You’ve probably heard the term “placebo” in relation to clinical trials. But what exactly does it mean? Basically, a placebo is a substance or treatment that is designed to have no therapeutic effect. Unlike the drug being studied, a placebo should cause no physiological response.

It should be mandated by our regulatory agencies (particularly the FDA), that clinical trials compare any new drug with a placebo. Why is that?

In order to ensure that a new drug is safe and effective, medical researchers need to conduct a randomized, controlled, double-blind study. What this means is that there are two groups of people studied: one group that takes the drug under trial, and another group that takes an inert substance — a placebo.

Furthermore, the groups are randomized for variables such as age, health status, and socioeconomic status so that the two groups are comparable to one another.

With those conditions in place, it should be easy to ascertain if the drug is causing adverse effects or having a positive benefit; you simply compare the results for the groups. If the only major variable between the two groups is the new drug, any adverse effects that occur in the drug group but not in the placebo group indicates a warning sign of possible problems with the drug.

Only by using a placebo can the differences — both positive and negative — between treatment groups be shown to be the result of a new drug (or vaccine).

When it comes to vaccines, some people claim that using a placebo and withholding treatment (the vaccine) is unethical. The problem with that line of thinking is that it’s impossible to be sure that a vaccine is safe (and effective) if there has never been a true placebo-controlled trial.

Most drugs are approved after a years-long process that includes using a true placebo-controlled trial. For example, Pfizer’s Enbrel, which is used to treat arthritis, went through six and a half years of safety review, including being compared to a placebo. Eliquis, another Pfizer drug that is used as a blood thinner, went through more than seven years of study (and placebo comparison) in its prelicensure trials. Lipitor — a statin that is the bestselling prescription drug of all time — went through a nearly five-year safety review process that used a true placebo.

In a perfect world, every new drug or vaccine would be studied against a true placebo before being brought to market. But as is crystal clear these days, we don’t live in a perfect world. Many Big Pharma manufacturers, particularly those that make vaccines, do not use true placebos in their prelicensing studies.