Well you did a much better job describing how you define retrospective vs. prospective trial design. I still think the way you are defining it is not accurate, since retrospective trial designs have nothing to do with self-selection. That is a separate matter. All retrospective means is "looks back in time" at data that has already been collected.
However, you argument stills doesn't hold much water. How can a psychiatric drug be used retrospectively unless it has already been approved for use? If you're complaining about trial data on off-label use, then I won't argue, but the FDA does not accept retrospective trials to support drug approval.
Then it's a good thing that I never said or implied that. The subjects must be drawn from a uniform population, not from a population that have already come forward for treatment -- otherwise the result is biased by the experimental population at the outset.
> Prospective simply means you have decided what the endpoints will be before the trial begins.
No, it means the experimental design doesn't recruit from a pre-existing population of subjects with a history or established preferences, instead you choose random subjects from the population at large.
> The inverse of a prospective trial is a retrospective trial where you have a set of data and you go looking for signals.
There's nothing stopping you from actually learning what these terms mean. A prospective study recruits subjects from the population at large, people with no particular interest in, or knowledge of, the topic being studied. A retrospective study relies on self-selected subjects, people who are already engaged with what you want to study.
For example, let's say I want to study the link between daily vitamin use and intelligence -- do people who take a daily vitamin become more intelligent as a result?
I begin to design a study. Shall I enlist people who already take a daily vitamin (retrospective), or do I enlist people with no interest in the issue, divide them into two groups, make one of the two groups take a daily vitamin, and make the other group take a placebo (prospective)?
See the difference? In the retrospective, any conclusion I make may result from a confusion of cause and effect -- for example, if the vitamin-takers turn out to be more intelligent, that might result from a factor like intelligent people taking a vitamin because of their increased awareness of health issues, in other words, it might be an effect, not a cause.
The prospective experimental and control groups, one of which got a vitamin, and the other which got a placebo, is much more likely to produce a meaningful result.