Normal Distribution
nothing is called 95% until it has been counted
Concept

Stratified randomisation — where it appears

An allocation rule running a separate block sequence inside each cell of the covariates' cross-classification. The number of cells grows multiplicatively in the covariates, so a design with four of them has cells with too few units to block inside.

Named by 4 essays across 2 fields — each of them below, with the objects they name alongside it.

What each rule leaves behind, at 120 patients. Four allocation rules over the same cohorts and the same seeds, each scored on three imbalances: the number of patients in each arm, the worst of the nine factor levels, and the worst of the 24 cells of the cross-classification. No rule holds all three. Permuted blocks hold the totals exactly and leave the margins near a coin's. Blocks inside every cell hold the cells and let the totals drift, because 24 part-filled blocks do not have to end level. Minimisation holds the margins and the totals and is at 83% of a coin's cell imbalance. Each of the three columns is somebody's definition of a balanced trial.

Balancing what is known in advance

Four allocation rules, three definitions of balance, and no rule that holds more than one of them. Minimisation keeps the worst factor margin near three patients whether the trial has forty or six hundred and forty — and lets the imbalance in the cross-classified cells climb to 86% of a coin's, because the cells are not what it is watching.

covadapt · Assignment Where one rule becomes three. Every arrival in 200 simulated trials is put to all three scores, and the picture is how often they would send that patient to different arms. The range and the pairwise sum are the same rule at two arms and at three — for sorted counts the pairwise sum is twice the range, so the arm that minimises one minimises the other — and they part company at four, where the pairwise sum is 3(d − a) + (c − b) and the range still sees only d − a. The variance disagrees with both from two arms onwards, on 5.4% of arrivals at two and 27.0% at five, because the scores are summed over 3 factors and a sum of squares does not order the candidates the way a sum of absolute values does. All three are called minimisation.

Three arms and three scores

Minimisation balances a trial by keeping the arms' counts even inside every prognostic factor. With two arms there is one way to measure how uneven two counts are. With three there are several, they are all called minimisation, and they send different patients to different arms.

multiarm · Assignment Four analyses of the same trials, with no treatment effect at all. 700 trials of 120 patients allocated by minimisation at p = 0.8, with the prognostic factors carrying a real effect on the outcome and no treatment effect — every rejection below is a false one. Two statistics, the plain difference and the same after adjusting for the balanced factors, each read against two reference distributions: a t table, and the set of allocations the rule could have produced from these covariates. The unadjusted comparison rejects 0.6% where it claims 5% — conservative, which is a loss of power rather than an error, and nothing on the output says so. Adjusting puts it back at 5.4%. Both re-randomised versions are at their nominal level by construction, whatever statistic goes into them.

The analysis has to know the rule

A trial balanced by minimisation and analysed by comparing the two arms' means rejects a true null 0.6% of the time where it claims 5%, and at full determinism 0.0%. That is not an error anybody complains about — it is a test that has stopped working, paid for by a balance the analysis then refused to use.

covadapt · Assignment Four intervals for the effect, minimisation at p = 0.8, 120 patients. Under minimisation at p = 0.8, 120 patients, over 600 trials with an additive effect of 0.45 and 199 re-run allocations per trial, the average width of four 95% intervals for the effect, and how often each covers it: unadjusted t interval 1.229 wide, covering 99.7%; unadjusted, test inverted 0.816 wide, covering 95.3%; adjusted t interval 0.723 wide, covering 96.0%; adjusted, test inverted 0.722 wide, covering 96.2%.

The interval the test inverts to

A randomisation test of no effect becomes an interval for the effect by testing every value at once: subtract the hypothesised effect from the treated outcomes and ask the same question again. Because the rule reads only covariates, one set of re-run allocations answers every value. Under minimisation the unadjusted t interval covers 99.7% at a width of 1.229; the inverted test of the same unadjusted difference covers 95.3% at 0.816, a third narrower, with no model of the outcome. Under complete randomisation the two are the same interval — which is what says the third was the rule's.

covadapt · Assignment

Named alongside it

The objects these essays reach for when they reach for this one.

Covariate-adaptive randomisationMinimisationPermuted blocksCovariate adjustmentCovariate balanceInteractionMonte CarloRandomisationRandomisation testReference distributionStudy designAllocation

All concepts