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In vehicle safety engineering, it is important to determine the severity of occupant injury during a crash. Computer simulations are widely used to study how occupants move in a crash, what they collide during the crash and thus how they are injured. The vehicle motion is typically defined for the occupant simulation by specifying a crash pulse. Many computer models used to analyze occupant kinematics do not calculate both vehicle motion and occupant motion at the same time. This paper presents a framework of response surface methodology for the crash pulse prediction and vehicle structure design optimization. The process is composed of running simulation at DOE sampling data points, generating surrogate models (response surface models), performing sensitivity analysis and structure design optimization for time history data (e.g., crash pulse).