The politicization of medication

There's been plenty of ridiculousness in the past few years, but to me -- perhaps influenced by my profession -- one of the greatest absurdities has been the touting of useless and dangerous medications as a partisan political cause. It makes no evident sense in terms of political ideology. There's nothing "conservative" about screaming that a useless medication actually works, or attacking doctors and hospitals for not prescribing it. There was however an insane idiot who was the leader of the Republican cult and he started it. Apparently that's all it takes nowadays.

So let's step back and consider how we determine that medications are safe and effective, and what the standard ought to be for making that decision. We can start with Carl Zimmer in the NYT today. If you have a subscription or a free read left this month you can take a look, but I'll tell you what you need to know in case you don't. First, ivermectin is completely useless against Covid-19. That is the conclusion of a well-conducted, fairly large clinical trial in which 679 people infected with the virus received the chemical and a comparably sized group did not. There was no difference in the risk of hospitalization.

As Zimmer explains:

Early in the pandemic, when researchers were trying thousands of old drugs against Covid-19, laboratory experiments on cells suggested that ivermectin might block the coronavirus. At the time, skeptics pointed out that the experiments worked thanks to high concentrations of the drug — far beyond safe levels for people. Nevertheless, some doctors began prescribing ivermectin for Covid-19, despite a warning from the Food and Drug Administration that it was not approved for such use.

Around the world, researchers carried out small clinical trials to see if the drug treated the disease. In December 2020, Andrew Hill, a virologist at the University of Liverpool in England, reviewed the results of 23 trials and concluded that ivermectin appeared to significantly lower the risk of death from Covid-19.

 

But critics pointed out that many of the studies had a high risk of bias and one was likely fraudulent. When Dr. Hill did a new review that included only higher quality trials, he found no evidence of benefit. Now the large scale trial has confirmed that. This is a consistent pattern in drug discovery. Small scale, weakly designed studies often find evidence of benefit, and it often gets hyped in the news media before large, well-conducted studies have concluded; and they often have negative findings. 

Why does this happen? There are a few reasons. One is that small scale studies may seem to show a benefit just by chance -- if you compare, say, 20 people who get the drug with 20 who don't, that can easily happen even if there is no real benefit. But the studies that do seem to see a benefit will be promoted and get public notice, while those that don't will quietly disappear. This problem is reinforced by cognitive biases. The people who conduct the studies want them to show benefit, as do the patients generally, and there are many ways this bias can subconsciously influence the results. I won't go into all of them here but I think we can all agree that wishful thinking is powerful.

That's why, when they are feasible and ethical, large scale, placebo controlled, double blind randomized trials are considered the gold standard for deciding whether a medication is effective. Double blind means that neither the investigators nor the patients know who is getting the real drug. Large scale means there are enough participants that differences will be unlikely to be due to chance. Randomized means the investigators don't get to choose who will be in the intervention arm. 

There are some problems and limitations with this, to be sure. There may be "heterogeneity of treatment effect," such that the medication benefits some people but harms others, and the effects cancel out. But obviously, until and unless we can sort that out, it doesn't make sense to prescribe the drug. 

 

Actually the problems are usually in the other direction -- there isn't long enough follow-up or sufficient monitoring to detect all the possible adverse side effects. And even in large-scale trials, apparent effects can actually be due to chance. Unfortunately in these cases, historically, the trials showing some effect were more likely to be published. There is also the problem of retrospective analysis, in which investigators look at end points they didn't originally hypothesize. Statistical theory tell us this invalidates any inferences. The FDA and NIH are trying to address this problem by requiring registration of trials in advance. 

In any case, for an unproven drug to be a political cause is ridiculous. I hope it never happens again.

Wednesday Bible Study: Construction Contract

The next couple of chapters describe the construction of the first temple. Most scholars think it probably existed, one reason being that its destruction, which is described later, happened within perhaps a generation of whoever wrote this. However, as I have noted earlier, archaeological excavation on the Temple Mount is not possible, so it can't be confirmed by physical evidence. (Archaeological finds which some have claimed to be evidence for the temple have either turned out to be fakes, or are of dubious meaning.) 

In any case, it was highly unlikely to have been as grand as is described here, and we don't know who built it and when. It was almost certainly later than is claimed here because, as I have also noted before, the kingdom at this time, if it really could be called a kingdom at all, did not have the resources for such an undertaking. Nevertheless we are getting to an era where there tend to be more and more grains of truth in the tales. Everything about Solomon's reign is wildly exaggerated if he existed at all, but it's important to the national mythology in a way that earlier stories are not, because it's so tied to a specific place. Note that this continues the Biblical tradition of multiplying numbers by 10 or 100 beyond what is plausible. Note verse 15 et seq. Seventy thousand burden bearers, 80,000 stone cutters and 3,000 construction supervisors for a building of about 250 square meters (see next chapter) would seem to indicate a lot of featherbedding.

5 ^[a] Now Hiram king of Tyre sent his servants to Solomon, when he heard that they had anointed him king in place of his father; for Hiram always loved David. ² And Solomon sent word to Hiram, ³ “You know that David my father could not build a house for the name of the Lord his God because of the warfare with which his enemies surrounded him, until the Lord put them under the soles of his feet. ⁴ But now the Lord my God has given me rest on every side; there is neither adversary nor misfortune. ⁵ And so I purpose to build a house for the name of the Lord my God, as the Lord said to David my father, ‘Your son, whom I will set upon your throne in your place, shall build the house for my name.’ ⁶ Now therefore command that cedars of Lebanon be cut for me; and my servants will join your servants, and I will pay you for your servants such wages as you set; for you know that there is no one among us who knows how to cut timber like the Sido′nians.”

⁷ When Hiram heard the words of Solomon, he rejoiced greatly, and said, “Blessed be the Lord this day, who has given to David a wise son to be over this great people.” ⁸ And Hiram sent to Solomon, saying, “I have heard the message which you have sent to me; I am ready to do all you desire in the matter of cedar and cypress timber. ⁹ My servants shall bring it down to the sea from Lebanon; and I will make it into rafts to go by sea to the place you direct, and I will have them broken up there, and you shall receive it; and you shall meet my wishes by providing food for my household.” ¹⁰ So Hiram supplied Solomon with all the timber of cedar and cypress that he desired, ¹¹ while Solomon gave Hiram twenty thousand cors of wheat as food for his household, and twenty thousand^[b] cors of beaten oil. Solomon gave this to Hiram year by year. ¹² And the Lord gave Solomon wisdom, as he promised him; and there was peace between Hiram and Solomon; and the two of them made a treaty.

¹³ King Solomon raised a levy of forced labor out of all Israel; and the levy numbered thirty thousand men. ¹⁴ And he sent them to Lebanon, ten thousand a month in relays; they would be a month in Lebanon and two months at home; Adoni′ram was in charge of the levy. ¹⁵ Solomon also had seventy thousand burden-bearers and eighty thousand hewers of stone in the hill country, ¹⁶ besides Solomon’s three thousand three hundred chief officers who were over the work, who had charge of the people who carried on the work. ¹⁷ At the king’s command, they quarried out great, costly stones in order to lay the foundation of the house with dressed stones. ¹⁸ So Solomon’s builders and Hiram’s builders and the men of Gebal did the hewing and prepared the timber and the stone to build the house.

Footnotes

1. 1 Kings 5:1 Ch 5.15 in Heb
2. 1 Kings 5:11 Gk: Heb twenty

No, it isn't over

The country as a whole, including apparently the CDC, has decided that the Covid-19 thing is over and done with. The Republicans in congress even insisted on stripping funding for Covid-19 testing and relief from the recent appropriation bill, and the Democrats went along with little protest. 

 

While it is true that most of the country right now is experiencing a lull, there has been a bump up in hospitalizations in Europe. Look at the far right of the chart:

 

 

As you can see the uptick so far is small, but it's just beginning. It's because of the new Omicron BA.2 variant, which is more transmissible than the previously prevalent Omicron variant and can infect people who have had previous infections and vaccination. Again, vaccination greatly reduces the risk of severe disease, bu vaccinated people can still get sick. The virus will continue to mutate, and there is no way to predict whether a future variant will cause more severe illness, or will be even better able to evade prior immunity, but there's no reason to assume it won't do either.

As Katherine J. Wu discusses in The Atlantic, we are totally unprepared for another surge. Not only do we have the political problem that a substantial proportion of the population will refuse to go along with mitigation measures or get vaccinated, we do not have the resources to respond. CDC has also decided that it won't recommend mitigation measures until hospitalizations and deaths are already at a critical level. No, I don't know what will happen, maybe this won't be so bad, or the worst will be localized. But the depth of denial in this country is just terrifying. 

Let me remind you that you want no part of this virus. "Mild disease" now means you don't end up in the hospital, but take it from me, that doesn't necessarily mean it's what you would consider mild. And something like 20-30% of people who get "mild" disease end up with symptoms that last for months, or maybe forever, and recent research finds they have an elevated risk of dying in the next six months. It can really knock the crap out of you. No, it isn't just like the flu.