The aircraft engines manufacturing industry is subjected to many dependability constraints from certification authorities and economic background. In particular, the costs induced by unscheduled maintenance and delays and cancellations impose to ensure a minimum level of availability. For this purpose, Prognostics and Health Management (PHM) is used as a means to perform online periodic assessment of the engines’ health status. The whole PHM methodology is based on the processing of some variables reflecting the system’s health status named Health Indicators. The collecting of HI is an on-board embedded task which has to be specified before the entry into service for matters of retrofit costs. However, the current development methodology of PHM systems is considered as a marginal task in the industry and it is observed that most of the time, the set of HI is defined too late and only in a qualitative way. In this paper, the authors propose a novel development methodology for PHM systems centered on an anticipated model-based validation of HI. This validation is based on the use of uncertainties propagation to simulate the distributions of HI including the randomness of parameters. The paper defines also some performance metrics and criteria for the validation of the HI set. Eventually, the methodology is applied to the development of a PHM solution for an aircraft engine actuation loop. It reveals a lack of performance of the original set of HI and allows defining new ones in order to meet the specifications before the entry into service.