Tuesday, 14 April 2020

Opening up Germany in a Randomized Controlled Trial

It is now clear that for now Germany has managed to avoid spiralling into a situation where the new Coronavirus overburdens the healthcare system. In fact, I think we can say that the number of cases is declining.

So in Germany the discussion has started about slowly opening up society again. On Wednesday the 15th of April the government wants to decide what to do next week. While the number of confirmed infections is going down, I feel it would be good to basically keep the current measures in place for two more weeks. This would lower the numbers to where the tracking and tracing of infected people becomes an effective way to keep infections down, which means less restrictions long-term.

But we could use this two weeks for an experiment, which will help us make better decisions. The best experiments are [[randomized controlled trials]], where you have two conditions and randomly one of them. This is typically how new medicines are tested. Here one would randomly assign a pill or a placebo to patients.

In case of COVID-19 measures the two conditions could be a relaxation of measures or not. Because this is about the spread of a virus in a community, you cannot randomly select people, you will have to randomly select regions. As Germany is a federal state, a logical selection would be randomly assigning states, but you could also do it for municipalities. That would be better scientifically, but harder to implement.

Without mitigation measures one infected person infects 2 or 3 others. We have to bring this number below 1 to stop the epidemic. About half of the infections are transmitted by people with symptoms and half by people before they have symptoms. Some are transmitted by people who will never get symptoms and some via the environment, without direct contact. So quarantining people (with symptoms) is important, but not enough, we also need to reduce the number of physical contacts between people without symptoms, that means basically all of us. But it does not have to go to zero, which is why essential people are still working and supermarkets are open.

So we have to decide which physical contacts to allow until we have a cure or a vaccine and which ones we do not. This is a compromise between how important the contact is and how dangerous it is. Keeping supermarkets open is clearly important, people have to eat. Most dangerous are close contacts, with many people, over a longer time, inside buildings. Parties with thousands of people are clearly dangerous and, while nice, less important.

Those two decisions are easy, supermarkets open, parties closed.

The most difficult decision I see is about whether to open or close school.

On the one hand, this would be important. We cannot have our kids locked in at home, children need to move. We cannot have them miss school for one and a half year, the more so as this sacrifice does not help them as school children do not get ill. Children not going to school also prevents many parents doing essential work from going to work or working from home efficiently.

On the other hand, going to school would be dangerous. With many children, this means an enormous number of contacts. And it will be hard to change the behaviour of kids at school to reduce the contacts. (Within one class I am not even sure whether we should try.)

What makes the decision even harder is the uncertainty in how infectious children are. We know they can be infected, but as they do not have many symptoms, they may be less efficient in spreading it than adults.

So studying the influence of opening schools would be a good use of a randomized controlled trial. You could do this carefully by only having one or two years go back to school. Rather than switching from compulsory schooling, to closings schools, back to compulsory schooling, we could also make it voluntary. Parents who are in a health risk group could then opt keeping their children at home. While parents who most urgently need to work could opt to send their children to school.

Whatever we decide, I think it would be a good use of our time to use it for an experiment that helps us make better decisions about a disease we do not know much about yet.

Related reading

The German National Academy of Sciences, Leopoldina, released their recommendation this Monday, they recommend opening the schools stepwise: Dritte Ad-hoc-Stellungnahme: Coronavirus-Pandemie – Die Krise nachhaltig überwinden

A privacy respecting track and trace app to fight Corona is possible and effective

German public radio channel NDR Info makes a daily podcast with virologist Christian Drosten, on my blog you can find translations of parts of these interviews.

The German CDC, the RKI makes wonderful informative daily situation reports, in German and English.

10 comments:

  1. > we could also make it voluntary

    Are you sure Germans can cope with something that is in neither of the clear categories of "forbidden" and "obligatory"?

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  2. Opening the schools whilst secluding the oldest might work. Keep the grandparents away from society.

    The youngest might well be the most likely to spread the virus. Keep them away from those most likely to die from it.

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  3. William, yes, perfectly, and likely much better than your countrymen.

    I think the main reason the epidemic was so much better on Germany was that the population was well informed, cares for each other and performed most of the measures weeks before the last holdouts were forced to do so by making them law. When you look at the law, Germany did a lot less than France, Spain and after much delay England.

    England should really try to get out of their mental cage and stop focussing on the last war they think they won, while actually others won it for them. You can see in The Netherlands that you can live a content good life as a former empire.

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  4. Jsam, I wonder whether there is a good scientific basis for this idea of "let's keep the virus away from old people". The virus will spread in any network that has less than 60-70% immune people. When the rest of society has 60% (a big when) the virus would still rage any time it got into an elderly home because there the local circumstances would still favor its spread. When the virus is everywhere because you try to force as many infections as possible, it will also get into the elderly homes, no matter how well you try.

    And to get all of society to 60-70% immunity, you would have to have a huge number of deaths. Even with the large number of ICU beds in Germany, it would take years to reach herd immunity, if you do not want people to die because of lack of ICU beds.

    Having so many people infected also makes the chance of a mutation larger. Then we would have the same catastrophe all over again.

    So my guess is that we will have to wait until there is a cure or a vaccine.

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  5. New Zealand is trying for eradication. For a small island nation this may be possible. Some people in Australia are suggesting it may also be possible for a large island nation. It would have obvious advantages in terms of allowing the economy to resume normal avtivity, albeit without international students (one of our main export industries) or international tourists.

    Eradication

    People appear to have heard the statement that a vaccine would take at least 12 to 18 months as meaning that we will have a vaccine in that time, and, if we pull out all the stops, even sooner. In fact no one has ever developed a vaccine for any corona virus (not SARS, not the common cold) and it is not certain that it is possible.

    Similarly it is not certain that herd immunity is possible, though it is more likely. We do not know if recovered patients are immune or for how long.

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  6. Here in the UK the supermarkets have brought in a scheme where only a set number of shoppers are allowed in the store at a given time. The rest must queue outside.

    I tried to shop in the town centre today. Had I chosen to stay, I'd have been in a queue for an hour or so, whereas under normal circumstances I'd have been in and out of the shop in 10 minutes.

    I live in a fairly posh town where people are well behaved, so the people in the queues were maintaining a distance of 2 metres or more. But the received wisdom of the "safe" gap of 2 metres seems dubious to me - especially if you were downwind of a carrier. Are the supermarkets really making things safer by their policy?

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  7. @Wombat. Eradication sounds very optimistic to me, but could be worth a try. That will not be easy even in splendid isolation and you will still need some goods from overseas and with that people who operate the transport. But if you add really good testing it should be possible to keep the case numbers really low and thus to make the testing and tracking really efficient.

    SARS was gone before the vaccine was ready, but they did not find any stumbling blocks. Developing a vaccine for a common cold is a lot of work for a product likely no one would buy because it is just a cold and just one of the viruses causing it.

    It is an unprecedented situation, so no prediction can be made with absolute confidence, but it is quite likely a vaccine will work. The virus does not attack the immune system itself like HIV or try to hide like Hepatitus. Any individual attempt can easily fail, but there are so many, that I do expect one of them will work. A much more likely worry is when it will be there, 12 to 18 months is a neck-breaking speed never seen before.

    By definition we do not know whether there is long-term immunity for a new virus. But there is a strong response by the immune system, which makes it likely it will. Many seem to confuse that after some years anti-bodies can often no longer being detected with that the immunity is gone, normally also then there is still immunity, just not as strong any more.

    There are people worrying about immunity because of cases where people were "re-infected". Likely these people were simply still healing and there were a few throat probes that gave negative results, but the virus was still in the lungs (possible already dead) and then gave positive results again later. That is likely just noise. See yesterday's podcast with German virologist Drosten in German.

    It is good to plan for any eventuality, and trying to eradicate the virus or keeping the number of cases really low would fit to such worst case scenarios, but these scenarios are not particularly likely.

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  8. One of my supermarkets in Bonn now also does this. Once they even had someone to disinfect the cards. Everyone how has to use a card as they are used to count the number of customers. I tend to go late, when it is quiet (but also much stuff is sold out), even then it can be hard to stay 2 meter away from people inside.

    If the queue is exactly in the wind direction, standing in line for an hour may pose some risk, otherwise I would expect that it is quite save. The droplets with the most virus, will also be heaviest ones that drop to the ground fastest. We do not have to get the transmission of the virus from one person to the next to zero, just below one. We are taking these precautions to protect others, for any individual the risk is low.

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  9. In Australia supermarkets have to keep the number of people in their shop at a level which allows 4 sq metres per person. This often involves queuing to enter the shop. Most people allow two metres between them and the next person in the queue but some just don't get it and have to be told.

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  10. Eradication sounds very optimistic to me, but could be worth a try. That will not be easy even in splendid isolation and you will still need some goods from overseas and with that people who operate the transport. But if you add really good testing it should be possible to keep the case numbers really low and thus to make the testing and tracking really efficient.

    Ensuring that foreign crews of ships and planes are kept isolated should not be difficult. Ensuring that crews of Australian planes operating internationally are safe while overseas may be more difficult but should be possible - there are no Australian flagged ships operating internationally.

    At present (23 April) Australia has identified 6659 cases of which 5045 have recovered and 75 have died leaving 1539 current cases all of whom are in isolation. The current estimate of R is 0.78 and the only 0.15% of tests prove positive.

    The difficulty for eradication is, of course, the fact that many infected individuals are asymptomatic. The current plan is extensive testing with aggressive contact tracing (assisted by a voluntary phone app).

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