Post #817: Vaccine and sins of omission.

Posted on September 19, 2020

I’ve had a series of posts arguing that Russia (and now the China) are doing the right thing by deploying their vaccines before they know their effectiveness.  That was stated most recently in Post #814.  Both countries are already providing those vaccines to high-risk populations such as health care workers, before they know how effective the vaccines are (or aren’t) in preventing (or lessening severity of) COVID-19 infection.

Today’s twist is that they are also winning allies and gaining international influence by supplying vaccines, now, to other countries that need them.  That’s written up in this Washington Post article.  So not only are they ahead in their own country, but they are gaining influence around the world by being first-to-market in a number of countries that need help right now.  (And, in an odd twist, they’ve decided to pool some efforts on their vaccines. )

In this post, I’m going to review the logic behind this one last time, and then do the grade-school arithmetic that validates that logic.  Something that, apparently, neither our elected officials nor our public health bureaucracy seems willing or able to do.  Or at least, to admit to doing, in public.

My best guess, using some quite conservative estimates, is that providing 10 million doses of vaccine now, instead of six months from now, would save just under 10,000 hospitalizations (worth about a quarter-billion dollars), and about 2800 lives.  This doesn’t even count other costs saved, such costs saved by avoidance permanent organ damage from COVID-19, or economic losses from work or school time not missed due to COVID-19 illness and quarantine.    Not only would the avoided hospital costs more than pay for the vaccine itself, these numbers are vastly higher than any plausible health or economic damage from any as-yet-undiscovered rare side effects of the vaccines.

Details follow.

What is gained, and what is lost, by using a COVID-19 vaccine before its effectiveness has been proven?

The logic is simple:  heads I win, tails I don’t lose.  If they are effective, then providing them early is a big win.  You get a jump-start on stopping the pandemic, and you provide protection for high-risk populations.  If not, all you’ve done is injected a whole bunch of people with a placebo.

First point:  there’s no huge direct health risk in providing these vaccines.  They aren’t somehow going to kill a bunch of people.  All of them passed Phase I safety trials months ago.  All have been given to thousands-to-ten-of-thousands of Phase II/III volunteers.  Possible serious side-effects are so rare that they make the news when one occurs, as with one person in a trial of the British (AstraZeneca) vaccine.

Thalidomide.  Invariably, when I read comments on newspaper articles about coronavirus vaccine, somebody always says they won’t take the COVID-19 vaccine because it could be another Thalidomide.  That’s so common that I’ll go ahead and address it.  Because the people who say that are clueless, and have never even bothered to look up the basic facts regarding Thalidomide.  First, there were never any human safety tests of Thalidomide.  In that era — the 1950s — safety tests were done using animals only.  Second, in the 65 years since Thalidomide was first marketed, the entire approach to testing and reviewing drug safety and efficacy has changed.  As tough as it is for many to grasp, they don’t test drugs the way they did 65 years ago, and standards for safety are vastly higher than they were years ago.  Best analogy I can think of is cars.  Saying COVID-19 vaccine is unsafe because of Thalidomide is like saying modern cars are unsafe because 1950s vehicles had no seat belts.  It’s a ridiculous non-sequitur.  Finally, the substances in question are completely different.  We know what these vaccines are supposed to do, and how they do it.  These mRNA vaccines boil down to injecting you with a known harmless virus that carries RNA encoding one surface protien of COVID-19.  This is in the hopes that you’ll get a little viral infection around the injection side, and thereby create antibodies to a key COVID-19 surface protein.  By contrast, Thalidomide is a biologically-active compound with diverse effects throughout the human body, and a correspondingly large array of side effects.  They still have no idea exactly how it works in most cases, and they still have no idea why it causes birth defects (Wikipedia).

In fact, Dr. Fauci expressly addressed the incorrect idea that COVID-19 vaccines might be unsafe due to their rapid development.  That’s an idea pushed by people who don’t understand how vaccine development has changed over time, as I explained back in May 2020 (Post #698).   Here’s Fauci’s explanation, emphasis mine:

He (Fauci) specifically debunked the idea that speed equates to recklessness.

“I think people need to understand that speed is not related to a compromise of safety nor to a compromise of scientific integrity,” Fauci explained. “The fact that we've been able to move so fast is a real reflection of the extraordinary technological advances that have been made in the development of vaccines.”

Fauci largely attributed the ability to move so quickly in developing a treatment for the coronavirus to technological innovation. He stated that growing or sequencing a virus to make a vaccine used to take years, but can now be done within weeks or months. So the fact that a vaccine could be ready in such a short time frame relative to how long vaccines usually take to develop is not necessarily a sign of safety being compromised.

Source:  The Hill:  Fauci Predicts Pandemic Will end in Late 2021.

Second point:  You should not lose any adherence to existing COVID-19 safety precautions (such as distancing and mask use) by providing these vaccinesThat’s because nobody in a position of authority expects any of these vaccines to be 100% effective.  And most expect them to be only moderate effective, like the seasonal flu vaccine.  (Which I first started discussing back in early July, Post #741).  Accordingly, medical experts such Dr. Fauci are already telling people that they’re going to have to keep up all existing precautions in addition to being vaccinated.  From the same article cited above:

Notably, however, Fauci emphasizes that a combination of both a vaccine and adherence to public health protocols will be key to beating back COVID-19.

“You never should abandon the public-health measures. And the intensity of the public-health measures would depend on the level of infection in the community.”

Source:  The Hill:  Fauci Predicts Pandemic Will end in Late 2021.

Third point:  On the other hand, you may not gain a whole lot of immunity with the Russian and Chinese vaccines.   There’s a good reason to think that neither the Russian nor the Chinese vaccine is going to be particularly effective. It boils down to the use of a common human virus as the “carrier” for the vaccine.  Many people have already encountered that virus and have antibodies for it.  Those individuals have immune systems that will attack and (may) kill that virus before it has done its job.  Many people will be literally immune to the vaccine.

This scenario — the immune system destroys the medicine — is actually common for modern “monoclonal antibody” biological drugs.  This is why some MABs such as infliximab (Remicade ™) are often given with immune suppressants such as methotrexate, and why effectiveness of those drugs often fades over time.  Patients literally develop antibodies against the biological.  This is also why at least one of the leading US candidates uses a virus found in monkeys, not humans.  They want to avoid having the vaccine destroyed by the immune system before it has a chance to work.

Fourth point:  And yet, the person chosen to express “the US point of view” invariably condemns Russia and China for early vaccine release.  Typically, they point to the potential for some rare, as-yet-undiscovered, but potentially serious side-effect of the vaccine.  Side effects that haven’t shown up yet in the tens of thousands of person-months of exposure to those vaccines so far.  Or, in the case of the Chinese vaccine, despite hundreds of thousands of person-months of exposure so far.  That sentiment is attributed to unnamed “physicians” in this Washington Post article.

But here’s an odd thing.  I’m pretty sure that a fairly common and well-recognized side effect of COVID-19 is death.  And yet, the people who condemn the early release somehow never seem to mention that.  And COVID-19 has some fairly important other side effects too, ranging from permanent organ damage (heart, lung, kidney), down to simple loss of work time and disruption of schooling.  (And here, I’m not talking about societal losses, such as lost GDP and tax revenues.  I’m talking about the fact that people who get this disease, even a mild case, have to quarantine themselves for two weeks.)

So let’s do some simple grade-school arithmetic on the benefits of releasing 10 million vaccine doses now, versus releasing them six months from now.  When, plausibly, the Phase III trials will have had enough person-months of exposure to have drawn some conclusion about effectiveness.  Because, apparently, nobody in the US government or representing the US position on this issue appears to be willing to do that.

Calculation Part 1:  Infections avoided = doses given x infection rate per day x vaccine effectiveness x days not delayed.

By assumption, doses delivered in this calculation is 10 million doses delivered now.

The current US infection rate is 12 new cases of COVID-19 per 100,000 population per day.  For the time being, let me ignore the fact that the vaccine would be targeted to high-risk groups first (see Post #812).  Or, possibly, targeted first to areas with outbreaks.  So, arguably, we ought to use a much higher number.  (And note that that’s diagnosed cases, because that affects the benefit calculation that comes next, which is based on adverse events per diagnosed case.)

Let me assume that the US vaccines will be mediocre, just 60% effective.  The FDA says they won’t allow them to be released if they are less than 50% effective.  (Although it uses a very loose definition of that.)   Let me assume they’ll be 60% effective, just like the seasonal flu virus in good year (when the vaccine exactly matches the most common viruses that are circulating).

And let me assume that if we waited until Phase II/III trials were complete, that would take another six months.  (Or, six months from when we should have started using the vaccine, which was at least a month ago.)

So my calculator yields:  10,000,000 x (12/100,000) x 0.60 x 180 = 129,600 cases of COVID-19 avoided, by giving that vaccine now, as opposed to six months from now.

Calculation part 2:  Benefit = cases avoided x typical harm per case.  E.g., hospitalization or death per COVID-19 case.

Currently (9/19/2020), in Virginia, we have seen 139,655 cases, 10,562 hospitalizations, and 2,990 deaths from COVID-19.  That means that 7.6 percent of diagnosed cases resulted in hospitalization, and 2.1 percent resulted in death.

Again, this is a conservative calculation, because it ignores the fact that the vaccine would be targeted to high-risk groups such as the elderly, nursing home residents, and those with comorbidities.  This just assumes it would be given to the average Virginia resident. (And deaths may be modestly under-reported due to reporting issues that Virginia is trying to fix.)

That means early distribution of vaccine would save (129,600 x 0.076 =) ~9800 hospitalizations and (129,600 x 0.021 = ) ~2775 deaths.   That doesn’t count avoidance of organ damage, treatment costs for non-hospitalized patients, work loss, school loss, and other such items.

The traditional (fee-for-service) portion of the Medicare program provides a reliable benchmark for average payment (roughly equal to cost) for COVID-19 discharges.  Medicare has paid an average of just over $25,000 per discharge so far (per this reference on the Medicare website).  Assuming I’ve done the math right, the total hospital cost savings works out to just about a quarter-billion in hospital costs, and just under $25 per dose of vaccine administered.  Even with this extremely conservative calculation, the savings in hospitalization costs alone more than pay for the vaccine.  (I believe that the Federal government is paying something like $10/dose for the vaccines that it is purchasing.)

Conclusion:  Sins of Omission.

Given the tens to hundreds of thousands of individuals who have already taken these vaccines, it’s inconceivable that there is some as-yet-unnoticed major side effect whose estimated costs could more than offset these estimated benefits.  Under a reasonably conservative set of assumptions, early provision of vaccine in a pandemic scenario is a winner, both from the standpoint of health, and from the standpoint of dollars and cents.

Those of us of a certain age, and raised in a certain faith tradition, understand that there are both sins of commission and sins of omission.  The former is doing something that you shouldn’t have.  The latter is not doing something that you should have.

By not releasing vaccines early, we’re committing a sin of omission.  And if I can do that arithmetic, so can our health bureaucracy.  But like all bureaucracies, they are inherently conservative.  You can get fired for the bad decision that you made.  You are rarely fired for the even worse non-decision that you made.

And so, even though they are perfectly capable of doing this arithmetic, nobody in the health care bureaucracy is going to come out in favor of early release.  It’s just not in their DNA.  And as a result, people in third-world countries will be getting vaccinated, courtesy of Russian and China, while we sit here until our health bureaucracy ensures that all the i’s are dotted and t’s are crossed.

In the end, a rational policy here is all about balance.  You don’t make knee-jerk reactions.  You don’t blithely do business-as-usual.  You don’t take poliics into consideration.  You carefully assess costs and benefits of action.  And you assess the costs and benefits of inaction.  And you do what’s best for the country.

But that assumes we have any rational policy.  Really, all this requires is for those in charge to wake up and realize that we’re in the middle of a deadly pandemic.  That, by itself, radically alters the cost/benefit calculus in favor of early vaccine release.  But instead, the bureaucracy plods along, insisting that business-as-usual is the only possible course.  While, what, 1000/day are dying from COVID-19, every day vaccine release is delayed?

Man, I am tired of being on Team Stupid.