Monday, May 18, 2020

Challenge Trials

This is Joseph

I am a bit late to the Challenge Trial debate for covid-19. Here is a great piece written by Thomas Lumley, who points out the speed advantages in getting a vaccine to market. It is also likely that there will be several possible candidate vaccines. Derek Lowe discusses nine advanced candidates, with different approaches:
So by my count, the biggest and most advanced programs include two inactivated virus vaccines, three different adenovirus vector vaccines, two mRNA possibilities, a DNA vaccine, and a recombinant protein.
At least a couple look to be in Phase II human trials, which the the precursor to phase III (where we evaluate effectiveness). Now, one major barrier is manufacturing the doses, especially since we decided to off-shore a lot of our biomedical capacity in the name of efficiency (at the cost of robustness).

Now these are very important. First, it is possible for the vaccine to increase the cytokine storm intensity and make the disease more fatal. The good news is the immunology is suggesting good targets that should avoid this issue.  But the word "should" is important and it is rather important to be clear about this before millions of people are inoculated.

Second, we want an effective vaccine and it may be the case that candidates vary in their effectiveness. There are successful vaccines that do not grant 100% immunity. The original polio vaccines were only 60-70% effective versus one of the strains, but that still led to a vast decrease in the number of infections in the United States once vaccination became standard.

So, clearly we want trials. While manufacturing is about to be a massive hurdle, the vaccine can be focused on the most vulnerable first, which can help a lot, while slowly covering the whole population. Combined with public health measures, a vaccine would be pure good news.

Now we get to the point about medical ethics. A phase III trial takes a long time to conduct and there is some political pressure for a fast solution. It is exceedingly unhelpful that there is a US presidential election in November, as one can imagine there being a big difference in feelings towards the incumbent who botched the public health response versus the incumbent who started out poorly but managed to lead a uniquely fast solution to the crisis.

Now, if the virus is mostly under control, you need a lot of people and a long time to evaluate the effectiveness of a vaccine. People are rarely exposed so it takes a long time for differences in cases between the arms to show up. If it is not, that is a place where it is hard to run a trial. Just consider the dire conditions in New York city -- while clearly a place one could have tested a vaccine it may not be the best environment to run a medical experiment in.

Another option is the challenge trial. Likely only taking a few hundred participants, it would have no more deaths than a regular trial. But it would involve infecting people, treated with a placebo(!!), with a potentially fatal infectious disease. There are greater good arguments here, but the longer I think about them the more dubious they get to me. Informed consent for things that are so dangerous really does suggest coercion. In the comments, Thomas Lumley points out that organ harvesting could be consented to if the payout was big enough but that isn't evidence that it is ethical or morally defensible. This suggestion, for example, suggests immigration reform as a goal and not medical experiments:
If all you are asking for is “free informed individual consent”, the inhuman cruelties of first world immigration and asylum laws create plenty of opportunities where deliberate COVID-19 infection is better than any other option. 
For a healthy adult in the 20s a deliberate COVID-19 infection has a lower mortality than paying a smuggler to put him on a shaky boat over a sea hoping to get asylum elsewhere.
My concern is that the political pressure on scientists to cut corners and find ways to speed up the testing will be enormous. It isn't clear that in a crisis it is impossible to justify a challenge trial, at some point there are arguments about brave heroes and the sheer scale of the suffering (in the people killed by the virus, directly and indirectly). But I think there are a lot of issues that need to be carefully thought out first and I have concerns that the pressures of this unique situation will make it harder to think them through.


Posted by at No comments:

Friday, May 15, 2020

How did we get here?

This is Joseph

From public comments by the president of the University of Washington:
As doctors, nurses, health professionals and researchers save lives threatened by the coronavirus, academic medical centers and their affiliated public hospitals and clinics on the front lines of this fight have been among the hardest hit financially. Unfortunately, UW Medicine is not immune. As you may have read, even as it has led our state and country in responding to the coronavirus – tracking its spread, treating those who fall ill and researching new treatments – UW Medicine is projecting a loss of more than $500 million by the end of this summer. While we continue to pursue federal and state emergency funding to support this critical work, without urgent mitigation efforts this shortfall jeopardizes our ongoing mission to improve the health of the public.
On Monday, UW Medicine CEO Dr. Paul Ramsey outlined the steps being taken to protect UW Medicine’s hospitals’ and clinics’ ability to care for patients. These will include temporary furloughs and reduced hours and compensation for staff, with the goal of minimizing the number of permanent layoffs that are needed. As a reminder, furloughs are temporary and allow employees to keep their benefits, including health insurance. Leaders at UW Medicine are voluntarily contributing part of their own salaries back to the University in light of these extraordinary circumstances, as are Provost Richards and I and many other UW leaders across our three campuses.
This is a consequence of ideology. Medical costs are not well aligned with free markets and, as a result, when there is an unexpected medical crisis it is actually causing the medical infrastructure to begin to fail. You will notice the exact opposite of "raise the line" to the point where using it in the US context seems disingenuous, as health system capacity is dropping and not rising.

I think this ideology is also showing up in the medical supply chain. The decision to off-shore the production of reagents for medical testing left the supply chain vulnerable when the primary exporter was the first country hit by the pandemic.   Similarly, fee trade with China ended up costing many jobs and is likely a source of discontent among those who suffered through this experience. It is fine to say that it is too late to get these jobs back now -- it likely is. Nah smith notes:
The authors suggest that real-world economies may simply be much worse at adjusting to big changes than most economic models assume. It is expensive and time-consuming for workers to train for new jobs and to move to new locations. It also takes time and money for businesses to figure out how to change their business models in response to the new landscape presented by a global economy with China in it. These adjustment costs might overwhelm the gains from trade.
In other words, it is probably a very good time to consider the costs of the economic choices that we are making. Now, please do not straw person this -- one can decide that the direction of change is misguided without calling for a socialist revolt.

But maybe the real lesson here is one of institutional strength and the building in of resilience. The love of silicon valley tech is  the love of the "fails easily but moves fast and reduces cost" model. It just happens to be a dangerous approach to pandemic mitigation.
Posted by at No comments:

Thursday, May 14, 2020

What we said before, only worse


Though there were still some suckers (Rolling Stone's messianic profile was still months away), 2017 may have been the year that people really started catching on to the scam. The speed of Musk's reputational implosion was a bit surprising,but the trends have been apparent for a long time.

Tuesday, July 25, 2017

A few points to keep in mind when reading any upcoming story about Elon Musk

First, a quick update from the good people at Gizmodo, specifically Ryan Felton:

Elon Musk awoke on Thursday with the intention of sending Twitter into a frenzy by declaring that he received “verbal govt approval” to build a Hyperloop in the densest part of the United States, between New York City, Philadelphia, Baltimore, and Washington D.C. This is dumb, it’s not how things work, and requires, uh, actual government approval.

Felton goes on to contact the government agencies that would absolutely have to sign on to such a project. Where he was able to get comments, they generally boiled down to "this is the first we're hearing of it." The closest he came to an exception was the federal Department of Transportation, which replied

We have had promising conversations to date, are committed to transformative infrastructure projects, and believe our greatest solutions have often come from the ingenuity and drive of the private sector.
This is a good time to reiterate a few basic points to keep in mind when covering Elon Musk:

1.    Other than the ability to make a large sum of money through some good investments, Elon Musk has demonstrated exceptional talent in three (and only three) areas: raising capital for enterprises; creating effective, fast-moving, true-believer corporate cultures; generating hype.

2.    Though SpaceX appears to be doing all right, Musk does not overall have a good track record running profitable businesses. Furthermore, his companies (and this will come as a big slap in the face of conventional wisdom) have never been associated with big radical technological advances. SpaceX is doing impressive work, but it is fundamentally conventional impressive work. Before the company was founded, had you spoken with people in the aerospace community and asked them "what is closest to being Mars ready, who has it, and who are the top people in the field?", the answers would have been the type of engine SpaceX currently uses, TRW (which sued SpaceX for stealing their intellectual property), and the chief rocket scientist SpaceX lured away from TRW. By the same token, Tesla is pretty much doing what all of the other major players in the auto industry are doing in terms of technology.

3.    From the beginning, Musk has always had a tendency to exaggerate and overpromise. Smart, skeptical journalist like Michael Hiltzik and the reporters at the Gawker remnants have taken any claim from Elon Musk with a grain or two (or 20) of salt.

4.    That said, in recent years things have gotten much, much worse. Musk has gone from overselling feasible technology and possibly viable business plans to pitching proposals that are incredibly unlikely then supporting them with absurdly unrealistic estimates and sometimes mere handwaving.

5.    The downward spiral here seems to have started with the Hyperloop. This also seems to be the point where Musk started trying to do his own engineering rather than simply taking credit for the work of those under him. On a related note, it is becoming increasingly obvious that Elon Musk has no talent for engineering.

6.    Musk’s increasingly incredible claims have started to strain the credulity of most of the mainstream press, but the consequences have been too inconsistent and too slow-coming to have had much of a restraining influence on him. Even with this latest story, you can find news accounts breathlessly announcing that supersonic travel between New York and DC is just around the corner.

7.    Finally, it is essential to remember that maintaining this “real-life Tony Stark” persona is tremendously valuable to Musk. In addition to the ego gratification (and we have every reason to believe that Musk has a huge ego), this persona is worth hundreds of millions of dollars to Musk. More than any other factor, Musk’s mystique and his ability to generate hype have pumped the valuation of Tesla to its current stratospheric levels. Bloomberg put his total compensation from Tesla at just under $100 million a year. When Musk gets tons of coverage for claiming he's about to develop telepathy chips for your brain or build a giant subterranean slot car race track under Los Angeles, he keeps that mystique going. Eventually groundless proposals and questionable-to-false boasts will wear away at his reputation, but unless the vast majority of journalists become less credulous and more professional in the very near future, that damage won’t come soon enough to prevent Musk from earning another billion dollars or so from the hype.
Posted by at 4 comments:

Wednesday, May 13, 2020

This post was perfect

This is Joseph

I thought that this cartoon captured the spirit of the times perfectly:


It isn't that experts do not have blind spots, they do. But replacing a blind spot with actual blindness seems to be a risky strategy in a crisis.
Posted by at No comments:

Ideological versus partisan -- pandemic edition



 

There has been a ton of research (some of it good, most of it not) on the question of what makes one person ideologically inclined to be conservative and another to be liberal. Lots of issues here, particularly with tying political leanings to some innate trait (never understood why most people with the conservative gene just happened to cluster around areas with agricultural or extraction-based economies), but that’s a topic for another post. Instead, I want to step back and ask is the question meaningful at all..

Many of the best indicators of a person's political position, quite possibly the majority of the best indicators, make  no sense if you approach them in terms of either conservative/liberal ideology or psychology. They fall into place perfectly, however, when you start making the distinction between the partisan and the ideological, particularly when you add a layer of Straussian disinformation and cult of personality dynamics.

We’ve discussed this before, but the pandemic has given us a wealth of new examples.

What possible ideological basis is there for arguing for the relative contagiousness of one virus over another? Or of insisting on the efficacy of a particular drug? And yet, how one answers questions like these have become arguably the defining political positions of the day, particularly in conservative media and the far right.

I’m certain someone out there is working on a painfully epicyclic model to explain this (does R have a spirograph package?), but the picture becomes remarkably straightforward if you approach it in partisan terms.

From a conservative/Republican standpoint, when it comes to a potential collapse in support for President Trump, timing matters more than magnitude. A bad Q3 is worse for them than a terrible 2021 would be. Prematurely lifting lock downs is unlikely to buy them more than a dead cat bounce, but might be enough to avert a GOP bloodbath.

Add to that the constraint of not infuriating Trump. The base is (for the moment at least) personally loyal to him, not to the party, and temperamentally he is more than willing to bring the temple down with him.

Obviously, the memes and narratives of Fox et al. are often ideological and partisan, but when you look at the odd quadrants, you see lots of stories that advance a partisan aim with no significant ideological component, relatively few that go the other way.

This isn't to say that ideology -- it's what keeps the money flowing -- but much of what we talk when we talk politics , particularly in 2020, are non-ideological means to ideological ends, and if we want to keep our thinking clear, we have to know when to make the distinction.
Posted by at 2 comments:

Tuesday, May 12, 2020

Tuesday Tweets -- the wheels come off the Tesla




 

 
Read this thread.



 



 












 

 



        


Posted by at No comments:

Monday, May 11, 2020

There’s a lot to talk about here, and I mean that in the worst possible way.

If I try to address everything at once, I’ll never maintain the momentum to finish. Instead, I am going to have to take small bites.
We can start by picking up where Andrew Gelman left off in his recent post on the return of the red state blue state fallacy. We tend to associate NIMBYism with big cities and big cities tend to be liberal, so op-ed writers often assume liberals are driving NIMBY policies. This sometimes left as subtext, but this piece by Farhad Manjoo (referenced in the Gelman post) pretty much spells things out from the title on.

"America’s Cities Are Unlivable. Blame Wealthy Liberals."

It was another chapter in a dismal saga of Nimbyist urban mismanagement that is crushing American cities. Not-in-my-backyardism is a bipartisan sentiment, but because the largest American cities are populated and run by Democrats — many in states under complete Democratic control — this sort of nakedly exclusionary urban restrictionism is a particular shame of the left.
...

Reading opposition to SB 50 and other efforts at increasing density, I’m struck by an unsettling thought: What Republicans want to do with I.C.E. and border walls, wealthy progressive Democrats are doing with zoning and Nimbyism. Preserving “local character,” maintaining “local control,” keeping housing scarce and inaccessible — the goals of both sides are really the same: to keep people out.
Putting aside the bothsiderism (he's writing for the New York Times. It's probably in his contract.), how does the rest of his thesis hold up?

Two cities are mentioned, Beverly Hills and La Caรฑada Flintridge. Are either of these what you'd call liberal hotbeds? Let's start with Beverly Hills.

The region overwhelmingly backed Democratic presidential nominee Hillary Clinton in Tuesday’s election — except for one precinct in Beverly Hills.

Here, along Sunset Boulevard in the shadow of the Beverly Hills Hotel, voters picked Donald Trump over Clinton, creating an island of red in a sea of blue.

Even many residents were puzzled about why this particular slice of the Westside went for Trump, especially when some neighboring precincts in the Hollywood Hills, Bel-Air and Westwood went for Clinton by huge margins.
How about La Caรฑada Flintridge?

La Caรฑada Flintridge has historically been a Republican Party stronghold. However, in 2004, Democratic Party registered voters increased by 18%, while decline-to-state voters increased by 31%, and registered Republicans declined by 9.3%. In the 2008 US Presidential Election, Democrat Barack Obama received 10 more votes than Republican John McCain. In the 2012 US Presidential Election, most La Caรฑada Flintridge voters supported Republican Mitt Romney over Democrat Barack Obama. In the 2016 US Presidential Election, approximately three out of every five voters supported Democrat Hillary Clinton over Republican Donald Trump.

Compare that to the county totals.

Year GOP DEM Others
2016 22.41% 769,743 71.76% 2,464,364 5.83% 200,201
2012 27.83% 885,333 69.69% 2,216,903 2.48% 78,831
2008 28.82% 956,425 69.19% 2,295,853 1.99% 65,970

It's possible that progressive Democrats really are the drivers of NIMBYism. Manjoo might just be really bad at picking examples.

(He's bad at other things too, but we'll have to save that for later in the thread.)
Posted by at No comments:

Friday, May 8, 2020

Weekend


I don't actually have a corner that looks that good. I go to the patio for my meetings.



When Andrew commented on The Untouchables being Mamet in Hemingway stupid profundities mode, my first thought was "No, that would be the Edge." According to Les Stroud, the stupidity goes beyond the dialogue.

(And though "the Chicago way" is a contender, the best speech in a bad movie is Roscoe Lee Browne's prayer before hanging in the Cowboys [Originally left out the title, sorry -- MP].)



I never thought about money being heavy.




Now You See Me was also a stupid movie but in the opposite way, thinking it was being clever.





Posted by at No comments:

Thursday, May 7, 2020

Kevin and the Stegosaurus -- special Thursday tweet post


 

  

 

 

 

 


 

  

 




Posted by at No comments:

Wednesday, May 6, 2020

"Not like those bumbling polynomial people"


We ran a piece on Monday that made the point that not only ignoring the track records of clowns like Kevin Hassett, but actually putting them in positions of responsibility was a really bad idea. I wrote the post over the weekend, before this story broke.

From Josh Marshall.
One of the most depressing and least surprising developments in the last 36 hours is that the White House is apparently relying on a “cubic model” of the COVID19 epidemic prepared by White House economist Kevin Hassett to craft its crisis response. I have not seen any statisticians or epidemiologists who know precisely what “cubic” refers to the in this context – though there are some promising speculations based on simply plugging in one of the default trend lines (third degree polynomial) in Microsoft Excel. The more relevant point is that, according to The Washington Post, the model predicts the number of people dying of COVID19 in the US will fall to close to zero by May 15th – a scenario that seems all but impossible.

Here I can’t help but note a basic point. Hassett is not a health care economist, let alone someone at the crossroads of behavioral economics and epidemiologists. Indeed, his record as an economist is rather notorious.

Perhaps Hassett’s biggest claim to fame is coauthoring a 1999 book entitled Dow 36,000: Dow 36,000: The New Strategy for Profiting From the Coming Rise in the Stock Market. The book argued that traditional metrics for evaluating stock prices were outdated and that the stock market was dramatically undervalued. The Dow, then a bit over 10,000, would rise to 36,000 over the next three to four years. These are the kinds of predictions one often hears at the top of a bull market. And indeed the market hit its peak within months of the book’s publication and continued to fall for almost the next four years. Needless to say, that was two and a half market collapses ago. 21 years later the Dow stands at 23,749, though it did approach 30,000 before the COVID19 collapse.





Just to be clear, this all happened after the Washington Post broke the story of Hassett's bungling at the beginning of the pandemic. Nothing was learned. It just got worse. On the bright side, if Hassett was able to correctly apply the trend line option, that speaks well for the easy of use of MS Office






Posted by at 1 comment:

Tuesday, May 5, 2020

Tuesday Tweet Dump -- double Bayesian edition



 
You should read the whole thread, but I wanted to call it this tweet in particular.

  

We may disagree on the meaning of contained.

  


 


 


  


 


 


 


 


 


 

The teen years will not be easy in this household.


  
Posted by at No comments:

Monday, May 4, 2020

"Kevin (Dow 36,000) Hassett" should be more than just a cheap shot. It needs to be a reminder. UPDATED


I'm supposed to start this with the standard nobody's perfect/we've all made mistakes boilerplate, but I'm not going to. I have never screwed up as badly as Hassett. I very much doubt that anyone reading this has either. And yet, other than a few jokes at his expense, he seems to have paid no price. His post Dow 36,000 career seems to have been one long concatenation of sinecures.

That's a problem.

There needs to be a consequence for being wrong, a penalty, a demotion or at the very least a loss in credibility until we see proof that a lesson was learned. If we don't demand that damaged reputations have to be rebuilt and lost trust has to be regained, the screw-ups will just get bigger and more dangerous.

Incredibly depressing case in point.from Philip Rucker.

So the White House considered its own analysis. A small team led by Kevin Hassett — a former chairman of Trump’s Council of Economic Advisers with no background in infectious diseases — quietly built an econometric model to guide response operations.

Many White House aides interpreted the analysis as predicting that the daily death count would peak in mid-April before dropping off substantially, and that there would be far fewer fatalities than initially foreseen, according to six people briefed on it.

Although Hassett denied that he ever projected the number of dead, other senior administration officials said his presentations characterized the count as lower than commonly forecast — and that it was embraced inside the West Wing by the president’s son-in-law, Jared Kushner, and other powerful aides helping to oversee the government’s pandemic response. It affirmed their own skepticism about the severity of the virus and bolstered their case to shift the focus to the economy, which they firmly believed would determine whether Trump wins a second term.

For Trump — whose decision-making has been guided largely by his reelection prospects — the analysis, coupled with Hassett’s grim predictions of economic calamity, provided justification to pivot to where he preferred to be: cheering an economic revival rather than managing a catastrophic health crisis.
__________________________________________

UPDATE:




Posted by at No comments:

Friday, May 1, 2020

Transparency

This is Joseph

There is a good conversation about transparency going on right now. The gist of it is that the 2016 elections have created perverse incentives for being transparent. If you release information then the press hunts through it looking for a series of mini-scandals. If you release nothing then people quickly lose interest. This creates a serious incentive to minimize transparency.

When talking to people about this, it has been speculated that the 2016 election was rather unique. And so it was. But the pattern continues. It has been three and a half years since the 2016 election and the question of whether congress can see the president's taxes is still being litigated.  This includes attempts to source these records from third party sources, such as banks.

It would be less of an issue if people were not suddenly asking Joe Biden to make as many records available as possible. What I find perplexing here, is that people have lost perspective on the size of the offence (as well as their ability to blame their own conduct). The question of how separate business interests are from the presidency is a perfect area for transparency.

What we need is the press to stand above "false equivalency" and make lack of transparency carry a political price, via repetition of the issues and refusing to punish openness on the part of candidates.
Posted by at No comments:

Weekend Morricone

I've been making extensive use of my local libraries' e-book collection. One recommendation is a collection from Dr. Seuss's stint as a political cartoonist for PM in the early forties. You've probably seen a few of these but it's worth going through the whole set for both the unmistakable art and cross-section of liberal but definitely not leftist views (the difference being very  sharp while the non-aggression pact was still in place).

Some of the recurring targets included isolationists, racial discrimination and especially Charles Lindbergh.














I have some writing to do over the weekend. Harlan Ellison used to listen to Ennio Morricone film scores while he worked, so I thought I'd give it a try. Morricone has over 500 IMDB credits (the latest in pre-production), so if I like the results I'm set for a while.







I hesitated for a moment on this one because it is, in retrospect, a really stupid film  that arguably manages to be less historically accurate than the TV show.


Posted by at 1 comment:

Thursday, April 30, 2020

Lowering the line

This is Joseph

I want to follow up on Mark's post earlier today. I think that a major concern that we have all had for awhile was whether or not there would be forward planning in the epidemic. After all, early in the epidemic there were problems because pandemic response had been under-funded and epidemiologists were caught by surprise at how unprepared we are.

Now we are seeing the same lack of forward planning. There is a principle of marshalling resources, even when there are free markets, that is being ignored. Few countries are happy if they are far from being food sufficient (and, when they are, they have a lot of planning around this), In the same vein, the United States has an energy reserve to prevent oil disruption, despite oil being part of a free market.

Why is healthcare so different?

Clearly it makes no sense to be cutting capacity here. You want to develop a healthcare reserve to handle the risk of a covid-19 hospitalization surge, not shrink capacity so people later in the epidemic have even worse care. Like with food and energy, one presumes the only rational provider of this financing is the government.

Why is this a partisan issue? Starving and freezing are bad, so we have a reserve against a disruption, but dying of a virus isn't a bad thing?
Posted by at No comments:
Subscribe to: Posts (Atom)