Updating of covariates and choice of time origin in survival analysis: problems with vaguely defined disease states

This paper discusses survival analysis based on updated covariates with focus on proportional hazard regression in situations where some disease states may be vaguely defined. Analyses of a trial in liver cirrhosis are used to motivate the discussion. We use problems caused by inclusion of recordings from unscheduled follow-ups to illustrate the importance of appropriate coding of covariates and describe how such problems may be approached using appropriately 'lagged' covariates. The choice of time origin is discussed with emphasis on situations where disease initiation is difficult to define. Simulations are used to assess the effect of an erroneously specified time origin. It is argued that age or calendar time may frequently be sensible time variables. Copyright (C) 2002 John Wiley Sons, Ltd.