Aug 03 2018

Placebo Controlled Trials of Vaccines

There is a strong scientific consensus that vaccines generally are an effective approach to preventing infectious illness. The vaccine schedule is arguably the most effective and cost effective health promotion intervention ever devised. Vaccines are a public health home-run.

How, then, to explain the anti-vaccine movement? The anti-vaccine movement is based mainly on science-denial and conspiracy theories. This means they spread a lot of misinformation – the bits of misinformation become articles of faith, and any evidence to the contrary is denied or dismissed.

I recently received the following question, which is framed as a sincere question, but I have my suspicions that it may not be:

Have just read your article.

I fully agree that herbal medicines/substances should have full clinical trials but can never find anyone able to refer me to
any clinical trials placebo versus substance to be tested on vaccines.
So wondered if you could help me as you are obviously a man of science.
Would be very grateful as there must have been clinical trials sometime.
Even my Dr draws a blank.
Many thanks

Pam may simply be the victim of anti-vaccine propaganda, and may simply lack all Google skills, but the phrasing strongly suggests an anti-vaxxer goading a skeptic with a “gotcha” question. Since this is a common anti-vaccine trope, let me dispel it once again.

First – yes, there are numerous placebo-controlled trials of vaccines determining safety and efficacy. If Pam were genuinely interested in finding an answer to this sincere question, a few minutes on Google would have satisfied her. If she were ambitious an hour or two of dedicated searching would provide an embarrassment of riches.

One way deniers persist in their denial, despite readily available evidence, is that they rely entirely on secondary hostile sources for their information. They are trapped in an anti-vaccine echochamber and have no idea they are essentially being gaslighted.

Here are a few examples of placebo-controlled trials in vaccines:

A 2012 Cochrane systematic review of the safety and efficacy of the MMR (mumps-measles-rubella) vaccine found:

We included five randomised controlled trials (RCTs), one controlled clinical trial (CCT), 27 cohort studies, 17 case-control studies, five time-series trials, one case cross-over trial, two ecological studies, six self controlled case series studies involving in all about 14,700,000 children and assessing effectiveness and safety of MMR vaccine. Based on the available evidence, one MMR vaccine dose is at least 95% effective in preventing clinical measles and 92% effective in preventing secondary cases among household contacts.

That’s six controlled trials of MMR. But I start with this review because it also makes an important point – Pam is unwittingly presenting a false dichotomy. She is implying that the only scientific studies of safety and efficacy are placebo-controlled, but in reality there are a range of study designs that provide useful information. As you can see from the review, there are cohort studies, case-control studies, and a variety of observational study designs. Different study designs have different strengths and weaknesses, and they work together to create the whole picture.

There are also different ways to control an efficacy or safety trial. You can use a completely inert placebo, or you can use an active placebo. Here, for example, is a placebo-controlled trial of MMR for safety, using an inert placebo. An active placebo can be designed to mimic the treatment so as to obscure blinding, but it also can provide established treatment.

For example, here is a controlled trial looking at the MMR vaccine vs MMRV (adding varicella). This is a study of the efficacy of the varicella component of the vaccine, comparing it to the current standard of care, the MMR alone.

There are placebo-controlled trials of pertussis vaccine, HPV vaccine, polio vaccine, Hep B vaccine, pneumococcal vaccine, and flu vaccines – even in subpopulations, such as children with asthma, and patients with MS. There are published studies of placebo-controlled vaccine trials that are negative, such as this one of a malaria vaccine. The authors conclude:

“We conclude that SPf66 does not protect against clinical falciparum malaria and that further efficacy trials are not warranted.”

Negative studies and calling for the abandonment of specific vaccines that don’t work are important to show that this research is a legitimate attempt to find what works and what doesn’t.

How best to design vaccine trials is a matter of intense discussion. The reason is – it is unethical to withhold effective standard treatment from subjects in a clinical trial. Here is an interesting discussion from the World Health Organization (WHO) about when it is appropriate to use placebo controls in vaccine trials.

Vaccines are extensively studied, and must prove their safety and efficacy before they are allowed to be used, and certainly before they are added to the vaccine schedule. The evidence is robust. It is also easily accessible to anyone who is sincerely interested.

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