The Basics of Randomized Controlled Trials

A randomized controlled trial starts with a cohort of volunteers. Researchers typically seek participants with specific characteristics—like being non-pregnant or within a certain age range—to minimize complications. This selection helps ensure that the study results are applicable to the general population.

However, this approach can introduce some bias. For instance, if a medication is only tested on people aged 18 to 49, marketing it to other demographics could be problematic. Additional studies may be necessary to ascertain the effects on those outside that age range, all for safety concerns and potential legal implications.

Once the volunteers are gathered, they are randomly assigned to different groups. Randomization is crucial to ensure that these groups are as similar as possible. If a balanced representation of genders is desired, both males and females should have an equal opportunity to be placed in any group. Subsequently, data analysis reveals whether there are statistically significant differences between the groups.

This is the moment where we hope differences are minimal.

In these trials, one group (the control group) receives no intervention, while other groups receive the treatment (e.g., a vaccine). If an effective intervention already exists, the control group might receive that existing treatment rather than a placebo. Ethical considerations play a vital role in these decisions.

Why Ethics Matter in Vaccine Trials

The measles-mumps-rubella (MMR) vaccine has played a crucial role in controlling measles outbreaks in the Americas and beyond. If we were to randomly assign children to vaccinated and unvaccinated groups, the unvaccinated ones would lack protection against a serious disease. Measles can lead to severe health complications and even death, a fact that becomes painfully clear when considering the millions who have suffered due to this disease.

In the event that a new measles vaccine is developed, the study would involve groups receiving the current MMR vaccine, the new vaccine, or possibly both, depending on the safety data from initial trials. Any approach that leaves children unprotected would be deemed unethical, and no reputable review board would approve such a study.

Moreover, it's unlikely that anti-vaccine parents would agree to a 50-50 chance of placing their children in the vaccinated group. This potential bias can skew the results of the study.

Understanding Blinding in Trials

Blinding in controlled trials refers to the practice of keeping participants unaware of which group they belong to. Double blinding means that both the participants and researchers are kept in the dark until the study concludes. Triple blinding extends this to data analysts as well.

This method minimizes the chance of participants crossing over between groups based on their beliefs about the study. For example, if someone is aware they are in the placebo group for a weight loss drug trial, they might change their exercise habits, affecting the outcomes.

The same principle applies to researchers who might inadvertently influence results by including or excluding certain individuals based on prior knowledge of their health status.

Are Vaccines Tested in RCTs?

Yes, vaccines have undergone randomized and blinded controlled trials. During Operation Warp Speed in 2020, companies like Pfizer and Moderna conducted such studies. I can personally attest to this, as my wife participated in one where approximately 43,000 individuals were involved.

After receiving her first dose, she experienced flu-like symptoms for about a day, which led us to suspect she was in the intervention group. The trial was structured as a "nothing" versus "vaccine candidate" scenario, where "nothing" shouldn't cause any symptoms—unless, of course, there were other factors at play.

When the vaccines received emergency authorization, participants were informed whether they had received a vaccine or a placebo. My wife found out she had received the vaccine, while I had to wait a few days for my own vaccination.

A Historical Perspective: The Polio Vaccine

In the 1950s, a large-scale trial was conducted in various cities across the U.S. Parents and their children eagerly lined up for either the polio vaccine developed by Jonas Salk or a saline shot. The results were compelling: children diagnosed with polio were significantly more likely to have received the saline solution or no injection at all. As a result, millions of children were vaccinated, leading to the near eradication of polio in the Americas.

Today, only one of the three wild human polioviruses remains in small areas of Afghanistan and Pakistan. The hope for complete eradication is on the horizon.

Addressing Misconceptions About Placebos

My cousin raised another common argument from anti-vaccine circles, claiming that vaccines in controlled trials were tested against diluted solutions rather than saline. His inconsistency was glaring: “You previously claimed there were no trials, but now you’re saying there are, just not against a true placebo?” I pressed.

In response, I referred to pediatrician and vaccine developer Paul Offit’s essay on placebo-controlled trials. He explained that pharmaceutical companies submit their trial designs to the FDA, which mandates that placebos must be inert and harmless. Trials involving vaccines cannot proceed without the FDA's approval of true placebos.

The argument that vaccine trials lack placebo controls does not imply that vaccines are unsafe or ineffective. In fact, post-licensure studies consistently demonstrate the safety and efficacy of vaccines.

Moreover, the assertion that only water or saline could serve as true placebos is flawed. Various substances, including stabilizers or adjuvants, can be used as placebos in trials. At the concentrations present in vaccines, all these substances are deemed safe by the FDA.

Understanding Limitations in Discussions

The troubling reality is that conversations like the one I had with my cousin are occurring everywhere, often driven by individuals lacking a foundational understanding of epidemiological research. Influencers with large followings invite guests who may not grasp the nuances of vaccine science, leading to oversimplified soundbites that mislead the public.

This phenomenon stems from what I term "Social Mediosis," where entertainment and profit motives drive content creation. Misleading statements like “there have never been randomized clinical trials on vaccines” gain traction because they resonate with certain audiences.

It is vital for us to recognize our limitations and understand the expertise of professionals in the field. We should value the efforts of those dedicated to public health over influencers who may lack proper scientific grounding. Most importantly, we must remember that science is not determined by public opinion or legal outcomes.

I sincerely hope that we foster a culture that appreciates the dedication of healthcare professionals and prioritizes scientific understanding above all else.

Thank you for your time and engagement!

René F. Najera, MPH, DrPH, is a public health expert and epidemiologist. He teaches at a university in Northern Virginia and works as a director of a public health center. His opinions here are his own and do not necessarily reflect those of his employers.