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.

COVID $1m+ in prizes

#COVID $1m+ in prize money for important: blogs, journalism, innovation, public policy and other COVID ideas. "The prizes on offer:

1. Best investigative journalism on coronavirus — 50k

2. Best blog or social media tracking/analysis of the virus — 100k

3. Best (justified) coronavirus policy writing — 50k

4. Best effort to find a good treatment rapidly — 500k, second prize 200k

5. Best innovation in social distancing — 100k

6. Most important innovation or improvement for India — 100k

What might be an example of a winning project? What if this attempt to build scalable respirators succeeded? That would be a natural winner. Or a social distancing innovation might be the roll out of more meals on wheels, little libraries, online worship, easier ways to work from home, and so on. The vision is to give to people whose work actually will be encouraged, not to give to Amazon (sorry Jeff!), no matter how many wonderful things they do. These are not prizes you apply for, they will be awarded by Emergent Ventures when a significant success is spotted." …. via Tyler Cowen, Marginal Revolution - Emergent Ventures.

Details here.

COVID, resources, notes, thoughts on present and future

As of 7 March, my updated view (subject to wide change). COVID is worse than seasonal flu by 10x - 20x and Pandemic flu (Swine Flu) by 4x, but the worse case panic (eg Spanish flu, 1918 )is overstated because treatment is likely (60% chance IMO) coming in 6 months and there is decent chance (but not overwhelming) that hot weather will slow progression (although not completely halt). So reality lies between, “don’t panic, it’s flu” and “panic, it’s Spanish ‘flu pandemic”.

IMG_1401.png

Risk is around healthcare services being swamped by exponential growth of critical cases before treatment is approved. Medium-term (1-2 year), est of 50% infection rate is plausible. 6-12 months for treatment (80% chance, my view; remdesivir my top choice, baricitinib others possible). 24 month+ for vaccine (70% chance, timing a challenge).

IMG_1381.jpeg

The political fall out is unknown. The US has been unexpectedly poor. South Korea and Singapore have been (expected?) good. China after a (arguably) slow start has since performed strongly. UK response (as judged by testing seems OK but NHS beds already stretched over winter.

The second order economic impact also quite varied, base case is a 6 - 12 month slow down (50% recession chance) with recovery thereafter, but with downside risk from US particularly given impact to small business. Markets to remain volatile. (OECD downgraded World GDP from 2.9% to 2.5% on containment scenario, but would fall to 1.5% under a non-containment scenario).

Good single source data: World In Data

Useful Dashboard from @avatorl

Further round up below.

Present

-WHO report and collections of COVID resources

-Prediction markets

-My notes from healthcare conference 

-health/economics/social/market impacts

Future

-what to do about  future pandemics

-incentives for innovation and stores of knowledge

-dissuade state-appropriation, but increase state capacity

I thought I’d put my growing collection of COVID thoughts in one place. There is much expert information on the web so I would point you to that. I have studied healthcare investing for 20 years, but the still puts me in a distinctly amateur category. My major contribution here is to think about what to do about the medium to long term, as it looks highly like there will be recurring pandemics (as there have been before). But before getting to that have a look at a collection of papers sources to start.

Current Resources

On what to do this is WHO: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public. (Mostly you can find advice on this readily on the web)

This WHO report: Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) is pretty much (as of early March) one of best details one stop information sources. 

“…In the face of a previously unknown virus, China has rolled out perhaps the most ambitious, agile and aggressive disease containment effort in history. The strategy that underpinned this containment effort was initially a national approach that promoted universal temperature monitoring, masking, and hand washing. However, as the outbreak evolved, and knowledge was gained, a science and risk-based approach was taken to tailor implementation. Specific containment measures were adjusted to the provincial, county and even community context, the capacity of the setting, and the nature of novel coronavirus transmission there.

…. China’s bold approach to contain the rapid spread of this new respiratory pathogen has changed the course of a rapidly escalating and deadly epidemic. A particularly compelling statistic is that on the first day of the advance team’s work there were 2478 newly confirmed cases of COVID-19 reported in China. Two weeks later, on the final day of this Mission, China reported 409 newly confirmed cases. This decline in COVID-19 cases across China is real…”

But

“…COVID-19 is spreading with astonishing speed; COVID-19 outbreaks in any setting have very serious consequences; and there is now strong evidence that non-pharmaceutical interventions can reduce and even interrupt transmission. Concerningly, global and national preparedness planning is often ambivalent about such interventions. However, to reduce COVID-19 illness and death, near-term readiness planning must embrace the large-scale implementation of high-quality, non-pharmaceutical public health measures. These measures must fully incorporate immediate case detection and isolation, rigorous close contact tracing and monitoring/quarantine, and direct population/community engagement.”

Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China. Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention (Feb 24)

Also very good overview of China situation. JAMA article: https://jamanetwork.com/journals/jama/fullarticle/2762130

There are many non-symptom carriers (see notes below from HC conf). But NEJM letter shows it by case study: https://www.nejm.org/doi/full/10.1056/NEJMc2001899

My own notes on COVID from a recent healthcare conference are here:

Notes on #COVID from Healthcare Conference (Boston). 

Prof. Suggests many (>50% ?) of ppl at conference likely already exposed. 

40 - 60% eventual exposure rate for US population plausible (and in his view likely but timing unknown). 

(Based on Washington State and several papers) seems many ppl show no/mild symptoms, many still have virus post-symptoms, unknown if still shed virus post symptoms/asymptomatic but likely. Many likely undetected so death rate still unclear. Info. v. Fluid. (Lots of papers suggest this, also suggestion two strains already in circulation, one more virulent)

Good news: Children seemingly not at higher risk of death. 

Bad news: Elderly, and already ill, at higher risk. 

Unknown but possible: 

-if summer/heat will kill off virus (to what extent, as it is heat sensitive; but it’s novel)

-if mutation and numbers make this another seasonal infection on going (hiigh uncertainty, but mosre seem to be leann this way)

US hosp. Could be overwhelmed (mixed views in room, decent votes for stretched, decent votes for very overwhelmed). 

Future cures/vaccines: Possible treatments in 2020 (not advice, but Gilead’s Remdesivir on treatment, Incyte/Lilly’s baricitinib; Moderna on speed of its novel vaccine) plus quite a few more.

Commercial vaccines not likely for 18-24 months+, but from 2022 vaccines possible + maybe routine. Treatment could be in 2020.

Large debates on exponential compounding (or not) and views on risk plus uncertain second order impacts on business, supply chains, remote working, politics etc. Plus observations that if we can manage for COVID can we manage for eg. Air pollution or other big killers.

Now for more quirky resources:

A daily newsletter summarising developments: https://cronyclecovid19.substack.com/

This GJ Open Prediction market on COVID. I am participating (and along with other questions). My Brier score current 0.7 vs crowd at 0.8 (so I’m 0.1 better - scale is 0 to 2), but some of the questions very hard!

Screenshot 2020-03-05 at 09.36.31.png

It really focuses the mind if you try and actively predict and record why you are predicting an item.  https://www.gjopen.com/challenges/43-coronavirus-outbreak

In that worth looking at Tyler Cowen’s column on exponential growth forecasting (and compounding) vs base rate effects.  https://www.bloomberg.com/opinion/articles/2020-03-03/how-fast-will-the-new-coronavirus-spread-two-sides-of-the-debate

And my own previous blog on how to forecast drug success rates.

Future

Very broadly there are a few interlinked impacts to think about.

  1. Public Health impacts

  2. Economic Impacts

  3. Social Impacts (cultural change, and interlink with economic)

  4. (Maybe less important but who knows) Financial market impacts

My sense is that people in the US thought the US system would have handled this better (especially the testing, which is behind). And while the population in China are upset and emotional, the WHO have come down positive on China’s handling, and looks like South Korea and Singapore also faring well. The end game looks like 50%+ of US (and world) eventual infection. Death rates are always difficult to put in context - as most people had no idea that season flu was such a big killer, and most completely underestimate the killer effects of eg. Air pollution.

Still - my *amateur* sense is that this is broadly in the 2009 swine Flu pandemic bucket. This was:

“…estimated that 11–21% of the then global population (of about 6.8 billion), or around 700–1400 million people contracted the illness -  About 150,000–575,000 fatalities..” see https://www.cdc.gov/flu/spotlights/pandemic-global-estimates.htm

So if COVID is going to hit about 50% - that’s about 4bn people (or 4x swine flu), with an unknown death rate.

If the range is 0.01% to 3% (worse case) that’s about 400,000 to 140m deaths.

IMG_1398.png

The Economist put it:

A broad guess is that 25-70% of the population of any infected country may catch the disease. China’s experience suggests that, of the cases that are detected, roughly 80% will be mild, 15% will need treatment in hospital and 5% will require intensive care.

So it’s in line.

Set against that is if drugs we have are effective and when (and there’s good reason to believe that we have some effective treatments which we are testing now) and longer term how quickly we can develop a vaccine.

There is also going to be much scrutiny about capacity in this area.

The above picture is why some are calling for much stricter/organised public health interventions. They argue that flattening the potential exponential growth and extending the time allows for treatments and less stress on health capacity.

Especially it is about 5% of cases in ICU eventually.

(2) China is showing signs of slowly starting a normalising process - from companies I speak to - but it looks like economic impacts from lost work and supply chains etc. will last longer than recent swine flu or SARS.  So 6 to 12 months+. A good portion of that doesn’t come back. (eg a shoe maker who makes a shoe a day, is going to lose all those shoe-days) but productivity levels should come back as it has done previously.

So large short term impact, but world recovers. This is essentially the Ray Dalio view (see end) but large uncertainty and caveats. This is mostly because of the intersection with social-politics eg inequality, wroker protection. If people are forced not to work, and they don’t have any safety net then this hits poor people and gig economy people potentially very hard. Lots more possible here to think about.

(3) More lasting could be social impacts. Will we find new ways of working and learning? That actually work for us. Will remote working start to show its worth. How will we think of events? 

How will US politics change ? China politics ? Singapore has seemingly strengthened its reputation. Healthcare could rise up the US political agenda and weak economies tend to be no good for incumbent politicians. Will this be bad for Trump?

Does China become restricter or does free speech become easier?

Could this be better for the environment? Air pollution?

Will we travel less for a time? Or even longer?

How successful will our open collaborations be? Will this spur future investment in more healthcare infrastructure and genomic technologies.

Will this cause a re-think of long global supply chains, and spur investment in local supply for food, energy, staples? Does this strengthen localism? Populism?

COVID is going to throw many of these social-political questions open. Especially the intersection with the poor and the healthcare questions in the US.

(4) Markets both debt and equity have displayed volatility as they deal with both emotion and evolving data.

To the extent that they impact funding for businesses (eg capital raising for innovation) and that bear markets are hard on the psyche then they may have an evolving role.

But mostly (from what I see) economists (eg Larry Summers, Jason Furman) have identified fiscal responses as most appropriate. See: https://www.washingtonpost.com/opinions/2020/03/03/how-economic-policymakers-can-respond-growing-economic-shock-coronavirus/

OK. On to my contribution here about the long term and innovation:

Future innovation

Pandemics are very likely (over 90% chance) to occur (again) over the next 50 years and likely over 100 years+ time frames. This pandemic was predicted by pandemic experts.

This is because:

-humans are increasingly interconnected at speed

-the way we treat/breed animals is not changing any time soon

-wet markets and similar not likely to change soon (though I think in eg China there will be a crack down)

-current viruses/germs eg influenza, pneumonias have been around for 1000s years

-virus/germs will constantly mutate

-containment will slow, likely never stop, transmission

I don’t have more room to explain these assumptions but will leave links at the end, but if you don’t accept this premise then you will under-rate what follows

What to do about future pandemics

-cultural learnings eg greetings

-innovation

We can slow transmission and in small cases potentially even stop by a change in cultural norms. We know the behaviours - washing hands, hygiene, don’t shake hands, cough into elbow  - but compliance can be greatly improved. This is inexpensive. Still, it is unlikely to stop all future pandemics. It’s worth recommending more strongly. Sanitation has already given use huge gains here and can gives us further gains.

That leaves us with treating pandemics and vaccinating once pandemics start. This is a question of innovation.

Incentivising Innovation

The market arguably has inefficiencies with dealing with i) rare diseases and ii) developing world diseases and iii) diseases that have not occurred, but we can predict are likely to occur.

This is due to those markets being risky and/or commercially small and/or commercially small risk-adjusted (a market might be worth $2bn but at 1% chance of success, $20m risk-adjusted would be of small value).

Policy solutions that have (at least partially) worked have been  a) granting longer/extra intellectual protection for rare diseases and b) agreed forward purchasing contracts for developing world diseases.

(a) Has helped areas such as rare genetic diseases, and multiple sclerosis (and other classified rare diseases) in the developed world (mostly) and 

b) has helped in malaria and certain other developing world diseases (where commercial markets are smaller) - forward buying by the Gates Foundation amongst others.

Such mechanisms have mostly failed in I) developing new antibiotics against resistant strains, II) certain other developing world diseases,  III) pandemics.

One negative factor in this is state appropriation of (mostly) private innovation. Rich countries eg US have been guilty of this as much as poor countries. The US essentially disregarded protection (or threatened to break the patents) on anthrax treatments in seeking to stockpile such medications cheaply. [https://www.wsj.com/articles/SB1003966074330899280 ]

This causes a large disincentive to work on vital areas, if profit-seeking entities will lose out on their R&D development costs for such treatments.

I would propose:

-partial speed up of regulatory response for areas of unmet medical need

-international “state capacity” in anteviral, antiobiotic, mRNA, pandemic research

-forward purchase fund for pandemic vaccines and medications

Partial speed up of regulatory response for areas of unmet medical need

The gold standard in medical research are randomised controlled trials (RCTs). They are costly and slow, but typically generate the most robust results.

For low commercial value areas, RCTs (and previously trials needed before RCT) are too costly for entities to perform give the risk. 

But, mostly health regulators will need RCTs before approval of a drug to be able to know the risk/benefit of a medication vs standard of care.

This has led some thinkers (eg Peter Thiel) to argue that regulators need to change or relax standards to allow quicker and more innovation on to the market. The challenge is that this may let onto the market ineffective treatments that cost lives or damage the credibility of the system.

One compromise would be to let medications on to the market where - in a controlled fashion - when there is enough evidence of safety/efficacy but no RCT. A full approval would be contingent on  future RCTs being performed in a reasonable time frame else the drug would be with drawn from the market. The drug would also be withdrawn if the RCT fails.

If medications for areas of high unmet need - for instant pandemics or other diseases with limited treatment options - would be released this way, the net benefit would be positive.

Industry would pay for such a faster service, and this could cut drug development time in half.

International/national “state capacity”

Faster regulation alone would not help unless there were medications to test.  Given the long and uncertain cycles for viral pandemics, it’s beyond the risk tolerance for many private entities. There are further complications because mutations might mean the plan A vaccine proves to be relatively ineffective and has to be made again under plan B.

However, I believe this is an area where even libertarians or perhaps “state capacity” libertarians might concede a non-private institution or set of institutions might be useful.

Essentially, I would be arguing for a form of Health ARPA where a part of the HARPA is focused on pandemic anteviral research, and antibiotic research and possibly other areas of unmet medical need. This is a sibling idea to the NIH but more targeted at likely pandemics.

If such an organisation had capacity to response quickly to evolving pandemics, then it should be able to share royalties with any other parties needed to scale medications to commercialisation, if it needed private partners to help scale quickly.

There should be positive spillover (cf NIH) in the years when no pandemics occur.

Forward purchase fund for pandemic vaccines and medications

Now (A) We have an organisation that can respond quickly with a new medication, and (B) a regulatory process which can speed through medications for high unmet need (eg pandemic) but how will we pay and keep incentives especially if we need multi-stakeholders to develop the medication.

This is where a forward purchasing fund or contract comes  into play. This fund acts as a guarantee that a certain amount will be paid for the innovation in a swift manner.

On the one hand this should give a guarantee to private or other players that the innovation won’t be appropriated for nothing. But, also given that it’s a guaranteed market, and the risk is lower, the price for the medication can be set in a more fair manner especially for poor countries (cf HIV).

This is similar to were the Global fund and GAVI already sit. I do note the US govt has approved funding quickly on COVID, but still better to have it already in place.

Conclusion

Given pandemics will re-occur, we should look to set up capacity to deal with pandemics, regulation that can be swift and responsive and a fund to guarantee a fair price for innovation and set incentives accordingly

Post Script: It turns out Bill Gates haas also written on this topic and he many similar ideas and sources (and talks more about infrastructure build) examples of certain pandemic preparation here. https://www.nejm.org/doi/full/10.1056/NEJMp2003762

On why Pandemics will (re)occur: https://www.worldbank.org/en/topic/pandemics#1

Ray Dalio on COVID

Life expectancy Race, child mortality and GDP

Looking at how life expectancy has risen globally and in a few countries over time.

A large driver of this has been the fall in childhood mortality.

This paints a picture that we’ve achieved much but we still have many challenges to go.

GDP is up. Ideas are up. But other aspects like natural capital are down. And deep poverty while down is still in the hundreds of millions.

UK life expectancy and healthcare spend vs OECD. NHS success story?

UK life expectancy expanded - in line with the OECD average (more or less, there was a little catch up) until recently where (like in a few countries) it seems to be flattening. This is a blunt but well understood measure of a population’s health.

A similar type of trend can be seen in childhood mortality. Although experts can gripe with the data, the overall trend is likely robust. There is also some catch up from OECD average from a poorer start.

This is a good achievement by the UK given what the UK has spent on healthcare since the 1970s.

My general observation here is that the UK has underspend / invested less in healthcare but has managed to obtain an average to above average results.

The under spend as % GDP has been 2 to 4 percent points lower than OECD peers on average. This has been going on since the 1970s. (The World bank data is from 2000, sourced from WHO)

There are many factors that combine to impact life expectnacy and health. Correlation is not causation.

However, I think there is enough data and evidence to suggest that given the amount the UK has invested in health (and social care and education) that if the UK wants to continue the positive trends in health, it will likely have to spend more or at current levels of spend the health out comes will - in my view - likely to continue to tail off.

In this sense, the UK’s NHS has been a unique system that has enabled outsized gains in health outcomes for the amount of spend over the last 50 years.

OECD data.

OECD data.

I can’t make a nice graph widget, but I can show how this % spend on GDP goes back to the 1970s. so this is arguably about 50 years of under spend, at even the lower end of 2% of GDP that’s somewhere in the region of £500bn to £1,000 bn (yes 1 £trillion) in culmulative under spend compared to what would have been spent on the OECD average %.

(Now whether it would have been well spent or what else the UK spent the money on is another debate - maybe the OECD over spent given its outcomes… but given the UK is uniquely low (though Italy is close in some years and has slightly worse outcomes broadly) .

You can see how Germany is approx matching the UK since 1970 on life expectancy and trend (OK it did slowly gain beofre mathcing), but was spending much more of GDP to achieve that.