By now, most everyone knows that the Food and Drug Administration withdrew its emergency-use authorization for hydroxychloroquine for the treatment of SARS-CoV-2.
The FDA authorization was based on a few small, poorly controlled clinical studies.
If there’s a silver lining, it’s that this fiasco has given the public a better idea of what constitutes a high-quality study. The highest quality are randomized, double-blinded, placebo-controlled studies. Licensure of a vaccine always requires at least one study that meets this high standard.
In double-blinded studies, neither the research volunteer nor the researcher are aware of whether the subject received a vaccine or a placebo. Saline (salt water) is frequently used as the placebo as it has few if any side effects. The placebo allows the researcher to see which reported symptoms are a result of the vaccine.
For example, if a volunteer receives a study injection and has a headache, was the headache actually because of the vaccine or was it just one of those common headaches some people suffer occasionally? Comparing the data reveals the answer.
If headaches occur at the same rate in the vaccine and placebo volunteers, the vaccine didn’t cause the headache. If headaches are more common among those receiving vaccine compared to placebo, the vaccine causes headaches.
It’s important that the volunteer is blinded. People frequently attribute things that happen to them to a recent vaccine. The myth that the flu vaccine causes flu comes from this bias.
People who get a cold or maybe even the flu within several days of vaccination often blame the vaccine. Blinded, placebo-controlled studies show these type of illnesses occur at the same rate in the placebo and vaccine groups.
Study staff that work with the volunteers need to be blinded as well. People tend to be suggestible. A staff member knows the subject is receiving the vaccine and believes the vaccine causes muscle aches, may say something like, “I’d take some ibuprofen if I were you as you are likely to be sore tomorrow.”
Not only can such interactions influence volunteers, they can also make volunteers aware they’re receiving the vaccine.
Researchers also need to remain blinded until all of the data has been collected. They tend to be an opinionated group with their own beliefs, prejudices and conflicts of interest.
A researcher wanting a study vaccine licensed may have the tendency to attribute symptoms in vaccine receivers to other things like colds or prescription medications — not the vaccine.
Even worse, unethical researchers could “jiggle” the data or even drop volunteers from the study analysis that don’t fit their desired outcome.
Randomization is a method that assigns study participants to a treatment group by chance. Randomization is necessary to keep researchers, staff and volunteers blinded and the study free of their biases.
Many of the initial studies showing hydroxychloroquine effective reflected the beliefs and hopes of the research staff and subjects.
Reassuringly, SARS-CoV-2 vaccine licensure requires high-quality studies that are randomized, double-blinded and placebo-controlled.