Monthly Archives

August 2020

Coronavirus

Covid-19 policy: Assertions and provocations

August 29, 2020

Our last post tackled various of the paradoxes embedded in the development of a Covid-19 vaccine, which in reductionist form come down to these two points:

  • Setting everything equal, vaccine trial sponsors will be able to unblind their Phase 3 clinical trials and see if their vaccine is effective sooner if disease is spreading rapidly in the population in which they are studying their vaccine than if it is not. In other words, more cases now gets us the vaccine faster.
  • Setting everything equal, vaccines that are less effective will get to a data “readout,” as the biotech folks say, faster than vaccines that are more effective. (The reasons for this are complicated and highly qualified, but the short version is that trials will be structured to read out when a set number of infection cases are registered, in the aggregate, in both the vaccine and placebo arms of the trial. If a vaccine is super effective, the vast majority of the requisite infections for a readout will have to come from the placebo arm. If it is less effective, there will also be a fair number of infections in the vaccine arm — even if still fewer than in the placebo arm — and those will help generate the requisite number of cases for the readout faster.)

With that background in mind, our love for the ironic and our fellow man leads to a number of assertions and provocations.

Assertion: Because Covid-19 is just not that dangerous for most people who get it, Americans are distancing, avoiding family and social life, staying out of crowded indoor places (meaning most fun places, plus church), and wearing masks only because they expect a technological solution — either a vaccine or a reliable treatment — in a matter of months rather than years. Vaccines have gotten by far the most attention, including from both the president and Dr. Anthony Fauci, so Americans are more focused on them than potential transforming therapies. So, it is only the prospect of a near-term vaccine that is sustaining all this social distancing, at least for the many people who are not at high risk of mortality or permanent consequences of Covid-19, or have not been scared in to thinking they are.

Provocation: Looked at this way, the Trump Administration’s Operation Warp Speed is the most important government policy sustaining American compliance, because it dangles the possibility of a near term vaccine. It, er, trumps all the bleatings of all the governors and mayors and scientists, which would not keep Americans away from each other and out of the bars — “Covideasies” would definitely become a thing — for very long if we did not expect a vaccine for, say, the usual 5-10 years.

Assertion: Donald Trump and Anthony Fauci have been more consistently aligned on the prospects for a near-term vaccine than on many, if not most, other issues. We believe that is because Fauci understands that hope for a vaccine is sustaining American social distancing. He probably also actually believes we will get a vaccine quickly, which certainly helps, but scientific reticence and regard for his own reputation might ordinarily restrain him from making aggressive Trump-esque predictions. We propose that Fauci has made those predictions because he believes that believing in a quick vaccine will help fight the disease now.

Assertion: As has been pointed out elsewhere, in the United States we have a profound division, aligned in large part by political tribe, about the purpose of social distancing, rules that shut businesses, and mask mandates. One camp, aligned with the left, believes that public policy ought to work almost without qualification toward the suppression of Covid-19 cases. This “disease suppressionist” camp believes that disease suppression is a necessary precondition to confident social and economic engagement. It further believes that disease suppression is sustainable for a long time via a regime of “testing and tracing,” whereby we test for the disease incessantly, and trace the contacts of people who test positive, presumably to isolate them.

The other camp, aligned with the right, are “flatten-the-curvists,” and believe that the point of social distancing during this pandemic, at least, is only to protect the capacity of the healthcare system to treat both Covid-19 cases and the usual diseases and injuries. The curvists do not support reducing cases of Covid-19 as an end in itself, believing both that “testing and tracing” will not work in the United States because people do not trust government and will not cooperate, and also that most people will in any case be infected eventually at little or no consequence before a vaccine becomes widely available. The curvists look forward to the day when enough people have had the disease or are otherwise immune that the chances that a still-susceptible person gets the disease in any encounter become very small. This is not the same as “herd immunity,” which is a mathematical concept, but the idea is that once infection has spread significantly in a population the number of new cases will dramatically decline regardless of government policy. A leading thoughtful articulation of this position is here. It is a long read, but worth your time.

Provocation: Disease suppressionists want to stamp out community spread of the disease over the long term, but if their policy were implemented and successful in the United States there would be no chance for vaccine Phase 3 trials to read out on anything like the promised schedule. If the political support for disease suppression is in part predicated on the hope for a vaccine sooner than the usual 3-5 years, then disease suppression is an inherently self-defeating policy because it delays vaccine trials.

When we have pointed this out to suppressionists in friendly social media interlocution, they have usually asked whether we could suppress cases in the United States and sponsor vaccine trials in other countries, such as Brazil, that have allowed Covid-19 to spread wildly. While such free-riding on developing world misery might deliver vaccine data quickly, it carries with it a host of practical and moral questions. Among them, would Americans then have the same claim on the first doses of the vaccine, either morally or lawfully? And — sometimes we crack ourselves up — do these mostly left-wing suppressionists who advocate doing vaccine trials elsewhere have a good justification for their rank neo-colonialism?

No, actually that is a real question.

Assertion: If you need spreading disease to conduct an adequate vaccine trial, how is China, which claims to have suppressed the Wuhan virus virtually out of existence, conducting vaccine trials? Partly via the aforementioned neo-colonialism:

Ironically, China is not in a position to test the vaccines on the required scale at home because it’s been so successful at containing the spread of the virus within its borders…

…China has already confirmed it is involved in official, advanced trials of a vaccine on thousands of people in countries including the UAE, Peru and Argentina.

This, however, is the seriously Commie part:

Then there’s unpublicised trials. In what appears to be linked to the emergency powers vaccination experiments, and not the official phase three trials, a group of Chinese miners were refused entry to Papua New Guinea recently after their employer revealed it was using them for vaccine trials.

Some 48 workers were injected in early August, according to a statement from the Chinese state-owned company that runs the mine in the Pacific islands nation.

The PNG authorities were concerned they’d been kept in the dark and that some of the workers may have tested positive for Covid-19.

Now, we are not against running clinical trials in special situations, such as on the employees on the insides of mines. Meat-packing plants or college campuses might be good places to recruit for vaccine trials. However, one might not be faulted for wondering, you know, out loud, whether such imperialist running dog niceties as informed consent mean anything at all when the employees in question work for a business owned by a police state.

Provocation: As the linked article makes clear, the Chinese are very interested in using their vaccine for their virus for geopolitical gain. We’ll say it: We guess that in addition to taking “volunteers” from state enterprises, the Chinese are conducting “challenge trials,” in which vaccine trial subjects are deliberately exposed to the disease. Challenge trials are rarely ethical in running dog countries, but we doubt that a Chinese institutional review board would have many qualms about approving them to speed a Covid-19 vaccine program that is an important project of the state.

Hey, wait a minute! Concentration camps are famously useful for human experimentation. How convenient that China has a few.

Coronavirus Freedom ain't free

A Covid-19 vaccine paradox and a few related speculations

August 8, 2020

To the extent we are all waiting for a vaccine to let us “get back to normal” — whatever “normal” is for a traumatized and transformed world — we will wait much longer if we do “too good” a job controlling the spread of Covid-19 now. This fact leads to a number of interesting and troubling speculations, of which more below after some background.

Earlier this week we received a report from one of the Wall Street analysts (Michael Yee at Jefferies) who covers Moderna, Inc. (NASDAQ: MRNA), the developer of one of the front-running vaccines for the prevention of Covid-19. It came by email and has no public link, so we shall provide a fair use reproduction of its key point, which is that the pace of the clinical trials to ascertain the safety and effectiveness of the various vaccines for Covid-19 depend highly on the rate of infection.

Big Picture: With MRNA’s recent initiation of the Phase III, we’ve fielded many investor questions as to (1) the different enrollment and infection scenarios and (2) various timing at which we could see data. Based on a statistical model and range of scenarios, we think fast enrollment and above-average infection rate in hot spots will drive a good chance (70%) we could see MRNA data by Oct/Nov. We think PFE/BNTX [Pfizer’s program – Ed.] will be similar if not earlier into September due to global enrollment and other minor details (shorter 3-wk dosing regimen) and AZN [AstraZeneca’s program – Ed.] may be Fall w/ more EU based enrollment and infection rate sensitivities.

Perhaps a short bit on vaccine trials would be useful. Basically, the trial sponsor rounds up thousands of volunteers who are at theoretical risk to catch the disease being studied, in this case Covid-19. These volunteers receive either the vaccine candidate or a placebo, and nobody — neither the volunteers, nor the people administering the injections or taking care of the patients — knows who got which. The study has a “statistical plan” — essentially, the scientific hypothesis being tested in the experiment — that depends on a certain number of people getting the infection over a certain period of time. Once you have hit that number of new infections, plus a few more to be on the safe side, you crack the code and figure out whether the volunteers who got the placebo had a greater propensity to be infected than the volunteers who got the vaccine candidate. If so by a statistically significant difference, voila! You’ve got yourself a vaccine.

Therefore, the faster the disease is spreading, the faster you will get to the “end point” of the trial. You would not conduct a Covid-19 trial in New Zealand or most European countries right now, but Mississippi might make sense.

Yee’s model, which includes such things as assumptions about infection spread under a “bear case” (low rates of infection, which would be good for the people not getting sick but delay the data readout for the Moderna trial and therefore bad for Moderna’s stockholders and “getting back to normal”) to a “bull case” (the reverse), suggests that we could see an “interim” readout — some statistical plans allow for an early peek at a subset of the patients — under a high infection scenario as early as late October 2020 and final analysis by Thanksgiving.

If, however, we break the back of the virus and infections decline dramatically, Yee’s model delays a readout — an essential predicate for FDA approval, even on an emergency basis — until March 24, 2021.

As we all have learned, five extra months of this shitshow comes at a huge cost, not just economically but emotionally, socially, and culturally.

Nobody planned it this way, but the spread of the infection in the United States right now (as opposed to earlier in the year when there were no vaccine candidates in Phase 3 trials) has the potential to be of enormous value to those parts of the country which have already been through their big spike. Because science. Let that sink in, Andrew Cuomo.

All of this arouses interesting political thoughts which will please nobody. President Trump’s fortunes may depend on infections declining substantially. There is at least some evidence that Trump’s poll results are correlated with daily infections in the United States. At the same time, though, he and his team have made all sorts of rosy predictions about the speed with which a vaccine may be available.

Going out on a limb here, but it doesn’t seem as though either Trump or the reporters bathing him in snark every day realize that a fast track to a vaccine depends on a high rate of infection somewhere in the United States. We have not seen anybody on the left or in the press accuse Trump of promoting infections to speed the vaccine trials. We find it difficult to believe that in the current climate that accusation would not surface, at least as a “some critics say” smear, had anybody thought of it. And, for that matter, neither has Trump raised the faster vaccine timeline as a silver lining of the high infections, which one could easily see him doing. When that tweet comes, you read it here first!

One can also imagine that the arc of infections will let through a vaccine — say, Moderna’s — that is not the best ultimate vaccine, and then delay or prevent other vaccines that might be better. No vaccine will be effective on everyone (which is why a Covid-19 vaccine will provoke complex political and social questions). Yee imagines that Moderna’s vaccine might range from 50% effective to 90% effective, so we don’t really know anything other than that no vaccine works on everyone. Well, a 50% effective vaccine first out of the gate would be a lot better than nothing, and it could easily happen. Why? Because the lower the effectiveness of the vaccine the faster the clinical trial will experience the required number of infections to hit the end point and final readout!

But that will drive another paradox: What if the first approved vaccine drives infections to the point where it takes forever to prove the effectiveness of subsequent superior vaccines, but not so low as to move us to “herd immunity”? That would suck, because it would make it politically much harder to require universal vaccination, which will be essential if we are going to protect people whose immune systems do not generate resistance to Covid-19 even after vaccination.

But that’s a whole ‘nother thing.