No Fair Peeking? More Questions about Early Stopping of Trials

In the previous post I mentioned the recent findings about ezetimibe, which happened to be part of the study called ARBITER 6. As one evidence-based blogger, Dr. David Rind has noted--
http://www.evidenceinmedicine.org/2009/11/arbiter-6-and-combining-therapies-with-statins.html
--the results as published could be consistent with three different possibilities:

1. Ezetimibe adds nothing to heart disease prevention; niacin is helpful
2. Niacin is slightly helpful or neutral and ezetimibe actually worsens arterial plaque
3. All the results of the study are due to chance alone

Option #3 becomes meaningful when we note that the actual hard outcomes in the study were 2 bad events in the niacin arm and 9 bad events in the ezetimibe arm. That is, move just a couple of bad events to a different column and the whole outcome changes.

If the study had been continued longer and more hard outcomes accumulated, we'd know a good deal more about which option made the most sense. (And, of course, knowing which means a lot in terms of what treatments docs should recommend to patients.) So it was therefore very interesting that the study was stopped early. The authors state that this was due to a predetermined efficacy endpoint having been reached:
http://content.nejm.org/cgi/content/full/NEJMoa0907569

In theory, a data safety and monitoring board is supposed to be completely independent of the investigators and the commercial sponsor of a study. In actuality, in the past (as I have noted in other posts a while back), some decisions of the "independent" boards have been eerily like the decisions that a commercial sponsor would have made had the goal been to maximize the marketing advantage of the study outcomes. In this case a quick stoppage of the study may have favored the extended-release niacin product being promoted by sponsor Abbott Labs. And a stoppage due to efficacy is stranger than stoppage due to safety concerns, especially when the main outcome measure--thickening of the wall of an artery--is a surrogate marker rather than an actual disease outcome, as Dr. Rind notes.

I remain ignorant of the exact means by which a data monitoring board might be secretly influenced by commercial marketing pressures. But if a further hint is needed that somebody just may be sneaking a peek where they are not supposed to, ARBITER 6 may provide the hint.

(Hat tip to Marilyn Mann for Dr. Rind's blog.)