Devices and methods for improving device therapy such as cardiac resynchronization therapy (CRT) by determining a desired value for a device parameter 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 pacing to various heart chambers, 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 in response to a stimulation, a signal metric variability in response to a stimulation, or a covariability between two or more signal metrics in response to a stimulation. 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.