Devices and methods for improving device therapy such as cardiac resynchronization therapy (CRT) are described. An ambulatory medical device can receive one or more physiologic signals and generate multiple signal metrics from the physiologic signals. The ambulatory medical device can determine a desired value for a device parameter, such as a timing parameter used for controlling the delivery of CRT, using information fusion of signal metrics that are selected based on one or more of a signal metric sensitivity to perturbations to the device parameter, a signal metric variability, or a covariability between two or more signal metrics. The ambulatory medical device can program a stimulation using the desired device parameter value, and deliver the programmed stimulation to one or more target sites to achieve desired therapeutic effects.