How COVID-19 Vaccine Trials Are Designed

November 12, 2020

There’s been a lot of talk lately about whether or not the fast-tracked COVID-19 vaccine will in fact be safe and effective. While vaccine makers insist that any vaccine reaching the market will have undergone rigorous testing, the way trial protocols are designed suggests these vaccines may leave a lot to be desired.

As reported1 by Forbes contributor William Haseltine, a former professor at Harvard Medical School and Harvard School of Public Health, while Moderna, Pfizer, AstraZeneca and Johnson & Johnson have all published their vaccine trial protocols in a rare display of transparency, “close inspection of the protocols raises surprising concerns.”

In a nutshell, the trial designs are such that the vaccines will get a passing grade even if their efficacy is minimal. Of course, we must also consider vaccine side effects and I’ve also written several articles about mounting safety concerns.

COVID-19 Vaccine Trials Designed to Pass Efficacy Test

As noted by Haseltine, prevention of infection would typically be a critical endpoint of any vaccine trial. In other words, you want to ensure that when you take the vaccine, your risk of infection is significantly reduced.

However, when it comes to the COVID-19 vaccine, shockingly, preventing infection is not a criterion for success in any of these trials. The only criterion for a successful COVID-19 vaccine is a reduction of COVID-19 symptoms, and even then, the reduction required is minimal.

“We all expect an effective vaccine to prevent serious illness if infected. Three of the vaccine protocols—Moderna, Pfizer, and AstraZeneca—do not require that their vaccine prevent serious disease only that they prevent moderate symptoms which may be as mild as cough, or headache,” Haseltine writes,2 adding:

The pharmaceutical companies intend to do trials ranging from 30,000 to 60,000 participants. This scale of study would be sufficient for testing vaccine efficacy.

The first surprise found upon a closer reading of the protocols reveals that each study intends to complete interim and primary analyses that at most include 164 participants. These companies likely intend to apply for an emergency use authorization (EUA) from the Food and Drug Administration (FDA) with just their limited preliminary results.

To get a “passing” grade in the limited interim analysis, a vaccine must show a 70 percent efficacy. However, again, this does not mean it will prevent infection in seven of 10 people. As explained by Haseltine:3

For Moderna, the initial interim analysis will be based on the results of infection of only 53 people. The judgment reached in interim analysis is dependent upon the difference in the number of people with symptoms … in the vaccinated group versus the unvaccinated group. Moderna’s success margin is for 13 or less of those 53 to develop symptoms compared to 40 or more in their control group.

The other vaccine makers are basing results on a similar protocol, where only a limited number of vaccinated participants are exposed to the virus to evaluate the extent of their symptoms.

Johnson & Johnson’s interim analysis will include results from 77 vaccine recipients who have been infected with SARS-CoV-2, and if fewer than 18 of them develop symptoms of COVID-19, compared to 59 in the control group, the vaccine will be considered successful.

In AstraZeneca’s case, the interim analysis includes 50 vaccine recipients. The vaccine will be a success if 12 or fewer develop symptoms after exposure to SARS-CoV-2, compared to 19 in the 25-person control group.

Pfizer’s interim analysis is the smallest of the bunch, with just 32 vaccine recipients. Their success margin is seven or fewer vaccine recipients developing symptoms, compared to 25 in the control group. In the primary analysis, efficacy is set to about 60 percent, and at most, 164 volunteers will be included in that analysis.

Especially concerning are that those receiving the vaccine in these trials are young and healthy individuals who are not really at high risk of dying from COVID-19. This makes the results of these trials highly questionable in the far more vulnerable population of the elderly.

Trials Are Merely Testing Reduction of Common Cold Symptoms

As if that’s not eyebrow-raising enough, the minimum qualification for a “case of COVID-19” amounts to just one positive PCR test and one or two mild symptoms, such as headache, fever, cough or mild nausea. As noted by Haseltine, “This is far from adequate.”

All they’re doing is testing to see if this COVID-19 vaccine will minimize common cold symptoms. They are not actually ensuring the vaccine will prevent serious COVID-19 complications. Johnson & Johnson’s trial is the only one that requires at least five severe COVID-19 cases to be included in the interim analysis.

“One of the more immediate questions a trial needs to answer is whether a vaccine prevents infection. If someone takes this vaccine, are they far less likely to become infected with the virus? These trials all clearly focus on eliminating symptoms of COVID-19, and not infections themselves. Asymptomatic infection is listed as a secondary objective in these trials when they should be of critical importance. It appears that all the pharmaceutical companies assume that the vaccine will never prevent infection. Their criteria for approval is the difference in symptoms between an infected control group and an infected vaccine group. They do not measure the difference between infection and noninfection as a primary motivation,” Haseltine writes.4

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