Before I go into them, there's one aspect I didn't touch in the first part, and that is the business aspect. And that's what concerns Schering-Plough -- if they were unblinded to trial results they could possibly make financial decisions, such as "cashing out" while shareholders are stuck footing the bill for trial results. I usually don't mess with that end of things, but it's a very important one for management of companies.
Ok, so back to things that go bump:
- It's hard to make a placebo. Sometimes, it's really hard to match the drug. If there's an actively-compared trial, what happens if the active control is an intravenous injection and the experimental treatment is a pill? You could dummy up so that everybody gets an IV and a pill (and only one is active), but if you get too complicated, there's too much room for error.
- The primary endpoint is not the only expression of a drug. For example, if your drug is known to dry out skin, and a patient presents with a severe skin drying adverse event, your investigator has a pretty good idea of what the assigned treatment is.
- If all outcomes come back pretty close to each other, relative to uncertainty in treatment, you have a pretty good idea the treatment has no effect. While this may not unblind individual patients, it gives a pretty good idea of trial results during the writing of analysis programs, and presumably to senior management so they can make decisions based off "very likely" results.