Things that have never been tested in a placebo-controlled double blind study:
- New HIV medications
- Most new cancer drugs
There are a number of reasons for this, but the major one is that it is not ethical to deny people treatment. So, for example, you can’t test HIV meds against a placebo pill because it’s not ethical to leave people dying of AIDS so that your study is more scientific.
Similarly, it is not ethical to let children die of measles to run a randomized-controlled trial. Instead, we look at large population studies of millions of children who have and haven’t been vaccinated, to see which group gets sicker more. And every single time, it’s the kids who aren’t vaccinated who get sick.
The exception to the rule is when a vaccine is entirely new. In this case, when we don’t know if it will do anything or not, we test it rigorously in randomized trials. The HPV vaccine is a great example — there were numerous RCTs looking at whether it worked or not, some of them using a saline placebo and some an adjuvant placebo. The point here being that if you have no idea whether you’re preventing disease, like with a totally new vaccine, you can ethically deny people treatment because it could turn out that your vaccine doesn’t actually work. In the case of HPV vaccination, of course, the opposite is true — cervical cancer as a disease may well be eliminated in our lifetimes because of the amazing effectiveness of the vaccine.