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We present an approach coupling a limited experimental number of tests with numerical simulations regarding the design of radiation-hardened (RH) rare earth (RE)-doped fiber amplifiers. Radiation tests are done on RE-doped fiber samples in order to measure and assess the values of the principal input parameters requested by the simulation tool based on particle swarm optimization (PSO) approach. The proposed simulation procedure is validated by comparing the calculation results with the measured degradations of two amplifiers made with standard and RH RE-doped optical fibers, respectively. After validation, the numerical code is used to theoretically investigate the influence of some amplifier design parameters on its sensitivity to radiations. Simulations show that the RE-doped fiber length used in the amplifier needs to be adjusted to optimize the amplifier performance over the whole space mission profile rather than to obtain the maximal amplification efficiency before its integration in the harsh environment. By combining this coupled approach with the newly-developed RH RE-doped fibers, fiber-based amplifiers nearly insensitive to space environment may be designed in the future.