Merck, Schering Unable to Stop Digging in Vytorin Mess

As an example of how not to handle a corporate crisis, it’s hard to beat the growing scandal over Vytorin. That’s the blockbuster anti-cholesterol drug whose clinical-trial data Merck and Schering-Plough sat on for a year or two after it showed that Vytorin was apparently no better than a generic statin drug.

Now that both House and Senate committees are looking into what Merck and Schering knew and when they knew it, a plausible narrative of corporate skulduggery is starting to take shape. It goes something like this: The two companies, dismayed when a trial called Enhance appeared to suggest that neither Vytorin nor its cousin Zetia represented an improvement over current therapies, aimed first to protect the drugs’ annual sales of $5 billion-plus. So they delayed release of the Enhance findings, initiated a since-aborted effort to “move the goalposts” in that study to make Vytorin look better, and apparently ginned up “minutes” from an advisory-panel meeting to support the idea that outside experts had recommended decisions Merck and Schering actually wanted to make.

It’s good stuff, much of it straight from documents the committees have requested from the companies. (The House Energy and Commerce Committee made the latest document dump available on Friday.) Weirdly, neither drugmaker seems the slightest bit willing to get out in front of the story — that is, to tell the truth about what happened before the drip-drip-drip of congressional disclosures grows unbearable. Instead, they’re pretty much in modified limited hangout mode.

The juiciest stuff in the new documents involves a Nov. 16, 2007 meeting of mostly outside experts called by the two companies to go over the Enhance results. According to James Stein, a cardiologist at the University of Wisconsin, the experts were told that no minutes or transcripts of the meeting would be taken. A month later, however, attendees received draft minutes for that meeting by email and were given two days to reply with any changes. Interestingly enough, those minutes circulated just a week after the House investigation began.

Stein did reply to the draft minutes, laying out a neutrally worded but unmistakable argument that they amounted to an after-the-fact con job. His opening summary says it all (click image for a closer look):

One major subject of that meeting had been whether it made sense — more than a year after the trial was completed — to change the study’s primary “endpoint,” the data measurement that would determine whether Vytorin worked or not. Technically, this would have involved substituting a single measurement of carotid-artery thickness (itself a proxy for the progress of arterial blockage) for an average of three artery measurements.

This sort of change, of course, would pretty much render the Enhance trial worthless. (The  conspiracy-minded might even be tempted to conclude that was the point.) Changing the rules once the game is over is verboten in clinical trials for a variety of reasons, chief among them that it would allow researchers to pick the yardstick that best fits their observed results after-the-fact.

In any event, Schering-Plough and Merck felt free to claim in November that their panel had “recommended” the change. Stein remembered things differently,  noting that the change in question “was not a conclusion of the meeting.” It’s unclear how other panel members viewed the meeting, although Stein’s contemporaneous notes are pretty good evidence that things went the way he described them.

Now, of course, the companies are looking down the barrel of a subpoena cannon, which is a position relatively few oversight targets escape from unscathed. The House committee has posed several sharp questions to the Merck and Schering CEOs and is showing every sign of wanting to make an example of the two companies — which they may well richly deserve, the way things are going. As everyone knows, it’s frequently the coverup, not the crime, that trips you up.

(Hat tips to Pharmalot and the WSJ Health Blog, which have covered the Vytorin scandal extensively.)