Normally when somebody finds an association in an epidemiological study people are quick to point out that it doesn't prove causality, that there are problems of missing co-founders, that it is at best hypothesis generating and at worst spurious. This leads to people not putting much weight on associations found in epidemiological studies.
What if it goes the other way around? Say I already have a theory, maybe with some small earlier studies to back it up and even a good theoretical explanation for the effect. Then I do a big, well powered, epidemiological study and fail to find the association the theory predicts. How much weight can I put on the result now?
Intuitively it seems to me that the result would be quite damning, despite it being only a epidemiological study. But I have long since learned not to trust my intuition when it comes to statistics.
Do all the weaknesses of associations found in epidemiological studies also apply to when you fail to find an association?