If a regression response is observed but covariate is sometimes missing, likelihood inference requires a joint model: for example . An incomplete record contributes to the observed-data likelihood. Missing at random with distinct parameters allows the missingness mechanism to be omitted; it does not remove the need to integrate over .
For conditional individual response profiles use a logistic random-intercept model for repeated binary outcomes. Introduce a subject effect independently across subjects and independently of treatment and baseline covariates, under the specified model. Conditional on , assume the three responses are independent Bernoulli random variables with
Here is persistent unmeasured subject heterogeneity and its variance. It induces dependence after integration: for distinct visits, the response covariance is , generally positive. This is a complete joint generalized linear mixed model, unlike a mean-only GEE specification.
Under missing at random conditional on the observed responses and baseline variables, with distinct parameters for missingness and outcomes, the missingness model is ignorable for likelihood inference. Let . The outcome observed-data likelihood is
The omitted Bernoulli factors sum to one over missing outcomes. Fit the fixed coefficients and by maximizing this integrated likelihood, with suitable quadrature or another justified integration method. If , use the limiting point-mass model. Correct response and random-effect distributions, identifiable coefficients and regularity are needed; the latent distribution assumption is not merely a convenient working covariance.
For patient , combine the fitted model with the posterior density of proportional to its normal density times that patient's observed Bernoulli factors. Integrating over this posterior gives a patient-specific predicted response profile. The treatment odds ratio for a fixed and the same baseline variables is . This conditional contrast does not by itself identify each person's unobserved causal treatment effect: a parallel-arm trial observes only one treatment per person. Random slopes or heterogeneous treatment effects require further modelling and sufficient information; they are not implied by fitting a random intercept.
The population-averaged logistic regression describes after averaging over unmeasured individual heterogeneity. Its intercept is a marginal log odds at reference baseline values and time zero, its treatment coefficient is a population conditional-on-baseline log odds ratio, and its time coefficient is the change in that marginal log odds per month. Time zero is an extrapolation here because the recorded visits begin later; centring time at the first visit would give a more interpretable intercept.
In the random-intercept logistic model, the intercept is instead the conditional log odds for a subject with . The treatment and time coefficients apply at fixed ; the subject's actual intercept is . Even with a treatment-independent random intercept, the conditional and marginal coefficients generally differ through noncollapsibility of the odds ratio. Indeed, if , marginalization gives
which is not generally a logistic curve with the same linear coefficients. To quantify random-intercept attenuation of marginal logistic slopes, let . Then
For a nondegenerate finite random intercept this derivative lies strictly between zero and one and usually varies with . Thus the marginal treatment contrast is an integrated, attenuated version of the conditional contrast, and the marginal time slope need not be constant. One should not equate the two sets of coefficients, even in a randomized controlled trial without treatment confounding.
For missing completely at random, an unweighted observed-response GEE with cluster-robust standard errors can consistently fit the marginal mean, and a correctly specified integrated GLMM likelihood is valid as well. Under missing at random depending on previous observed outcomes, ordinary unweighted GEE is generally biased because the remaining responses are selected by informative observed history. Correct inverse-observation-weighted estimating equations for longitudinal dropout recover the marginal target under the sequential MAR and positivity assumptions already stated. Covariate-only observation mechanisms are a simpler special case in which correctly conditioned unweighted mean equations can remain valid.
A correctly specified joint response GLMM, fitted by observed-data likelihood, is valid under ignorable missing at random with distinct parameters, including dependence of missingness on observed response history. This is a likelihood property, not a claim that every mixed model automatically fixes missingness. Under missing not at random, neither ordinary GEE, MAR-based weights nor a response-only GLMM is generally valid; the unseen-outcome dependence requires further modelling and sensitivity assumptions.
First investigate what predicts dropout among variables actually observed, record reasons where possible, and seek additional outcome follow-up. Dependence on observed history alone can be missing at random; informative dependence on unseen responses or latent heterogeneity requires a missing not at random analysis. Observed data do not ordinarily distinguish MAR from all MNAR explanations.
An explicit selection model for informative longitudinal dropout can augment a joint response model by dropout hazards. Define as above and, among subjects retained through visit , put
Omit the previous-response term at the first visit. A nonzero makes dropout depend on the currently missing response. For monotone observation indicators , let
The appropriate observed-data likelihood is
Thus a patient's dropout pattern contributes information in the model; dropping the factor is not justified under this informative mechanism.
Another option is a shared-parameter model for informative dropout: retain the conditional Bernoulli response model, but let the dropout logit contain the same latent effect, for example . Conditional on the shared effect and observed history the processes can be independent, while marginally dropout remains associated with unseen responses. The joint likelihood must integrate the response factors and dropout factors together over . A response-only mixed-model fit does not generally account for this dependence.
Because or can be weakly identified from the observed outcomes, report sensitivity of the treatment conclusion to plausible informative-dropout assumptions. One can fix a range of these dependence parameters and refit, or use pattern-mixture sensitivity analysis that shifts the imputed post-dropout log odds by a specified amount from the MAR prediction. Present population risks and treatment contrasts across these scenarios with their uncertainty. These are explicit identifying assumptions, not an empirical test proving which missingness mechanism is true. Neither a complete-case analysis nor carrying forward the last response supplies such a justification.
For the moment approach, write and let be a positive-definite working covariance constructed from the proposed moment formulas. For identifiable mean coefficients , let . Generalized estimating equations take the form
Across independent students, correct mean specification and standard regularity conditions give consistent identifiable mean coefficients even if the working covariance is wrong. Sandwich covariance matrix standard errors use
Residual second-moment estimating equations can estimate identifiable dispersion and association parameters. The marginal mean only identifies , not and separately. Moment restrictions beyond the mean would be needed to separate them; as shown below, the printed restrictions do not generally recover the intended latent parameters.
For the hierarchical approach, maximize the observed-data likelihood after integrating out the random effect. Set , , and . The joint likelihood contribution is
The integral comes from multiplying three conditional Poisson mass functions by the Gamma density and integrating over . Independent students give . Direct numerical maximum likelihood or an expectation-maximization algorithm can be used; in an EM algorithm an all-zero profile has an uncertain latent component membership. Information-based likelihood standard errors apply under regular interior conditions, with special care for parameter boundaries.
Four unsuccessful attempts have conditional probability . The outcome is then unobserved, so the observed-data likelihood integrates over it:
This is a probability, whereas a responder contributes a joint density in the observed outcome. The sequential response selection model keeps outcome-dependent nonresponse in the likelihood; evaluating the product at an imputed mean would not be this likelihood.
Under missing completely at random, the observed second-year outcomes form a random subsample, so the direct pooled complete-case analysis estimate is
It is valid under missing completely at random because dropout no longer changes the marginal distribution of second-year use. Pooling is simpler than reporting separate conditional probabilities, but MCAR alone does not make this estimate more efficient than the estimate in the previous part. The fully observed first-year variable carries useful outcome information and can improve precision even when dropout is completely random.
To make the qualification explicit, write , , and for the constant response probability. For patients the leading variance of the pooled estimator is . The standardization estimator in the preceding part has leading variance
Indeed its first-order centered contribution is : the two terms have zero covariance, and their variances give that expression. The law of total variance therefore yields
The inequality is strict when there is dropout and first-year use predicts second-year use, as the distinct conditional rates suggest here. Thus the requested universal efficiency claim needs qualification. In the unrestricted joint binary-outcome model, maximizing the observed-data likelihood under either missing at random or missing completely at random gives the same standardization estimate : the all-patient first-year proportion and the two observed conditional second-year proportions maximize its factored outcome likelihood. Restricting the distinct missingness parameters to a common response probability affects their factor, not this estimate. The pooled value is the simple valid MCAR answer; retaining the first-year information gives the efficient MCAR answer and does not require replacing the previous estimate.
An ignorable missingness mechanism need not be absent from the data-generating process. It means that likelihood inference about the data-model parameters can omit the missingness factor, while still integrating over missing values.
Write the complete joint data statistical probability density as and the conditional missingness probability as . All values and only are observed. Under missing at random, is constant as varies with fixed. The actual observed-data likelihood is therefore
The assumed distinctness is understood as independent variation of and . Maximizing over multiplies by a factor independent of ; likelihood ratios, scores and likelihood curvature for are therefore unchanged by omitting . This proves likelihood ignorability.
For implementation of the observed-data likelihood with a missing covariate, a linear regression model for must be accompanied by an appropriate model for the distribution of . For independent individuals, write for the regression statistical probability density and for the age statistical probability density. Up to the ignorable factor,
Ignorability does not authorize discarding missing-age cases or assuming their ages have the distribution seen in the complete cases. It removes the need to model the observation mechanism for likelihood inference under the stated conditions, not the need to handle the missing covariates.