And I'd expect some of the present investigators might choose to back out.

And some of the IRBs and ethics committees that have to review and approve clinical trials might refuse to allow the study at their institutions.

And recruiting thousands of new patients into the study may prove to be impossible, due to the same problem as for the present volunteers already in the study: when presented with the new informed consent form, who will sign on for 5+ years during which they may be receiving a drug that has repeatedly been shown to have a cardiovascular risk?

Finally, it's quite possible that the FDA's partial hold on the study is a preliminary indicator that FDA will be pulling Avandia off the market soon. Dr. Steven Nissen, who spoke against Avandia at the AdComm, has been quoted as saying that holding enrollment in the TIDE trial was "the ethically correct thing to do... I still think there's a very good chance that the FDA will decide to remove Avandia from the market," Nissen told the AP.

If so, the TIDE study will inevitably be terminated. Which will be safer for patients, but will mean that we'll never get the hard facts about just how high the cardiac risk might be from Avandia compared to Actos.