Dr. Gwaltney is certainly correct in stating that proper blinding is an important element in clinical trial design [1]. However, as they pointed out elsewhere, Mossad and colleagues were unable to demonstrate unblinding in the two study groups, despite conscientious efforts to do so [2]. Moreover, because there would be no way participants could know a priori what the active agent was supposed to taste like, it is difficult to see how tasting only a single type of lozenge would give participants in either group any meaningful basis for deciding whether the type assigned to them contained the "active" agent. They might have received some clue (however unreliable) if they had been able to compare the taste of the two lozenges, but they were not allowed to do so.

Mr. Eby raises an interesting physicochemical point in suggesting that some zinc preparations contain an excess of negatively charged chelating agents, such as citrate, which prevent zinc ions from local release and may bind native zinc and other divalent cations locally. At the same time, it is also possible that in the complex environment of an inflamed pharynx, the citrate is metabolized or displaced (for example, by negatively charged proteins, and by mass action of other anionic species, such as chloride), thus freeing up zinc locally. This problem is amenable to study.

The issue Dr. Hollister raises-that of "purity"-is generally kept at the periphery in discussions of bias but is really quite important. It is difficult, on the one hand, to argue with the moral imperative of staying "clean" when it comes to dealing with potential bias. On the other hand, there is a seemingly inevitable tendency, particularly for those of us who struggle publicly with conflict of interest, to become moralistic, to be drawn into a kind of snobbery about "who's the purest of them all" in these matters. The sin of pride, perhaps? In any event, Dr. Hollister is probably right that even we editors, generally the most modest of people, could use an additional touch of humility from time to time.