Category: Medicine

Update on Rapid Tests for COVID

Nearly a year ago, I wrote Frequent, Fast, and Cheap is Better than Sensitive, arguing for rapid antigen tests:

A number of firms have developed cheap, paper-strip tests for coronavirus that report results at-home in about 15 minutes but they have yet to be approved for use by the FDA because the FDA appears to be demanding that all tests reach accuracy levels similar to the PCR test. This is another deadly FDA mistake.

See also my posts Infected versus Infectious and Rapid Tests. The EMA and then the FDA finally did start approving these tests. So how well are they working? Pretty damn well. Canada has two innovative programs. First, in Nova Scotia pop-up clinics have been using rapid tests for asymptomatic people:

During the third wave that hit Nova Scotia over the past month, the province’s community rapid testing centres have correctly sniffed out at least 285 COVID-19 cases in asymptomatic people, or about 10 per cent of all confirmed cases in this time period, according to the Nova Scotia Health Authority.

While most provinces reserve testing only for symptomatic people or close contacts of a case, Nova Scotia’s pop-up centres allow asymptomatic people to simply show up and get a rapid test for free, with results sent to them within an hour. The whole process relies largely on volunteers without a health-care background.

Furthermore, the true number of cases credited to rapid testing is probably much higher. When a rapid test correctly identifies a positive case, the person’s close contacts such as their family get PCR lab tests that don’t show up in the rapid test statistics.

Lisa Barrett, an infectious diseases specialist and the driving force behind the rapid testing program, said it’s hard to say for certain, but taken altogether it’s possible rapid antigen testing has helped Nova Scotia find up to 18 per cent of all cases during the third wave.

“This is the early detection system,” Barrett said. Rapid testing tends to catch people early on in their infection when they’re full of virus, meaning positive cases are found and put into isolation fast — likely days before they would have been found with a PCR test, if they were found at all.

Michael Mina argues that since the rapid antigen detected cases are among the most infectious cases, detecting these cases is probably worth half of all the PCR testing.

Second, Canada’s CDL Rapid Screening Consortium is now in 200 sites with 50 large companies and rapidly expanding. A very interesting, just published paper in The Lancet runs an experiment that suggests that these testing regimes can work. The experiment rapidly tested 1000 people and the negatives were then randomly assigned either to be sent-home to conduct their regular life or to attend a multi-hour concert with masks but also singing, dancing, alcohol and no-social distancing. After 8 days there were two infections in the at-home group and no infections in the Concert group which suggests that this type of rapid testing can be used to open and keep-open concerts, schools, universities, airplanes and workplaces.

What’s the point of testing now that we have vaccines? Two reasons. First, most of the world still hasn’t been vaccinated so testing will be a very useful stop-gap measure until vaccination is more widely distributed. Indeed, the success of these programs shows what we lost by not acting more quickly a year ago. Second, although the pandemic is (essentially) over in the United States (as predicted) there will likely be an uptick in the fall among the unvaccinated and you want rapid tests to be available rapidly in hot-spots. In other words, rapid deployment of rapid tests will help us to avoid outbreaks in the future.

Do individuals make more rational decisions when the stakes are higher?

Often yes, but this is a shibboleth of economics that doesn’t always fit the facts, as has been illustrated starkly by our behaviors during the pandemic.  Many people have taken too much risk, or been too risk-averse, even with high stakes on the line.  Here is one excerpt from my recent Bloomberg column:

You might wonder why we are getting these big, important decisions so wrong. I have at least two hypotheses. One is that anxiety causes people to make worse decisions. Facing the danger of a deadly pandemic, for example, the higher stakes might induce me to shift into denial, if only to protect my sanity and peace of mind. I might make worse decisions than if I were simply trying to avoid the common cold, for which the stakes are far lower.

My other hypothesis involves identity and the desire for belonging. It is no accident that red states in the U.S. are under-vaccinated relative to blue states; vaccine skepticism is in part an identity marker for Trump supporters. People tend to see big decisions as more important in shaping their identity than small ones. In essence, the significance of a decision induces all kinds of surrounding social forces to “infect” that decision with partisan influences, and that decision in turn becomes a truly credible signal of what we believe.

For most economic decisions, people do still make better choices when the stakes are higher — but this isn’t a universal principle. Are you so sure, for example, that decisions about who to marry are made more rationally than those about which TV show to watch? Maybe they are, but it’s not entirely obvious.

Note that it is now much easier to make good small stakes decisions, largely because of the internet:

An accompanying change is that low-stakes decisions are easier than ever, due largely to the internet, with one crucial caveat: The decision-maker must be relatively rational. Several decades ago, if you wanted to figure out the best paper towels to buy, you might have asked around and then collated a lot of information yourself. These days it is easy enough to search the internet for the answer. Or consider the example of credit-card rewards, which are far easier to collect, manipulate and use because of the internet.

The danger of course is that the sum of all these smaller triumphs convinces people that they are rational about big dilemmas too — despite the fact that they choose rather poorly on some of them. We are not used to a world where we are worse at big decisions than the small ones. But it has been hurtling our way for some while now.

Recommended.  I also cite this: “Bryan Caplan, a colleague who studies human rationality, has put the individual Covid response in only the second percentile of “my initially mediocre expectations.””

Vaccinations at Indian hotels?

The Centre [national government] has asked states and Union Territories to initiate legal or administrative action against private institutions which are offering packages for COVID-19 vaccination in collaboration with hotels, noting that this is in violation of prescribed guidelines.

In a letter to all states and UTs, Additional Secretary to the health ministry, Manohar Agnani, said it has come to the notice of the ministry that some private hospitals have been offering vaccination packages with hotels, against the guidelines issued for the National COVID-19 Vaccination Programme.

Here is more from The Wire, via Rama.  Obviously running vaccines through hotels adds explicit pricing and tends to allocate more vaccines to the wealthy (on average the relatively productive), and to boost total vaccine supply.  So economists will see more merit in this idea than the Indian government does.

Why the lab leak theory matters

Here is Ross Douthat at the NYT:

…there’s a pretty big difference between a world where the Chinese regime can say, We weren’t responsible for Covid but we crushed the virus and the West did not, because we’re strong and they’re decadent, and a world where this was basically their Chernobyl except their incompetence and cover-up sickened not just one of their own cities but also the entire globe.

The latter scenario would also open a debate about how the United States should try to enforce international scientific research safeguards, or how we should operate in a world where they can’t be reasonably enforced.

I agree, and would add one point about why this matters so much.  “Our wet market was low quality and poorly governed” is a story consistent with the Chinese elites not being entirely at fault.  Wet markets, after all, are a kind of atavism, and China knows the country is going to evolve away from them over time.  They represent the old order.  You can think of the CCP as both building infrastructure and moving the country’s food markets into modernity (that’s infrastructure too, isn’t it?), albeit with lags.  “We waited too long to get rid of the wet markets” is bad, but if anything suggests the CCP should have done all the more to revolutionize and modernize China.  In contrast, the story of “our government-run research labs are low quality and poorly governed”…that seems to place the blame entirely on the shoulders of the CCP and also on its technocratic, modernizing tendencies.  Under that account, the CCP spread something that “the earlier China” did not, and that strikes strongly at the heart of CCP legitimacy.  Keep in mind how much the Chinese apply a historical perspective to everything.

A number of you have asked me what I think of the lab leak hypothesis.  A few months ago I placed the chance of it at 20-30%, as a number of private correspondents can attest.  Currently I am up to 50-60%.

Fractional Dosing Trials Now!

Fractional dosing has the potential to massively increase the supply of COVID vaccine. The Moderna Phase I clinical trial and Pfizer Phase I/II trials already indicated a substantial immune response with smaller doses but the vaccine companies are under-incentivized to run additional fractional dosing trials (they won’t gain trillions, at best they will gains billions and might even lose some profit) and governments and private organizations are not picking up the ball. There are just two small trials underway that I am aware of:

N.B. now that we know that the vaccines work. we don’t need to study every dosage for efficacy against the virus. Instead of efficacy studies we can study how the vaccine is working in the body compared to those fully immunized, immunogencity trials (which is what the above trials are doing) and then use data and theory to infer effectiveness. If we felt it necessary to study effectiveness, human challenge trials would be ideal in this situation as you can study gradually smaller doses with little risk to the patients. But given the urgency, immunogenicity trials should provide enough information to make decisions on the ground. To limit risk, one could do a half-dose on the second dose or one could do a half-dose in people under the age of 50. Both of these regimens would still create significant increases in supply. Recall that in 2018, facing a yellow fever epidemic and a shortage of vaccine, Brazil used 1/5th doses to break the epidemic.

There are no guarantees but the world is ignoring a potential trillion dollar bill lying on the sidewalk.

Hat tip for discussion: Witold and Amrita.

Vaccine wastage, toward a general theory of multilateral institutions

South Sudan, for instance, recently destroyed nearly 60,000 doses it received from Covax; Malawi destroyed 20,000. Neither were able to distribute their entire allotments before the vaccines expired. Kenya, with more than 50 million people, received over a million doses from Covax in early March, but had used less than one-fifth by late April. The Ivory Coast similarly distributed less than a quarter of the over 500,000 doses it received in late February, raising fears that doses will expire before they are used. The problem goes beyond lower-income countries. More than 600,000 Covax-provided AstraZeneca vaccines sit in Canada at risk of spoilage, while Canadians debate whether it is safe to use them. Vaccinations can begin to confer meaningful protection in under 14 days. Freed from freezers, these vaccines could have saved many lives in Peru, India or Brazil, where the pandemic is raging.

Here is more from Zeke Emanuel and Govind Persad (NYT).

Cold Storage No Longer a Constraint

Yahoo: With little fanfare, the U.S. Food and Drug Administration gave Pfizer permission this week to store its COVID-19 vaccine in a typical refrigerator for one month — freeing the vaccine from the need to be shipped in cumbersome boxes stuffed with dry ice.

Among authorized COVID-19 vaccines, Pfizer’s vaccine was notorious for its ultra-cold storage requirements. Now, as the only vaccine authorized for children ages 12 to 17, this new flexibility could dramatically accelerate the effort to vaccinate America’s teens and adolescents.

Pfizer spent millions on its cold storage technology and now discovers that it isn’t strictly necessary–that wasn’t a mistake, Pfizer did the right thing–but it’s a good reminder of how new this technology is and also how the clinical trial decisions are not written in stone.

Straussian take: Investigate fractional dosing.

Shower Thoughts on IP

Tim Harford has an excellent column on IP:

There is a broad logic to intellectual property, then. But the specifics can be questioned. For example, just how temporary is the monopoly? F Scott Fitzgerald published The Great Gatsby in 1925 and died in 1940. The work only entered the public domain in 2021, after several posthumous copyright extensions, none of which can have been much of an incentive for him to write more.

Then there is the question of what deserves protection. At the height of the dotcom boom, an economics professor, Alex Tabarrok, was taking a shower when he dreamed up the idea of using cell phones to scan barcodes in a store, compare prices and order the product online. Alas, someone else had beaten him to the patent office by mere months. The idea, once unthinkable, was by 1999 rather obvious.

But why should society award 20 years of monopoly rights for the kind of idea that an amateur could dream up in the shower? Tabarrok suggests — rightly — that a 20-year patent should be awarded only if the inventor can prove the idea was expensive to develop. Without that, a five-year patent should be sufficient reward — and, more importantly, sufficient incentive.

I agree entirely with Harford’s concluding comments:

…If we are to produce the extra doses we need, we should focus on lifting every constraint. Perhaps patents fall into that category, but it seems more likely that they are a distraction from the expense of subsidising new factories and more doses for low-income countries. We should spend that money willingly, both for moral and for self-interested reasons.

As for intellectual property, the system needs to change in a hundred ways, some of which require the weakening of intellectual property and the strengthening of other incentives such as prizes and targeted subsidies. When we think through those changes, we should spend less time looking for victims and villains in the creative sphere — and more time thinking about where new ideas come from, and how they can be nurtured.

Read my piece on patent reform. Astute readers will note that there’s no contradiction between thinking that the patent system is in general too strong and that pharmaceutical patents increase innovation and that patents are not a major bottleneck to COVID vaccines. It’s all about evaluating tradeoffs in different scenarios.

Emergent Ventures winners, 14th cohort

Center for Indonesian Policy Studies, Jakarta, to hire a new director.

Zach Mazlish, recent Brown graduate in philosophy, for travel and career development.

Upsolve.org, headed by Rohan Pavuluri, to support their work on legal reform and deregulation of legal services for the poor.

Madison Breshears, GMU law student, to study the proper regulation of cryptocurrencies.

Quest for Justice, to help Californians better navigate small claims court without a lawyer.

Cameron Wiese, Progress Studies fellow, to create a new World’s Fair.

Jimmy Alfonso Licon, philosopher, visiting position at George Mason University, general career development.

Tony Morley, Progress Studies fellow, from Ngunnawal, Australia, to write the first optimistic children’s book on progress.

Michelle Wang, Sophomore at the University of Toronto, Canada, to study the causes and cures of depression, and general career development, and to help her intern at MIT.

Here are previous cohorts of winners.

Prescription Only Apps????

Scott Alexander has a good post on prescription only Apps.

Trouble falling asleep? You could take sleeping pills, but they’ve got side effects. Guidelines recommend you try Cognitive Behavioral Therapy For Insomnia (CBT-i), a medication-free process where you train yourself to fall asleep by altering your schedule and sleep conditions.

…Late last year, Pear Therapeutics released a CBT-i app (formerly “SHUT-i”, now “Somryst”) which holds the patient’s hand through the complicated CBT-i process. Studies show it works as well as a real therapist, which is very well indeed. There’s only one catch: you need a doctor’s prescription.

The app is $899. The surprise is that it doesn’t seem that this is an FDA requirement (at least on the surface. It’s murky why no one else is offering a cheap app). Scott thinks it’s a play on the insurance companies:

My guess is that prescription-gating is necessary because it’s the last step in the process of transforming it from an app ($10 price tag) to a “digital therapeutic” ($899 price tag). The magic words for forcing insurance companies to pay for something is “a doctor said it was medically necessary”. Make sure that every use of Somryst is associated with a doctor’s prescription, and that’s a whole new level of officialness and charge-insurance-companies-lots-of-money-ability.

The good news is, Somryst has partnered with telemedicine provider UpScript. I know nothing about UpScript, but I suspect they are a rubber-stamping service. If you don’t have a doctor of your own, you can pay their fee, see a tele-doctor, and say “I would like a prescription for Somryst”. The tele-doctor asks if you have insomnia, you say yes/no/maybe/no hablo inglés, and the tele-doctor hands you a Somryst prescription and charges you $45.

On the one hand, at least this saves you from Doctor Search Hell. On the other, it involves paying $45 for the right to pay $899. So it’s kind of a wash.

In a way this is worse than an FDA requirement because at least we could mock an FDA requirement mercilessly and perhaps change it. Instead it seems that a combination of incentives and murky constraints have pushed patients, insurers and innovators into an equilibrium in which cheap things become expensive. It’s enough to keep anyone up at night.

India Delays the 2nd Dose; Delaying 2nd Dose Improves Immune Response; Fractional Dosing

India has delayed the second dose to 12-16 weeks.

In other news, delaying the second dose of the Pfizer vaccine appears to improves the immune response (as was also found for the AstraZeneca vaccine). The latter is a news report based on a press release so some caution is warranted but frankly this was always the Bayesian bet since most vaccines have a longer time between doses as that helps the immune system. As Tyler and myself both argued, the short gap between the first and second dose was chosen to speed up the clinical trials not to maximize immunity. That was the right decision in the emergency but it was never the case that following the clinical trial regimen was “going by the science” no matter what Fauci said.

Many lives have been lost by not going to first doses first earlier, both here and in India.

Every country should move to a regimen in which the second dose comes at 12-16 weeks, even the United States, as this may improve the immune response and help other countries get a little bit ahead in their vaccine drives.

May I now also beat the drum some more on fractional dosing? Many people (not everyone) report that the second mRNA dose packs a wallop. I suspect that a half dose at 12-16 weeks would be plenty and that would free up significant capacity to vaccinate more people with first doses. We could also run some trials on half-doses for the young as a way to balance dosing and risk. Again this will matter for the rest of the world more than the United States but stretching doses in the United States will help the rest of the world and the arguments against stretching doses are now much diminished.

The Economist on Patent Waivers

A good statement from The Economist:

We believe that Mr Biden is wrong. A waiver may signal that his administration cares about the world, but it is at best an empty gesture and at worst a cynical one.

A waiver will do nothing to fill the urgent shortfall of doses in 2021. The head of the World Trade Organisation, the forum where it will be thrashed out, warns there may be no vote until December. Technology transfer would take six months or so to complete even if it started today. With the new mRNA vaccines made by Pfizer and Moderna, it may take longer. Supposing the tech transfer was faster than that, experienced vaccine-makers would be unavailable for hire and makers could not obtain inputs from suppliers whose order books are already bursting. Pfizer’s vaccine requires 280 inputs from suppliers in 19 countries. No firm can recreate that in a hurry.

In any case, vaccine-makers do not appear to be hoarding their technology—otherwise output would not be increasing so fast. They have struck 214 technology-transfer agreements, an unprecedented number. They are not price-gouging: money is not the constraint on vaccination. Poor countries are not being priced out of the market: their vaccines are coming through COVAX, a global distribution scheme funded by donors.

In the longer term, the effect of a waiver is unpredictable. Perhaps it will indeed lead to technology being transferred to poor countries; more likely, though, it will cause harm by disrupting supply chains, wasting resources and, ultimately, deterring innovation. Whatever the case, if vaccines are nearing a surplus in 2022, the cavalry will arrive too late.

Elsewhere in this issue they draw on my work with Kremer et al.

The increase in capacity seen over the past year was brought about in large part because of government interventions, most notably Operation Warp Speed in America and the activities of the Vaccine Taskforce in Britain, which guaranteed payments and drove the expansion of supply chains.

These efforts splashed around a lot of money which, if none of the vaccines had worked, would have been lost. But with the benefit of hindsight it is now hard not to wish they had been more generous still. In March Science, a journal, published estimates from a group of economists of the total global economic loss that would have been avoided if enough money to produce vaccines for the entire world had been provided up front, rather than enough for most of the rich world. They calculated that if the world had put in place a vaccine-production infrastructure capable of pumping out some 1.2bn doses per month by January 2021, it would have saved the global economy almost $5trn (see chart).

Eric Budish of the Chicago Booth School of Business, one of the model’s authors, explains the situation using a plumbing metaphor: it is faster to lay down a wider-bore pipe at the start of a project than to expand a narrow one later. The rich world succeeded in producing effective vaccines remarkably quickly in quantities broadly sufficient to its needs: an extraordinary achievement. But the capacity of the system it built in order to do so created constraints that the rest of the world must now live with. That was a choice, not destiny.

Cash transfers vs. in-kind health care assistance

The benefit of Medicaid coverage received by a newly insured adult is less than half what that coverage costs taxpayers, which is about $5,500 a year.

The reason is simple: The uninsured already receive a substantial amount of health care, but pay for only a very small portion of it, especially when their medical bills are high.

We have estimated that 60 percent of government spending to expand Medicaid to new recipients ends up paying for care that the nominally uninsured already receive, courtesy of taxpayer dollars and hospital resources. In other words, from the recipient’s perspective the alternatives are $5,500 in cash or only about 40 percent of that — $2,200 — in health insurance benefits, on top of the care they were already receiving.

That is from Amy Finkelstein at the NYT.

Where Next? Forecasting COVID in India

The Development Data Lab has put together a real-time forecast of COVID by district in India.

The underlying dataset of the portal is open-access and has information on total cases, deaths, estimated reproductive rate, total clinics and hospitals at the district level. Our hope is that residents of high-risk district will adjust behavior if their area has a precariously increasing reproduction rate over time. Even better if aid and medical support that many organizations are mobilizing at an impressive pace could be allocated based on district-level evidence. District-level bureaucrats can incorporate this additional information in planning their pandemic response (most of us have read about the striking example of what the District Collector of Nandurbar was able to achieve to prepare against the second wave). Finally, central and state governments could tailor their pandemic response given the obvious paucity of resources and time based on district-level risk estimates.

Overall, knowing where the virus will strike next can help save lives — by guiding behavior change, local public health measures, and allocation of scarce resources.

This is an important resource. Anup Malani, Satej Soman, Sabareesh Ramachandran, Ruchir Agarwal, Sam Asher, Tobias Lunt, Paul Novosad, and Aditi Bhowmick are some of the people working on this.