Should Challenge Trials Have a Placebo Arm?

I have done my share of complaining about human subjects review by “Institutional Review Boards.” They can sometimes get worried about things that pose no real danger to experimental subjects or survey respondents. But if I were on a human subjects review board myself, I would be skeptical about a challenge trial with a placebo arm. Given the benefits of getting vaccines vetted quickly, I think challenge trials that expose volunteers to a virus after they have been vaccinated can be justified, but exposing volunteers to a virus without vaccinating them seems a bad idea to me. The statistical purity of having the placebo arm where someone randomly doesn’t get the vaccination and then is exposed to the virus is of some value, but to me doesn’t have enough value to warrant exposing unprotected people to the virus.

In “What Fraction of Participants in a Randomized Controlled Trial Should Be Treated?” I look at how a greater cost of treatment as compared to having someone be in the placebo arm could make it optimal to treat less than 50% of the subjects in a double-blind placebo-controlled trial. In a challenge trial, after including the danger to the subject, having someone in the placebo arm is much more costly than giving someone the treatment. As a result, the roles of the treatment arm and the placebo arm in the equation shift. It would be optimal to have far more than 50% of the experimental subjects and have much less than 50% in the dangerous placebo arm.

But even that calculation pretends that only those randomized to the placebo before being exposed to the virus provide information about what happens when someone is not vaccinated. What is happening “in the wild” in the pandemic provides some information about what happens when someone unvaccinated is exposed to the virus. And what happens in vaccine trials that do not involve deliberate exposure to the virus also provides evidence about the placebo. The most crucial input for vaccine development is to know what happens when someone is vaccinated and then exposed to the virus.

In the UK a human subjects review panel is allowing something of a placebo arm, but the amount of the virus the volunteers are exposed to is to be kept very small. Here is the description in the Wall Street Journal news article “U.K. Approves Trials That Will Deliberately Infect Volunteers With Coronavirus”:

With medics and scientists standing by 24 hours a day, researchers will inject closely controlled doses of coronavirus into the noses of quarantined volunteers. This set of volunteers won’t have received vaccines. The idea is to start with the smallest possible amount that allows researchers to gauge infection levels, symptoms and transmission methods while trying to ensure the volunteers’ safety.

If that goes well, a second stage of the trials is planned to include the use of vaccines—researchers haven’t specified which ones—to test how well they protect against symptoms and possibly transmission. Vaccines would be administered to healthy volunteers, who would then be purposely infected with coronavirus, again in closed-off quarters to contain the virus.

One thing I have learned from this pandemic is the importance of the quantity of viral particles one is exposed to. So there may be a quantity of viral particles low enough that a placebo arm for a challenge trial is reasonable, but it would be easy to get that quantity wrong. And if you have to start at very low levels and then go to higher levels, you are using up some of the speed advantages challenge trials. Still, it may make sense.

Are Nuts Inflammatory?

I heard it claimed that nuts were inflammatory. It is not easy to google up any evidence to back that idea up; conversely, it is easy to google up evidence that nuts are either anti-inflammatory or have no substantial effect on inflammation.

The article shown at the very top of this post is a meta-analysis looking at a number of studies on nuts, finding little overall effect on inflammation. There is, however, an intriguing drop in leptin from eating nuts, which suggests that nuts may be less satiating than one would otherwise expect, making it easy to eat a lot of them. The current version of the Wikipedia article “Leptin” says “Leptin (from Greek λεπτός leptos, "thin") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate energy balance by inhibiting hunger …”

The second article shown above suggests that nuts are anti-inflammatory. Part of the difference may be the emphasis in this second article on nuts crowding out less healthy foods. Often, the question “Is food X healthy?” should be the questions “Compared to what?” Many, many things are quite unhealthy compared to nuts, making nuts healthy compared to them.

A comparison of nuts to eating nothing might give a different answer about whether nuts are inflammatory. That is, compared to a water fast—eating nothing, but still continuing to drink water—nuts could cause some inflammation. This would not at all contradict the idea that eating nuts instead of, say, eating potato chips, was anti-inflammatory. Not that the comparison to something like potato chips is a very relevant comparison for daily eating habits. (See “Our Delusions about 'Healthy' Snacks—Nuts to That!”)

In any case, if nuts were strongly inflammatory, this would probably be quite visible in experiments that have been done. So the available evidence does provide some confidence that they are not strongly inflammatory for the average person who does not have a specific nut allergy. And it isn’t just nuts in general: no particular type of nuts seems to show up as strongly inflammatory in prominent studies.

What I was looking for as evidence of an inflammatory effect was the short-term response of inflammation immediately after eating nuts along the lines of evidence about the insulin-response to food and the glycemic response to food, but with a short-run inflammatory outcome measure. (On this type of measure for insulin response and glycemic response, see “Forget Calorie Counting; It's the Insulin Index, Stupid” and Using the Glycemic Index as a Supplement to the Insulin Index.) I did not immediately find evidence like that on short-run inflammatory responses soon after eating nuts or other foods.

I’d be glad to hear more opinions on the question of whether nuts are inflammatory and on other questions about how healthy nuts are in general and whether some nuts are healthier than others.

For annotated links to other posts on diet and health, see:

The Federalist Papers #25: Prohibiting a Standing Army in Time of Peace Would Be a Mistake—Alexander Hamilton

Before its ratification, one of the big objections to the proposed Constitution of the United States was that it allowed a standing army in time of peace. Superficially, the idea of prohibiting a standing army in time of peace was attractive. Having begun to address the issue in previous numbers of the Federalist Papers, Alexander Hamilton continues the argument against such a prohibition in the Federalist Papers #25. There are two main parts to his argument in #25, with subparts:

  1. State militias are not an adequate substitute for a national military

    • Some states would provide inadequately for defense

    • Some states would maintain large enough militias to scare the other states—with reason

    • States are less likely to put adequate political safeguards on their militias than the Union is to put adequate political safeguards on the national army

  2. A prohibition against a standing army would be unenforceable; it is a bad idea to have unenforceable provisions

    • The definition of something like “imminent danger” is quite elastic, but any prohibition of maintaining an army that did not allow an exception like this would be foolhardy

    • Not having a national army is a big military disadvantage

    • Even when legal provisions are clear, they tend to be flouted when survival is at stake

    • Having provisions likely to be flouted encourages disrespect for a constitution

Below is the full text of the Federalist Papers #25, with my headings added in bold italics, and the main two heading centered:

FEDERALIST NO. 25

The Same Subject Continued: The Powers Necessary to the Common Defense Further Considered

From the New York Packet
Friday, December 21, 1787.

Author: Alexander Hamilton

To the People of the State of New York:

1. State militias are not an adequate substitute for a national military.

IT MAY perhaps be urged that the objects enumerated in the preceding number ought to be provided for by the State governments, under the direction of the Union. But this would be, in reality, an inversion of the primary principle of our political association, as it would in practice transfer the care of the common defense from the federal head to the individual members: a project oppressive to some States, dangerous to all, and baneful to the Confederacy.

Some states would provide inadequately for defense. The territories of Britain, Spain, and of the Indian nations in our neighborhood do not border on particular States, but encircle the Union from Maine to Georgia. The danger, though in different degrees, is therefore common. And the means of guarding against it ought, in like manner, to be the objects of common councils and of a common treasury. It happens that some States, from local situation, are more directly exposed. New York is of this class. Upon the plan of separate provisions, New York would have to sustain the whole weight of the establishments requisite to her immediate safety, and to the mediate or ultimate protection of her neighbors. This would neither be equitable as it respected New York nor safe as it respected the other States. Various inconveniences would attend such a system. The States, to whose lot it might fall to support the necessary establishments, would be as little able as willing, for a considerable time to come, to bear the burden of competent provisions. The security of all would thus be subjected to the parsimony, improvidence, or inability of a part. Some states would maintain large enough militias to scare the other states—with reason. If the resources of such part becoming more abundant and extensive, its provisions should be proportionally enlarged, the other States would quickly take the alarm at seeing the whole military force of the Union in the hands of two or three of its members, and those probably amongst the most powerful. They would each choose to have some counterpoise, and pretenses could easily be contrived. In this situation, military establishments, nourished by mutual jealousy, would be apt to swell beyond their natural or proper size; and being at the separate disposal of the members, they would be engines for the abridgment or demolition of the national authcrity.

Reasons have been already given to induce a supposition that the State governments will too naturally be prone to a rivalship with that of the Union, the foundation of which will be the love of power; and that in any contest between the federal head and one of its members the people will be most apt to unite with their local government. If, in addition to this immense advantage, the ambition of the members should be stimulated by the separate and independent possession of military forces, it would afford too strong a temptation and too great a facility to them to make enterprises upon, and finally to subvert, the constitutional authority of the Union. States are less likely to put adequate political safeguards on their militias than the Union is to put adequate political safeguards on the national army. On the other hand, the liberty of the people would be less safe in this state of things than in that which left the national forces in the hands of the national government. As far as an army may be considered as a dangerous weapon of power, it had better be in those hands of which the people are most likely to be jealous than in those of which they are least likely to be jealous. For it is a truth, which the experience of ages has attested, that the people are always most in danger when the means of injuring their rights are in the possession of those of whom they entertain the least suspicion.

Some states would maintain large enough militias to scare the other states—with reason (reprise). The framers of the existing Confederation, fully aware of the danger to the Union from the separate possession of military forces by the States, have, in express terms, prohibited them from having either ships or troops, unless with the consent of Congress. The truth is, that the existence of a federal government and military establishments under State authority are not less at variance with each other than a due supply of the federal treasury and the system of quotas and requisitions.

2. A prohibition against a standing army would be unenforceable; it is a bad idea to have unenforceable provisions

There are other lights besides those already taken notice of, in which the impropriety of restraints on the discretion of the national legislature will be equally manifest. The definition of something like “imminent danger” is quite elastic, but any prohibition of maintaining an army that did not allow an exception like this would be foolhardy. The design of the objection, which has been mentioned, is to preclude standing armies in time of peace, though we have never been informed how far it is designed the prohibition should extend; whether to raising armies as well as to KEEPING THEM UP in a season of tranquillity or not. If it be confined to the latter it will have no precise signification, and it will be ineffectual for the purpose intended. When armies are once raised what shall be denominated "keeping them up," contrary to the sense of the Constitution? What time shall be requisite to ascertain the violation? Shall it be a week, a month, a year? Or shall we say they may be continued as long as the danger which occasioned their being raised continues? This would be to admit that they might be kept up IN TIME OF PEACE, against threatening or impending danger, which would be at once to deviate from the literal meaning of the prohibition, and to introduce an extensive latitude of construction. Who shall judge of the continuance of the danger? This must undoubtedly be submitted to the national government, and the matter would then be brought to this issue, that the national government, to provide against apprehended danger, might in the first instance raise troops, and might afterwards keep them on foot as long as they supposed the peace or safety of the community was in any degree of jeopardy. It is easy to perceive that a discretion so latitudinary as this would afford ample room for eluding the force of the provision.

The supposed utility of a provision of this kind can only be founded on the supposed probability, or at least possibility, of a combination between the executive and the legislative, in some scheme of usurpation. Should this at any time happen, how easy would it be to fabricate pretenses of approaching danger! Indian hostilities, instigated by Spain or Britain, would always be at hand. Provocations to produce the desired appearances might even be given to some foreign power, and appeased again by timely concessions. If we can reasonably presume such a combination to have been formed, and that the enterprise is warranted by a sufficient prospect of success, the army, when once raised, from whatever cause, or on whatever pretext, may be applied to the execution of the project.

If, to obviate this consequence, it should be resolved to extend the prohibition to the RAISING of armies in time of peace, the United States would then exhibit the most extraordinary spectacle which the world has yet seen, that of a nation incapacitated by its Constitution to prepare for defense, before it was actually invaded. As the ceremony of a formal denunciation of war has of late fallen into disuse, the presence of an enemy within our territories must be waited for, as the legal warrant to the government to begin its levies of men for the protection of the State. We must receive the blow, before we could even prepare to return it. All that kind of policy by which nations anticipate distant danger, and meet the gathering storm, must be abstained from, as contrary to the genuine maxims of a free government. We must expose our property and liberty to the mercy of foreign invaders, and invite them by our weakness to seize the naked and defenseless prey, because we are afraid that rulers, created by our choice, dependent on our will, might endanger that liberty, by an abuse of the means necessary to its preservation.

Not having a national army is a big military disadvantage. Here I expect we shall be told that the militia of the country is its natural bulwark, and would be at all times equal to the national defense. This doctrine, in substance, had like to have lost us our independence. It cost millions to the United States that might have been saved. The facts which, from our own experience, forbid a reliance of this kind, are too recent to permit us to be the dupes of such a suggestion. The steady operations of war against a regular and disciplined army can only be successfully conducted by a force of the same kind. Considerations of economy, not less than of stability and vigor, confirm this position. The American militia, in the course of the late war, have, by their valor on numerous occasions, erected eternal monuments to their fame; but the bravest of them feel and know that the liberty of their country could not have been established by their efforts alone, however great and valuable they were. War, like most other things, is a science to be acquired and perfected by diligence, by perserverance, by time, and by practice.

Even when legal provisions are clear, they tend to be flouted when survival is at stake. All violent policy, as it is contrary to the natural and experienced course of human affairs, defeats itself. Pennsylvania, at this instant, affords an example of the truth of this remark. The Bill of Rights of that State declares that standing armies are dangerous to liberty, and ought not to be kept up in time of peace. Pennsylvania, nevertheless, in a time of profound peace, from the existence of partial disorders in one or two of her counties, has resolved to raise a body of troops; and in all probability will keep them up as long as there is any appearance of danger to the public peace. The conduct of Massachusetts affords a lesson on the same subject, though on different ground. That State (without waiting for the sanction of Congress, as the articles of the Confederation require) was compelled to raise troops to quell a domestic insurrection, and still keeps a corps in pay to prevent a revival of the spirit of revolt. The particular constitution of Massachusetts opposed no obstacle to the measure; but the instance is still of use to instruct us that cases are likely to occur under our government, as well as under those of other nations, which will sometimes render a military force in time of peace essential to the security of the society, and that it is therefore improper in this respect to control the legislative discretion. It also teaches us, in its application to the United States, how little the rights of a feeble government are likely to be respected, even by its own constituents. And it teaches us, in addition to the rest, how unequal parchment provisions are to a struggle with public necessity.

It was a fundamental maxim of the Lacedaemonian commonwealth, that the post of admiral should not be conferred twice on the same person. The Peloponnesian confederates, having suffered a severe defeat at sea from the Athenians, demanded Lysander, who had before served with success in that capacity, to command the combined fleets. The Lacedaemonians, to gratify their allies, and yet preserve the semblance of an adherence to their ancient institutions, had recourse to the flimsy subterfuge of investing Lysander with the real power of admiral, under the nominal title of vice-admiral. This instance is selected from among a multitude that might be cited to confirm the truth already advanced and illustrated by domestic examples; which is, that nations pay little regard to rules and maxims calculated in their very nature to run counter to the necessities of society. Having provisions likely to be flouted encourages disrespect for a constitution. Wise politicians will be cautious about fettering the government with restrictions that cannot be observed, because they know that every breach of the fundamental laws, though dictated by necessity, impairs that sacred reverence which ought to be maintained in the breast of rulers towards the constitution of a country, and forms a precedent for other breaches where the same plea of necessity does not exist at all, or is less urgent and palpable.

PUBLIUS.

Links to my other posts on The Federalist Papers so far:

The Economist: 7 Republican Votes to Convict Donald Trump is a Big Deal

I am a glass-half-full person. (I wasn’t always so; see “How I Became Optimistic” and “Five Books That Have Changed My Life.” In the case of the Senate’s failure to convict Donald Trump after his second impeachment, I find the Economist agreeing with me in a glass-half-full take. (How I would have voted if I were a senator is clear from “The Federalist Papers #22 C: Pillars of Democracy—The Judicial System, Military Loyal to the Constitution, and Police Loyal to the Constitution” and “Peggy Noonan: Bring the Insurrectionists to Justice.”)

The February 14, 2021 Economist op-ed “Donald Trump’s second impeachment ends in a second acquittal” (from which all quotations in this post are taken) begins by explaining why low expectations for conviction were warranted:

Few expected that Donald Trump’s impeachment for inciting the mob that stormed the Capitol on January 6th would lead to his conviction. That would have needed the unlikely votes of 17 Republican senators.

Party loyalty is strong, and there is enough affection for Donald Trump left in the Republican primary electorate that many Republican senators would worry about losing in the next primary election they face if they voted to convict Donald.

Moreover, historically it has been difficult to same-party votes to convict a president or former president:

That seven senators turned against a still popular former president from their own party is striking. It was a different story last year, when Mr Trump was impeached for abuse of office after he put pressure on Ukraine’s government to investigate his main political opponent, Joe Biden, now president. On that occasion, Mitt Romney was the only Republican senator ready to vote to convict him. (That, in turn, was the first time any senator had voted against a president from his own party in an impeachment trial).

To those seven senators can be added one more who voted to acquit, but had remarkably sharply-worded criticism for a same-party ex-president:

On January 19th a visibly angry Mr McConnell had told the Senate of how “the mob was fed lies” and was “provoked by the president and other powerful people”. On February 13th, following the acquittal, Mr McConnell repeated that “there is no question, none, that President Trump is practically and morally responsible for provoking” the rioters’ attack. Mr McConnell, however, voted “not guilty”, arguing that the Senate lacked jurisdiction to punish Mr Trump once he had left office. He dropped strong hints that others might yet prosecute the ex-president, saying: “We have a criminal-justice system in this country. We have civil litigation. And former presidents are not immune from being accountable by either one.”

Nikki Haley also had sharp words for Trump:

To the number of senior Republicans turning their backs on Mr Trump may be added Nikki Haley, a former ambassador to the United Nations, who in an interview published on Friday said she was “disgusted” by his treatment of his vice-president, Mike Pence, and suggested he had “no future” in the party.

“Donald Trump’s second impeachment ends in a second acquittal” also directly addressed the question “Did the failure to convict Mr Trump mean it was a mistake to try?” It argues no. First, there wasn’t much choice but to try:

Not trying him for “high crimes and misdemeanours”, would have been to overlook egregious misbehaviour.

Second, the trial helped convince the public to take Donald’s offenses seriously:

The Senate trial drew avid public attention. Dramatic fresh footage of the assault by the mob, presented this week by Democratic congressmen serving as the prosecution, was witnessed by millions of Americans following events online and on television.

Third, the objective of trying to get an acquittal led Donald’s lawyers to concede important points:

Even Mr Trump’s lawyers frankly condemned the assault on the Capitol as “horrific” and said it was conducted by criminals. Whatever the result, the trial may thus have gone some way to helping to draw a line against antidemocratic violence—as low a bar as that might seem.

To these points by the Economist, I’ll add a fourth by Noah Smith: in Donald’s last days as a lame duck worrying about impeachment helped keep Donald occupied and possibly distracted him from other mischief he might have done as part of his endgame as president.

We certainly could have wished for a more decisive outcome, but it is an imperfect world. I am grateful that under serious strain from Donald’s antidemocratic behavior, the system held, and has delivered some rebuke to him. I say this despite how much he pretends to have won the election and despite how much he proclaims victory from the fact that only 57 senators voted to convict rather than 67.

Going forward, it matters a lot for what becomes of the Republican Party whether the bulk of the Republican Party continues to honor Donald or whether or not in the next two elections they begin to distance themselves from Donald, both rhetorically in 2022 and perhaps by voting against him in the primaries leading up to 2024.

Let me share my even more optimistic spin on Donald Trump’s time as our president (a spin that could easily be wrong). It just may have been worth it if, in the long run, Donald Trump tars being anti-immigrant as the despicable thing that it is in the eyes of a solid majority of the electorate. On my views on immigration, see “It Isn't OK to Be Anti-Immigrant” and “‘The Hunger Games’ Is Hardly Our Future--It's Already Here.” And on the geopolitical danger of becoming #2 in the world if we don’t allow more immigration, see “Benjamin Franklin's Strategy to Make the US a Superpower Worked Once, Why Not Try It Again?” and Matthew Yglesias’s book One Billion Americans.








Semaglutide Looks Like the First Truly Impressive Weight-Loss Drug

Link to the article shown above. Thanks to Joel Becker and Jess Riedel for pointing me to this article.

Link to the article shown above. Thanks to Joel Becker and Jess Riedel for pointing me to this article.

A large number of coauthors, with John P. H. Wilding as first author, report in the New England Journal of Medicine remarkable weight-loss results from semaglutide. The New England Journal of Medicine gives you two free articles a month if you sign up, and the article is relatively short, so you can easily read the results yourself.

I didn’t find any flaw in this study: “a total of 1961 participants were randomly assigned to receive semaglutide (1306 participants) or placebo (655 participants).” It was a “randomized, double-blind, placebo-controlled trial at 129 sites in 16 countries in Asia, Europe, North America, and South America” based on “68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo.”

Here are the bottom-line results of the study, in quotations from the article with bullet points added to distinguish different passages:

  • The mean change in body weight from baseline to week 68 was −14.9% in the semaglutide group as compared with −2.4% with placebo, for an estimated treatment difference of −12.4 percentage points (95% confidence interval [CI], −13.4 to −11.5; P<0.001).

  • Participants who received semaglutide were more likely to lose 5% or more, 10% or more, 15% or more, and 20% or more of baseline body weight at week 68 than those who received placebo (P<0.001 for the 5%, 10%, and 15% thresholds; the 20% threshold was not part of the statistical testing hierarchy) … Among the participants for whom data were available at the week 68 visit (1212 participants in the semaglutide group and 577 in the placebo group), these thresholds were reached by 86.4% (1047 participants), 69.1% (838 participants), 50.5% (612 participants), and 32.0% (388 participants), respectively, in the semaglutide group, as compared with 31.5% (182 participants), 12.0% (69 participants), 4.9% (28 participants) …

  • Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo.

  • Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time.

  • Similar percentages of participants in the semaglutide and placebo groups reported adverse events (89.7% and 86.4%, respectively) (Table 3). Gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation) were the most frequently reported events and occurred in more participants receiving semaglutide than those receiving placebo (74.2% vs. 47.9%).

To summarize, with one shot a week, participants achieved major weight loss with the kinds of health benefits one might expect from weight loss. Semaglutide did seem to cause gastrointestinal disorders (especially nausea and diarrhea) for many people, so it isn’t for everyone. But for those who don’t have those side effects, or only quite mild side effects, it sounds like a good deal. Note that these side effects are much less serious than the heart problems that can result from taking amphetamines, which do cause weight loss, but at a high cost.

Besides the nausea and diarrhea (which you would soon know whether you suffered from the drug or not), the most important caveat about the study is that its results were for people who had tried to lose weight in the past and were encouraged to eat less and exercise more during the study. Thus, the effects of semaglutide might be somewhat dependent on motivation to lose weight. The mechanism hypothesized by the authors of the study also suggests this as a real possibility. They write:

Weight loss with semaglutide stems from a reduction in energy intake owing to decreased appetite, which is thought to result from direct and indirect effects on the brain.

There are habit patterns and stress-related eating that might make It easy to eat a lot even if you aren’t hungry. The effects of semaglutide may be dependent on making an effort not to eat unless hungry. But that will be unclear until a semaglutide trial is done with less motivated participants.

When I was younger, I thought often that a drug solution to weight loss was only a few years off. That day was delayed long enough that I lost that confidence. But now, close on the heels of my finding the non-drug solution of fasting, perhaps the day of effective and relatively safe weight-loss drugs has arrived. There may come a time when fasting is only for health and not for weight-loss, since weight-loss has become easy.

For annotated links to other posts on diet and health, see:

The Four Horsemen of Relationship Destruction

I have often devoted my Valentine’s Day posts to ideas I think might help relationships. John Gottman is one of the foremost experts on the scientific evidence about relationships. From what he and his colleagues observed in the “Love Lab,” they identified the “Four Horseman” shown on the left in the graphic above as especially dangerous to relationships. But each of the four horsemen has an antidote, shown on the right in the graphic above. With this few words, it would be hard to do more for relationships than this.

Other Valentine’s Day Posts:

What Do Happiness Data Mean? Theory and Survey Evidence—Dan Benjamin, Jakina Debnam Guzman, Marc Fleurbaey, Ori Heffetz and Miles Kimball

Papers using happiness, life satisfaction or “Where do you stand on the ladder of life?” data (“self-reported well-being data”) make strong assumptions about how that data relates to theoretical utility notions. In this paper, my coauthors Dan Benjamin, Mark Fleurbaey, Jakina Debnam Guzman, Ori Heffetz and I bend over backwards to make that OK, but it just isn’t. Different authors either explicitly or implicitly assume self-reported well-being data like this corresponds to different, mutually incompatible utility notions. For example some assume it represents flow utility while others assume the very same data represents lifetime utility. And data we collected about how survey respondents interpret these self-reported well-being questions indicates that the respondents include a little of everything in how they interpret the questions—something that isn’t consistent with any obvious theoretically attractive utility notion.

There is hope for dealing with these problems, but not with the usual approaches. We give suggestions in the paper for a way forward.

One overall lesson I have taken from an extensive research agenda I have been involved in using self-reported well-being data is that it takes a lot of careful, mathematically and econometrically intensive work—and careful data collection—to get things right. And by “getting things right” I mean to something that doesn’t have an obvious problem that I personally am quite worried about, not solving all the problems that someone else might worry about. I am optimistic about the ultimate potential of this research agenda for informing policy choices for governments and other institutions in the light of the effects of those choices on the full range of things people care about, including non-market goods that don’t generate transaction data. But it is a long journey from where we are to where we need to go. That is a journey my coauthors and I have set out on.

For more on some of the difficulties in the road ahead, see the paper I highlight in this post:

National Well-Being Indexes and Goodhart’s Law

On the Keto Diet

There is a lot of hype over diets. But when you eat is much more important for weight loss—and in many dimensions for health—than what you eat. In my view, the typical keto diet is a bit heavy on animal protein, but in its exclusion of sugar, bread, rice, potatoes and most other high-insulin-index foods, and its emphasis on non-starchy vegetables, it is reasonably close to what I eat. But the following graphic from Julia Belluz’s June 13, 2018 Vox article “The keto diet, explained” illustrates why many people don’t lose much weight on a keto diet: the “Low-carb diet” on the left has someone eating three meals a day plus snacks!

Screen Shot 2021-02-06 at 10.38.34 PM.png

To a reasonable approximation, being in ketosis—fat-burning mode—is what it takes to make calories in/calories useful rather than misleading. (See “How Low Insulin Opens a Way to Escape Dieting Hell.”) But if you are eating three meals a day plus snacks, the difference between losing weight and gaining weight can be a subtle difference in how much you eat that might be hard to notice in practice—or so the evidence about how people do on the diet over the course of a year or more suggests. (Suppose, for example, that eating keto caused you to burn 100 calories more a day. You don’t have to eat much extra to counteract that effect.) By contrast, during periods of eating nothing (or almost nothing), you know what your calorie intake is. And a long enough fast (drinking water and maybe unsweetened tea or coffee, but not eating food) always puts you in ketosis.

I have no confidence that I would meet weight-loss goals if I were eating three meals a day plus snacks in a keto way. In what I eat, my low-insulin-index approach (see “Forget Calorie Counting; It's the Insulin Index, Stupid”) is reasonably close to keto. But I see the biggest benefit of eating that way that it makes it relatively painless to fast—whether for about 20 hours between a 4-hour eating window on two successive days or for a longer period of time. If my weight creeps up, as it often does, all I have to do is add in a few longer fasts.

The idea that keto helps reduce appetite is totally consistent with what I am saying: if you eat low on the insulin index, you can eat less and you won’t suffer. But no matter what you are eating, it tends to be relatively easy to slip in some extra calories. So to get real mileage out of a keto/low-insulin-index diet you really have to take advantage of the fact that eating that way makes it relatively painless to shift to eating nothing or very little for a time. If you don’t take advantage of that opportunity to eat nothing or very little without suffering, then the magic from a keto/low-insulin-index diet is likely to be of quite modest power.

In addition to working well with fasting, eating lowcarb can help with diabetes. I find this comment by Stephen Guyenet quoted in “The keto diet, explained” likely to be misleading to people looking for practical advice (though it might have some merit inside a technical debate relatively far afield from practical advice):

“What’s been demonstrated is that [the ketogenic diet] controls blood glucose levels,” explained Guyenet. “That’s a good thing. But to show true remission or reversal, you have to show a person can go back to being able to eat carbs without having diabetes again.” And that has never been proven with the ketogenic diet.

To translate: if you have diabetes, a lowcarb diet will help if you keep doing it. But doing a lowcarb diet for a short time and then returning to eating the way you were will pretty quickly put you back in the same trouble you were in. This is the nature of most good practices: you have to keep doing them to keep getting the benefits. (For weight loss I said similarly in “Kevin D. Hall and Juen Guo: Why it is So Hard to Lose Weight and So Hard to Keep it Off” that “permanent weight loss requires permanent changes in behavior.”)

In this post, I have been blurring over some of the distinctions between keto and low-insulin-index eating. To see some of the differences, take a look at my post “The Keto Food Pyramid.” But either can be combined with fasting reasonably well. Fasting—periods of time with no food are almost no food (but plenty of water)—is the key.

I also talk about the strategy of just adding more long fasts when weight creeps up in my post “Maintaining Weight Loss.”

For annotated links to other posts on diet and health, see:

The Federalist Papers #24: The United States Need a Standing Army—Alexander Hamilton

In the Federalist Papers #24, Alexander Hamilton makes three arguments in favor of the proposed constitution’s provisions in relation to a standing army:

  1. The Articles of Confederation and almost all the state constitutions also allowed for a standing army.

  2. A standing army that needs legislative approval is less of a problem than a standing army that the executive branch can raise without legislative approval.

  3. The United States face enough military dangers that an army (and a navy) is needed.

I think Alexander Hamilton underplays the danger of the President of the United States, using the military, and his position as commander in chief, to take over the government of the United States. But the third point, that it would hard for us to do without a standing army, is a strong one. It is then important that the legislative branch—in part through its power over the military budget—insist that those in the military be rigorously trained that their highest loyalty is to the Constitution, not to the commander in chief (while stressing the importance of obedience to the commander in chief when that obedience doesn’t contradict the constitution or the basic morality of avoiding war crimes). I talk more about that in “The Federalist Papers #22 C: Pillars of Democracy—The Judicial System, Military Loyal to the Constitution, and Police Loyal to the Constitution.”

Part of Alexander Hamilton’s first argument is disingenuous. Although the Articles of Confederation allowed for a standing army, the weakness of the Articles of Confederation were likely to leave any standing army seriously underfunded. That would make the standing army weaker relative to local militias. The very strength of the proposed Constitution was likely to lead, in practice, to a stronger standing army. That was a big deal. I do think that stronger standing army was necessary, however.

Here is the full text of Alexander Hamilton’s arguments in the Federalist Papers #24.

FEDERALIST NO. 24

The Powers Necessary to the Common Defense Further Considered

For the Independent Journal.

Author: Alexander Hamilton

To the People of the State of New York:

To THE powers proposed to be conferred upon the federal government, in respect to the creation and direction of the national forces, I have met with but one specific objection, which, if I understand it right, is this, that proper provision has not been made against the existence of standing armies in time of peace; an objection which, I shall now endeavor to show, rests on weak and unsubstantial foundations.

It has indeed been brought forward in the most vague and general form, supported only by bold assertions, without the appearance of argument; without even the sanction of theoretical opinions; in contradiction to the practice of other free nations, and to the general sense of America, as expressed in most of the existing constitutions. The proprietory of this remark will appear, the moment it is recollected that the objection under consideration turns upon a supposed necessity of restraining the LEGISLATIVE authority of the nation, in the article of military establishments; a principle unheard of, except in one or two of our State constitutions, and rejected in all the rest.

A stranger to our politics, who was to read our newspapers at the present juncture, without having previously inspected the plan reported by the convention, would be naturally led to one of two conclusions: either that it contained a positive injunction, that standing armies should be kept up in time of peace; or that it vested in the EXECUTIVE the whole power of levying troops, without subjecting his discretion, in any shape, to the control of the legislature.

If he came afterwards to peruse the plan itself, he would be surprised to discover, that neither the one nor the other was the case; that the whole power of raising armies was lodged in the LEGISLATURE, not in the EXECUTIVE; that this legislature was to be a popular body, consisting of the representatives of the people periodically elected; and that instead of the provision he had supposed in favor of standing armies, there was to be found, in respect to this object, an important qualification even of the legislative discretion, in that clause which forbids the appropriation of money for the support of an army for any longer period than two years a precaution which, upon a nearer view of it, will appear to be a great and real security against the keeping up of troops without evident necessity.

Disappointed in his first surmise, the person I have supposed would be apt to pursue his conjectures a little further. He would naturally say to himself, it is impossible that all this vehement and pathetic declamation can be without some colorable pretext. It must needs be that this people, so jealous of their liberties, have, in all the preceding models of the constitutions which they have established, inserted the most precise and rigid precautions on this point, the omission of which, in the new plan, has given birth to all this apprehension and clamor.

If, under this impression, he proceeded to pass in review the several State constitutions, how great would be his disappointment to find that TWO ONLY of them 1 contained an interdiction of standing armies in time of peace; that the other eleven had either observed a profound silence on the subject, or had in express terms admitted the right of the Legislature to authorize their existence.

Still, however he would be persuaded that there must be some plausible foundation for the cry raised on this head. He would never be able to imagine, while any source of information remained unexplored, that it was nothing more than an experiment upon the public credulity, dictated either by a deliberate intention to deceive, or by the overflowings of a zeal too intemperate to be ingenuous. It would probably occur to him, that he would be likely to find the precautions he was in search of in the primitive compact between the States. Here, at length, he would expect to meet with a solution of the enigma. No doubt, he would observe to himself, the existing Confederation must contain the most explicit provisions against military establishments in time of peace; and a departure from this model, in a favorite point, has occasioned the discontent which appears to influence these political champions.

If he should now apply himself to a careful and critical survey of the articles of Confederation, his astonishment would not only be increased, but would acquire a mixture of indignation, at the unexpected discovery, that these articles, instead of containing the prohibition he looked for, and though they had, with jealous circumspection, restricted the authority of the State legislatures in this particular, had not imposed a single restraint on that of the United States. If he happened to be a man of quick sensibility, or ardent temper, he could now no longer refrain from regarding these clamors as the dishonest artifices of a sinister and unprincipled opposition to a plan which ought at least to receive a fair and candid examination from all sincere lovers of their country! How else, he would say, could the authors of them have been tempted to vent such loud censures upon that plan, about a point in which it seems to have conformed itself to the general sense of America as declared in its different forms of government, and in which it has even superadded a new and powerful guard unknown to any of them? If, on the contrary, he happened to be a man of calm and dispassionate feelings, he would indulge a sigh for the frailty of human nature, and would lament, that in a matter so interesting to the happiness of millions, the true merits of the question should be perplexed and entangled by expedients so unfriendly to an impartial and right determination. Even such a man could hardly forbear remarking, that a conduct of this kind has too much the appearance of an intention to mislead the people by alarming their passions, rather than to convince them by arguments addressed to their understandings.

But however little this objection may be countenanced, even by precedents among ourselves, it may be satisfactory to take a nearer view of its intrinsic merits. From a close examination it will appear that restraints upon the discretion of the legislature in respect to military establishments in time of peace, would be improper to be imposed, and if imposed, from the necessities of society, would be unlikely to be observed.

Though a wide ocean separates the United States from Europe, yet there are various considerations that warn us against an excess of confidence or security. On one side of us, and stretching far into our rear, are growing settlements subject to the dominion of Britain. On the other side, and extending to meet the British settlements, are colonies and establishments subject to the dominion of Spain. This situation and the vicinity of the West India Islands, belonging to these two powers create between them, in respect to their American possessions and in relation to us, a common interest. The savage tribes on our Western frontier ought to be regarded as our natural enemies, their natural allies, because they have most to fear from us, and most to hope from them. The improvements in the art of navigation have, as to the facility of communication, rendered distant nations, in a great measure, neighbors. Britain and Spain are among the principal maritime powers of Europe. A future concert of views between these nations ought not to be regarded as improbable. The increasing remoteness of consanguinity is every day diminishing the force of the family compact between France and Spain. And politicians have ever with great reason considered the ties of blood as feeble and precarious links of political connection. These circumstances combined, admonish us not to be too sanguine in considering ourselves as entirely out of the reach of danger.

Previous to the Revolution, and ever since the peace, there has been a constant necessity for keeping small garrisons on our Western frontier. No person can doubt that these will continue to be indispensable, if it should only be against the ravages and depredations of the Indians. These garrisons must either be furnished by occasional detachments from the militia, or by permanent corps in the pay of the government. The first is impracticable; and if practicable, would be pernicious. The militia would not long, if at all, submit to be dragged from their occupations and families to perform that most disagreeable duty in times of profound peace. And if they could be prevailed upon or compelled to do it, the increased expense of a frequent rotation of service, and the loss of labor and disconcertion of the industrious pursuits of individuals, would form conclusive objections to the scheme. It would be as burdensome and injurious to the public as ruinous to private citizens. The latter resource of permanent corps in the pay of the government amounts to a standing army in time of peace; a small one, indeed, but not the less real for being small. Here is a simple view of the subject, that shows us at once the impropriety of a constitutional interdiction of such establishments, and the necessity of leaving the matter to the discretion and prudence of the legislature.

In proportion to our increase in strength, it is probable, nay, it may be said certain, that Britain and Spain would augment their military establishments in our neighborhood. If we should not be willing to be exposed, in a naked and defenseless condition, to their insults and encroachments, we should find it expedient to increase our frontier garrisons in some ratio to the force by which our Western settlements might be annoyed. There are, and will be, particular posts, the possession of which will include the command of large districts of territory, and facilitate future invasions of the remainder. It may be added that some of those posts will be keys to the trade with the Indian nations. Can any man think it would be wise to leave such posts in a situation to be at any instant seized by one or the other of two neighboring and formidable powers? To act this part would be to desert all the usual maxims of prudence and policy.

If we mean to be a commercial people, or even to be secure on our Atlantic side, we must endeavor, as soon as possible, to have a navy. To this purpose there must be dock-yards and arsenals; and for the defense of these, fortifications, and probably garrisons. When a nation has become so powerful by sea that it can protect its dock-yards by its fleets, this supersedes the necessity of garrisons for that purpose; but where naval establishments are in their infancy, moderate garrisons will, in all likelihood, be found an indispensable security against descents for the destruction of the arsenals and dock-yards, and sometimes of the fleet itself.

PUBLIUS.

  1. This statement of the matter is taken from the printed collection of State constitutions. Pennsylvania and North Carolina are the two which contain the interdiction in these words: "As standing armies in time of peace are dangerous to liberty, THEY OUGHT NOT to be kept up." This is, in truth, rather a CAUTION than a PROHIBITION. New Hampshire, Massachusetts, Delaware, and Maryland have, in each of their bils of rights, a clause to this effect: "Standing armies are dangerous to liberty, and ought not to be raised or kept up WITHOUT THE CONSENT OF THE LEGISLATURE"; which is a formal admission of the authority of the Legislature. New York has no bills of rights, and her constitution says not a word about the matter. No bills of rights appear annexed to the constitutions of the other States, except the foregoing, and their constitutions are equally silent. I am told, however that one or two States have bills of rights which do not appear in this collection; but that those also recognize the right of the legislative authority in this respect.

Links to my other posts on The Federalist Papers so far: