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

Covariate adjustment — where it appears

Estimating a treatment effect from a model that includes the baseline covariates, rather than by comparing the arms' raw means. It recovers most of what a balancing rule buys and does so after the fact, which is why the two are alternatives rather than complements.

Named by 25 essays across 11 fields — each of them below, with the objects they name alongside it.

The rule is parity, and it runs both ways. At a correlation of 0.5, four combinations of a dictionary and an outcome shape. The joint sign flip (X, Y) → (−X, −Y) leaves the bivariate normal alone at every correlation, so a function that changes sign under it is orthogonal to one that does not. A product of two odd functions is even; a product of an odd and an even one is odd. So an odd dictionary removes exactly none of the first and something of the second, and an even dictionary does the reverse — which it does, to machine precision, in both of the two rows that should be zero. This is one rule where there had been two: that a median split's square is constant, and that a polynomial dictionary contains the products a correlation generates.

A dictionary that is neither

A rule handed two median splits removes none of their interaction; a rule handed two covariates removes none of their product. Those were two results with two explanations, and they are one result with one — and finding it corrected the number underneath both.

dict · Criterion One zero is arithmetic and one is a symmetry. What two balancing rules remove of the interaction they are aimed at, on five joint laws of the ranks matched at a Spearman correlation of 0.4, with a normal covariate throughout. A rule holding a median split of each covariate removes exactly nothing of the product of the splits under every one of them, including the two that are not symmetric under reflection — and the reason is not a symmetry at all: a centred median split takes the values ±½, so its square is a quarter identically, and the interaction is orthogonal to both main effects whatever the joint law is. A rule holding the mean of each removes exactly nothing under the three radially symmetric copulas and 7.71% under the two that are not. Bars at the floor are exact zeros; the axis cannot draw 9e-32.

A zero that is arithmetic

A median split's exact zero was explained by a symmetry of the latent normal. It holds under a Clayton copula, which has no such symmetry, because a centred median split squares to a quarter identically.

copula · Criterion One zero holds and one does not. Three rules, at a correlation of 0.5, against the skewness of the covariate. A rule balancing the mean of each covariate removes exactly nothing of their product when the marginal is symmetric — including the heavy-tailed symmetric one at skewness zero, which is what says the guarantee needs symmetry rather than normality — and removes up to 29.7% when it is not. A rule balancing a median split of each removes exactly nothing of the product of the splits under every marginal here, to 1e-30: both sides are functions of the sign of the latent normal, and a monotone transformation moves neither. A rule balancing a threshold at a value on the covariate's own scale removes between 4.9% and 22.5% — it never had a zero to lose, under any marginal at all.

A zero that rests on a symmetry

A balancing rule removes exactly none of an interaction between two odd functions, at every correlation. The argument needs the joint sign flip to preserve the law, and no real covariate is symmetric about anything.

skew · Criterion The fourth-order expectation, by two routes. Every inner product in an eight-term slice of the dictionary at ρ = 0.5, computed from the linearisation and Mehler's formula and counted from two hundred thousand draws of a correlated pair. The entries that matter are the ones off the main effects: ⟨f(X)u(Y), g(X)v(Y)⟩ is a fourth-order expectation, which the independent-covariate field could not write down. The worst departure is 1.99 standard errors over 36 pairs, measured in each pair's own error because the entries differ in size by two orders of magnitude.

The fourth moment that was missing

Mehler's formula makes the main effects exact at any correlation and stops there, because the interactions need an expectation of four Hermite functions rather than two. A linearisation turns the four into two, and the whole geometry becomes closed again.

joint · Blocking What a mean split leaves, with both halves varying. The share of a mean split's interaction that survives the rule balancing it, at every copula and every marginal, matched at a Spearman correlation of 0.40. The three radially symmetric copulas leave exactly nothing with a symmetric covariate and rise steeply with the skew. The two asymmetric ones start at 7.707% and go opposite ways: the lower-tail copula falls to 0.002% at a skewness of 0.95 — the two failures cancel almost exactly, and a guarantee both fields report as broken is restored — while the upper-tail one climbs to 40.288%. And the heavy-tailed symmetric covariate, which leaks exactly nothing on its own, doubles what the asymmetric copulas leak: 14.229% against 7.707%.

Two failures that cancel

A mildly skewed covariate under a lower-tail copula leaks 0.002% of an interaction where each failure alone leaks eight and seven per cent. Turn the copula over and the same pair compounds.

compound · Adjustment 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 Where the two kinds of cut sit. Six covariates, each a monotone transformation of the same latent normal. The vertical line at zero is where every median split sits, on every one of them, because a monotone map preserves order: the median of the covariate is the image of the median of the latent normal. The marks on the curves are where a threshold at 1 on the covariate's scale falls — 1.000, 0.881, 0.875, 0.783, 0.713, 0.337 — and none of them is at zero. That is the whole of the difference. A function of the sign of the latent normal is odd, and a rule made of odd functions removes exactly nothing of an interaction between two of them; a threshold anywhere else is neither odd nor even and removes something.

A split survives what a mean does not

The two things every trial balances come apart on a skewed covariate. A median split is a function of the sign of the latent normal whatever the marginal is; a mean is not, and its exact zero is gone at a skewness of one.

skew · Criterion The same copula, turned over. A Clayton copula and its reflection, at the same Spearman correlation of 0.40 and the same Kendall tau of 0.275, against the covariate's marginal. With a symmetric covariate the two are the same number to nine decimals — 7.707% apiece — because the leak then depends on how much asymmetry the copula has and not on which way it points. Skew the covariate and they come apart: at a skewness of 2.26 the lower-tail copula leaves 3.431% and the upper-tail one 36.213%, a factor of 10.6. Both halves of the dependence are asymmetries and an asymmetry has a direction; a lower-tail copula concentrates the dependence where a right-skewed marginal is compressed and the two distortions partly undo each other, and an upper-tail one concentrates it where the marginal is stretched.

A symmetry that was not enough

A heavy-tailed symmetric covariate has a skewness of zero and leaks exactly nothing under three copulas. Under the two asymmetric ones it doubles the leak, from 7.707% to 14.229%.

compound · Adjustment The zero was a fact about independence. What a balancing rule handed every main effect of both covariates removes of a pure interaction, as the covariates are allowed to move together. At ρ = 0 it is exactly nothing — at machine precision, at any number of main effects — which is the independent-covariate result and is correct. It is not small anywhere else: the product of the two covariates loses 64.0% of itself by ρ = 0.5, because h₁h₁ = h₀ + √2·h₂ and Mehler pairs h₂ with h₂ at ρ². Four interactions are drawn and none of them keeps the zero.

A zero that was an assumption

A rule handed every main effect of both covariates removes exactly none of a pure interaction. That is true at machine precision, it is a fact about independence, and it dies as the square of the correlation.

joint · Criterion The mean's zero is the copula's symmetry. Five copulas, each at a Spearman rank correlation of 0.4, with a normal covariate throughout — so nothing here is about the marginal, which is the whole of the earlier field. Horizontally: how far the copula's density is from its own reflection through the centre of the unit square, measured rather than read off the family's name. Vertically: what a rule balancing the mean of each covariate removes of their product. The three copulas at zero on the horizontal axis remove exactly nothing, to thirty decimal places. The two that are not symmetric remove 7.71%. A guarantee that held for six marginals turns out to have needed something the marginals could not have told anybody about.

The symmetry the marginals could not show

A mean's interaction zero needs the covariate to be symmetric and the copula to be symmetric under reflection. Six marginals could only ever test one of those, and the other is broken by the commonest kind of dependence there is.

copula · Criterion What the worst case is worth, one function at a time. The smallest share each dictionary removes, over seven outcome shapes, at a correlation of 0.5. A rule balancing the mean of each covariate has a worst case of exactly zero — against the square, and against both products. Adding a median split to it, which is the second thing every trial balances, leaves the worst case at exactly zero, because a median split is odd and so is a mean. Adding the square instead moves it to 6.8%, and the extra functions after that move it to 7.4%. The worst case is decided by which parities the dictionary contains rather than by how many functions are in it.

What the extra function buys

A rule balancing the mean of each covariate has a worst case of exactly zero. Adding the median split — the other thing every trial balances — leaves it at exactly zero, and one square moves it.

dict · Criterion Three copulas that break nothing, and a factor of two between them. The three radially symmetric copulas, at a matched Spearman correlation of 0.40, against the covariate's marginal. All three leave exactly nothing with a symmetric covariate — that is the guarantee, and it holds to twenty decimal places. What they do to a skewed covariate is not the same at all: at a skewness of 2.26 a Frank copula leaves 12.118% where a Gaussian leaves 21.539% and a t on four degrees of freedom leaves 23.640%. A factor of 2.0 between two copulas that are both symmetric, both matched on rank correlation, and both harmless on their own. So the copula matters to the marginal's leak without breaking any symmetry of its own, which is a milder version of the same finding and applies to every trial rather than to the asymmetric ones.

A copula that halves a marginal

Three copulas break nothing on their own and put a factor of two between the same skewed covariate's leaks — 12.118% under a Frank against 23.640% under a t, at the same rank correlation.

compound · Adjustment 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.

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 Three analyses of the same trials, none of them wrong about the data. 320 trials at n = 60 with no treatment effect at all, so every rejection counted is a false one, and a covariate that drives the outcome with coefficient 1. The unadjusted comparison is at 5.94% after a coin — its level — and at 0.00% after the rule that reads the covariate: the design removed the imbalance and the analysis is still pricing it. Adjusting for the covariate gives 4.06%, and the rule's own reference distribution — hold the outcomes, re-run the rule 199 times, count — gives 3.13% against the 4.5% that 199 draws can deliver. The last of the three has to be told the assignment rule and nothing else, which is the one thing the experimenter certainly knows.

What the balanced trial is worth

A rule that reads the covariate removes three quarters of the imbalance. An analysis that does not know it happened prices the imbalance anyway, rejects one true null in two hundred instead of one in twenty, and finds a real effect less often than a coin-tossed trial does.

continuous · Randomisation Which tail the threshold is in. What a rule balancing a threshold at 1 on each covariate's own scale removes of the interaction between the two thresholds, on five copulas matched at a Spearman rank correlation of 0.4 with a normal covariate throughout. This rule never had a zero to lose — the earlier field establishes that under every marginal — so what is left is a size, and the size depends on where the dependence lives. A Clayton copula, whose density piles up in the lower tail, leaves 5.33%; the same copula turned over, so that it piles up in the upper tail where the threshold is, leaves 33.36%. Same rank correlation, same Kendall tau, same marginal, same threshold: 6.26 times the leak, decided by which end of the distribution the dependence and the cut are both in.

Which tail the cut sits in

The same copula and its reflection have the same rank correlation, the same Kendall tau and the same marginals. A balancing rule holding a threshold at a dose leaves 5.33% under one and 33.36% under the other.

copula · Criterion 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 each analysis does at a true null, by shape. Four analyses of the same trials — 500 of them at each shape, 120 units, assigned by the rule that reads the covariate. Every rejection is false. The unadjusted analysis is the one that moves: 1.60% against a linear outcome, where the design removed a great deal that the standard error still prices, and 5.20% against a quadratic, where it removed nothing and the standard error is right. Adjusting holds the level in all three columns, and so does the design's own reference distribution, which needs to be told the rule and nothing else.

The analysis and the shape

An unadjusted analysis after a rule that read the covariate is too cautious — by a third against a linear outcome, by nothing at all against a quadratic. And an adjustment for the wrong function recovers almost none of the precision the right one would.

shape · Randomisation The allocations this trial could have made, and the ones it could not. One 120-patient trial allocated by minimisation at p = 1, re-randomised 399 times. No outcome is redrawn anywhere in this figure: each re-randomisation runs the rule again over the same patients in the same order with the same recorded factors, so what is drawn is the set of experiments that could have happened. The bars are that set; the outline is what shuffling the labels gives, which is the reference distribution of a coin and is what every off-the-shelf permutation routine assumes. The coin's is wider — its 5% point is 1.95 against the rule's 1.09 — because a coin's allocations are less balanced and a less balanced allocation gives a larger statistic. Reading this trial against it makes the test conservative rather than anti-conservative, which is the opposite error from the outcome-adaptive case and for the same structural reason.

The reference the covariates supply

Hold the outcomes fixed, re-run the rule that assigned them, count. The same construction cost nineteen points of power in the adaptive field, because its rule chased outcomes and its critical value depended on a rate nobody has. Here the rule reads only what was recorded before anything happened, and the same unadjusted statistic goes from 20.3% power to 55.0% by being read against the right distribution.

covadapt · Assignment The one zero neither half of the dependence can touch. A median split's interaction leak at all 30 combinations of copula and marginal, on a log scale. Every one is under 10⁻¹⁶ and the largest is 1.74e-20, which is the quadrature's own noise rather than a leak. The reason is arithmetic and it is short: a centred median split takes the values ±½, so its square is a quarter identically — for every unit, on every draw, whatever the covariate's scale is and whatever joint law the ranks have. The interaction is then orthogonal to both main effects by construction, and there is nothing for either half of the dependence to break. Both of the fields this one joins report this zero holding under their own variation; running both variations at once is what establishes that it is not two coincidences.

The zero that survives both

A median split's interaction leak is under 10⁻¹⁶ at all thirty combinations of copula and marginal. It is the only guarantee in the collection that neither half of the dependence can touch.

compound · Adjustment A covariate that is prior to everything and still ruins it. A covariate measured before the treatment, caused by neither the treatment nor the outcome, and not a common cause of them. Two unmeasured variables sit behind it: one reaches the treatment, the other reaches the outcome, and both reach the covariate. Every rule of thumb for including a baseline variable is satisfied, and the regression that leaves the covariate out estimates the treatment's effect of 0.50 without bias, while the regression that includes it is off by −0.2000 — because the covariate is a common effect of the two unmeasured causes, and conditioning on a common effect makes its causes dependent. The path it opens runs from the treatment back through the first unmeasured cause, through the covariate, and out through the second to the outcome.

A collider before the treatment

A covariate measured before the treatment, on no causal path, and not a common cause of anything, still biases the estimate by exactly −0.2000 against an effect of 0.5 — while the regression that leaves it out is exact. The bias saturates at 0.3536, and the two paths that make it a collider do not appear in that bound.

collider · Conditioning 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 A cohort screened once, the top tenth enrolled, and followed up with nothing given — correlation 0.6. 2000 people read once at screening and once at follow-up, with a test–retest correlation of 0.6 and no treatment. The 215 above a cut at the top ten per cent of one reading (1.282 standard deviations) are enrolled. Their mean screening reading is 1.744 and their mean follow-up reading 0.982, a fall of 0.762 ± 0.055 with nothing done to anyone. The closed form for the fall is (1 − ρ) times the truncated-normal mean, (1 − 0.6) × 1.755 = 0.702.

The measurement that got them enrolled

Enrol the top tenth of one screening reading and give them nothing, and they fall by 0.702 standard deviations at follow-up. Measured from a fresh reading taken after enrolment they fall by nothing. Averaging ten screening readings still leaves 0.101, and it takes twenty-one to get under 0.05.

paradox · Rtm The covariate the treatment caused, and what it hides. A covariate on the causal path: the treatment causes it and it causes the outcome, so the treatment's total effect of 1.130 runs partly through it. Adjusting for it returns the direct edge alone, 0.500, which is what somebody wanting the total effect should not have asked for. The dashed variable is the second problem: an unmeasured cause of both the covariate and the outcome. It does not touch the treatment, so the unadjusted regression still recovers 1.130 exactly. It does touch the covariate, so once the covariate is conditioned on the treatment and the outcome are linked through it, and the adjusted coefficient lands on 0.050 — neither the total effect nor the direct one.

The variable the treatment caused

Adjusting for a covariate the treatment caused stops estimating the total effect and starts estimating the direct one. When that covariate shares an unmeasured cause with the outcome it estimates neither: the total effect is 1.1300, the direct effect is 0.5000, and the regression returns 0.0500.

collider · Conditioning A proxy removes less than its reliability, always. The share of the confounding bias removed by adjusting for a proxy, against how well the proxy measures the confounder. The diagonal is the answer a reader would guess — a covariate that is 80% signal removes 80% of the problem. The curve is what the arithmetic gives: the reliability, times one minus the squared correlation between the treatment and the confounder, divided by one minus the product of those two. That squared correlation is 0.4475. A reliability of 0.8 removes 68.85% and one of 0.6 removes 45.32%. The two agree only at the ends, and the gap is widest where most applied covariates sit.

Adjusting for a shadow

A covariate that is 80% signal removes 68.85% of the confounding, not 80% — the share is λ(1 − ρ²)/(1 − λρ²) and it is below the reliability everywhere. The residual bias is 0.1084 against an effect of 0.5, and at 25,600 rows it is 17.6 standard errors wide.

collider · Conditioning

Named alongside it

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

Covariate balanceInteractionClosed formMarginal distributionOrthogonalityBasis functionsMedian splitExperimental designMonte CarloSymmetryContinuous covariateGaussian copula

All concepts