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Explainer: How clinical trials test COVID-19 vaccines

Explainer: How clinical trials test COVID-19 vaccines

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3 years ago

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A lab technician holds a vial of a COVID-19 vaccine candidate during testing at the Chula Vaccine Research Center, run by Chulalongkorn University in Bangkok, Thailand on May 25, 2020. (AP Photo/Sakchai Lalit)

On Sept. 4, 2020, President Donald Trump announced that we will have a vaccine for COVID-19 “before the end of the year and maybe even before Nov. 1.” As an election looms in the United States, the declaration fuelled worry that a COVID-19 vaccine may be approved before scientific vetting is complete.

In the United States, review and licensure of vaccines is the responsibility of the Food and Drug Administration (FDA). But the agency’s handling of emergency use authorizations for two anti-malaria drugs and convalescent blood plasma for the treatment of COVID-19 have led to claims it has become politicized.

A purple-gloved hand is selecting one of nine vials of blood in a green stand.
Blood samples from volunteers are handled in the laboratory at Imperial College in London, on July 30, 2020. Imperial College is working on the development of a COVID-19 vaccine. (AP Photo/Kirsty Wigglesworth)

Such is the worry about the impartiality of the FDA that pharmaceutical companies drew a line in the sand and pledged publicly to “only submit [a vaccine] for approval or emergency use authorization after demonstrating safety and efficacy through a Phase 3 clinical study.”

“Hell has frozen over,” remarked commentators.

But what is a Phase 3 clinical study? And how does scientific testing provide us with reliable evidence that vaccines not only work but are safe?

Vaccine development

Vaccine development can be thought of as the process of separating the parts of an infectious agent that make us sick, from those that induce an immune response and protect us from future infection. As this separation can be accomplished in myriad ways, vaccines are diverse.

Vaccine candidates for COVID-19 illustrate these diverse approaches. Some, such as SinoPharm’s inactivated coronavirus vaccine, use killed whole coronavirus. Others, such as the Oxford University-AstraZeneca vaccine, modify a different virus (in this case, chimpanzee adenovirus) to express coronavirus proteins. Yet others, such as Moderna’s mRNA vaccine, use only small bits of viral genetic material.

In Canada, the oversight of vaccines is shared by Health Canada and the Public Health Agency of Canada. The scientific evaluation of vaccines involves animal testing, human clinical trials and post-approval surveillance. In many regards, the evaluation of vaccines is the same as the process for drugs. Because vaccines are given to healthy people, however, there is an even greater emphasis in vaccine testing on safety.

Animal testing

The first step in evaluating a vaccine is animal testing. Animals are given differing doses of vaccine to check for adverse events and an immune response.

As the virus that causes COVID-19 is new, there was no animal model for the disease. Recent work has demonstrated that ferrets, cats and some non-human primates are prone to infection and can spread it to others. Animal testing provides information about safety (and perhaps efficacy) before a vaccine is tested on humans.

What is vaccine development, and how can it be done faster during a pandemic?

Human clinical trials

Human testing in clinical trials is divided into three phases. Ensuring the safety of a vaccine is the prime concern through all phases of clinical trials. Vaccine efficacy is evaluated in different ways across the trial spectrum. Early-phase trials look for the production of antibodies against the virus, while late-phase trials evaluate whether the vaccine in fact prevents people from getting sick.

Phase 1 trials are the first evaluations of a vaccine in humans. These trials recruit 10 to 100 healthy volunteers who receive different doses of vaccine. Common adverse events to a vaccine include redness or soreness at the injection site, muscle pains, headache and fever. Blood is also drawn from the volunteers to assess the immune response to the vaccine, particularly the rise in antibodies and whether antibody levels are similar to those in people who have had the disease.

Phase 2 vaccine trials are similar to Phase 1 trials in terms of their focus on adverse events and immune response. Phase 2 trials, however, include hundreds of healthy volunteers who are more diverse to give a better indication of the safety and immune response in people likely to receive the vaccine in the future.

A woman with her back to the camera sits on the examination table in an examination room as a man in a white coat and purple gloves gives her an injection in her upper left arm.
Pharmacist Michael Witte, left, gives Rebecca Sirull, right, a shot in the first-stage safety study clinical trial of a potential vaccine for COVID-19 on March 16, 2020, at the Kaiser Permanente Washington Health Research Institute in Seattle. Sirull was the third patient to receive the shot in the study. (AP Photo/Ted S. Warren)

As Phase 1 and 2 trials involve relatively small numbers of people, they only give us information on vaccine side-effects that are very common (affecting more than 10 per cent of people) and common (affecting more than one per cent of people). Vaccine efficacy is only evaluated indirectly through measuring antibody levels.

It is only the Phase 3 trials that can provide a pivotal demonstration that a vaccine both works and is safe. Phase 3 vaccine trials are large randomized controlled trials conducted in the community. In these trials people either receive the vaccine or a placebo. If fewer people who received the vaccine become sick compared to those who received placebo, we have direct evidence that the vaccine prevents disease.

Read more: Ethics must not be ignored when testing COVID-19 vaccines

A Phase 3 trial may involve tens of thousands of volunteers who receive the vaccine, further providing reliable information on adverse events, including those that are uncommon (affecting fewer than one per cent of people) or rare (affecting fewer than 0.1 per cent of people).

A vaccine may be licensed for use after a successful Phase 3 trial.

Of the 321 vaccines for COVID-19 in development, 27 are in Phase 1 or 2 trials and six are being evaluated in Phase 3 trials. In total, these trials seek to enrol 280,000 people from 34 countries. No COVID-19 vaccine has been licensed in Canada or the United States.

Post-approval surveillance

Once a vaccine is licensed, continued monitoring for safety is critical. Reliable detection of very rare (affecting fewer than 0.01 per cent of people) vaccine adverse events requires information on hundreds of thousands of people. The Canadian Adverse Events Following Immunization Surveillance System monitors the safety of marketed vaccines, publishes reports regularly and identifies the need for further study should a safety issue be identified.

Provided that a COVID-19 vaccine successfully navigates human clinical trials and is subjected to continuing safety monitoring after it is licensed, we have good grounds to believe that the vaccine both works and is safe.

Charles Weijer consults with Cardialen, Eli Lilly & Company, and Research Triangle Institute (RTI) International.

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Home buyers must now navigate higher mortgage rates and prices

Rates under 4% came and went during the Covid pandemic, but home prices soared. Here’s what buyers and sellers face as the housing season ramps up.

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3 hours ago

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March 17, 2024

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Springtime is spreading across the country. You can see it as daffodil, camellia, tulip and other blossoms start to emerge. 

You can also see it in the increasing number of for sale signs popping up in front of homes, along with the painting, gardening and general sprucing up as buyers get ready to sell. 

Which leads to two questions: 

  • How is the real estate market this spring? 
  • Where are mortgage rates? 

What buyers and sellers face

The housing market is bedeviled with supply shortages, high prices and slow sales.

Mortgage rates are still high and may limit what a buyer can offer and a seller can expect.  

Related: Analyst warns that a TikTok ban could lead to major trouble for Apple, Big Tech

And there's a factor not expected that may affect the sales process. Fixed commission rates on home sales are going away in July.

Reports this week and in a week will make the situation clearer for buyers and sellers. 

The reports are:

  • Housing starts from the U.S. Commerce Department due Tuesday. The consensus estimate is for a seasonally adjusted rate of about 1.4 million homes. These would include apartments, both rentals and condominiums. 
  • Existing home sales, due Thursday from the National Association of Realtors. The consensus estimate is for a seasonally adjusted sales rate of about 4 million homes. In 2023, some 4.1 million homes were sold, the worst sales rate since 1995. 
  • New-home sales and prices, due Monday from the Commerce Department. Analysts are expecting a sales rate of 661,000 homes (including condos), up 1.5% from a year ago.

Here is what buyers and sellers need to know about the situation. 

Mortgage rates will stay above 5% 

That's what most analysts believe. Right now, the rate on a 30-year mortgage is between 6.7% and 7%. 

Rates peaked at 8% in October after the Federal Reserve signaled it was done raising interest rates.

The Freddie Mac Primary Mortgage Market Survey of March 14 was at 6.74%. 

Freddie Mac buys mortgages from lenders and sells securities to investors. The effect is to replenish lenders' cash levels to make more loans. 

A hotter-than-expected Producer Price Index released that day has pushed quotes to 7% or higher, according to data from Mortgage News Daily, which tracks mortgage markets.

Home buyers must navigate higher mortgage rates and prices this spring.

TheStreet

On a median-priced home (price: $380,000) and a 20% down payment, that means a principal and interest rate payment of $2,022. The payment  does not include taxes and insurance.

Last fall when the 30-year rate hit 8%, the payment would have been $2,230. 

In 2021, the average rate was 2.96%, which translated into a payment of $1,275. 

Short of a depression, that's a rate that won't happen in most of our lifetimes. 

Most economists believe current rates will fall to around 6.3% by the end of the year, maybe lower, depending on how many times the Federal Reserve cuts rates this year. 

If 6%, the payment on our median-priced home is $1,823.

But under 5%, absent a nasty recession, fuhgettaboutit.

Supply will be tight, keeping prices up

Two factors are affecting the supply of homes for sale in just about every market.

First: Homeowners who had been able to land a mortgage at 2.96% are very reluctant to sell because they would then have to find a home they could afford with, probably, a higher-cost mortgage.

More economic news:

Second, the combination of high prices and high mortgage rates are freezing out thousands of potential buyers, especially those looking for homes in lower price ranges.

Indeed, The Wall Street Journal noted that online brokerage Redfin said only about 20% of homes for sale in February were affordable for the typical household.

And here mortgage rates can play one last nasty trick. If rates fall, that means a buyer can afford to pay more. Sellers and their real-estate agents know this too, and may ask for a higher price. 

Covid's last laugh: An inflation surge

Mortgage rates jumped to 8% or higher because since 2022 the Federal Reserve has been fighting to knock inflation down to 2% a year. Raising interest rates was the ammunition to battle rising prices.

In June 2022, the consumer price index was 9.1% higher than a year earlier. 

The causes of the worst inflation since the 1970s were: 

  • Covid-19 pandemic, which caused the global economy to shut down in 2020. When Covid ebbed and people got back to living their lives, getting global supply chains back to normal operation proved difficult. 
  • Oil prices jumped to record levels because of the recovery from the pandemic recovery and Russia's invasion of Ukraine.

What the changes in commissions means

The long-standing practice of paying real-estate agents will be retired this summer, after the National Association of Realtors settled a long and bitter legal fight.

No longer will the seller necessarily pay 6% of the sale price to split between buyer and seller agents.

Both sellers and buyers will have to negotiate separately the services agents have charged for 100 years or more. These include pre-screening properties, writing sales contracts, and the like. The change will continue a trend of adding costs and complications to the process of buying or selling a home.

Already, interest rates are a complication. In addition, homeowners insurance has become very pricey, especially in communities vulnerable to hurricanes, tornadoes, and forest fires. Florida homeowners have seen premiums jump more than 102% in the last three years. A policy now costs three times more than the national average.

Related: Veteran fund manager picks favorite stocks for 2024

 

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Mistakes Were Made

Mistakes Were Made

Authored by C.J.Hopkins via The Consent Factory,

Make fun of the Germans all you want, and I’ve certainly done that…

Published

23 hours ago

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March 17, 2024

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Mistakes Were Made

Authored by C.J.Hopkins via The Consent Factory,

Make fun of the Germans all you want, and I’ve certainly done that a bit during these past few years, but, if there’s one thing they’re exceptionally good at, it’s taking responsibility for their mistakes. Seriously, when it comes to acknowledging one’s mistakes, and not rationalizing, or minimizing, or attempting to deny them, and any discomfort they may have allegedly caused, no one does it quite like the Germans.

Take this Covid mess, for example. Just last week, the German authorities confessed that they made a few minor mistakes during their management of the “Covid pandemic.” According to Karl Lauterbach, the Minister of Health, “we were sometimes too strict with the children and probably started easing the restrictions a little too late.” Horst Seehofer, the former Interior Minister, admitted that he would no longer agree to some of the Covid restrictions today, for example, nationwide nighttime curfews. “One must be very careful with calls for compulsory vaccination,” he added. Helge Braun, Head of the Chancellery and Minister for Special Affairs under Merkel, agreed that there had been “misjudgments,” for example, “overestimating the effectiveness of the vaccines.”

This display of the German authorities’ unwavering commitment to transparency and honesty, and the principle of personal honor that guides the German authorities in all their affairs, and that is deeply ingrained in the German character, was published in a piece called “The Divisive Virus” in Der Spiegel, and immediately widely disseminated by the rest of the German state and corporate media in a totally organic manner which did not in any way resemble one enormous Goebbelsian keyboard instrument pumping out official propaganda in perfect synchronization, or anything creepy and fascistic like that.

Germany, after all, is “an extremely democratic state,” with freedom of speech and the press and all that, not some kind of totalitarian country where the masses are inundated with official propaganda and critics of the government are dragged into criminal court and prosecuted on trumped-up “hate crime” charges.

OK, sure, in a non-democratic totalitarian system, such public “admissions of mistakes” — and the synchronized dissemination thereof by the media — would just be a part of the process of whitewashing the authorities’ fascistic behavior during some particularly totalitarian phase of transforming society into whatever totalitarian dystopia they were trying to transform it into (for example, a three-year-long “state of emergency,” which they declared to keep the masses terrorized and cooperative while they stripped them of their democratic rights, i.e., the ones they hadn’t already stripped them of, and conditioned them to mindlessly follow orders, and robotically repeat nonsensical official slogans, and vent their impotent hatred and fear at the new “Untermenschen” or “counter-revolutionaries”), but that is obviously not the case here.

No, this is definitely not the German authorities staging a public “accountability” spectacle in order to memory-hole what happened during 2020-2023 and enshrine the official narrative in history. There’s going to be a formal “Inquiry Commission” — conducted by the same German authorities that managed the “crisis” — which will get to the bottom of all the regrettable but completely understandable “mistakes” that were made in the heat of the heroic battle against The Divisive Virus!

OK, calm down, all you “conspiracy theorists,” “Covid deniers,” and “anti-vaxxers.” This isn’t going to be like the Nuremberg Trials. No one is going to get taken out and hanged. It’s about identifying and acknowledging mistakes, and learning from them, so that the authorities can manage everything better during the next “pandemic,” or “climate emergency,” or “terrorist attack,” or “insurrection,” or whatever.

For example, the Inquiry Commission will want to look into how the government accidentally declared a Nationwide State of Pandemic Emergency and revised the Infection Protection Act, suspending the German constitution and granting the government the power to rule by decree, on account of a respiratory virus that clearly posed no threat to society at large, and then unleashed police goon squads on the thousands of people who gathered outside the Reichstag to protest the revocation of their constitutional rights.

Once they do, I’m sure they’ll find that that “mistake” bears absolutely no resemblance to the Enabling Act of 1933, which suspended the German constitution and granted the government the power to rule by decree, after the Nazis declared a nationwide “state of emergency.”

Another thing the Commission will probably want to look into is how the German authorities accidentally banned any further demonstrations against their arbitrary decrees, and ordered the police to brutalize anyone participating in such “illegal demonstrations.”

And, while the Commission is inquiring into the possibly slightly inappropriate behavior of their law enforcement officials, they might want to also take a look at the behavior of their unofficial goon squads, like Antifa, which they accidentally encouraged to attack the “anti-vaxxers,” the “Covid deniers,” and anyone brandishing a copy of the German constitution.

Come to think of it, the Inquiry Commission might also want to look into how the German authorities, and the overwhelming majority of the state and corporate media, accidentally systematically fomented mass hatred of anyone who dared to question the government’s arbitrary and nonsensical decrees or who refused to submit to “vaccination,” and publicly demonized us as “Corona deniers,” “conspiracy theorists,” “anti-vaxxers,” “far-right anti-Semites,” etc., to the point where mainstream German celebrities like Sarah Bosetti were literally describing us as the inessential “appendix” in the body of the nation, quoting an infamous Nazi almost verbatim.

And then there’s the whole “vaccination” business. The Commission will certainly want to inquire into that. They will probably want to start their inquiry with Karl Lauterbach, and determine exactly how he accidentally lied to the public, over and over, and over again …

And whipped people up into a mass hysteria over “KILLER VARIANTS” …

And “LONG COVID BRAIN ATTACKS” …

And how “THE UNVACCINATED ARE HOLDING THE WHOLE COUNTRY HOSTAGE, SO WE NEED TO FORCIBLY VACCINATE EVERYONE!”

And so on. I could go on with this all day, but it will be much easier to just refer you, and the Commission, to this documentary film by Aya Velázquez. Non-German readers may want to skip to the second half, unless they’re interested in the German “Corona Expert Council” …

Look, the point is, everybody makes “mistakes,” especially during a “state of emergency,” or a war, or some other type of global “crisis.” At least we can always count on the Germans to step up and take responsibility for theirs, and not claim that they didn’t know what was happening, or that they were “just following orders,” or that “the science changed.”

Plus, all this Covid stuff is ancient history, and, as Olaf, an editor at Der Spiegel, reminds us, it’s time to put the “The Divisive Pandemic” behind us …

… and click heels, and heil the New Normal Democracy!

Tyler Durden Sat, 03/16/2024 - 23:20

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“Extreme Events”: US Cancer Deaths Spiked In 2021 And 2022 In “Large Excess Over Trend”

"Extreme Events": US Cancer Deaths Spiked In 2021 And 2022 In "Large Excess Over Trend"

Cancer deaths in the United States spiked in 2021…

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1 day ago

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March 16, 2024

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"Extreme Events": US Cancer Deaths Spiked In 2021 And 2022 In "Large Excess Over Trend"

Cancer deaths in the United States spiked in 2021 and 2022 among 15-44 year-olds "in large excess over trend," marking jumps of 5.6% and 7.9% respectively vs. a rise of 1.7% in 2020, according to a new preprint study from deep-dive research firm, Phinance Technologies.

Algeria, Carlos et. al "US -Death Trends for Neoplasms ICD codes: C00-D48, Ages 15-44", ResearchGate, March. 2024 P. 7

Extreme Events

The report, which relies on data from the CDC, paints a troubling picture.

"We show a rise in excess mortality from neoplasms reported as underlying cause of death, which started in 2020 (1.7%) and accelerated substantially in 2021 (5.6%) and 2022 (7.9%). The increase in excess mortality in both 2021 (Z-score of 11.8) and 2022 (Z-score of 16.5) are highly statistically significant (extreme events)," according to the authors.

That said, co-author, David Wiseman, PhD (who has 86 publications to his name), leaves the cause an open question - suggesting it could either be a "novel phenomenon," Covid-19, or the Covid-19 vaccine.

"The results indicate that from 2021 a novel phenomenon leading to increased neoplasm deaths appears to be present in individuals aged 15 to 44 in the US," reads the report.

The authors suggest that the cause may be the result of "an unexpected rise in the incidence of rapidly growing fatal cancers," and/or "a reduction in survival in existing cancer cases."

They also address the possibility that "access to utilization of cancer screening and treatment" may be a factor - the notion that pandemic-era lockdowns resulted in fewer visits to the doctor. Also noted is that "Cancers tend to be slowly-developing diseases with remarkably stable death rates and only small variations over time," which makes "any temporal association between a possible explanatory factor (such as COVID-19, the novel COVID-19 vaccines, or other factor(s)) difficult to establish."

That said, a ZeroHedge review of the CDC data reveals that it does not provide information on duration of illness prior to death - so while it's not mentioned in the preprint, it can't rule out so-called 'turbo cancers' - reportedly rapidly developing cancers, the existence of which has been largely anecdotal (and widely refuted by the usual suspects).

While the Phinance report is extremely careful not to draw conclusions, researcher "Ethical Skeptic" kicked the barn door open in a Thursday post on X - showing a strong correlation between "cancer incidence & mortality" coinciding with the rollout of the Covid mRNA vaccine.

Phinance principal Ed Dowd commented on the post, noting that "Cancer is suddenly an accelerating growth industry!"

Continued:

Bottom line - hard data is showing alarming trends, which the CDC and other agencies have a requirement to explore and answer truthfully - and people are asking #WhereIsTheCDC.

We aren't holding our breath.

Wiseman, meanwhile, points out that Pfizer and several other companies are making "significant investments in cancer drugs, post COVID."

Phinance

We've featured several of Phinance's self-funded deep dives into pandemic data that nobody else is doing. If you'd like to support them, click here.

 

Tyler Durden Sat, 03/16/2024 - 16:55

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