In the interest of “transparency”, Pfizer CEO Dr. Albert Bourlas released a statement on Friday outlining the timeline for when its experimental COVID-19 vaccine might be ready for approval for regular, non-emergency use. Much to Trump’s chagrin, CEO Dr. Albert Bourla said the earlier the company expects to apply for an emergency-use approval from the FDA would be the third week of November, after the election has come and gone.
While JNJ executives insisted their vaccine candidate likely wasn’t the cause, they brought in investigators and are now working to get the trial going again as quickly as possible. If what happened with the AstraZeneca-Oxford vaccine is any guide, it could be weeks before US regulators sign off on allowing the trial to resume. AstraZeneca-Oxford trial in the US has been paused for more than a month.
Back in September, AstraZeneca briefly halted global studies after UK regulators investigated a pair of patients who came down with symptoms of a rare illness which scientists worried might be connected with the vaccine. Trials in the UK and elsewhere restarted days later, but in the US, regulators have refused to allow the trials to resume.
Already, the time lost by JNJ and AstraZeneca-Oxford has pushed them out of the lead in the race to apply for an emergency use authorization from the FDA. Vaccine candidates being developed by Moderna and Pfizer-BioNTech have taken the lead.
But as Bloomberg pointed out in a piece published Saturday morning, both the AZ and JNJ vaccines relied on the same technique: the so-called adenovirus vector which was also used by the Gameleya Institute’s vaccine (aka Sputnik 5) and at least one of the leading Chinese vaccines.
And this year, with Covid-19 vaccines entering strongly into the politics of the hour, transparency and trust are key to fighting a virus that’s hit more than 39 million people globally and hamstrung economies. If concerns about side effects in experimental vaccines in trials using adenoviruses are validated, it could boost skepticism in the general public and raise questions for other drugmakers.
It would also amount to a considerable setback to adenovirus vector vaccines.
As Bloomberg explains, the adenovirus vaccine vector is nothing new to medicine. They are well studied and versatile, according to Bloomberg. Humans have been shown to easily tolerate them, which is what initially attracted scientists to experiment with this method for COVID-19. A J&J vaccine based partially on the method was recently approved to guard against Ebola.
However, the technique already has a couple of conspicuous blemishes on its safety record. Here’s one example: An AIDS vaccine based on the technique was abandoned after the virus was potentially tied to increased infections among those who received it.
In other experiments, though, there were disappointing results. In 2008, a vaccine using an adenovirus developed by Merck & Co. to prevent HIV was tied to increased infections among some who received it in a trial. Merck abandoned the shot, and several similar programs fell by the wayside.
Not surprising to most who are familiar with the ‘science’ that goes into vaccines in general, writing for Forbes, William A. Haseltine, professor at Harvard Medical School and Harvard School of Public Health says that the vaccine protocols are designed to succeed. Haseltine notes that preventing COVID-19 infection isn’t even being tested. With world leaders and people like Bill Gates stating that we cannot return to ‘normal’ until everyone is vaccinated, it’s concerning that the vaccine trials are not concerned with if the vaccines prevent infection at all.
Prevention of infection must be a critical endpoint. Any vaccine trial should include regular antigen testing every three days to test contagiousness to pick up early signs of infection and PCR testing once a week to confirm infection by SARS-CoV-2 test the ability of the vaccines to stave off infection. Prevention of infection is not a criterion for success for any of these vaccines. In fact, their endpoints all require confirmed infections and all those they will include in the analysis for success, the only difference being the severity of symptoms between the vaccinated and unvaccinated. Measuring differences amongst only those infected by SARS-CoV-2 underscores the implicit conclusion that the vaccines are not expected to prevent infection, only modify symptoms of those infected.
Essentially they’re only looking at the difference in severity between the vaccinated and unvaccinated, not whether one got infected and one did not as most people would assume is the purpose of the vaccine to begin with.
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.
The greatest fear people have is dying from this disease. A vaccine must significantly or entirely reduce deaths from Covid-19. Over two hundred thousand people have died in the United States and nearly a million worldwide. None list mortality as a critical endpoint.
The bar for these manufacturers to claim “effiacy” is so low that they cannot miss, meaning that not only will the public be subject to dangerous vaccines, but they’re not likely to even work.
Interim analysis success requires a seventy percent efficacy. The vaccine or placebo will be given to thousands of people in each trial. 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, which may be mild, 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. For Johnson & Johnson, their interim analysis includes 77 vaccine recipients, with a success margin of 18 or less developing symptoms compared to 59 in the control group. For AstraZeneca, their interim analysis includes 50 vaccine recipients, with a success margin of 12 or less developing symptoms compared to 19 in the 25 person control group. Pfizer is even smaller in its success requirements. Their initial group includes 32 vaccine recipients, with a success margin of 7 or less developing symptoms compared to 25 in the control group.
The second surprise from these protocols is how mild the requirements for contracted Covid-19 symptoms are. A careful reading reveals that the minimum qualification for a case of Covid-19 is a positive PCR test and one or two mild symptoms. These include headache, fever, cough, or mild nausea. This is far from adequate. These vaccine trials are testing to prevent common cold symptoms.
These trials certainly do not give assurance that the vaccine will protect from the serious consequences of Covid-19. Johnson & Johnson is the only trial that requires the inclusion of severe Covid-19 cases, at least 5 for the 75 participant 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.
The study of Johnson & Johnson’s Covid-19 vaccine has been paused due to an unexplained illness in a study participant.
A document sent to outside researchers running the 60,000-patient clinical trial states that a “pausing rule” has been met, that the online system used to enroll patients in the study has been closed, and that the data and safety monitoring board — an independent committee that watches over the safety of patients in the clinical trial — would be convened. The document was obtained by STAT.
Contacted by STAT, J&J confirmed the study pause, saying it was due to “an unexplained illness in a study participant.” The company declined to provide further details.
“We must respect this participant’s privacy. We’re also learning more about this participant’s illness, and it’s important to have all the facts before we share additional information,” the company said in a statement.
J&J emphasised that so-called adverse events — illnesses, accidents, and other bad medical outcomes — are an expected part of a clinical study, and also emphasised the difference between a study pause and a clinical hold, which is a formal regulatory action that can last much longer. The vaccine study is not currently under a clinical hold. J&J said that while it normally communicates clinical holds to the public, it does not usually inform the public of study pauses.
The data and safety monitoring board, or DSMB, convened late Monday to review the case. J&J said that in cases like this “it is not always immediately apparent” whether the participant who experienced an adverse event received a study treatment or a placebo.
Though clinical trial pauses are not uncommon — and in some cases last only a few days — they are generating outsized attention in the race to test vaccines against SARS-CoV-2, the virus that causes Covid-19.