We note with great interest the findings of Crawford and colleagues
in their study of the “waiting time paradox” in endometrial cancer (1).
This phenomenon is also well recognised in the field of motor neuron
disease (MND) (2). In our analysis of 841 patients seen in a tertiary MND
centre over a 10-year period, the mean waiting time (or referral delay,
defined as time from date of symptom onset to date of diagnosis in the
clinic) was 22 months (range 0-214 months) (3). In a Kaplan-Meier analysis
of survival this variable was highly significant, with a shorter delay
strongly associated with a worse prognosis (p<0.0001). We believe the
explanation for this phenomenon is that waiting time is acting as a
surrogate marker for rapid progression of aggressive disease. This “
paradox” will therefore be seen in all conditions with a variable
prognosis that are either uniformly incurable like MND, or incurable in
their aggressive, rapidly progressive forms, for example malignancy.
We recommend the specific inclusion of this parameter in any
subsequent multivariate analysis using the Cox proportional hazards model,
to avoid any possible confounding effect on other variables. Using this
approach, with other potentially prognostic factors in MND as covariates,
we demonstrated that waiting time retained independent prognostic
significance (p<0.0001). Furthermore, a “prognostic score” can be
calculated from such a model using the sum of the relative risk minus the
covariate mean for each variable, and this produced a robust predictive
model of survival in MND (3).
1. Crawford SC, Davis JA, Siddiqui NA, de Caestecker L, Gillis CR, Hole D
et al. The waiting time paradox: population based retrospective study of
treatment delay and survival of women with endometrial cancer in Scotland.
2. Iwasaki Y, Ikeda K, Ichikawa Y, Igarashi O, Kinoshita M. The
diagnostic interval in amyotrophic lateral sclerosis.
3. Turner MR, Bakker M, Sham P, Shaw CE, Leigh PN, Al-Chalabi A.
Prognostic modeling of therapeutic interventions in amyotrophic lateral
sclerosis. Amyotroph.Lateral.Scler.Other Motor Neuron Disord. 2002;3:15-
Competing interests: No competing interests