Sunday, May 25, 2008

Blinding and randomization, Part II

I could title this post "things that go bump with blinding and randomization." The nice, clean picture I presented in the first part of this series works a lot of the time, but usually, there are problems.

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:

  1. 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.
  2. 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.
  3. 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.
It's the third case I want to treat in some detail, and the third case that relates to the ENHANCE trial.