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.

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.

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

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.

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.

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 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 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).

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

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)

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.

What mindsets for investing markets can help with COVID thinking

What Markets can teach us

Markets are humbling.

As an intelligent - even extremely intelligent - young analyst. No matter how good she is. There will be decisions she misjudges. 

There are many uncertainties in markets and as I’ve referred to in my aphorisms - and others - one of the only certainties are the uncertainties.

The mental mindset to deal with those uncertainties and still make decisions - that have great weight as measures in millions or billions of dollars - takes training. By the time a young person forms into an adult much of that mindset may already be settled although more can be trained and the mindset can be continually worked upon.

This resilience or even antifragility (where you thrive on the uncertainty)  to deal with this in typical financial markets turns out to be useful for COVID.

There are uncertainties with COVID, tail (small but with large effects) risks, but decisions have to be made and may turn out to be wrong. Yet, you will have to make them.

Many analysts turn out not to be cut out for markets and investing as the strain on the mental mindset is too much. Unsurprisingly, COVID has caused strain on the mental health of many I know but there are lessons to be learnt for dealing with such risks.

• Rely and assess the data. (see previous thoughts on forecasting and decision making).

• Change mind if needed and reassess.

• Don’t let the weight of the decision damage you.

• You can control, what you can control.

• What you can not control - you have to make peace with - as it is out of your control.

The same can be said for living with many aspects of special needs (disability) or other circumstances…

Here’s a piece on finding insights in the ordinary or even “boring” from travels with autism: Mindfulness and trains and here on what do you “see” when travelling on trains and buses

My book of aphorisms

Previous blogs on forecasting and decision making

COVID, UK Critical care patient characteristics

• Cytokine Release Syndrome (CRS) + COVID

• UK ICNARC study (27 March)  of COVID and critical care (The ICNARC report contains data on all confirmed COVID-19 cases reported to ICNARC up to midnight on 26 March 2020 from critical care units participating in the Case Mix Programme).

A smart correspondant to Tyler Cowen writes:

“I’ve now seen multiple studies suggesting that up to 80 or 90 percent of patients who end up on ventilators ultimately die. At this point, I guess there’s no way to know if the other 10 percent would have lived without the ventilators.  From what I can tell, most other hospitalized patients are getting supplemental oxygen, IV fluids and antibiotics.  I have not seen any evidence on the effectiveness of these treatments.  Many of those patients live, but we don’t know whether they would have recovered without hospitalization.  It would obviously be impossible to do a RCT on that at the moment… “

My reading of those studies is that the death rate - on average - is lower than that - not typically as high as 90% - (the one below is 66%) if you look at the spread of studies. Still, the thrust of the argument is taken.

I have two observations around:

1. Cytokine Release Syndrome (CRS) + COVID

2. UK ICNARC study (27 March)  of COVID and critical care.

On,

1. A significant number (although exact % seems to be varying) are dying due to the “cytokine storm” or cytokine release syndrome (CRS) that can happen in late stage COVID infection. CRS is an indirect effect (of the immune system going into inflammatory overdrive) which can be devastating. 

The Roche drug, an anti-IL-6, Actmera (or tocilizumab) is know to have an anti-CRS effect. The drug is approved in China and is in trials in US. Roche donated drug to Italy as well. Other anti-CRS drugs are also being tested for COVID-related CRS (eg Incyte’s ruxolitinib)

To the extent that ventilators can keep you alive while treatments come on board for CRS, if you develop it, I would expect that to be a positive outcome of critical care.

You will not survive CRS outside of hospital.

As yet, not everyone is using tocilizumab as it’s not approved although mostly the doctor community is aware (I sesne as it’s used against CRS in other areas (for instance, CRS is a major side effect of certain CAR-T cell therapies and anti-IL-6 is used in that setting).

2. There is a small study out of the UK that has compared COVID critical care outcomes to viral pneumonia outcomes. This is not a RCT but it gives some speculative insight:

COVID is hitting males harder (this seems to be now seen in multiple studies). 71% (COVID) vs 54% (viral pneumonia)

Mechanical ventilation: 79% of COVID  vs 43% (viral pneumonia, VP)

Survival:  52% (COVID) vs 78% (VP)

Of those who received advance respiratory support 34% survived still low (but not as low as the 80 - 90% figure).

In sum, to me that suggests while hospitalisation is not as life saving as it is with viral pneumonia, there is a benefit to lives saved. One other trade-off is the risk to healthcare workers - especially if the theories around viral load (that doctors are receiving large doses of virus and this is causing more severe disease) are true.

Addendum: FT article looking at Venice vs Lombardy and suggesting hospitals in Lombardy a source of infection

Sources:

Tyler Cowen’s Marginal Revolution Blog: https://marginalrevolution.com/marginalrevolution/2020/04/how-many-lives-is-hospitalization-saving-in-the-pandemic.html

ICNARC study: https://www.icnarc.org/DataServices/Attachments/Download/b5f59585-5870-ea11-9124-00505601089b

Paper on COVID and CRS, Cytokine Release Syndrome: https://www.sciencedirect.com/science/article/pii/S0924857920301047

Lancet article on CRS and COVID: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext

Covid. England, Notes from epidemiologist, Neil Ferguson.

-Current England strategy = <20K Deaths from COVID (vs 500k no strategy)

-Peak ICU demand in 2.5 to 3 weeks 

-With current strategies + recent surge in NHS capacity = ICUs will have enough capacity though may get close on local level.

-Testing needs significant ramp for strategy shift in 3-4 weeks

-Current strategy => 5 - 10% London is infected, will vary across country. 

-Without suppression/current strategies, Ferguson et al model still suggests 500K deaths and overwhelmed health service 

-Original modelling did not include much on testing + contact tracing as Public Health England made clear that testing was not going to be anywhere near sufficient in Feb/March. 

Notes on listening to epidemiologist, Neil Ferguson (NF), give evidence to Parliament Select committee. Video is below + links to papers. Matters still moving fast and there’s uncertainty (though NF expresses reasonable confidence at times) but as of 25 March, this provides a base case scenario for England. This are my interpretations of the meeting, mistakes possible. Full video source is below. Full Transcipt available here.

-SAGE gives advice on science, does not set policy.

-On assessing true NHS capacity - especially for mechanical ventilation and ICU - was only available in early/mid March.

-Based on original capacity estimates, NHS would be overwhelmed 8x without suppression

-NHS has brought on new capacity as of mid March, but would still be overwhelmed 3x without suppression. NHS capacity estimates are rising.

-“Reluctant” conclusion that suppression only viable strategy. Reluctant because of huge economic damage. 

-UK examined many strategies. (A few other counties did too, but UK comprehensively looked at many strategies).

-“Reasonably Confident” that with current strategies + recent surge in NHS capacity then NHS  ICUs will have enough capacity nationally. It may get close on local level. (BY, I had the sense it might get very close on local levels from the tone of his response. Increase NHS capacity from eg “Nightingale” hospitals being built in a few days in several places eg London ExCeL Centre).

-On why we could not follow a South Korea “Contact + trace” strategy:

-Very clear that England did not have testing capacity in Feb to do this

-South Korea also has distancing and other strategies not only testing

-Very clear mass testing is very important going forward

-Peak infections in London - many variations locally -  likely to be 5 - 10%.

-Current England strategy = fewer than 20K Deaths (vs no supression strategy or no strategy = 500K deaths)

-Peak ICU demand likely in 2.5 to 3 weeks (from 25 March)

-Suggestion that in 3 to 4 weeks, a shift in strategy will be needed. Implication that this shift will need mass testing.

-There is an impact on health from economic damage. This work was mostly weighting the strategies needed to keep the NHS from being overwhelmed

-Summer may have an impact on virus transmission. NF suggests this may only be in the 10% to 20% range based on other viruses. Expressed uncertainty here.

-Reproduction rate “What we can see though in Europe in the last week or two is a rate of growth of the epidemic which was faster than the expected from early days in China. And so we are revising upwards our central best estimate of the reproduction. To something more a little bit about of the order of 3 or a little bit above rather than about 2.5 levels”

-“Adds more evidence to support the more intensive social distances measures applied this week because of the the higher the reproduction number…But the current value is still within the wide range of values modelled previously”

-Suggestion that vaccine or similar or transition first (BY: a testing + tracing? is an exit strategy as suppression not sustainable long term. (BY: That’s why my idea focuses on vaccine speed).

NF is suffering from COVID himself. Tyler Cowen awarded his group one of the first prizes from his awards on solutions to COVID-19 (Emergent Ventures). I believe the committee was focused on England as opposed to the whole UK.

The whole set of papers from SAGE can be found here and his video evidence plus more evidence is in the video below. SAGE =Scientific Advisory Group for Emergencies.

The Imperial College papers are here. The link to the video is here on Parliament TV.

My thought on speeding the pathways on regulatory approval for vaccines.

---

There are a set of valid criticisms/queries on (amongst many others):

-whether SAGE took enough evidence from Chinese scientists and others outside of UK

-why UK testing hasn’t scaled up faster (and involved those who do have testing capability)

-why preparedness was not better given . eg SARS-classic, and many thinkers (eg Bill Gates) forecasting the scenario we are now seeing.

But, IMO, there are misplaced criticisms on the Ferguson model and what it was suggesting. It was this model that convinced UK government to move to a supression strategy to keep from overwhelming the NHS. This has almost certainly saved thousands of lives and not overwhelmed the NHS albeit at an economic cost that also has second order negative impacts. (Note, a skeptical view can be found at Hector Drummond)

Full Transcipt available here.

Policy Idea: Regulators Could Allow Early Use of COVID-19 Vaccine or Treatment

My paper was accepted by the Mercatus Center at George Mason University:

Quickly developed therapeutic, prophylactic, and vaccine treatments will be essential to defeat the COVID-19 pandemic. Standard regulatory and development protocols typically yield drug development in 6 to 11 years. However, experimental vaccines and prophylactics against COVID-19 are in development and currently in trials, making deployment after safety trials feasible within months. Though efficacy of these treatments is uncertain, with probability of success, on average, at just 16 percent, efficacy can still be tested in real-world settings by adopting an approach that allows patients to begin drug treatments earlier in the regulatory process.

After phase I trials have been completed and data have been gathered, an expert committee should be convened to advise on the risk, benefit, and chance of success of the novel agent with a view toward distribution to the public through patient choice. There is limited downside risk and a good chance of a positive outcome with this approach. The US Food and Drug Administration (FDA) has the authority to approve pharmaceuticals requiring further trials, but the success of this approach will depend on coordination between sponsoring research organizations, trial designers, and regulators. International pharmaceutical regulators, such as those in the United Kingdom, Europe, or Japan, can also adopt this approach.

At this point, a clear indication of regulators’ openness to this approach would provide certainty for organisations and accelerate development of possible vaccines and treatments. When adjusting for probability, this approach may save hundreds of thousands of lives in the United States and more globally.

More here at this link at Mercatus. Or full PDF here.

Under a traditional approach, a 50 person phase I trial might not be considered enough data to make strong judgments on safety and efficacy. It’s considered exploratory. However imagine…

10 separate Phase I trials (or trials with adaptive design) start in April 2020 across multiple countries. Patient numbers and characteristics (eg age, presence of COVID-19 antibodies, sex) are careful considered. The statistical power of multiple trials is stronger than one or two trials. 10 trials of n = 50 (say, up to 100) could be run in US, China, Italy, UK, Germany, France, South Korea to name a few countries with R&D capabilities with either commercial or non-profit led organisations that could run such trials. Results could be available in July. These data would include safety data, and preliminary measurements of efficacy such as COVID-19 antibodies.

Each interested country could convene its own expert and stakeholder committee. That committee could vote on if tentative approval should be given based on a benefit and risk assessment of the data. This meeting should be held in public and take submissions from stakeholders potentially replicating FDA advisory committee meeting processes or similar. A citizen’s jury process could run given the state of public interest.  

In an optimistic scenario of no safety signals and strong efficacy signals, this would allow a September 2020 launch with high risk populations such as over-65s and healthcare workers prioritised. This is subject to commercial scale up of manufacturing. Funding for this should be given in April in hope of a positive scenario. In a pessimistic scenario, negative safety signals would not warrant tentative approval. The downsides would be limited to the volunteer trial participants and the investments taken.

The cost of running 10x phase I/II trials now is perhaps between $200m to $1bn. Given that this could solve the problem - it seems to be something that governments should be doing or incentivising. Especially vs fiscal bail outs wheich are 1000x this amount.

Now the data might come back negative - in which case there is no quick vaccine. But, if there were very strong efficacy signals and no safety signals then this should be something for governments and regulators to consider.

COVID, UK Imperial College team, modelling scenarios

Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand…. The Imperial team, led by Ferguson writes:

“The global impact of COVID-19 has been profound, and the public health threat it represents is the most seriousseen in a respiratory virus since the 1918 H1N1 influenza pandemic. Here we present the results of epidemiological modelling which has informed policymaking in the UK and other countries in recent weeks. In the absence of a COVID-19 vaccine, we assess the potential role of a number of public health measures –so-called non-pharmaceutical interventions (NPIs) –aimed at reducing contactrates in the population and thereby reducing transmission of the virus. In the results presented here, we apply a previously published microsimulation model to two countries: the UK (Great Britain specifically) and the US.

We conclude that the effectiveness of any one intervention in isolation is likely to be limited, requiring multiple interventions to be combined to have a substantial impact on transmission.

Two fundamental strategies are possible: (a) mitigation, which focuses on slowing but not necessarily stopping epidemic spread –reducing peak healthcare demand while protecting those most at risk of severe disease from infection, and (b) suppression, which aims to reverse epidemic growth, reducingcase numbers to low levels and maintaining that situation indefinitely.Each policy has major challenges.

We find that that optimal mitigation policies (combining home isolation of suspect cases, home quarantine of those living in the same household as suspect cases, and social distancing of the elderly and others at most risk of severe disease) might reduce peak healthcare demand by 2/3 and deaths by half.

However, the resulting mitigated epidemic would still likely result inhundreds of thousands of deaths and health systems (most notably intensive care units) being overwhelmed many times over. For countries able to achieve it, this leaves suppression as the preferred policy option. We show thatin the UK and US context, suppression will minimally requirea combination of social distancing of the entire population, home isolation of casesandhousehold quarantine of their familymembers. This may need to be supplemented byschool and university closures, though it should be recognised that such closures may have negative impacts on health systems due to increased absenteeism

The major challenge of suppression is that this type ofintensiveintervention package –or something equivalently effective at reducing transmission –will needto be maintained until a vaccine becomes available (potentially 18 months or more) –given thatwe predict thattransmission will quickly rebound if interventions are relaxed. We show that intermittent social distancing –triggered by trends in disease surveillance –may allow interventions to be relaxed temporarily in relative short time windows, but measures will need to be reintroduced if or when case numbersrebound.

Last, while experience in Chinaand now South Korea showt hat suppression is possible in the shortterm, it remains to be seen whether it is possible long-term, and whether the social and economic costs of the interventions adopted thus far can be reduced.

Full Paper here. As of 16 march 2020. Whole paper is accessible to the lay person although does contain some technical terms.