Interim analysis — where it appears
Named by 11 essays across 3 fields — each of them below, with the objects they name alongside it.
When the looking happens
A p-value is defined relative to a sampling plan, so the same data means different things under different stopping rules. Testing five times at the nominal level rejects a true null 14% of the time, and no observation in the dataset changed.
Dropping the losers
Carrying the best of eight arms forward and testing it at 1.96 rejects a true null 10.3% of the time — the hypothesis was chosen by looking at the data, so the statistic is a maximum wearing a single comparison's clothes. The value that holds the rate is 2.313, and it has to be solved for.
The effect a stopped trial reports
An O'Brien–Fleming trial at 88.45% power holds its error rate exactly and reports an effect 9.6% too large on average. The 11.39% of trials that stop at the second look report 1.83 times the truth, the ones that cross at the last look report 0.80 times it, and pooling every trial by its size gives the truth back to the last digit.
The estimate after the choice
An arm chosen for being ahead is ahead by more than it should be, and the trial then publishes the average of the stage that chose it and the stage that did not. The unbiased estimate is the one built from a third of the data — and it is the least accurate of the three.
The outcomes a trial could have stopped with
A trial that stops at its second look with z = 3.3 has a two-sided p-value of 0.000969, 0.000987, 0.00187 or 0.0421, depending on how the outcomes it could have stopped with are ordered. One of the four orderings does not change when the looks the trial never reached are replanned, and the same one gives a trial that ran to the end with z = 6 a p-value of 0.0256.
A simulation that stops when it looks settled
A simulation of an interval that covers exactly 95%, checked every 250 replications for a significant departure and stopped when it finds one, flags that correct interval on 29.54% of runs. Stopped instead as soon as its estimate reaches 95%, it reports an interval that covers 94% as meeting its level on 37.21% of runs. Stopped when the estimate stops moving, it reports the right number — and has quietly chosen to run about fifteen hundred replications.
A boundary for giving up
Adding "stop if z is below zero" to an O'Brien–Fleming trial costs 5.20 points of power at the effect it was designed for and halves the observations a trial with no effect uses. Stopping when conditional power at the observed trend falls under 10% costs 13.23 points and stops 21.28% of trials with a real effect. Making that rule binding lowers the benefit boundary from 2.040 to 1.901, and a binding rule that is then ignored rejects a true null 3.523% of the time instead of 2.5%.
Shrinking the arm that was chosen
A trial that carries the best of eight arms forward reports it as better than it is — by +0.123 when the eight arms are alike — and its second stage alone is unbiased but the least accurate of the estimates. Pulling the chosen arm's first stage back towards the eight arms' mean before combining removes most of the bias when the arms are alike (+0.020) and gives the smallest error of any estimate, 0.133 against the published 0.182. When one arm really is ahead by half a standard deviation, the same shrinkage pulls the true winner back towards the losers and understates it by 0.103, with more error than the published estimate. The weight is estimated from eight numbers, and it is right when the selection was noise and wrong when the selection was right.
A look the trend asked for
Under an O'Brien–Fleming-type spending function, every schedule of looks fixed in advance spends exactly 5.0000%. A committee that adds a look at three quarters of the trial whenever the interim z is 1.5 or more spends 5.2323% — 5.315% counted over a hundred thousand trials — and the most a committee choosing among six schedules could spend is 5.4390%.
A look added by a rule
A monitoring committee's rule — add a look at three quarters of the trial when the interim |z| is at least 1.5 — spends 5.2323% under O'Brien–Fleming-type boundaries. Written into the protocol it can be given boundaries that spend exactly 5%, three ways: raise the added look's boundaries by 2.05%, raise every later boundary by 0.99%, or preserve at each interim value the chance of crossing the plan would have given. All three cost the same, 0.38 points of power, from 88.94% to 88.56%, because the power the uncorrected rule seemed to keep was the excess error. Made exact, the rule is a design between the two fixed schedules — and at every trigger slightly better than randomising between them.
The variance that contains the effect
A monitoring committee that adds an interim look because the variance came in higher than planned is reading a nuisance quantity, and a look added on a nuisance quantity should leave the spending function's 5% alone. It does, exactly, when the variance is the within-arm one, and when the trigger is the calendar. It does not when the variance is the one computed with the arm labels hidden: that variance is the within-arm sum of squares plus the interim statistic squared, so it is high more often when the trend is strong. The excess is 0.069 points at a twenty-patient interim and falls as one over the square root of the interim's size — a tenth of what a trigger on the trend itself spends, and never zero.
Named alongside it
The objects these essays reach for when they reach for this one.
Error rateStopping ruleClosed formStatistical powerGroup-sequential designO'Brien–FlemingSelection biasAdaptive designMonte CarloAlpha spendingThe Pocock boundarySample size