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What a sample-size calculation was given

A sample-size calculation takes a standard deviation, an effect and an outcome as given, and each is usually a choice or an estimate. Sized from a pilot of ten's standard deviation, 55.9% of trials have less than their planned 80% power and 11.1% less than half, although the planned sample is right on average; sizing from the pilot's 80% upper confidence limit leaves 19.8% short at 1.65 times the patients. With the effect believed to be half a standard deviation give or take a quarter, a trial of sixty-four per arm succeeds 69.2% of the time, and no trial of any size can succeed more often than the planners believe the effect is positive. Cutting the outcome at a threshold keeps at most 63.7% of its information, and a responder threshold one standard deviation out needs twice the patients.

The power trials actually have when sized for 80% from a pilot of 10. Four thousand pilots of 10 observations, each sizing a trial for 80% power at half a standard deviation from its own standard deviation. 55.9% of the trials have less than 80% power and 11.1% less than 50%; the median trial has 76.8%.

The spread a pilot supplies

A trial sized for 80% power from a pilot's standard deviation is sized from an estimate that is too small more often than not. With a pilot of ten, 55.9% of the trials it sizes have less than 80% power and 11.1% less than 50%, although the planned sample is right on average. Sizing from the pilot's 80% upper confidence limit instead leaves 19.8% short, at 1.65 times the sample; from its 90% limit, 10.0% short at 2.12 times.

The chance a trial succeeds

A trial of sixty-four per arm has 80% power at an effect of half a standard deviation. If the effect is only believed to be about half a standard deviation, give or take a quarter, the chance the trial reaches significance is 69.2%; give or take a half, 61.4%. Reaching 80% then takes 113 per arm, or 1,268 — and when the belief is uncertain by three quarters of a standard deviation no number of patients reaches 80%, because the chance can never exceed the 74.8% probability that the effect is positive at all.

How much of a normal outcome's information survives cutting it into two, by where the cut is. For a small shift, a cut at the mean keeps 63.7% of the information, so the trial needs 1.57 times the sample. A cut at the top tenth keeps 34.2% and needs 2.92 times; a cut two standard deviations out keeps 13.1%.

An outcome cut in two

Replacing a measured outcome with whether it crossed a threshold keeps 63.7% of the information when the cut is at the mean, 34.2% at the top tenth and 13.1% two standard deviations out. A trial that needs 63 patients per arm on the measured outcome needs 102 cut at the mean and 185 cut at one and a half standard deviations. The responder rates that result read as a share of patients who respond — 50.0% against 69.1% — when every patient moved by the same amount; and a cut chosen after looking turns a 5% test into a 17.7% one.

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