Tag: saline placebo

Where are the Saline Placebos?

Remember when anti-vaccine folks used to say that there were no double-blind, placebo-controlled randomized clinical trials for vaccines?

What happened once they realized that there actually were?

They moved the goal posts…

Where are the Saline Placebos?

Okay, they said.

So you have done double-blind, placebo-controlled randomized clinical trials when testing vaccines, but what placebo did you use?

Was it a pure saline placebo?

“Placebo Control – A comparator in a vaccine trial that does not include the antigen under study. In studies of monovalent vaccines this may be an inert placebo (e.g. saline solution or the vehicle of the vaccine), or an antigenically different vaccine. In combined vaccines, this may be a control arm in which the component of the vaccine being studied is lacking.”

WHO on the Guidelines on clinical evaluation of vaccines: regulatory expectations

Although no guidelines actually call for using a pure saline placebo, that’s all anti-vaccine folks will accept these days.

Why?

That’s there MO – or method of operation.

When one theory or myth gets squashed – they move to another.

They move the goalposts.

It doesn’t matter that there are often ethical and logistical problems with using pure saline placebos, that’s all they want to hear about it.

That they wouldn’t be satisfied and start vaccinating their kids if all vaccine studies started to use saline placebos should be evident when you consider that many vaccine studies have already used saline placebos!

There are many more vaccine studies that have used saline placebos and like other vaccine studies, have found vaccines to be safe and effective.

But how do you know that they used a real saline placebo and not some kind of saline solution with other stuff in it?

If it isn’t clear to you in the methods section of the study, go to the source – the original clinical trials record and it will be listed there.

What are you going to be worried about now?

More on Saline Placebos

What Is a Vaccine?

You know what a vaccine is, right?

The word vaccine comes from the vaccinia virus that was in the original smallpox vaccine.
The word vaccine comes from the vaccinia virus that was in the original smallpox vaccine.

The flu shot you get each year is a vaccine.

Vaccine: A product that stimulates a person’s immune system to produce immunity to a specific disease, protecting the person from that disease. Vaccines are usually administered through needle injections, but can also be administered by mouth or sprayed into the nose.

Immunization: The Basics

The smallpox shot that Edward Jenner developed was a vaccine.

Vaccine Definitions

While that is an easy enough definition to understand, that there are many different types of vaccines does make it a little more complicated.

There are:

  • Live-attenuated vaccines – made from a weakened or attenuated form of a virus or bacteria
  • Inactivated vaccines – made from a killed form of virus or bacteria
  • Subunit, recombinant, polysaccharide, and conjugate vaccines – made from only specific pieces of a virus or bacteria
  • Toxoid vaccines – made to target a toxin that a bacteria makes and not the bacteria itself

And of course all of these types of vaccines work to produce immunity to specific diseases – vaccination.

Immunization: A process by which a person becomes protected against a disease through vaccination. This term is often used interchangeably with vaccination or inoculation.

Immunization: The Basics

What other definitions are important to know when you talk about vaccines?

  • active immunity – immunity that you get from having a disease (natural immunity) or getting a vaccine and making antibodies
  • adjuvant – a substance that helps boost your body’s immune response to a vaccine so that you can use a minimum amount of antigen, reducing side effects
  • antibodies – protective proteins that you make against antigens
  • antigens – specific substances (can be part of a virus or bacteria) that trigger an immune response
  • attenuation – a virus or bacteria that is made less potent, so that it can produce an immune response without causing disease
  • elimination – getting rid of a disease in a specific area
  • endemic – the baseline level of disease in an area
  • eradication – getting rid of a disease everywhere (smallpox)
  • epidemic – an increase in the number of cases of a disease over a large geographic area
  • herd immunity – when enough people in a community are protected and have immunity, so that disease is unlikely to spread
  • immunity – protection against a disease
  • incubation period – how long it takes to develop symptoms after you are exposed to a disease
  • outbreak – an increase in the number of cases of a disease over a small geographic area
  • pandemic – an increase in the number of cases of a disease over several countries or continents
  • passive immunity – temporary immunity that you get after being given antibodies, either via a shot of immunoglobulin or a mother’s antibodies are transferred to her baby through her placenta
  • placebo – classically defined as “a comparator in a vaccine trial that does not include the antigen under study”
  • quarantine – isolating someone so that they don’t get others sick
  • titer – an antibody count that can often be used to predict immunity

Got all of that?

So what about variolation, the process that was used before Jenner developed his smallpox vaccine? Was that also a vaccine?

It did produce immunity to smallpox, which is the basic definition of a vaccine, but still, variolation is typically concerned an immunization technique and not a vaccine.

More on Vaccine Definitions

About the Cochrane HPV Controversy

Have you heard about the Cochrane HPV controversy?

What controversy?

Well, yeah, but anti-vaccine folks are crowing about what is essentially a letter that was published in BMJ Evidence-Based Medicine journal.

About the Cochrane HPV Controversy

What’s the controversy?

Seems that the folks at Cochrane Reviews recently published a review, Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors, which concluded that the HPV vaccines work and that they are safe.

That doesn’t sound controversial…

Well, it seems that some other folks, associated with the Nordic Cochrane Center, disagreed. They published an “analysis” in BMJ Evidence-Based Medicine, The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias.

So who do we believe when we have Cochrane vs Cohrane?

Who is the Nordic Cochrane Centre?

Some people will be familiar with the Nordic Cochrane Centre because of their involvement in complaints about the HPV vaccine that were investigated by the European Medicines Agency.

Cochrane Nordic has been filing multiple complaints with the EMA about HPV vaccine safety for years.
Cochrane Nordic has been filing multiple complaints with the EMA about HPV vaccine safety for years.

Complaints that were initially triggered by a case series that was published by Dr. Louise Brinth, when she was head of the Danish Syncope Group, but who is now part of the Nordic Cochrane Centre.

While the Cochrane Collaboration has a very good reputation, you can't really say the same about the Nordic Cochrane Centre.
While the Cochrane Collaboration has a very good reputation, you can’t really say the same about the Nordic Cochrane Centre.

Complaints that were not approved by the Cochrane Collaboration and that were not an official Cochrane viewpoint!

“…we highlight here how academic colleagues, under the purported banner of a respected authority, raise concerns about the HPV vaccine but they cite an evidence base of small and poor quality studies and ignore the extensive wealth of global literature that vividly demonstrate the excellent efficacy and safety record of the vaccine.”

Head et al on Inadvisable anti-vaccination sentiment: Human Papilloma Virus immunisation falsely under the microscope

Complaints that had already been investigated and dismissed by the European Medicines Agency.

“In conclusion, in clinical trials conducted in the 9 to 26-year- old age range, vaccination was generally well tolerated with no apparent adverse health impact following completion of the vaccination regimen.”

Block et al Clinical trial and post-licensure safety profile of a prophylactic human papillomavirus (types 6, 11, 16, and 18) l1 virus-like particle vaccine.

Complaints that are also refuted by many other studies.

So we don’t actually have Cochrane vs Cochrane…

The Cochrane HPV Review

Once you read the complaint against the Cochrane HPV review, you realize that this isn’t even just about the Cochrane HPV review.

The main faults that the Nordic Cochrane Centre folks found is that the Cochrane review left out a bunch of what they consider to be eligible HPV vaccine trials, even though “twenty-six randomised trials were identified that contained data on vaccine efficacy and/or safety, which all together enrolled 73,428 women.”

But if this was just about a systemic review which didn’t stick to protocol about which studies to include, then why do the Nordic Cochrane Centre folks go on and on about placebos and active comparators?

“The Cochrane authors mistakenly used the term placebo to describe the active comparators.”

Lars Jørgensen et al. on The Cochrane HPV vaccine review was incomplete and
ignored important evidence of bias

Would you be surprised to know that one of Nordic Cochrane Centre’s arguments to the EMA was about placebos?

“In all the vaccine trials apart from a small one, the “placebo” contained aluminium adjuvant, which is suspected of being neurotoxic.”

Cochrane Nordic Complaint to the European Medicines Agency (EMA) over maladministration at the EMA

Why do they talk about placebos?

Most of these folks want pure saline placebos to be used in clinical trials, even though doing so would make it hard to keep the trials blinded.

Placebos don’t have to be inert though. The BMJ and the Nordic Cochrane Centre authors mistakenly corrected the Cochrane authors on their use of the term placebo.

They make plenty of other mistakes too.

“The Cochrane authors did not mention a study from 2017 by the WHO UMC that found serious harms following HPV vaccination overlapping with two syndromes: postural orthostatic tachycardia syndrome (POTS) and complex regional pain syndrome (CRPS).”

Lars Jørgensen et al. on The Cochrane HPV vaccine review was incomplete and
ignored important evidence of bias

What study?

Jørgensen cites a commentary that describes “a signal based on both spontaneous reports and published case series that is best characterized as a potential association between HPV vaccination and dysfunction of the autonomic nervous system.”

“There is currently no conclusive evidence to support a causal relationship between the HPV vaccine and POTS. It is of utmost importance to recognize that although temporal associations may be observed, conclusions of causality cannot be drawn from case reports and case series due to the small sample size and lack of control population inherent to this type of scientific literature. If POTS does develop after receiving the HPV vaccine, it would appear to do so in a small subset of individuals and would be difficult to distinguish from the normal prevalence and incidence of the disorder.”

Butts et al on Human Papillomavirus Vaccine and Postural Orthostatic Tachycardia Syndrome: A Review of Current Literature

So who do you believe?

Researchers who published a systemic review as part of the Cochrane Review Groups that confirms that the HPV works and that it is safe, or a group who seems to have an axe to grind against the HPV vaccines?

Update on the Cochrane HPV Controversy

Apparently, Cochrane has taken the Nordic Cochrane Centre complaints seriously enough to launch an investigation.

“Our current investigations appear to show that there may be a handful of missed but potentially eligible studies, but that this falls substantially below ‘nearly half of the eligible trials’.”

David Tovey, editor-in-chief of the Cochrane Library

And not surprisingly, Tovey stated that “To date, we also have no reason to believe that the main conclusions of the review relating to benefit and serious adverse effects are unsafe.”

And yet, as with their complaints to the EMA, resources get wasted as the attacks are put down.

More on the Nordic Cochrane Centre HPV Attacks

What Are the Demands and Goals of the Anti-Vaccine Movement?

So what exactly do anti-vaccine folks want?

What are they trying to do?

Are they trying to scare parents away from getting vaccinating and protecting their kids, hoping to drag us back to the pre-vaccine era?

What Are the Demands and Goals of the Anti-Vaccine Movement?

Of course, some of the folks who are anti-vaccine don’t actually like to be called anti-vaccine. Instead, they prefer to say that they are pro-safe vaccines. So for them, it is rather obvious – they want safer vaccines without toxins.

Now, since vaccines are already safe and don’t contain any toxic ingredients, it would seem like their work is done already, right?

Another goal is having fewer vaccines on the immunization schedule. Jenny McCarthy often pushes the Turn Back the Clock immunization plan, wanting kids to only get vaccines that were on the 1983 immunization schedule, back when kids still died of meningitis, pneumonia, blood infections, severe dehydration, epiglottitis, and cancer from Hib, pneumococcal disease, rotavirus, hepatitis B, hepatitis A, chicken pox, HPV, and meningococcal disease, which are now vaccine preventable.

Other members of the anti-vaccine movement talk about vaccine choice. They want to be able to choose whether or not they should have to vaccinate their kids.

Again, done. No one is forcing parents to vaccinate their kids. We may not have a choice on whether or not your unvaccinated child gets sick and puts someone else at risk for getting a vaccine-preventable disease because they were too young to be vaccinated, had a medical exemption, or their vaccine didn’t work, but you can certainly make the choice to skip or delay any vaccines you want.

“I also warn them not to share their fears with their neighbors, because if too many people avoid the MMR, we’ll likely see the diseases increase significantly.”

Dr. Bob Sears in The Vaccine Book

What are other goals of the anti-vaccine movement?

Johns Hopkins Medicine, which includes the Johns Hopkins University School of Medicine and the The Johns Hopkins Hospital and Health System went out of their way to correct this anti-vaccine misinformation.
Johns Hopkins Medicine went out of their way to correct this anti-vaccine misinformation about shedding.

Have you heard about the anti-vaccine folks who want to quarantine all kids who have recently been vaccinated for at least six weeks? Why quarantine kids who have been vaccinated? They are worried about shedding

Would anyone go so far as wanting to ban vaccinations? Yup. So much for vaccine choice.

Some others want to rescind the 1986 National Childhood Vaccine Injury Act, which they think will help make it easier to sue vaccine manufacturers. That’s one of Andrew Wakefield‘s demands in his movie VAXXED. He and others never mention that if you are suing in civil court, then you must meet a higher burden of proof for vaccine injury than you do in Vaccine Court.

Remember when Robert F. Kennedy, Jr. thought he would be appointed to some special Trump commission on vaccines?

“We want safe vaccines, robust transparent science and an honest and independent regulatory agency focused narrowly on public health rather than industry profit.”

Robert F. Kennedy, Jr. on Mercury, Vaccines and the CDC’s Worst Nightmare

Kennedy’s vaccine commission never happened, but that hasn’t stopped him from pushing for an independent regulatory agency.

I’m not sure who would run or be a part of Kennedy’s independent regulatory agency though, as he believes that “Congress, the regulatory agencies, FDA and CDC, the IOM, the NIH, the AAP, the science journals, the university science departments and the press” have all been compromised by Pharma.

Kennedy also wants thimerosal out of vaccines, which, as most people know, is already out of all vaccines on the immunization schedule, including about 100 million doses of flu shots this past year. But like others, he seems to be moving on to aluminum as his new target.

What else?

Fortunately, it is easy to see why the demands and goals of the modern anti-vaccine movement are dangerous, unethical, and unnecessary, and like parents who decide to skip or delay vaccines, will simply put us all at risk for more outbreaks of vaccine-preventable disease.

What to Know About the Demands and Goals of the Anti-Vaccine Movement

Whatever their demands and goals of the anti-vaccine movement, the effect is that they are scaring parents away from vaccinating and protecting their kids from life-threatening vaccine-preventable diseases for no good reason.

More on the Demands and Goals of the Anti-Vaccine Movement

Where are the Double Blind Placebo Controlled Randomized Trials about Vaccines

Have you ever heard that there are no double-blind, placebo-controlled randomized clinical trials for vaccines?

It isn’t true.

There are many double-blind, placebo-controlled randomized clinical trials that involved:

  • flu shots
  • pneumonia shots
  • HPV vaccines
  • potential HIV vaccines
  • malaria vaccines
  • rotavirus vaccines
  • Dengue vaccine
  • Staphylococcus aureus vaccine

That’s good, because double-blind, placebo-controlled randomized clinical trials are considered the “gold standard” when you do medical research.

“Placebo Control – A comparator in a vaccine trial that does not include the antigen under study. In studies of monovalent vaccines this may be an inert placebo (e.g. saline solution or the vehicle of the vaccine), or an antigenically different vaccine. In combined vaccines, this may be a control arm in which the component of the vaccine being studied is lacking.”

WHO on the Guidelines on clinical evaluation of vaccines: regulatory expectations

Tragically, many more folks got pneumonia and died if they got the saline placebo instead of the vaccine in this study.
Tragically, many more folks got pneumonia and died if they got the saline placebo instead of the vaccine in this study.

But do they all use a saline placebo?

No, not always, which typically leads anti-vaccine types to dismiss them outright and push anti-vaccine misinformation, including that they are never done.

It seems that they aren’t worried so much about the antigens in vaccines anymore (the Too Many, Too Soon argument), but are now more concerned about other vaccine ingredients. They will only be satisfied with a saline placebo, but they must miss the part about wanting the trial to be double-blinded, which gets harder to do if the placebo doesn’t look and “feel” like the vaccine.

And they miss the part that “not always” doesn’t mean never.

Gardasil is a good, recent example of a vaccine that had a double-blind, placebo-controlled (using a saline solution without an adjuvant) trial for safety.

Others vaccine trials use a saline control too, including efficacy and safety trials for a new recombinant, live, attenuated, tetravalent dengue vaccine (it worked and had a good safety profile), a malaria vaccine (a phase I dose escalation study), a universal flu vaccine, a Staphylococcus aureus vaccine, etc.

The Ethics of Placebo Use in Vaccine Trials

So why haven’t placebo control studies been done even more routinely then?

Why isn’t every vaccine on the immunization schedule or every combination of vaccines tested using a double-blind, placebo controlled study?

“Placebo use in vaccine trials is clearly acceptable when (a) no efficacious and safe vaccine exists and (b) the vaccine under consideration is intended to benefit the population in which the vaccine is to be tested.”

Placebo use in vaccine trials: Recommendations of a WHO expert panel

Of course, the answer is that in order to do this type of study, you would have to have a very good justification for leaving many of the kids unprotected and at risk for a vaccine-preventable disease.

Instead, as is discussed in the article “Current topics in research ethics in vaccine studies,” if a vaccine is “already in use in some other country or community which is more or less comparable to site where the trial is planned, that vaccine should be used as the comparator.”

So instead of a placebo, it is more common “to give another vaccine that provides comparable benefit against another disease, or more willingly, against similar disease caused by different agents.”

When can you use a placebo control?

The article states that “placebo controls are ethically acceptable when there is no proven vaccine for the indication for which the candidate vaccine is to be tested.”

But get educated and don’t be fooled, many double-blind, placebo-controlled randomized clinical trials have been done with vaccines.

What to Know About Placebo Use in Vaccine Trials

When it is ethical to do so, placebos have been used in vaccine trials, even saline placebos.

More on Placebo Use in Vaccine Trials