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

More arms than two

Minimisation balances a trial by making the arms' counts even inside every factor level. 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 — while the ratio a trial was designed to deliver quietly disappears unless the score was told about it.
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.

 A trial designed 2:1:1, and what two scores deliver. 500 trials of 180 patients, three arms, a target of 2:1:1. The shaded bars are a minimisation score that divides each arm's count by the share that arm is supposed to receive before measuring the spread; it delivers 49.9% : 25.1% : 25.1%. The others are the same rule with the counts left raw, which delivers 33.4% : 33.3% : 33.3% — the balance it enforces inside every factor level is equality, and equality is what it gets. The marks are the shares that were asked for.

Balancing towards unequal targets

A three-arm trial allocating two to one to one is the ordinary case, and a balancing rule built from raw counts does not know it. It balances the arms towards equality inside every factor level, delivers a third to each arm, and reports that it minimised imbalance.

 Four analyses of the same 3-arm trials, under a true null. 250 trials of 150 patients, 3 arms, minimisation with p = 0.85, 99 re-randomisations for each exact test. Two statistics — an F on the arms alone and an F on the arms after the balanced factors — against two reference distributions: the table the statistic is named for, and the distribution the allocation rule itself generates when the outcomes are held fixed and the rule is re-run. Only the first cell is wrong, and it is wrong in the direction that costs power rather than the one that manufactures findings: 0.0% where 5% is claimed. Either repair works — adjusting for what the rule balanced, or asking the rule what it would have done.

The analysis after three arms

An unadjusted analysis after a two-arm balancing rule rejects 0.6% of true nulls where it claims 5%. With three arms and a deterministic rule it rejects none at all — and the repair is the same repair, which is a sentence and a column in the model.

 What a guesser gets, and what a guesser gets for nothing. 600 trials of 150 patients under a fully deterministic rule, with an investigator who knows the rule, the factors and every assignment so far. The guess rate falls with the number of arms — 87.8% at 2, 86.2% at 3, 81.0% at 4 — which reads like a trial getting safer and is not: what a guesser can trade on is the excess over the 50%, 33%, 25% they would get by naming an arm at random, and that goes the other way, from 1.76× chance at two arms to 3.24× at 4. The gap a guesser manufactures between the best and worst arm under a true null is 0.759, 0.733, 0.711 standard deviations — nearly unchanged.

Guessing one arm in three

A balancing rule is guessable because it is balancing. With three arms the next assignment is worked out less often than with two — and by more, relative to what a guesser gets for nothing, and the damage they can do is almost unchanged.

 What a guesser gets from less than everything. 1,000 three-arm trials of 150 patients under minimisation on three factors with the preferred arm taken with probability 1, and five investigators guessing each next assignment from different information. Knowing the rule, the factors and every assignment so far: 86.3%. Knowing everything about the patients at their own centre and nothing about the others, and applying the rule's own score to that: 52.8%. Knowing only how many of their own centre's patients went to each arm: 55.5%. Knowing only the trial's arm totals, which a drug-supply system shows anyone who reorders: 54.5%. A guess at random gets 33.3%. The cruder the information, the less the guesser gets — except that the rule's own score, applied to a partial record, does worse than simply counting.

A guesser who sees the totals

The bound on how guessable a three-arm minimisation is assumes an investigator who sees everything. One who sees only the arm totals — what a drug-supply screen shows — names the next arm 54.5% of the time against a chance 33.3%, and manufactures 45% of the full guesser's bias.

 The guess rate through a trial. Guess rates in each tenth of a trial of 150 patients on three arms with the rule taking its preferred arm with probability 0.8, over 1500 trials. knowing everything: 65.9%, 72.2%, 72.0%, 72.8%, 72.4%, 72.2%, 72.5%, 72.7%, 72.7%, 72.4%. a joint table learned in earlier trials: 53.4%, 55.4%, 54.8%, 55.1%, 54.3%, 53.8%, 54.9%, 54.8%, 54.1%, 54.8%. the centre's totals: 45.4%, 50.3%, 50.2%, 50.8%, 49.8%, 50.2%, 50.9%, 50.6%, 50.4%, 50.7%. following whichever has been right: 46.5%, 50.2%, 49.3%, 49.6%, 48.9%, 48.7%, 49.3%, 49.0%, 49.0%, 48.7%. a joint table learned in this trial: 36.4%, 43.8%, 45.0%, 46.2%, 46.7%, 46.8%, 48.1%, 48.5%, 47.9%, 48.9%. the centre's own factors, scored: 46.8%, 51.4%, 49.7%, 49.9%, 48.4%, 48.6%, 48.5%, 47.7%, 47.6%, 46.7%. Chance is 33.3%.

The guesser who learns

An investigator who watches a three-arm minimisation can tally which of several partial readings has been right so far and follow the leader. It does not help. Following the leader names 48.9% of assignments where the best single reading names 49.9%, and a table of what the three readings say together, learned inside the trial, starts at 36% and has not caught up by a hundred and fifty patients. Learned over earlier trials, that table reaches 54.5%. The full guesser's 71.8% stays out of reach of all of them, because the gap to it is information rather than practice.

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