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

Confounding — where it appears

A third quantity related to both the treatment and the outcome, so that a comparison of arms measures it as well. Randomisation removes it in expectation rather than in any one experiment, which is what a balancing rule is for.

Named by 11 essays across 7 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 Which allocations reverse the overall comparison. The per-group success rates are held fixed; only the split of each group between treatment and control changes. 32% of the allocations reverse, and the worst reverses by 13.1 percentage points.

Simpson's reversal is a region, not a table

The treatment wins in both groups and loses overall. That is normally shown with one famous table, which cannot answer the two questions a reader has — how often, and how large. Swept, it turns out to occupy 31% of the allocation space.

paradox · Simpson The same covariate, three ways round. Three worlds over a treatment, an outcome and a covariate, joined by the same three edges at the same three strengths — 0.90, 0.50 and 0.70 — differing only in which way the two edges touching the covariate point. In the first the covariate causes both and adjusting for it recovers the effect of 0.50 exactly. In the second the treatment causes the covariate, the effect is 1.13, and adjusting returns 0.50 — the direct edge alone, with the part that travels through the covariate deleted. In the third the treatment and the outcome both cause the covariate, the effect is 0.50, and adjusting returns -0.087. The regression that produces those three numbers is one formula, and nothing in the data says which panel it is being run in.

One arithmetic, three decisions

A covariate beside a treatment and an outcome can be a common cause of both, a step on the path between them, or an effect of both. The regression that includes it is the same arithmetic in all three, and it is right in one — returning 0.5000, deleting 0.6300 of the effect, and turning 0.5000 into −0.0872.

collider · Conditioning 20 adaptive trials, 45% against 25%. Each line is one trial allocating patients one at a time by the arm's own posterior. The average final share on the better arm is 84.7%, with a standard deviation of 10.3 points across these 20 trials. The rule does not deliver a fixed advantage: it delivers one that depends on how the first few patients came out.

Randomising towards the winner

Allocating more patients to the arm that is doing better is the humane thing to want and it buys nothing statistically: at a fixed total it costs thirty points of power. And because the allocation is a function of the outcomes, the ordinary test on it rejects a true null 7.8% of the time before any time trend is applied — and 58% after one.

adaptive · Randomisation What a rule gives away by being predictable. Minimisation run at every probability from a coin to fully deterministic, over 500 cohorts of 120 at each. The upper line is the share of assignments an investigator who knows the rule and the enrolled patients can name in advance: 49.7% at p = 0.5, which is a coin and cannot be beaten, and 87.6% at p = 1 — short of everything only where the two arms tie and the rule falls back on a coin. The lower line is what that is worth: an investigator who enrols a patient 0.5 of a standard deviation better than average whenever they predict their favoured arm produces a treatment effect of 0.75 where the truth is zero. Nothing about the randomisation was broken; the bias entered through who was enrolled, which is the one thing an allocation rule cannot control. The dashed line is the closed form 2δ(2g − 1).

The rule that can be guessed

A balancing rule improves as it becomes more deterministic, and a deterministic rule can be worked out in advance from information the person enrolling the patient already has. At full determinism 87.6% of assignments are guessable, and an investigator who acts on the guess produces a treatment effect of three quarters of a standard deviation where the truth is zero.

covadapt · Assignment One odds ratio in every stratum, and a different one marginally. Five strata with baseline risks from 5% to 85%, a treatment allocated by a coin in each, and a conditional odds ratio of exactly 2.5 throughout. The marginal odds ratio is 1.789. Nothing is confounded; the odds ratio is simply not a weighted average of odds ratios.

The change that is not confounding

Five strata, a treatment allocated by a coin in every one, and an odds ratio of exactly 2.5 in all five. The odds ratio computed on the pooled table is 1.789. Nothing is confounded — an odds ratio is not a weighted average of odds ratios, and the risk difference, on the same table, is exactly its own stratum value.

reversal · Simpson 16 groups shrunk towards a fitted line, at γ = 1.2. Hollow circles are the groups' own values, filled ones the estimates after pooling, and the diagonal is the line fitted through them with each group weighted by how well it is measured — slope 1.21, intercept 0.20. The horizontal rule is where the same 16 groups would have been shrunk to with no covariate. The spread left to borrow against is 0.64 with the covariate against 1.28 without, so every group is pulled further in than it would otherwise have been.

Borrowing towards a line

A group shrunk towards the average of all groups is being compared with groups it has nothing in common with. Fit a group-level predictor and it is shrunk towards what the predictor says a group like it should be — which halves the spread left to borrow against and takes a quarter off the squared error.

multilevel · Levels Two structures in three are made worse. What adjusting for every covariate measured does to the bias in the treatment's estimated effect, against adjusting for none, over 4000 randomly drawn structures of 6 covariates each. Each covariate is independently a common cause with probability 0.25, a cause of the treatment only, a cause of the outcome only, a cause of neither, a step on the causal path, or a common effect. The rule leaves a larger bias on 65.5% of structures, a smaller one on 33.8%, and the same on 0.7%. The share is a property of that population of structures rather than of adjustment, which is why the weights are stated; what does not depend on them is that the rule has no direction — it is not a conservative default that occasionally overcorrects, it is a rule whose error is whatever the structure happens to be.

Adjusting for everything

"Control for every covariate that was measured" leaves a larger bias than controlling for nothing on 65.5% of four thousand randomly drawn structures and a smaller one on 33.8%. Its squared error is 4.110 times that of using no covariate at all, and half of it sits in its worst tenth of structures.

collider · Conditioning What stratifying on a mediator estimates, and what it does not. The direct effect stays at -0.109 throughout, because it is defined with the mediator held fixed. The total effect runs from -0.218 to 0.027 and crosses zero at 1.5. On 15% of the sweep the two have opposite signs, and both are correct answers.

Conditioning on what the treatment caused

When the grouping variable lies on the path from treatment to outcome, the stratified answer is the direct effect and the aggregate is the total effect. Both are correct. Over 15% of a sweep of the indirect path they have opposite signs, and no arithmetic on the table says which question was being asked.

reversal · Simpson Two groups, a baseline and a follow-up, and nothing happening in between — baseline reliability 0.6. 600 units in two pre-existing groups whose true means are 1.00 apart, read once at baseline and once at follow-up, with no change for anybody. The two groups' mean changes are −0.075 and −0.032, so the change-score analysis reports a group difference of 0.043. The regression of follow-up on baseline and group reports 0.409, against a closed form of (1 − λ) × 1.00 = 0.400: at any one baseline reading the two groups' lines sit that far apart, because each group's units regress towards their own group's mean. The pooled slope in this sample is 0.614, the baseline's reliability.

Two analyses of one baseline

Two groups read at baseline and again at follow-up, with no change for anybody. Subtracting the baseline reports a group difference of −0.0014 and adjusting for it reports 0.4008 — and each analysis is exactly right about one reason the groups started apart and wrong by 0.40 about the other.

paradox · Rtm What a 8-run fraction of 4 factors confounds. The defining relation is I = ABCD, so the resolution is 4. A is estimated as A + BCD; B is estimated as B + ACD; C is estimated as C + ABD; D is estimated as D + ABC. Each of those is an identity about the design rather than an approximation about the data.

The word a fraction costs

A half fraction estimates each main effect as an exact sum of that effect and everything it is confounded with — no error term, no sample-size argument. With every interaction at 0.8 the design reports a true effect of −1 as −0.20, and the design cannot test the assumption that makes the number mean anything.

design · Factorial

Named alongside it

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

RandomisationAggregationCausal diagramCovariate adjustmentLeast squaresMediatorStudy designAdjustment setAllocationColliderCovariate-adaptive randomisationCovariate balance

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