get on first infection may explain part of this.

We do know viral load can have an impact with other viruses.

Open: Why are some people more susceptible than others?

This goes across many subgroups: Children, Men, but also differences in the young who do get impacted.

Open Question: Why are death rates so low in children? This pattern is consistent across regions even if rates vary. Explanations include:

  • Children’s immune system being more flexible and rapid

  • Adult immune system may over react due to priming with other coronaviruses

  • Adult immune system being slower

  • Other varieties of explanation…

See: Christakis https://twitter.com/NAChristakis/status/1243883141900763137

Open Question: Why are death rates higher in men? (also Co-morbidities)

We don’t know. Partial explanations that I have seen touted but with no evidence include:

-men being worse at hand washing/hygiene 

-men being more likely to smoke or use vapes.

But, essentially whatever your underlying risk the virus seems to magnify it (eg age, male, underlying diseases)…

Open Question: How long will immunity last? (Likely ranges, we have looking to be quite a few months, I’d would hone in on at least a year) 

Partly Open Question: How long does a person remain infectious? (We have some likely ranges)

Partly Open Question: How exactly is the virus spreading? (While we know it’s via viruses in droplets, we don’t really know if it’s surviving to infect people in open spaces as opposed to enclosed spaces. There’s tentative evidence that open spaces are safer (some outdoor mass events protests have not lead to super-spreading spikes but some internal ones have, also cf. different experiences in Italian cities, also Brazil) . Even if viruses can survive on cardboard in a lab how that works in the real world is unclear.)

Vaccine hesitancy, UK (79%) would take vaccine

Source: https://www.weforum.org/agenda/2020/11/fewer-people-say-they-would-take-a-covid-19-vaccine-now-than-3-months-ago

Source: https://www.weforum.org/agenda/2020/11/fewer-people-say-they-would-take-a-covid-19-vaccine-now-than-3-months-ago

Vaccine hesitancy, the ‘reluctance or refusal to vaccinate despite the availability of vaccines’, was listed among the World Health Organisation’s top ten threats to health in 2019.

In an August 2020 poll around one in four (26%) adults globally disagreed that they would take a vaccine for COVID-19 if it were available, with worry about side effects, followed by perception of effectiveness being mentioned most frequently as reasonsfor not getting a vaccine. This slipped further down in October. The November report from Ispos here. And WEF link here.

COVID vaccines, timeline update

Short update on COVID vaccine timelines. US/EU timelines have slipped by 1 -3 months, but China has held up since my August estimates. Treat all estimates with caution etc.

I thought I would update on my speculative COVID vaccine thoughts given the moving timelines here. There are >100 vaccine projects and COVID treatments in motion, and although recent vaccine timelines have slipped, it looks ;like we will have a vaccine at some point. When? is a key debate. Given the challenges around public health interventions, (lockdowns etc.) in EU/NA - one way we can cut the knot is to go fast on the vaccine. This is one reason why (althoguh not without some downsides) I support the UK challenge trials starting in early 2021. That said we have some decent chances of vaccines by very late this year / Jan 2021. Below is a moderatel positive scenario of how the US could be vaccinated in 2021.

Oct 2020, estimates. Treat with caution.

Oct 2020, estimates. Treat with caution.

I think China will have a vaccine starting to distribute to the public by Dec 2020. Chinese officials have indicated data is positive and they are willing to approve.

The UK has an 80% chance (IMO) of a vaccine in Dec/Jan for at risk populations (AZ/Oxford, timelines, newspaper leaks) under emergency approval. The early data is promising and despite the delays, if there were serious safety issues I would have expected to have had more negative news here.

The US has a chance for an emergency vaccine approval late Dec (slipping) or Jan, there are two shots on goal here (Moderna and Pfizer), and I rate the chances around the 70% level (although 40% and dropping for before year end as both have slipped, but still at 70% or so in Q1 2021 time frame). (This is down slightly from earlier due to challenges in the trials). Again early data is promising and no catastrophic safety events seen. Full approvals are more debatable than emergency (as hurdles different, but mixed messages from FDA makes this uncertain). The AZ trial stalled for longer in the US, so is more likely a Q1 2021 event as US don’t seem to want to recognize the UK/EU regulators view here.

Antibody treatments (Regeneron/Roche, Lilly) have a 90% chance of emergency approval before year end, but are only available in limited doses of around 5m to 10m doses pa. Data has been positive especially in the mild-moderate pateients.

12 Oct, 2020 Source: Gallup for Sep survey.

12 Oct, 2020 Source: Gallup for Sep survey.

There are a lot of variations on scenarios here, and supply and distribution as well as anti-vax movements are all other factors to consider. Some polls but vaccine willingness only at or so 50% in the US. Debates  arise are on (1) Willingness to vaccinate (2) Regulatory caution around durability as well as efficacy (3) social-political pressures.

It is of note that China is more advanced here seemingly than NA/EU and generally the countries outside of EU/NA are potentially faring better.

15 Leading vaccine projects, Source: Milken, press releases

15 Leading vaccine projects, Source: Milken, press releases

COVID Vaccine coverage estimates

An assessment of COVID vaccine coverage in 2020 - 2022

—> 80% (*) chance of a US vaccine approval by year end 2020

—> 60% chance that the US will have enough supply of vaccine to cover the country by mid 2021

—> 60% chance significant part of world is covered by early 2022

(* This estimate dipped in Sep but has rised by Nov, and should probably now nudge 90% for Dec/Jan approval due to both Pfizer and Moderna vaccines hitting)

Table 1. Source: Milken Institute, Press Releases, Author estimates. No approvals are certain. One vaccine in Russia and one vaccine in China have been approved for certain use.

Table 1. Source: Milken Institute, Press Releases, Author estimates. No approvals are certain. One vaccine in Russia and one vaccine in China have been approved for certain use.

I estimate an 80% chance of a vaccine approval by year end 2020 and a 60% chance that the US will have enough supply of vaccine to cover the country in first wave by mid 2021. (Although note as counter point on the safety risk you can note this article on the 1976 Swine flu).

The base case uses the public announcements of the large sophisticated UK and US groups. (See Table above). 

Downsides are from (1) negative data and (2) negative regulators; other possible downside are from (3) manufacturing constraints and (4) distribution constraints; and (5) vaccine hesitancy (certain anti-vaccine sentiments). Note (1) and (2) are separate risks as there may be data positive enough for patient choice (or developers to submit) but not enough to convince (risk averse) regulators. 

Upsides are from (a) China developers and possibly  (b) Russian development although I do not see those vaccines coming to Europe or the US but may well go to Asia and LatAm in H2 2021. A detailed overview of the developer groups is available from the the Milken Institute (link end) and WHO. I select a highlight below to give a sense of (i) the variety of technology mechanisms in play here and (ii) the colloborative group nature of the development even while there typically is a lead group.

Source: Milken Institute, slight author edits.

Source: Milken Institute, slight author edits.

Further upside would be positive data from manufactured antibody studies (eg Regeneron/Roche) which are due Q4 2020. The two major studies due in Q4 2020 are (a) Regeneron/Roche and (b) Lilly/AbCellera. If these are positive, then the Regeneron collaboration would add 4m to 8m prevantative doses to the calculations below.

I am less worried about distribution because:

—>vaccination during the flu season routinely reaches 50% of the population, thus distribution efforts are likely surmountable (cf US wholesaler deal with McKesson which is an experienced organisation). Also fill/finishers (packing the finished product) such as Catalent are already involved.

—> some nucleic-acid based vaccines may be distributed frozen, but appear stable for several days in regular refrigeration

The leading makers are also fully flying on manufacturing and there is expertise from flu vaccine and animal vaccines and outsourced makers (eg Lonza). I have toured vaccine plants (which are typically under utilised compared to chemical plants) and the technology and expertise from the leading makers is competent at scale, although this current speed is much faster than before - in my view, it’s not been out of reach for biopharma.

There are previous papers on biopharma probability of success. And while certain technology is new eg mRNA-based vaccines, much of the expertise on coronavirus and vaccine understanding has a high degree of understanding. Severe side effects (or long-term side effects) are risks (particularly from our understanding of side effects from previous RSV vaccines) but current data from multiple trials are not yet picking up a nasty effect. Although the trials are small, and many are across different products, the fact that there are multiple trials running across different geographies and populations gives statistical strength to the net probability of success. (Link end, see my primer on forecasting).

Some vaccines will fail. Some supply bottlenecks will materialize. New bottlenecks, so far undiscovered will appear.  But the net effect of so many shots on goal is that a first wave of vaccinations can be done in the US by mid 2021 and quite likely globally by end 2021 / early 2022. The stated capacity up to 1bn doses of many of the possible successes balances out those vaccines that will fail.

Source: Author estimates, Company Press releases, transcripts of managment calls. This table looks only at US, however similar calculation can show reasonable global coverage by mid 2022. Note, vaccination = 2 x doses in most cases as two doses requ…

Source: Author estimates, Company Press releases, transcripts of managment calls. This table looks only at US, however similar calculation can show reasonable global coverage by mid 2022. Note, vaccination = 2 x doses in most cases as two doses required.

There will need to be boosters (maybe every 2 years, possibly every year) and possibly - like flu - new strains will have to be made yearly if the virus ends up mutating and still being lethal, but my view is that we now are looking pretty likely to be on track to solving this one.

Source: Milken Inst, Press releases, Author estimates. Note: Private funding may not be but have not assertained. DOD = Dept of Defence, HHS = Human Health Services. BARDA = Biomedical Advanced Research and Development Authority. CEPI = Coalition fo…

Source: Milken Inst, Press releases, Author estimates. Note: Private funding may not be but have not assertained. DOD = Dept of Defence, HHS = Human Health Services. BARDA = Biomedical Advanced Research and Development Authority. CEPI = Coalition for Epidemic Preparedness Innovations . EC = EU Commission. EIB = EU Investment Bank. GAVI = Vaccine Alliance. GAtes = Bill and Melinda Gates Foundation.

While there will be many debates on the public health responses of various countries, it’s notable that the US, China and the UK are the geographies where the developing makers are concentrated with honourable mentions to a few countries such as France (Sanofi) and maybe Germany (CuraVax). Adjusting for population keeps UK in the spotlight (note Tyler Cowen has highlighted this in his column, link end).

Understanding this is insightful as the observation centres around historic expertise in vaccines and biological manufacturing capability from GlaxoSmith Kline, AstraZeneca and the Jenner Institute (Oxford University).  There is a learning here too for the unfortunate circumstance of much of biopharma closing down antibiotic research (in reality because of lack of commerical markets arguably due to inability to be able to price effectively as generics for old drugs are cheap and systems won’t pay enough for novel antibiotics).

After arguably a slightly slow start US government, the BARDA programme, looks fairly effective and the US biopharma response across the spectrum has been pretty good (I’d also include most global biopharma where they have expertise eg Roche partnered with Regeneron as well as executing on diagnostics, Novartis where it had technology (hydroxychloroquine). 

China is hard to assess sitting at a desk outside China, but impressions also seem favourable given they have many shots in the leading group and the sheer number of smaller biotechs working in the area (see Milke Institute tracker) is large at earlier stage. 

Overall, this to me looks like a win for science and innovation and perhaps shows we as humans can still build things (fairly fast) when needed.

Background assumptions to consider:

Vaccine developers will begin delivery of vaccine at the earliest possible date of approval and deliver the purchased amount over 6 months. The exception to this logic is AstraZeneca where the purchase volume is significantly greater (although the terms of the agreement are unclear).

There is an adjustment from 'doses' to 'vaccinations' based on whether each vaccine will require a second dose (booster). Immunogenicity data from Pfizer, Moderna, AstraZeneca and Novavax all suggested that that a booster will likely be required. 

Limited EUA (emergency use authorisation) will likely prevent supply shortage even early on. If vaccines were approved for the entire US population in late 2020, there would be shortages until March 2021. Still this seems unlikely. The initial market entry based on EUA will be based on convincing efficacy data. In contrast, safety data will be broad (10,000s  patients) but of relatively short duration, as the trials are expected to accumulate events (infections) quickly. 

Given political pressures, historic risk aversion when full data lacking (also note recent complete response letters to novel treatments eg gene therapy haemophilia, JAK inhibitor, in Q2 / Q3 2020)  FDA would limit the use to high-need groups (essential employees, high-risk comorbidities). If this is the case, then pre-approval manufactured amounts will be sufficient to satisfy demand.

I would still support informed patient choice in this scenario (see my previous paper) but I doubt we will have it. 

Links:

My forecasting Primer including on drug probabilty forecasting.

Milken Institute Data

My early vaccine use idea based on patient choice.

Tyler Cowen on UK COVID response.

UK all cause death below 5 year average

UK all cause death now below 5 year average. (Still some COVID deaths offset by fewer non-COVID deaths).

Screenshot 2020-07-26 at 12.20.35.png

You can see the approx trend (ofc certain problems with data) on UK COVID deaths here from World in Data.

Screenshot 2020-07-26 at 11.21.08.png

Around 1200 to 1500 people die in the UK a day. As of end July around 60 of those deaths are COVID-realted. This suggests about 80 - 100 non-COVID deaths are currently not happening (although some of this is likely pull through where sick elderly died a little earlier in the year but were still likely to pass in 2020).

This - at least in the short term - suggest lockdown and perhaps certain areas of (lack of) activity are positive for death rate eg accidents, maybe drugs + alcohol ? I wonder about long-term eg diet and exercise? But, actually enforced home stay --> more home cooking --> healthier ? And maybe exercise is possibly over-rated??? (Maybe wishful thinking here).

In England and Wales you can see some COVID/Non-COVID splits here: (England/Wales were running below average in the early part of the year pre-COVID, so it’s possible there’s been a slight positive structural trend on a 5 year view eg via wealth and health effects, I’m unsure)

Screenshot 2020-07-26 at 12.31.20.png

Link to UK ONS here.

Link to World in Data.

Addendum: Turns out the Imperial team have looked at this. They note this:

Possible interpretations of excess non-COVID-19 deaths

If excess non-COVID-19 deaths are higher than expected deaths: First, it is possible that deaths actually caused by COVID-19 are incorrectly attributed to other conditions. This could be due to lack of a diagnosis, nonspecific symptoms before death, multimorbidity making attribution of death difficult, lack of knowledge by the reporting medical staff, or stigma-related concerns of family members. Non-COVID-19 related deaths could be genuinely higher during the pandemic. First, the pandemic has caused disruption to healthcare provision. Hospitals have cancelled elective surgeries in some weeks, possibly resulting in increased mortality in those patients. Second, even critically ill patients may be reluctant to access care, for fear of hospital-acquired infections. Both inability and reluctance to access care may have led to patients’ death, when they would have survived in the absence of the pandemic.

If excess non-COVID-19 deaths are lower than expected deaths: This finding could be due to irregularities in reporting. Second, the reduction in mobility and travel associated with control measures, particularly stay-at-home orders, may result in a reduction in accidents and associated deaths. Third, it is also possible that COVID-19 disease may cause mortality displacement, a short-term forward shift in mortality whereby a certain proportion of deaths due to COVID-19 occurred in patients that would have died of other conditions in the following weeks or months. This implies that over time, COVID-19 deaths that are higher than expected all-cause deaths are followed by lower than expected non-COVID-19 deaths in the following weeks and months, resulting in a deficit in excess non-COVID-19 deaths. In addition, hospitals have increased their capacity over time to treat non-COVID patients or patients changed their behaviour and started visiting hospitals again resulting in a reduction in deaths in line with expected levels.

Variations in deaths: The figures show steep increases and declines for COVID-19 deaths and unexplained deaths in some regions and for some ages over the weeks since March 2020. In some regions and weeks, excess non-COVID-19 deaths are even lower than expected deaths. These findings could have several explanations. First, case numbers vary over the pandemic, leading to variations in hospitalizations and deaths with a 2 to 3 weeks delay on average. Second, there may be irregularities in reporting. For example, in the first weeks of the pandemic, deaths due to COVID-19 may have been wrongly attributed to other conditions instead of COVID-19 but and in later weeks, non-COVID-19 deaths may have been wrongly attributed to COVID-19.

More details and splits here from the Imperial Team.

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