In an interview on Biotech Nation, Gary Cupit made an offhand remark about why so many drugs list headache as a possible side-effect: clinical trial participants are often asked to abstain from coffee during the trial. That also explains why those who receive placebo often complain of headache as well.
Cupit’s company Somnus Therapeutics makes a sleep medication for people who have no trouble going to sleep but do have trouble staying asleep. The medication has a timed-release so that it is active only in the middle of the night when needed. One of the criteria by which the drug is evaluated is whether there is a lingering effect the next morning. Obviously researchers would like to eliminate coffee consumption as a confounding variable. But this contributes to the litany of side-effects that announcers must mumble in television commercials.
Related: Adaptive clinical trial design