Upon reflection, and with the aid of other discussions of this very point, I have come to the conclusion that I’ll need to amplify Senator Grassley’s Febrary 11, 2008 concerns, in order to make them plain — to a wider-audience.

So, to amplify the Senator’s point:

If one is looking for **NON**-inferiority, one should expect to see statistically-significant * higher* values in some of the

*data, and statistically-significant*

**blinded****values in some of the blinded data. Said another way, there should be some set of**

*lower**STATISTICALLY-SIGNIFICANT differences*— in at least some groupings — of the “

*blinded*” data.

Now, if the “*blinded*” data ALL comes back (for the sake of a simple, clear example) with wall-thickness values between, say, .682 and .690, and there were about 640 patients in the study, ** all** of them between .682 and .690 (on whatever thickness scale we are measuring), one may readily, and confidently, deduce that there are

**— it’s a sort of regression analysis, built into all Excel spreadsheet software (and/or science-based, off-the-shelf, data analysis programs) — which would allow anyone,**

*NO STATISTICALLY-SIGNIFICANT differences in ANY possible COMBINATION of groupings**anyone*with access to

*NOTHING BUT THE “BLINDED” DATA-SET*, and a computer, to know that ENHANCE had failed.

As irony would have it, the above-made-up example is, in actuality, fairly close to what happened with Schering-Plough’s ENHANCE study — now, straight from the New England Journal of Medicine‘s just-published-chart on the outcome [**Click image to view full-size**.]:

One could have deduced that **NO** set of roughly-equally populated groupings (of about 320 patients each) * WOULD EVER YIELD *a statistically-significant difference. That is Senator Grassley’s — and, now, my — point.

All one with the “*blinded*” data-set need do, is enter the values into an Excel spreadsheet, then choose the “*auto-sort column data*” sub-menu, select “*lowest to highest*“, and then, start splitting the values — take the top of the column (lowest — assume that is a Vytorin/Zetia patient), and match it to the bottom of the column (highest — assume that is a statin-only patient). Now take the second-lowest data point, and match it against the second highest. . . . and so on, and so on, until one has reached the middle of the 642 patients. This simulation/permutation would assume that all the thinnest-walled patients were given Vytorin/Zetia, and all the thickest-walled patients were given statins only. In other words, this artificial sorting would * ASSUME* the best possible universe of outcomes for Vytorin/Zetia from the ENHANCE study. Looking at the above-chart, I think it almost a mathematical certainty that any variances between the two “

*best-case*” groups would be well-within the margin of error for the sample size.

Anyone with the “*blinded*” data could have done this, at Schering-Plough, in about one hour’s time — that’s all they’d have needed. And that would have been in January of 2007 — a full year *earlier* than SGP presently admits it “*knew anything*“.

Might this explain the hurried effort in January 2007 to query the ENHANCE “*outlier data*” — per the time-line SGP submitted to the SEC on January 25, 2008?

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[Much Later — it seems Melissa Davis (of “*The Street*“) reads this blog.]