Relevant and even prescient commentary on news, politics and the economy.

Covid Vaccine Dosing Trials ?

I asked if, given the data collected in Phase III trials, it might be wise to delay second doses of the Pfizer and Moderna Covid 19 vaccines until supplies are ample.

Since then the UK government has decided to give second doses three months after the first dose. The reason is explicitly to get first doses in more people quickly. This is highly controversial. I’m just going to name drop (actually link drop) to show I am not the only person outside of the UK who supports this.

Another approach to vaccinating more people with limited supplies of vaccine is to reduce the dose. This was proposed by the now former head of the US program formerly known as Warp Speed. Here the logic is based on a clinical trial — with a sample size of 42 — the Moderna Phase 1 trial . The trial includes an estimate of the amount of infection blocking antibodies in participants serum. The measure is the blocking antibody titer — how much the serum has to be diluted before it blocks only half of the virus from infecting cells. After the first dose and before the second, a dilution of 8:1 (the lowest) allowed more than half of the control infection (of cells in vitro). However, even with a dose of vaccine of 25 micrograms per kilogram (half of the dose of 100 micrograms per kg which people are getting) there was a high average titer by day 43 soon after the second dose.

The phase 1 results explain why 2 doses were used in the phasee III trial (and in Pfizer phase 1-2-3 all merged to speed things up trial). It also makes the rareness of infection in the phase III trials more than 10 days after the first dose a bit surprising. My guess is that the rapid induction of blocking antibodies after the second exposure is enough to block infection even if the second exposure is infection with Sars Cov2 and not a second vaccination. However note that I am not an immunologist (my dad is an immunologist and he said better half the dose twice than the full dose once back when I started talking about this — as usual he knew what he was talking about).

The 14 who got 25 compared to the 14 who got 100 strongly suggest giving 50 micrograms per kg twice is a better way to spread out the vaccine.

However, there is no way either will be done in the USA without a large clinical trial. Also there is no way that there will be a large clinical trial (who would pay for it for one thing). But the point of this post is to ask how such a trial could be ethical if it were financed (the cost is negligible compared to Federal Covid relief spending and roughly equal to the cost of a delay of effective herd immunity of about one hour). I’d say if people are given the chance to get a first dose sooner than they otherwise could (and the second dose as soon as they would be allowed to get the first if they weren’t in the trial) then it is ethical. The trial can’t be double blind (or at least people who get a second shot have to be told if their first was placebo so they should get a third shot which will be the second of actual vaccine).

Similarly people can be invited to get half a dose if the alternative is no dose (with option to get full dose when it would be granted even if they weren’t in the trial). I think this can be done. I think it should be done. I am sure this won’t be done.

update: There is evidence from Israel that one dose of the Pfizer vaccine is less effective than was suggested by the few person-days of evidence in the phase III trials. In Israel  “over 12,400 have people tested positive for coronavirus after receiving vaccine shots” Israeli health officials estimate that one shot is about 50% effective after 14 days . The control group is not matched, it’s not a randomized trial, but it is enough evidence that it’s hard to argue for clinical trials (as I did above).

Restore Medicaid to Its Former Self Quickly

Me – Talk: Recent article on Health Affairs I tapped into and decided to present here at AB. The topic? As expressed in the title, return Medicaid to its former self and improved upon by the new Biden Administration. I also have been working on additional posts touching upon the history of the opioid epidemic by the numbers, single payer, and a comparison to the a European healthcare model.


“In Its First 100 Days, The Biden Administration Must Restore The Soul Of Medicaid, Health Affairs,” Nicole Hubereld, Paul Shafer

Some Purpose . . .

The new administration should turn things around quickly and fix the damage trump and his administration did as sponsored by Republicans and supporters. This is as vital as getting stimulus money to people.

With the pandemic and many out of work, one of the top priorities for President Biden in his first 100 days should be: repeal the changes to Medicaid over the last 4 years by Republicans driving the Trump administration – bus. Medicaid provides a safety-net covering nearly one-quarter of the population today and will also cover those who have recently lost income and insurance. Nothing could be more vital during a pandemic than people needing healthcare.

The PPACA is not perfect but with the implementation of it, the expansion of Medicaid in 38 states and Washington D.C. came to be. It was “only” Republican opposition which stymied it in the other 12 states.

Covid related deaths to accelerate according to CDC

The Centers for Disease Control and Prevention has a dire warning about what is to come for the COVID-19 pandemic, according to its latest ensemble projections.

An “ensemble” forecast combines each of the independently developed forecasts (state and federal) into one aggregate forecast to improve prediction over the next 4 weeks.

  • The top row of the figure shows the number of new COVID-19 deaths reported in the United States each week from November 7 through January 9 and forecasted new deaths over the next 4 weeks, through February 6.
  • The bottom row of the figure shows the number of total COVID-19 deaths in the United States each week from November 7 through January 9 and the forecasted number of total COVID-19 deaths over the next 4 weeks, through February 6.
  • Models make various assumptions about the levels of social distancing and other interventions, which may not reflect recent changes in behavior.

The agency believes that as many as 92,000 Americans will die from COVID-19 in the next three weeks despite the rollout of the vaccine. This represents a 25% increase in total COVID-related deaths, which have now topped over 384,000, according to data from Johns Hopkins University.

The CDC’s forecast also suggests that total COVID deaths will reach up to 477,000 by Feb. 6.

How is the distribution of the covid 19 vaccines going in your neighborhood?

Having just had an operation at Mass General earlier this week, I was pleased to hear that the nurses I met had their first vaccination. But then I checked the Boston Globe and Med Page Today on our local progress in relation to my own turn. Worth a discussion and feedback on your own locality.

https://www.medpagetoday.com/blogs/marty-makary/90649

Quote:

This is a manufactured problem. The CDC, states, and hospitals should have distinguished frontline COVID-19 workers from everyone who has a job connected to healthcare. As University of Iowa immunologist and CDC committee member Stanley Perlman, MD, PhD, told the New York Times, the CDC never intended to include workers who don’t interact with patients, like administrators and graduate students, in the first tier of priority vaccinations. Yet weeks after the FDA authorized the life-saving vaccine, hospitals like Brigham & Women’s Hospitals, Massachusetts General Hospital, Columbia, and Vanderbilt raced to give the vaccine to young non-patient-facing students and staff. Many of those staff now realize the injustice in their allocation and admit they feel terrible displacing a vulnerable American in the vaccine line. Hospital leaders: this is a disgrace to our great profession. You should have known better.

Coronavirus dashboard for January 6, 2021: new infections vastly outpacing vaccinations

Coronavirus dashboard for January 6, 2021: new infections vastly outpacing vaccinations

Total confirmed COVID-19 infections: 21,046,195*

Infections last 7 days average: 219,253


Total deaths: 357,258

Deaths last 7 days average: 2,670

Total vaccinations: 4,836,489

*A study just released, based on random blood samples, suggests that as many as 50,000,000 Americans may have already been infected. Because some of the positive tests may be based on exposure to other coronaviruses, I do not think the number is that high. But my own guess is that the “true” number might be about 30,000,000, or 1 in every 11 Americans.


Today I want to focus on comparing this winter’s breakout with last spring’s and summer’s, by comparing the top and bottom 25 States with the “poster children” for each of the past breakouts.


Seven day average of new infectionsBottom 25

Top 25

Not only do *all* of the top 25 now exceed the infection rate of the 2 poster children for the previous breakouts, but many of the bottom 25 are in the same ballpark as well. Among the 50 States, only Vermont and Hawaii have some semblance of control.

Coronavirus dashboard for December 29: a final look back at the pandemic disaster in 2020

Coronavirus dashboard for December 29: a final look back at the pandemic disaster in 2020

US confirmed cases: 19,132,726*
Average cases last 7 days: 184,005
Total US deaths: 333,118
Average deaths last 7 days: 2,207 

Total vaccinated: 2,127,143 (per CDC via Bloomberg)

*Because many asymptomatic people probably never get tests, actual cases are probably more like 26 million, or about 8% of the US population

Source: COVID Tracking Project

The good news is, we finally have started the process of vaccination, and 1% of the population should be vaccinated by the end of this week. The bad news is, at the current rate, it would take over 4 years to vaccinate everyone in the US. I do expect this to ramp up, both as more States get more efficient at administering the vaccine, and because the Biden Administration will be much more activist and competent at ramping up production and improving the supply chain.


As we end 2020, let’s take a look at total infections and deaths per capita so far.

Violence Against Women Act Blocked

While everyone is social distancing (?), wearing masks when out, and staying at home (mostly); there has been an uptick in women and men not getting along together well when confined to apartments or homes. No place to go and the heart may not grow fonder of your-other when confined due to the COVID-19 pandemic.  

Domestic violence surges during mandatory lockdowns

USA Today: The National Domestic Violence Hotline reported a 9% increase from 2019 in calls between May 16 in 2020. During that period many states declared lockdowns.

The San Antonio Police Department received 18% more calls related to family violence March 2020 compared to March 2019, the New York City Police Department experienced a 10% increase in domestic violence reports over the same period, and the Portland Police recorded a 22% increase in arrests YOY in March related to domestic violence.  

Review of Act History

Status quo bias and vaccine supplies

Here is a simple thought experiment on the use of scarce vaccine supplies.

Suppose that we had tested the Pfizer/Moderna vaccines with one dose per person and discovered that they were 85% effective at preventing covid-19. However, due to an administrative error, we gave some people two doses, and when we analyzed the data it turned out that a two-dose regimen was 95% effective at preventing covid-19.

Only 200 million doses of vaccine will be available over the next six months.

Under these circumstances, the idea that we should switch from our initial vaccination plan of one dose per person to two doses would be regarded as insane. It is clearly better to give 200 million people 85% protection than it is to give 100 million people 95% protection.

Yet today, many people believe that we should vaccinate half as many people using two doses per person, simply because this was our initial plan. This certainly seems like an irrational framing effect, or a status quo bias of some kind, or hidebound, bureaucratic thinking, and it seems likely to lead to thousands of unnecessary deaths and prolong our social and economic misery by months.

Come on people! Let’s think outside the box.

Rolling Out the Vaccine

Rolling Out the Vaccine

 This morning’s (Dec. 25) New York Times offers a panel discussion on the question of who should get vaccinated against Covid first.  Broadly speaking, they take a utilitarian position: it’s interesting that none disagreed with the positions taken by panelist Peter Singer, the world’s most prominent utilitarian philosopher.  And I wouldn’t either, except for one thing.

The vaccines approved by the FDA, along with those approved by other countries like China and Russia, have gone through the fastest possible testing.  Tens of thousands of individuals have been placed in control and treatment groups in order to determine two things: to what extent do the vaccines reduce the likelihood of getting infected (efficiency) and how common and severe are the side effects (safety)?  Meeting both criteria is sufficient for approval, which is how it should be.

But there is another crucial question, to what extent do the vaccines reduce transmission of the virus to others?  The answer does not affect whether these vaccines should be employed, but they do have large consequences for other policies during this phase of the pandemic, such as rules for separation and masking, restrictions on activities and events, resumption of in-person schooling, and how much should be spent on interventions like ventilation overhauls. To the extent that vaccination reduces transmission, other restrictions and investments can be modified as the vaccinated portion of the population increases.  Unfortunately, our knowledge of this issue is minimal.  We don’t have any published lab results at all, and we are at least months away from meaningful epidemiological data.