There are plenty of placebo-controlled vaccine trials

The agglomeration of anti-vaxxers love to plague us with their pro-disease perfidy. They really enjoy wheeling out the lie that vaccines have never been tested with a placebo. Turns out, there are plenty of placebo-controlled vaccine trials. Let’s take a brief look at how wrong the anti-vaxxers are and in the process create another tool we can all use to if we choose to engage the strident screechies.

Babies rely on us for their future health. This is why we need to listen to those who know how to give them the longest healthiest lives that science and medicine can inform. Photo by Aditya Romansa on Unsplash

Another hardcore #prodisease dark alleyway is the one stating there has never been a study which directly compares a vaccine to a placebo that does not contain…

>insert chosen ingredient of the day, and any other required to move the goalpost in the next tweet, here<

This just so happens to be incorrect, as is usually the case from antivaxxers.

You’ll never move the cult.
From the #vaccinesworkblog.[1]

Knowingly withholding a disease-preventing medicine is kinda …unethical

A study without a placebo can be unethical.[4] If you withhold a vaccine which you know has been safe and likely to work based on all the studies done so far – you are knowingly condemning the people in one arm of the study – that which gets the placebo instead – to a greater risk of harm. You may be withholding the standard of care.

Having said that, these studies can be found.[4; see the list in [1], and find others using these search terms].

Examples of placebo use in vaccine studies

This one is quite clever.[2] The female population (mostly 16 to 26 years of age) had been previously vaccinated with the quadrivalent human papilloma (HPV) vaccine. One third were then given a placebo (just saline) and the other two-thirds given the newer 9-valent aluminium-adjuvanted formulation. There was a bit more pain, swelling, redness at the injection site and bruising among the vaccine group compared to those who received a saline placebo. The same was seen for headache, fever and dizziness. These are all ‘adverse events’ but they were overwhelmingly mild or moderate in severity. Out of 608 vaccinated, there were three severe adverse events in the vaccinated group and three in the placebo group.

Another study, also of an aluminium-adjuvanted HPV vaccine, enrolled 9 to 15-year-old boys and girls.[3] It administered the quadrivalent HPV vaccine to two thirds and a non-aluminium placebo to the other third. Children were followed up for 18 months. More people who got the vaccine reported injection site pain, swelling and redness for up to 5 days after injection compared to those who got the placebo. Headache and fever occurred only slightly more often in the group receiving the vaccine. There were five serious adverse events reported in the vaccine group over the 18 months of follow up, but none were deemed associated with the vaccine.

More examples

I’ll come back and write more about these peer-reviewed scientific and medical published studies when I have more time; I’m just going to drop them here for the moment. Some are open access, many are not so I will get back here.

I acknowledge Dr Dan Freeman who tweeted a nice thread containing these late last month (NOV2019).

Human papillomavirus (HPV) vaccines

  • Long-term Study of a Quadrivalent Human Papillomavirus Vaccine [5]

Measles virus vaccines

  • A comparative study of two live measles vaccines in Iran [6]
  • Cooperative measles vaccine field trial. I. Clinical Efficacy [8]
  • Edmonston B and a further attenuated measles vaccine-a placebo controlled double-blind comparison [9]

Influenza virus vaccines

  • Efficacy and Safety of 1 and 2 Doses of Live Attenuated Influenza Vaccine in Vaccine-NaiveChildren [10]

Rubella vaccines

  • Comparative Studies of Rubella Vaccines [7]

Haemophilus influenzae type-b (Hib) vaccine

  • Randomised trial of Haemophilus influenzae type-b tetanus protein conjugate for prevention of pneumonia and meningitis in Gambian infants [11]

So I think we can all agree that there are plenty of placebo-controlled vaccine trials


  1. There are no vaccine studies with saline placebo? | #vaccinesworkblog
  2. Safety and immunogenicity of a 9-valent HPV vaccine in females 12–26 years of age who previously received the quadrivalent HPV vaccine
  3. Safety and persistent immunogenicity of a quadrivalent human papillomavirus types 6, 11, 16, 18 L1 virus-like particle vaccine in preadolescents and adolescents: a randomized controlled trial.
  4. Placebo use in vaccine trials: Recommendations of a WHO expert panel
  5. Long-term Study of a Quadrivalent Human Papillomavirus Vaccine
  6. A comparative study of two live measles vaccines in Iran
  7. Comparative Studies of Rubella Vaccines
  10. Efficacy and Safety of 1 and 2 Doses of Live Attenuated Influenza Vaccine in Vaccine-NaiveChildren
  11. Randomised trial of Haemophilusinfluenzaetype-b tetanus protein conjugate for prevention of pneumonia and meningitis in Gambian infants [not saline]

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11 thoughts on “There are plenty of placebo-controlled vaccine trials”

    1. Giuseppe, I would like to see the rabies study you refer to. Please send the link in comments. Thanks

  1. I looked at the measles trial listed here, where 2 vaccines were compared & a placebo used, and the type of placebo was never mentioned. Considering the charts showed the placebo triggered significant adverse reactions can it be assumed it was not an inert saline or similar? I would think it important, if you’re going to use this trial as an example of a genuine ‘placebo’ trial, then the true description of the placebo used is critical advice should be included.

    1. I think it did say physiological saline. But the AE’s of the placebo group are the same symptoms caused by the common cold.

  2. I am in the COVId vaccine trial, no swelling at all or soreness at injection site after first shot, seems dead give away that I got the placebo

    1. I’m in a trial too, arm is a bit painful after an injection yesterday, wondered if that might just be because someone stuck a needle in my arm and whether saline can cause any reaction?

      1. Saline should cause no pain. But eth placebo might not be just saline – depends on your trial and its methods of course. A bit of heat and mild discomfort is an indicator that your immune response is firing up. A good thing. Too much and you should go back to your normal doctor/trial doctor.

    1. “Control groups, comparable in size, received placebos similar in preparation and appearance to the inactivated and live vaccines.”
      What do you know that the authors don’t?

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