Past exam of the mathematics course of the University of Cambridge / 2008 / iii / Paper 46 / 5

The Cox proportional-hazards model specifieswhere $h_0(t)$ is an unspecified common baseline hazard and $z_i$ is the individual's covariate vector. The hazard ratio for two fixed covariate vectors is $\exp [{\beta }^T(z_i-z_k)]$, constant in time. Assume independent subjects and independent censoring conditional on their covariates, and use the question's absence of tied events.

Let $t_j$ be an event time, $i_j$ its failing subject, and $R_j$ the risk set immediately before that time. In a short interval of length $dt$, the conditional probability that subject $i$ fails, given one failure among those at risk, isThe baseline hazard cancels. Multiplying the successive conditional event-identity factors gives the Cox partial likelihood for $\beta$:This is a partial likelihood, not the full survival likelihood for the unspecified $h_0$. Risk sets evolve with the observed history; the derivation uses their successive conditional hazards, rather than assuming the risk sets themselves are independent.

Define $w_{jk}(\beta )=e^{{\beta }^T{z}_k}/{\sum }_{\ell \in R_j}{e}^{{\beta }^T{z}_{\ell }}$ and ${\bar{z}}_j(\beta )={\sum }_{k\in R_j}{w}_{jk}(\beta )z_k$. For component $r$,Differentiating again givesThus the score and information of Cox partial likelihood are the sum of event-minus-risk-mean contrasts and the sum of risk-weighted covariance matrices, respectively. The Hessian is negative semidefinite; the likelihood is concave, with strict identifiability requiring variation in the relevant risk-set covariates.

At event time $t_j$, the vector Schoenfeld residual iswhere $\hat{\beta }$ is the fitted partial-likelihood coefficient. It compares the covariate of the person who actually failed with the covariate mean predicted for the failing person, using the fitted hazard weights over the risk set. Under the model at the true coefficient, the conditional expected failing covariate is precisely that weighted mean, so the corresponding Schoenfeld function is conditionally centered at zero. Residuals are defined at observed events, not at censoring times.

The score equation from part (a) is exactlyAt a finite interior unpenalized maximum, $U(\hat{\beta })=0$, soThis is the intended fitted-residual identity. For an arbitrary trial coefficient it is a score, not generally zero; a single event with covariates zero and one in its risk set can have Schoenfeld function $1/2$ at $\beta =0$. Penalized estimates or a boundary maximum also need their own score conditions rather than this unqualified zero-sum assertion.

Under proportional hazards, each coefficient is constant over event time. Examine the Schoenfeld residuals, preferably scaled Schoenfeld residuals, against time or a prespecified transformation such as log time, ranks or a fitted survival-time transformation. Plot a smooth trend and its uncertainty for each covariate. Under the working model there should be no systematic residual-time association; a persistent trend suggests a time-varying coefficient. In a coefficient-scale plot that adds $\hat{\beta }$ to the scaled residuals, the null trend is horizontal at the fitted coefficient.

A formal proportional hazards assumption test can add a time interaction, for example ${\beta }_r(t)={\beta }_r+{\theta }_{r}g(t)$, and test ${\theta }_r=0$ using a score test with information adjusted for the fitted constant coefficients. The score contributions involve the Schoenfeld functions weighted by $g(t_j)$. One can test each covariate and use a joint global test for a vector of time-interaction coefficients. Such an association would be possible despite the unweighted residual sum being zero, so that fitted identity does not establish proportional hazards.

A systematic nonhorizontal coefficient trend or significant residual-time association is evidence against a constant hazard ratio. Failure to reject is compatible with the assumption, not proof of it. These diagnostics target the proportionality restriction; they do not by themselves verify covariate functional form or independence of the censoring mechanism.