After the expected spike in covid-19 cases and deaths about two weeks after Thanksgiving, the rates have started dropping again, although they are still high. We will now have to brace ourselves for another spike about two weeks after Christmas when some people will violate the guidelines once again to visit with family and friends.
The incompetence of the Trump administration in its handling of the pandemic has been responsible for the massive numbers of infected people and deaths in the US. In terms of total numbers (though not per capita), the US easily leads the rest of the world with over 18 million confirmed cases and about 325,000 deaths. Currently those numbers are rising at an average daily rate of about 200,000 and 2,500 respectively. Those numbers could been much lower if from the beginning Trump had been urging everyone to adopt the common sense safety guidelines that scientists and public health experts were advocating, instead of mocking them and hosting events that openly violated them and dismissing the seriousness of the pandemic.
Trump, while avoiding any blame for these horrendous numbers, has been trying to claim credit for the rapid development of the vaccine, pointing to his Operation Warp Speed initiative that has poured billions of dollars into vaccine development and he does deserve some credit for it.
Carolyn Kormann has an excellent article in the December 14, 2020 issue of The New Yorker about how the vaccine trials were done. She discusses how much was spent and who got the money.
The program has so far provided at least twelve billion dollars to pharmaceutical companies for researching, developing, and manufacturing vaccines and drugs, with the biggest contracts awarded to Moderna, Sanofi (which is partnering with GlaxoSmithKline), Novavax, Johnson & Johnson, and AstraZeneca.
Note that Pfizer and its partner BioNTech are not among the companies that received Warp Speed funds.
Although Trump has been determined to blame China for the pandemic numbers, it was the Chinese scientists quickly identifying the sars-CoV-2 genome and publishing it on January 10th that enabled the vaccine development to get off to such a quick start. This enabled researchers to immediately begin work on an mRNA vaccine, using the same technique that they had used to develop a vaccine for the earlier MERS-CoV virus. This is an example of how the openness of scientists in sharing information overcomes the barriers raised due to the parochial conflicts of their political leaders.
Moderna started its Phase III trials with about 30,000 volunteers while Pfizer, working with BioNTech, had around 42,000. Since they cannot deliberately infect people with the virus, they had to perform a natural experiment. They split volunteers up into two groups, one of whom got the vaccine and the other a placebo. They then had to wait and watch the volunteers until enough people got infected so that a threshold number was reached that allowed for statistically valid conclusions to be drawn.
This is where Trump’s incompetence helped. Because the virus was raging out of control, the threshold number of infected people was reached in less than four months.
On the morning of November 11th, Moderna announced that it had hit that threshold. A few days later, the Data and Safety Monitoring Board held a call with Moderna’s management and N.I.H. officials, telling them that, of ninety-five confirmed cases of covid-19 among trial participants, ninety were in the placebo group. Eleven volunteers had developed severe cases; all of them were in the placebo group. The vaccine was nearly ninety-five per cent effective.
…On November 30th, Moderna announced that it had arrived at the end of its trial, with a hundred and ninety-six covid-19 cases among more than thirty thousand volunteers. A hundred and eighty-five of the people who got sick had received the placebo, indicating an efficacy rate of ninety-four per cent. All thirty people who got severely ill, including one person who died, were in the placebo group. The data was consistent across age, race, and ethnicity. Among the volunteers who contracted covid-19, twenty-nine identified as Latino, six as Black, four as Asian-American, and three as multiracial; thirty-three were older than sixty-five.
As a rough calculation, if 18 million people out of a total population of 330 million got infected over 10 months at a constant rate, then the number of people that you would expect to get infected in the placebo population of 15,000 over a two month period is about 160. So the number of 185 reported by the Moderna group is of the right order of magnitude.
Pfizer also reported safety rates of about 95%.
Sensitive to criticisms about how badly minority communities have been treated by the medical establishment in the past, efforts were made this time around to avoid that.
Moderna eventually recruited more than seven thousand Americans over the age of sixty-five, and more than five thousand with chronic conditions such as diabetes, obesity, and heart disease. Thirty-seven per cent of the study’s participants were from communities of color, which have historically been underrepresented in clinical research. But, according to a Stat-Harris poll conducted in early October, there remains a significant racial discrepancy in vaccine confidence. Only forty-three per cent of Black Americans said that they would agree to receive a vaccine as soon as one was available, versus fifty-nine per cent of white Americans.
As for safety, most vaccines show any adverse safety effects within the first two or three months so that period has passed. One question is when the people who got the placebo will be told so that they can take the vaccine. The longer they refrain from doing so, the longer the safety window can be statistically tested but that raises serious ethics concerns. Both Moderna and Pfizer have said that they will ‘track’ the vaccine participants for about two years to gauge the long term effects. There is a debate going on as to whether the placebo population will be told soon so that they can get the vaccine. That would undermine the double-blind nature of the trial to see the long term effects but would it be right to deprive them of the vaccine for so long? Many in the placebo group might suspect they got the placebo if they did not experience any of the commonly reported side effects like a sore arm or aches and fever and go and get the vaccine anyway. These side effects are supposed to be similar to those experienced after one gets the shingles vaccine. I got that one and the side effects, while noticeable, were mild and went away in about 24 hours.
One of the ideas proposed at FDA’s meeting two weeks ago to discuss emergency authorization for the Pfizer vaccine was to keep the vaccine trials blinded, but to give every participant a second pair of jabs. Those who had gotten the placebo for the trial would get the real thing, while those who got the vaccine the first time would get saline.
I think this is the likely path forward, since it avoids un-blinding the study. The only downside is that we might never know if there are side effects 2 years after the shot. Of course, that is extraordinarily unlikely at this point, so the sacrifice of that data seems completely justified.
Trump’s incompetence …
You apply Hanlon’s razor too generously here. In the case of Trump, we can confidently assign malice as a cause ahead of stupidity:
I have a co worker in the Pfizer study. They unblinded it this week and are offering vaccination to anyone in the placebo group that wants it. They intend to continue tracking for up to 7 years, but her next appointment isn’t until April.
Wouldn’t that just screw both groups, who would only get one shot of a two-shot regimen?
@Ridana,
Those who were in the vaccine cohort in the trial got two jabs. In the proposed scheme, everybody in the trial (both placebo and vaccine) get two more jabs, so everyone gets a full administration of the vaccine regardless of which cohort they were in, without unblinding the trial.
The issue of what to do about the placebo cohort in vaccine studies raises interesting questions. In Australia there is an “ongoing” phase-one trial of a sub-unit vaccine from the University of Queensland (UQ). This vaccine seems to produce a good antibody response to the spike protein of the Covid-19 virus. The major claim to fame of the technology is the use of a “molecular clamp” that prevents the protein from refolding into an ineffective form even at room temperature. The trial vaccine uses a protein fragment gp41 as the clamp.
The informed consent document given to potential participants for the trial revealed that there was a very small possibility that the vaccine would provoke false positives to an HIV screening test. Unfortunately almost all the participants in the trial who got the vaccine, rather than the placebo, are now getting false positives to the usual screening test for HIV. This result obviously dooms the vaccine for general use so the phase-three trial will not now go ahead.
Of course there is still useful science to be done on the phase-one participants, for example to measure the ongoing strength of the antibody response (to both covid and the HIV-test reagent). So they are asking participants to stay in the program until November 2021.
Given the likely effectiveness of the vaccine I would be happy to forego other vaccines until next November if I knew for certain that I was not in the placebo group. Conversely, if I knew I was in the placebo cohort I would line up for another vaccine as soon as it is available for those in my risk category. So far UQ has not agreed to unblind the study, so I may have to leave anyhow.