Vaccine Safety, Efficacy & Contrasts

Almost none of the vaccines on the list that weren’t licensed based on RCTs using saline controls are not first generation vaccines, which means that it would have been unethical to test them against a saline control.

The bottom line is that, if you trace back the history of the vaccines developed for a disease like, say, measles, you will eventually find the RCT testing the first effective vaccine against it and that vaccine will have had a placebo control. It might not have been saline (although in most cases decades ago it was), but it will have been a placebo that was “inert” with respect to preventing that disease. Also, clinical trial standards have evolved over the last 70 years. If a vaccine was approved 60+ years ago using methodology that today we might consider inadequate, that does not change the calculus when it comes to testing new vaccines against the same disease. Such vaccines can’t ethically be tested against saline placebo.