A recent podcast episode and a recent blog post show how screwed up the American drug market is, and in how many different ways.

In his Healthcare Unfiltered interview focused on generic drug shortages, the FDA Commissioner Robert Califf blamed Group Purchasing Organizations for driving down the cost of generic drugs to below what’s economically feasible. The manufacturers don’t have an incentive to shore up their process, the fragile production line fails, and presto, you have a shortage. Which is fine if you are manufacturing a placebo, but in recent years the FDA’s Drug Shortages Database has been ever-growing, and as of today includes potentially currative cancer drugs like cisplatin and carboplatin, many antibiotics, and even some formulations of sugar-water. Not to be confused with placebo.

This all reminds me a bit of my childhood in Serbia back in the mid-1990s, when bread was dirt cheap and never available. But that was too much price regulation. Here, we have too efficient of a market leading to a shortage. Only, I am sure there will be hands raised wanting to tell me that — well, actually — this was a clear example of over regulation, since new factories can’t just pop up too meet the demand and make use of the temporary market inefficiency, being dependent as they are on pesky FDA regulations — like the ones about drugs being safe. If only we could price in the risk of death by sepsis, we’d be in great shape!

So, on one end we have Medicare/Medicaid paying through the nose for brand name drugs because it is forbidden by law from negotiating for a better price, and on the other private GPOs negotiating too well for generics, to the point of extinction, forcing payers to get those expensive brand name drugs. Heads, brand-name pharmaceutical industry wins, tails, payers loose.

It was encouraging to see some movement in the price negotiation area: the comically misnamed Inflation Reduction Act allows for CMS to negotiate the price of some drugs, and the list of those drugs was recently made availalbe. Ideal? Far from it — in an ideal world the federal government would not be involved in any of this; but it’s not the world we live in. This is where the blog post comes in: from Alex Tabarrok, about how we are bad at pricing drugs because of unknown externalities (true!) but also with a side-comment reframing measures the IRA takes allowing nogiation as “price controls”, linking to [a policy paper][10] which suggests yet another set of measure to mitigate the adverse effects of IRA’s proposed solutions to the drug pricing problem. ⊕ Efficient markets for me, but not for thee, as Tabarrok’s writing partner would quip. And so the measures pile up from both the pro- and anti-regulation side. Ad infinitum, I suppose.

See also: better drugs don’t cost more, and a list of a few earnest but misguided attempts at cost control.

After more than a month, I wrote something in Serbian. It is about my disdain for Serbian journalists and the only (let’s hope) TV appearance there, from a few years ago. The disdain would probably apply to many other countries, seeing as the profession revolves around online lurking and email exchange at best, manufacturing consent at worst. Though there are, of course, exceptions.

Continuing the daily cadence of one photo followed by a complaint about America’s most hated board of medicine, ABIM has once again shown its complete deafness of tone. While almost 10% of its customers — for we are not members of this private club — rebelling against its practices, it still sent out an automated extortion reminder threatening to remove certification if you don’t pay up. Well, I don’t think I shall.

The campaign to end mandatory maintenance of certification is, as of yesterday, at 20,000 signatures. This is just shy of 10% of the people affected; what are the other 90+ percent thinking? Still, it was enough to make the professional societies pay attention.

From the Department of You Can’t Make This Up: the face of D.C. pedestrian safety was hurt in a hit-and-run. And not just a little bit:

Stephen Grasty was placed in a neck brace and taken to George Washington University Hospital, where doctors treated him for a long list of injuries, including a broken leg, foot and vertebra. His C6 vertebra was “hanging on a hair,” Shelly Grasty said.

D.C. could be one of the most pedestrian and bicycle-friendly cities in America (just look at these lanes!), but you just can’t get away from out-of-town drivers. (ᔥAxios)

🏀 USA Basketball coach Steve Kerr after FIBA World Cup semifinal loss to Germany:

“This team is very worthy of winning a championship. We just didn’t get it done.”

Hic Rhodus, hic salta, if I may say so.

Also: Go, Serbia! (ᔥBen Golliver)

You don’t need to live in DC to appreciate Martin Weil’s delightful prose about its weather this weekend:

Both days, Friday and Saturday, innocent of haze and atmospheric moisture as they were, seemed to celebrate change and assure us that in coming days, humidity would cease to be a concern.

These two days seemed to embody the exhilaration that comes of seeing blue skies, and nothing but blue skies, everywhere we looked.

Of course, when it comes to weather reporting nothing can beat Kevin Killeen’s story on why February is the worst month.

Kevin Kelley’s 10-year-old list of The Best Magazine Articles Ever has three from The Washington Post that are in the top 25:

• The Peekabo Paradox (2006), about Washington’s preeminent child entertainer, the Great Zucchini, and also about virtue and vice.
• Pearls Before Breakfast (2007), about a master violinist playing a 1713 Stradivari violin incognito in front of L’Enfant Plaza commuters.
• Fatal Distraction: Forgetting a Child in the Backseat of a Car Is a Horrifying Mistake. Is It a Crime? (2009), about, well, that.

The first two in particular are better than anything that will come out this week in any magazine, least of all in the Post. (↬The Technium)

Happy 20th birthday to the Marginal Revolution blog, by the way. I remember the first post I saw — an assorted link list featuring a memorable bear-hiker interaction — but of course it is now impossible to find thanks to MRs rudimentary search. It is a blog, through and through.

There was something particularly irksome about a USA Today article from a few days ago — it prompted 3, count them, three tweets posts Xs from me — and I wanted to figure out what bothered me so. Here is the headline:

Left or right arm: Choosing where to get vaccinated matters, study suggests. Here’s why

No, it’s not the typography, although they should either not have had a full sentence in their headline, or else should have finished it with a full stop. But then they would have lost the chance for the click-baity Here’s why as a prelude to an article ⊕ OK, this can get real confusing real fast since there are two articles I am writing about: the USA Today’s newspaper article, and the research article to which it refers. So, let’s use article for the newspaper, and manuscript for the research article. Because why not? about Real Science™ which — color me astonished — takes a hypothesis-generating study and presents the hypotheses it generated as the final results.

To its credit, the article starts of with a link to the manuscript and the name of the journal where it was published, which is eBioMedicine, part of the proliferating Lancet family, impact factor 11.1. ⊕ Although, you know what they say about impact factors.Good! They also invited an independent researcher to comment. And I am sure that his comments were similar to mine, although of course most of what he said (or more likely wrote in an email) didn’t make it. What ended up on the page were two blurbs about precise vaccination from the director of a Precision Vaccines program. Gasp.

But these are all side attractions. The biggest problem is this: scientists want to compare people who had a two-dose vaccine shot in the same arm to those who had it in different arms; in the manuscript, these were called ipsilateral and contralateral groups. They aren’t randomizing people to one versus the other, ⊕ What they describe as randomization isn’t really so, but that’s a rabbit hole we better not get into. but with these being generally healthy people, and with the participants not having a choice as to where they will get a vaccine, that is not too much of an issue. Then they ask them some questions about vaccine side effects and draw some blood. The questions are about side effects and the blood is to check for “the strength of the immune response”.

Note that they don’t say at the outset that the groups would be different, and how. Would the opposite arm have fewer side effects? Better immune response? If so, in what way? More antibody? Stronger antibody? A different subtype of antibody? Better or worse cellular immunity? Which cell (among dozens)? More cells, stronger cells, or different cells? Or maybe the same side would be better?

The beauty of hypothesis-generating research (for the researcher) is that it doesn’t matter. Whatever you get, you will get it published, sometimes in a double-digit impact factor publication. I’ve sat on many a lab meeting where things like this were proposed and always, always, the comment is that “the results will be interesting whatever they are”. And they are right! But you will not know — cannot know — whether the results you got are based on an underlying physiology, or occurred purely by chance. That is where confirmatory studies come in.

Neither the manuscript nor the article recognize this. Among the many things they looked at, the researchers found two things that were different between the two groups: those who had the vaccine in the same arm had “more” of a certain type of immune cell than the other, and the opposite-arm group had increased expression of a certain marker on yet another type of immune cell. “More” is in quotes because even that is more subjective than it appears — another rabbit hole — but even if true in this sample, it is at best a hypothesis that should lead to another, possibly smaller study, where you focus on these cells, with different operators counting them, and doing additional hypothesis-generating analyses on the side to figure out the why of it, which would lead into yet another confirmatory study… You get the idea.

This is not what the manuscript authors propose. Instead they take their result at face value and concoct a mechanism out of thin air that would explain the result. The journalist then takes the mechanism and presents it as the main research result, the Here’s why of that clickbait headline. There is a high bar for calling anything in science conclusive and the article does have the usual disclaimer that “more research and data is needed”. But the phrase has been repeated so much that it has lost all meaning, something you say to mark yourself as a “believer in science” while with a wink and a nudge you act as if the results were indisputable.

Fortunately, science is a strong-link problem: those who know what they are doing will adjust their beliefs accordingly, and down the line confirm or falsify these preliminary findings. Unfortunately, science doesn’t operate in a vacuum. If its covering of science is indicative, journalism, the fourth estate, is in a hole and digging deeper, taking others with them.