Wednesday, February 03, 2021

Randomized Controlled Trials and Covid-19

 Usually drug trial are divided in four phases:

 - (optional: phase 0): initial studies in animals and low doses for humans

 - phase 1: basic exploration. How does the medicine work? Is it safe? What dose is optimal?

 - phase 2: small scale test (25-100 patiĆ«nts): does it work?

 - phase 3: in a Randomized Controlled Trial the medicine is compared to placebos or existing products.

With the corona epidemic only phase 3 studies are done. The excuse is that we are in an emergency and that speed is essential. 

Sounds reasonable. Problem is that even if it results in a workable solution it may not be the optimal solution. We saw that illustrated when AstraZenica accidentally found that giving half a dose in the first round worked better. It may very well be that doses for other vaccines are far from optimal too. And although the claims of 90+% effectiveness for some vaccines may seem to leave little room for improvement both their need for a second dosage and their considerable side effects suggest otherwise.

The New York Times published an article "How the Search for Covid-19 Treatments Faltered While Vaccines Sped Ahead". According to the article:

The government poured $18.5 billion into vaccines, a strategy that resulted in at least five effective products at record-shattering speed. But its investment in drugs was far smaller, about $8.2 billion, most of which went to just a few candidates, such as monoclonal antibodies. Studies of other drugs were poorly organized.

But even given the 8 billion dollar expenditure, the results are very meager. Seeing how promising treatments like HCQ and Ivermectin are maltreated one has to wonder whether other motives play a role. Robert F. Kennedy, Jr. suggests that the interests of the vaccine producers play a role. If there is a medicine against Covid-19 it would no longer be possible to approve the vaccines according to the emergency rules.

What also plays a role that - given the absence of independent government institutes (many government paid experts have strong ties with the pharmaceutical industry) - it is hard to get the high volume research that would take away all doubts.

Thursday, January 28, 2021

The British variant of the corona virus: a sidestep?

There is a lot of noise about the B1.1.7 variant of the corona virus. This new "British" variant is claimed to be more contagious and more deadly. However, the evidence is mixed.

It started a few months ago when in most of Britain the number of infections was falling fast. There was one place that showed the opposite trend. Then some people noticed a new variety of the virus that included a mutation on the spike. A laboratory study that suggested that this variant is more contagious closed the deal. The hype about the British variant was born.

This evidence for a new dangerous variant is rather thin. There could have been other explanations for the increase in infections in this one place. Maybe they just had some superspreader event, like a big wedding or funeral or a bunch of youth partying.

England has nowadays a new wave of corona infections. But the great majority of those cases have the "normal" variety of the virus and it is usual assumed that lots of socializing around Christmas was the main cause and not the new variant.

Yet the new version is becoming more common. The question whether it is a second epidemic - as some publications suggest - or that it is actually replacing the old variant. My impression is the latter.

There are different models of how a flue epidemic works. And despite that corona is a more serious disease than the average flue my feeling is that such a model applies here too:

Every day we encounter some viruses. If it is a small quantity our immune system will deal with them. If there are too much we will get sick. It is well established that people will get more sick when they got a heavier dose of virus. The big question is whether when we meet a small dose that doesn't make us sick our immune system will build some resistance. My feeling is that it does. That would also explain why flue epidemics tend to disappear after one or two years. 

Already this summer we saw reports that corona seemed to have become less deadly. This showed that we were building up some immunity. This situation favors any variation that is just different enough to at least partially evade this immunity. Reports from Moderna that antibodies built by their vaccine were six times less active with the British variant confirm this image. For the strong immune reaction by the vaccine in a healthy person this may not be relevant as there is still enough residual resistance to avert infection. But for people who have built less immunity it can make the difference.

So the answer to the question whether the British variant is more contagious and more deadly is ambiguous. In the present situation it is - because we have less resistance against it. But if it had appeared in February it might well have been less dangerous than the variant that then became dominant. 

This might seem an academic discussion but it goes against the common narrative that the virus is becoming more and more dangerous with all those new variants (British, South African and Brazilian). As I see it the virus is mainly making sidesteps to evade the immunity that we have built. And my expectation would be that most of these sidesteps will be less serious than the original. The fact that they arise at such a late stage suggest that in an earlier stage they were less competitive. 

These new variants arise in former hotspots. Those are the places where people have built most resistance and as a consequence making a sidestep is the most profitable for the virus.

I don't see this as two separate epidemics. As I mentioned: the quantity of virus that you encounter determines how sick you become. Quite likely the two variants work together. So if you had already received 60% of your quota to become sick from the common variety you need only the remaining 40% filled in by the British variant. And as the British variant encounters less resistance in your body it has a better chance to become dominant once the illness starts.

So when one sees an effective reproduction number R of 0.9 for the common variant and 1.3 for the British (to mention just some of the many numbers that have been thrown around) one can take it with a grain of salt. The gap is mainly caused by the replacement effect.

Seeing the British variant as a sidestep changes how one evaluates it. No longer is it a sign that the epidemic is getting worse and worse. Instead it signals that the virus is under pressure and making an evasive maneuver. It is a first sign of weakness and as such reason for hope.

Sure, much of this is speculation. But it might explain a lot.

Thursday, December 24, 2020

The civil rights movement stopped the progress of the Blacks

 Recently the New York Time had an article "Why Did Racial Progress Stall in America?" in which the effects of the civil rights movement on the progress of Black people was discussed. The conclusion was sobering: In terms of material well-being, Black Americans were moving toward parity with white Americans well before the victories of the civil rights era. What’s more, after the passage of civil rights legislation, those trends toward racial parity slowed, stopped and even reversed.

The authors - who also wrote a book about the subject - seemed puzzled by it. For me it is a logical effect of polarization. As long as everything was quiet people tended to see Blacks just like everyone else. There was no reason to see them different.

Then came the unrest. Not only Martin Luther King, but also more radical Black leaders who claimed that Black were different and who didn't sound very friendly. There was also a lot of news about Black protests that weren't always that peaceful. That changed the picture for many White people. Sure, there might be some points in the Black arguments. But at the same time it was no longer possible to the Blacks as just another human being who just happened to have another skin. And when a situation becomes us-versus-them the default human reaction is to side with your own tribe.

That is also the reason why I find the present "sensitivity" campaigns against blackface, Confederate statues and other symbols so foolish. Study the 1500s and 1600s and you find stories about Catholics persecuting Protestants and burning them alive. Yet nowadays no Protestant will object against Catholic symbols for that reason. And that mutual tolerance was achieved without a phase of hypersensitivity. One day there may become a consensus that some people from the past don't deserve a monument or that some customs put some groups in a bad light. Nothing wrong with that.

But the present campaigns assume that things will also work in the other direction: that the more sensitivity you spread the more racism will decrease. But people are very good at detecting fakes. They can feel the difference between people who are really hurt by something and troublemakers who just feign indignation because they hope that it will lead to some desirable result. Such troublemakers mainly evoke resentment. Problem is that they may fool themselves to believe that they are sincere.

It is seductive to believe that the emancipation of women and blacks can follow the same pattern. But women and men are closely connected so the potential for polarization is limited. And once it became the norm for women to have a career they could when they grew up access the same cultural capital as their brothers. For Blacks there is a much bigger gap to cross.

We all know the studies that show that Blacks are underrepresented in certain professions - specially at the top. But a remedy is hard to find. Sometimes people can serve as role models. But when that becomes the main argument one will soon see counterarguments arising about quality.

Everyone has prejudices. The Implicit Association Test is a famous tool to prove that. But the best you can do is becoming aware of them and using your conscious mind to question them. Seeing a bunch of violent Black protesters or having a meeting with an aggressive Black person will teach the subconscious part of the brains of people such prejudices and are thus to be avoided.

Fighting racism is simple: just avoid and punish the excesses. Be aware that you too have prejudices and counter them. Most important: behave as if equality is normal. Sure, things will take time. But polarization is mainly counterproductive.

Saturday, August 08, 2020

Herd immunity is the wrong term for covid-19

It is well known that the severity of a covid-19 infection is directly related to the dose of virus that the patient encountered. A short encounter will seldom land you in the hospital. But having been in a small room for half an hour with somebody who is infected carries a significant risk.

 The question that is almost never addressed is what happens with all those people who get only very lightly infected. It is implicitly assumed that they don't build any resistance and will stay at risk of being infected.

I don't believe this. I consider it much more likely that the immune system each time builds a little bit of resistance. It may not be enough to make you immune at once. But very likely you will become less sick when you are infected with a heavy dose of the virus later on.

This makes the "herd immunity" discussion missing the point. Sure, you want that enough people to build immunity. But you want it to happen gradually. This may even happen one virus at a time.

We can see this light immunity already in action. In most areas covid-19 is nowadays much less deadly than a few months ago.

This is what naturally happens with influenza and corona viruses. Many people never get sick and yet after one or two years the virus disappears. Obviously they have built some kind of immunity.

One group that doesn't get this are the youth holding corona parties. Instead of building immunity with low doses they take a high dose at once - and take a considerable risk.

The other group that doesn't get it are the countries that impose a heavy lockdown. Yes, you may drive down the number of infections that way. But as everyone is locked up they don't get the light infections either and they don't build resistance. So those countries carry the highest risk for a second wave. 

It is Sweden that has understood this model the best. They underestimated the initial deadliness of the disease and as a consequence initially provided insufficient protection to vulnerable groups. But they were right to put the focus on stopping mass meetings and other situations where heavy infections were most likely to occur while simultaneously allowing lower intensity contacts to proceed normally.

Sunday, May 31, 2020

Inequality - Economics 101

In the long term an economy should be in equilibrium. That is: in every part of it as much money should go in as goes out.

The present Western economies obviously aren't in equilibrium: inequality is increasing. As the rich spend less and differently that means falling demand for many products. To repair that we have quantative easing - the cowardly cop-out by politicians afraid to raise the taxes on the rich. The problem is that it is not a real solution: after some time all the extra money will leak away towards the rich and the next stimulus is needed.

The world has faced a similar situation in the 1930s. Roosevelt too faced the problem that he needed to keep stimulating the economy. As soon as he relaxed the depression came back. Things only changed structurally after the war had led to a huge increase in the taxes for the rich.

Of course it is possible to imagine a country that is stable at a larger inequality. Piketty describes it as the 19th centrury's Jane Austen society. And at the moment Latin America still has a very similar society. But such a society as a whole is by definition poorer. Inequality is primarily about driving the poor in a more dependent position. They will get worse education, spend more time unemployed and their economic position will be more unstable. There needs to be a permanent "labor reserve" in order to keep the wages down. As a consequence their contributions to the economy will decrease. The contributions of the rich - on the other hand - will not increase: they will just get a bigger part of the national wealth at the expense of the poor.

Rising nations typically put a lot of effort in providing education, healthcare and other services to the whole of the population. They know that that is the key to economic growth. Even retirement benefits fit in that goal as they liberate the workers to focus on their jobs. But in the rich countries that goal tends to slowly get lost. Those still supporting more equality start to use bland arguments like that it is a sign of civilization. But that is a very subjective argument that can mean different things to different people.

So the road towards a more unequal society is a road with a shrinking economy. And that also means a shrinking tax base. This at a time when the demands on the system will increase due to an increase in the number of poor. That will cause demands for government budget cuts, resulting in more poverty. So there is self reinforcing process going on here.

The corona crisis has a very bad effect. Many people saw their wages suspended. But income from capital went nearly untouched. Hardly anyone saw his rent reduced. So the net effect is a huge transfer towards the wealthy.

Another issue that deserves our attention is how we deal with economic crises. The economy goes up and down and with it the stock prices. That wouldn't be problematic when the same people that owned the shares when they rose sky-high would still own when they sink. But that is often not the case and as a result you will see a lot of bankruptcies when things go down - what can be rather destabilizing for the economy. In reaction we see governments increasingly inclined to avoid such a mayhem. That means bailouts and other ways that allow the rich to avoid the effects of the downside of the economic cycle. This was what made Japan's lost decade(s) so problematic. 
Unfortunately we increasingly see similar policies in the US and the EU. The excuses are always the same: pension funds hold some of the shares and bonds too and if one company goes broke others may follow (the Lehman Brothers precedent). But the fact that some companies may go broke shouldn't detract our attention from the fact that the rising share prices in the past increased the share of capital in our economies and that when we support those failing companies we further support that process. It isn't that we never should do it. But we should be aware of the larger process and take compensating measures elsewhere in the economy.

Saturday, March 14, 2020

The two approaches to the Corona virus

The Western approach to Covid-19 is fundamentally different from that of China.

China treats Covid-19 as a kind of serious disease that must be eradicated. Just like you do with SARS or Ebola. Everyone who is contaminated is isolated - even when he doesn't have symptoms. And when you do that long enough the last patient will recover and the epidemic is stopped.

The West sees Covid-19 more as a kind of flue. It is impossible to stop the flue: it is too contagious and too many people who are contaminated don't show symptoms. Every year sees a new kind of flue. And in some years it is more lethal as in others. This happens usually when a new strain of virus appears. The Spanish Fever of 1918 and the Hong Kong flu of 1968 are good examples. Covid-19 is not some kind of Influenza virus. However, there are several Corona viruses that cause some kind of innocent cold.

So the Western assumption is that "everyone" will get it. Think of Merkel saying 70% of the population will get it and Rutte talking about 50%. The main issue in this vision is to slow down the epidemic so that the health care system doesn't get overwhelmed - as happened in Italy. So unlike in China the goal is not to stop the epidemic but to slow it down.

Both approaches have their risks.

In the case of China the main risk is that the epidemic will start again once the country restarts to function normally. Or that it will start again in the autumn if like the cold it is connected to the season. Officially less than 100,000 people were contaminated until now so the overwhelming majority of the population didn't build any resistance. When the virus reappears the 6 week lock-down would have been almost for nothing. What might change the picture is a vaccine. But until now this isn't available.

The Western approach takes it for granted that there will be casualties. But the number of casualties can be limited with good care. And there is a problem as it is very hard to predict how quick things will go. Nobody foretold the quick escalation in Italy. Many Western governments take a wait-and-see approach rather than being pro-active. Yet there are quite a few things a government can do:
- make testing easy and make the threshold low. Make it also quick. In some countries you need to wait a week for the results. That is not good.
- tell anyone who tested positive to self-isolate. Provide services for those for whom self-isolation is problematic.
- test anyone coming from high risk countries and tell them to self isolate for some time.
- take care that you have enough of everything you might need when the epidemic strikes in full force. Hospitals should be well stocked and its staff well-trained.
- things can get out of hand like in Italy. People who get Covid-19 in combination with pneumonia need two to three weeks of intensive care. So plan where you could put extra IC beds, how you could mobilize extra staff and what other things you could do.
- there will always be bureaucratic obstacles. It has been widely published how Chinese officials initially tried to suppress the news. But similar bureaucratic obstacles happen in Western countries too. In the US Trump's obstruction is well known. But there was also the case of the CDC that had problems creating its own test yet blocked the use of other tests. In fact the decentralized nature of Western medicine makes it more likely that bureaucratic problems will arise. It takes planning and effort to overcome such obstacles in the fight against the virus. This should be addressed before a crisis arises.

Apart from the fact that it requires serious preparation the success of the Western approach depends on how aggressive the virus really is. At some point the number of new cases exploded in China and Italy. Within days it went from tens to hundreds. But in both cases it is suspected that the virus had been around for weeks or even months. The problem with a severe Covid-19 infection is that the weakening of the patient causes other illnesses like pneumonia. So it is easy to label the illness just as pneumonia and overlook the virus. In the meantime nobody knows how many people have the virus but show no symptoms.

Here is the most extensive description I found of the treatment of Covid-19.

Wednesday, January 29, 2020

Why the "moderate" strategy won't work for the Democrats

Ezra Klein recently wrote an opinion article ("Why Democrats Still Have to Appeal to the Center, but Republicans Don’t") that argued that conservatives form a monolithic block and the US that is favored by the electoral system in a number of ways. And that to deal with that the Democrats should take a position a bit right from the center to cover enough people.

There is a lot wrong with this position. First of all, the right isn't monolithic. Look at other countries and you will see conservative parties that get nearly half of the vote only in two-party systems like the US. Conservatives have their own divisions. It is a kind of wonder that deeply religious evangelicals vote for such an immoral man as Trump. It is because they feel cornered. Do remember that case of the baker who refused to make a wedding cake for a gay couple and got in trouble for that? It crosses the boundary of live-and-let-live. It dehumanizes people who believe that gay marriage is not a good thing - until very recently a wide majority of the US population.

Any European politician who has had a look at the US will confirm that what in the US is called "moderate" would inside Europe be considered extreme right. The Democrats have already been following Klein's advice for many decades. And the results don't confirm the claim. Obama was to the left of Clinton. Yet he won elections and she lost. And the fact that many poor Democrats have voted for Trump while they might have voted for Sanders is he had been a candidate belies the claim that politics can be explained with a simple left-right continuum.

Politics is about ideas. But "moderate" Democrats don't have ideas. Their economic and defense policies are almost indiscernible from those of the Republicans. They are in fact a light version of the Republicans. And when people get a choice between a light version and real thing many choose the real thing - specially in times of discontent like we have now.

Many of the ideas of Sanders aren't that radical. If they would have been proposed by someone like Biden they would be widely embraced. But where someone like Sanders is focused on ideas on how to make the life of the common voter better Biden is primarily focused on pleasing his sponsors and not rocking the boat.

Many Democrats are amazed that Trump is getting away with so much immoral acts and lies. But what people like is that he is someone who stands for something - even when he faces criticism. That is what they like about Sanders too. And that was were Warren made a big mistake when she adapted her Medicare plan after criticism. Sure, if Sanders wins the elections he will have to negotiate with Congress to get his plans adopted and he might very well end with the kind of plan that Warren is proposing now. But that doesn't take away the fact that his present proposal is sound and defensible. Warren is ceding ground before the fight has even started.

What are Democrats like Biden really standing for? They like to spend a bit on social issues to keep people happy but they are afraid to make any structural changes that might get criticized. They like to criticize countries like Russia. But that looks suspiciously like yet another type of foreigner bashing - not that different from racism. They like also to go to extreme lengths to defend gays and transgender rights. But result looks a lot like the bashing of "deplorable" poor whites and evangelicals.

Parties that don't have plans to make people enthusiastic for are bound to focus on demonizing people instead. The Democratic Party has been falling in that trap. Unfortunately its leadership still seems to be unaware of the problem.

Thursday, December 19, 2019

The final OAS report on the Bolivian elections

As it proved to be rather difficult to find the final OAS report - that was published on 4 december - on the Bolivian elections here the link. Note that unlike the preliminary report and its annexes the final report is only in Spanish and only available as pdf. Obviously they are trying to restrict the distribution of the report. The report contains 95 pages and is accompanied by 9 appendixes that contain about 400 pages in total.

To help those who want to read it I hosted a machine translated (in English) copy of the main report. Note that the first page is mostly white.

An article on FAIR is the best rebuttal of the OAS claims that I have seen thus far.

Thursday, October 24, 2019

The US is not in Syria to fight ISIS

One often hears defenders of the US presence in Syria claiming that the US is there to fight ISIS. In contrast some opponents claim that the US created ISIS.

I won't enter the question whether the US was involved with the creation of ISIS here. Those claims are based on quotes from US official reports and some statements by US politicians. Instead I will discuss here the timeline of US involvement in Syria and what it actually did (and didn't do).

 - The US got involved after ISIS had made great advances in Syria and threatened the Kurds in Kobani. If the actions of the US had been purely logical it would have gotten involved earlier. It would have given some arms to the Kurds and dropped some bombs on ISIS and that would have been enough to turn the chances on the battle field. Instead it waited until there was an international uproar that gave it an excuse to enter Syria and a Congress resolution within the US. Without such an excuse its entrance would have been hardcore illegal.

 - After the US got involved they and their Kurdish allies conquered much of Northeastern Syria. After that they stopped. The Turks occupied Jarabulus and blocked the road to the West and further south there lived hardly any Kurds so the SDF wasn't enthusiastic about spilling blood to conquer those areas.

 - Then ISIS conquered Palmyra in May 2015. To come there it had to cross 200 km of desert. Yet the US didn't drop a single bomb to stop them. Shortly afterwards pro-Russian media reported that American diplomats were preparing Western capitals for the fall of Damascus to ISIS.

 - After Russia got involved one of its first actions was to go after the oil trade of ISIS that provided much of its income. A few bombs did a lot to stop that trade. The US had never bothered to do so.

 - In September 2016 the US - allegedly by mistake but many people don't believe that - bombed Syrian government troops in Deir Ezzor. This almost led to the fall of this government held enclave to ISIS.

 - Some time after Russia had become involved and the chances on the battlefield had changed the Syrian government started an offensive from Aleppo eastwards towards Raqqa. Suddenly the US felt the need to go south towards Raqqa too - at the end of 2016. Obviously preventing that Raqqa came in the hands of the government was more important as getting ISIS out of Raqqa.

 - The first thing the US/SDF coalition did near Raqqa was to cross the Euphrates and occupy Tabqa and its dam and surroundings. The obvious goal was block all the roads so that Syrian Army offensive couldn't go further south (further from the river there was desert). In the end the Syrian Army outsmarted them. But there were some very tense moments.

 - The attack on Raqqa lasted many months and completely destroyed the city. No other city in Syria is so destroyed. According to the Kurds the US refused to give them advanced weapons that would have made them more effective against ISIS.

 - The Syrian Army moved further south and conquered Deir Ezzor. Shortly south of the city it crossed the Euphrates in an effort to conquer the oil and gas fields there. However, they encountered fierce resistance from ISIS and didn't come far. The US - that still was stuck near Raqqa some 120 north - suddenly felt the need to move to the area too. In contrast to the Syrian Army they hardly faced any resistance from ISIS and could move tens of kilometers a day. It was the SDF/US coalition that ended up controlling the oil and gas fields - thanks to ISIS.

 - The Syrian Army moved still further south and ended up controlling the whole west bank of the Euphrates. However, the US forbade it to attack ISIS on the other bank of the river and threatened to bomb them if they tried. This alone delayed the defeat of ISIS in Syria by many months.

I don't know what the official mission of the US Army in Syria was but it doesn't look like defeating ISIS was the top priority.