The FDA has stated that including a control group when testing vaccines is unethical because vaccines are a proven “effective intervention”. Most vaccines are tested against other vaccines (multiple examples below) which makes it difficult to determine their effectiveness.
Before I started diving deeper into research on vaccines I had always thought, of course, before putting vaccines on the market each manufacturer must do studies with an inert placebo to be approved by the FDA. That’s the FDA approval process for every other drug- it is simple science. So vaccines would not be any different.
However, upon further inspection I found that in the world of vaccines the protocol for trials has been different than other pharmaceutical products, all the way back to the early 1950s.
Why a Placebo group in a Vaccine Trial is an Ethical Controversy
In 2008 the WHO published ethics guidelines and although acknowledging that,
“when the objective of a study is to establish the safety of a new vaccine, the use of a placebo is much more likely to produce a scientifically reliable result than the use of an active control,”
They further went on to state:
“as a general rule, research subjects in the control group of a clinical trial of should receive an established, effective intervention. In some circumstances, it may be ethically acceptable to use a placebo or “no treatment.”
What is an “active control” and what do they mean by “an established effective intervention?”
Usually in scientific studies or trials, half of the participants receive the drug or vaccine and half receive an inert placebo. The word inert means causing no change or having no chemical reaction. So, in the case of drugs usually participants are given a sugar pill that looks like a drug, but isn’t and in vaccine trials, recipients should receive a saline shot that looks like the vaccine but isn’t.
An active control is used in place of a true inert placebo. It is something that is chemically active, like another drug or drug ingredient. Usually, these are used when we want to compare two different drugs like ibuprofen vs. acetaminophen. In the case of vaccines the “established, effective intervention” talked about is another vaccine that has already been approved.
As the WHO goes on to plainly state,
“Using a placebo in the control arm would deprive subjects of an established effective intervention… therefore it would be unethical to use a placebo.”
The WHO reasons that if we were to deprive some children of the chance to get a vaccine it would be unethical because they may get sick and the point is to stop people from having an illness. Therefore all participants in the trial will get a vaccine. Either a vaccine that has been approved in the past or one that is on trial currently.
Cementing Ethics Policy Increases Issues for Trial Integrity
Testing one vaccine against another, while effective when trying to compare two vaccines is not able to produce the same effect as testing a vaccine against an inert placebo. In fact, the WHO acknowledges this stating, “It may be difficult to assess the reactogenicity of the trial vaccine.”
In other words, we will have no idea whether the vaccine caused any of these reactions or whether they were caused naturally because there is no placebo to measure by. This then leaves the manufacturers to do their best guesswork about what they think was caused by the vaccine and what was just a coincidence. We can see this even in the manufacturer’s own studies, which I will get to in a moment.
The WHO is very clear that a vaccine should be the intervention used as the control rather than an inert placebo- in fact, they discourage the use of a placebo.
“In situations where a vaccine is known to be effective, but the burden of disease in a trial country is uncertain, researchers should first consider study designs other than a placebo-controlled trial. Researchers proposing to use a placebo in a vaccine clinical trial when a vaccine already exists should explain clearly in the research protocol both the scientific rationale and the social value of using a placebo design.”
In 2016 the WHO doubled down on this protocol stating that if a product has shown a benefit to a consumer, it is unethical to not give both groups that benefit, which is why they go on to say,
“Therefore, as a general rule, participants in a new trial must receive an established effective intervention.” (The words “established effective intervention” again means another approved vaccine.)
I am sure that many are skeptical of this protocol as it again makes it practically impossible to know whether or not the vaccine has caused a reaction or the reaction came up as a coincidence.
However, this concept is not new and has been used since the 1950s.
Vaccine Inserts Showing Testing Without an Inert Placebo
It is easy to see that the statements above are true when reading the actual vaccine inserts. Vaccine inserts are paperwork directly from the manufacturer, that comes in the packaging of the vaccine. This paperwork is provided for health care workers to inform them of the product.
Package inserts must contain warnings, precautions, ingredients, pharmacological mechanisms, and all outcomes of testing done on the product to show safety and efficacy, among other things. Package inserts are a primary source of vaccine information as they come straight from those that created them.
While reading these inserts it is clear that vaccines are almost always tested against other vaccines, not against an inert placebo.
Here are just a few examples:
Menomune-A/C/Y/W-135 | Meningococcal vaccine | Manufactured by Sanofi Pasteur
ActHIB|Haemophilus influenza type b vaccine | Manufacturer- Sanofi Pasteur
Kinrix | Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus | Manufactured by Glaxo Smith Kline
TWINRIX | Hepatitis A and B vaccine | Manufactured by Glaxo Smith Kline
INFANRIX | Diphtheria, Tetanus, (acellular) Pertussis vaccine | Manufactured by Glaxo Smith Kline
FLUARIX | Influenza B vaccine | Manufactured by Glaxo Smith Kline
As you can see, even in safety testing to approve the product, most vaccines are tested against other vaccines and not against an inert placebo.
Finding the Control Vaccine
When reading vaccine inserts it is often difficult to tell which vaccine was used as the placebo because manufacturers are not required to list this information. However, if the placebo is truly inert you will see manufacturers list it as such. See the example of Shingrix below:
As shown in the Shingrix insert above most of the time an inert placebo is able to be given in vaccine trials that only include adults or for a disease that is passed sexually such as HPV.
However, when the placebo is not inert the vaccine insert will simply list “placebo.”
This screenshot is from the RotaTeq vaccine insert. Notice that the words inert or saline are never mentioned.
We can confirm that RotaTeq did not use an inert placebo by looking at the difference between how it is reported to ClincalTrials.gov, a US government site that is required to report every clinical trial of FDA approved interventions, in comparison to Shingrix, which we have established did use an inert saline placebo.
Notice that in Shingrix it was required to state that the placebo was a NaCI (salt/saline) solution, but in RotaTeq, it is just classified as “placebo” and “placebo to RotaTeq.” Because of these kinds of listing it is often near impossible to know exactly what the placebo solution was, you have to look up each individual study used in the vaccine trials to try and find the control vaccine given as a placebo.
How long has this been happening?
As I said earlier, the concept of using vaccines against other vaccines, or substances that are not inert, is not new. It has been happening at the latest since the 1950s, but probably earlier. As the concept of using a placebo, as we define it now was first introduced in 1920. We can see this fact with the infamous march of dimes and the polio vaccine.
The original study design was only meant to be observational. Meaning that some would get the shot and some would just get nothing at all. However, because of the fanfare surrounding the project, many doctors and scientists began to be involved in the project and finally, a placebo-controlled type study was decided upon.
However, it is not clear whether or not the placebo was actually an inert substance. The study states, “One half would receive vaccine; the other matching half, serving as strict controls, would receive a solution of similar appearance which should have no influence on immunity to poliomyelitis.”
It goes on to talk about how these children would receive the same lot of “material” labeled by code for all three vaccinations. What is the said material? The only stipulation is that it looks similar to the vaccine and that it wouldn’t affect the immunity to polio, not necessarily that it would not affect immunity at all. The actual contents of these materials are never mentioned, not once. They are furthermore just called “materials” or placebo. Not once is the word “inert” or saline used.
This substance was very likely another vaccine or vaccine component as during this time and hence forth using another vaccine or a “control vaccine” becomes the norm in vaccine trials.
We can see this in a presentation given in 1964. This presentation was given at the Division of Biologics Standards Conference on Rubella, Bethesda, Maryland, 30th April 1964. In attendance the Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health.
The presentations in the transcript go over many, many studies on rubella and the creation of the rubella vaccine, done from the 1940s through 1964. There are several mentions in these studies of using a control vaccine.
It is clear by the way and how many times it is mentioned in the transcript that this is a common practice. Here is another publication from 1964, again speaking about control vaccines.
This study published in 1961 is very similar, showing the control group also received the Sabin vaccine virus. Although this may be a comparative study, there is in effect no true control group, as is best practice today.
I have been scouring the internet and old archives trying to find exactly when the practice began, but it is more than a little difficult and many of the promising studies I have found are exorbitant to obtain. However, it is clear just doing a cursory search for “control vaccine” on archives.org that this approach has been around for a substantial time.
So Why Does it Matter?
It is important to remember that science, in most cases, steadily builds on itself. Many of the studies that are being used on vaccine inserts as proof of safety and efficacy are still studies from the late 1950s (take a look at the references at the bottom of this paper). We still harken back to these roots and build on these foundations. If that foundation is faulty, where does it leave us?
If we have always been testing vaccines against other vaccines or substances that are not inert, how do we truly measure the reactogenicity of those vaccines? How can we truly say that we understand all the outcomes, or that we even know all the outcomes?
If you’re wondering if a placebo was used in the testing of the Covid-19 vaccine, you’re not alone. Next week I’ll update you on what control groups where used during the creation of each of the four CV-19 vaccines.
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