Arbiter-6 is big news. CNBC will be reporting live from the convention hall on Monday when the results are released. Just in the last day or so the New York Times and the Wall Street Journal have discussed the significance– or lack of it– of the trial. On the one hand, most cardiologists I speak with don’t believe the trial is a big deal. On Wall Street, on the other hand, the feeling is very different, since analysts believe the trial might further threaten the embattled multibillion dollar Vytorin/Zetia franchise (and perhaps give a boost to Abbot’s niacin franchise).

At first glance, ARBITER-6 just isn’t important. From a purely scientific perspective ARBITER 6 doesn’t have much going for it. It’s a small trial with a surrogate endpoint. It won’t definitively answer any relevant clinical questions. So we might actually agree with the Merck PR person who asked CNBC reporter Mike Huckman: ”Why are you making this such a big deal? It’s a 200-patient study.”

But of course there’s another side to the issue. Because you can’t understand ARBITER-6 without understanding ENHANCE. ENHANCE, you will recall, was another small Vytorin study with a surrogate endpoint. No one except a few academics had ever heard of it or cared about it until Merck/Schering Plough, fearing negative results, tried to delay and manipulate the results of the trial. When their fumbling efforts became known their efforts backfired: suddenly a lot more people knew about and started to care about ENHANCE. Then the story snowballed…

But why was M/SP so desperate to un-enhance ENHANCE? The reason is simple. Many years earlier, the drug was approved and became a blockbuster due to M/SP’s prodigious marketing efforts. The one thing missing was that there was absolutely no evidence to demonstrate that the drug actually had any meaningful clinical benefits. M/SP realized: if you live by the surrogate endpoint then you can die by the surrogate endpoint. So M/SP sought to bury or delay the trial. They thought they had no defense against a negative trial (the emperor in this case knew he had no clothes on), but didn’t realize that by interfering with the trial they were actually elevating it in importance. Then the controversy grew, and when the trial ultimately provided no evidence to support Vytorin, the unimportant little trial became an important big trial.

But since ENHANCE had no ability to provide strong evidence about anything, the questions about Vytorin have remained hanging. And they will continue to hang until the very large trials now underway finally get completed at some indefinite time in the next decade. In the meantime now we will have ARBITER 6 to chew on. See you Monday.

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