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The capability of an inspection system is established by applications of various methodologies to determine the probability of detection (POD). One accepted metric of an adequate inspection system is that for a minimum flaw size and all greater flaw sizes, there is 0.90 probability of detection with 95% confidence (90/95 POD). Directed design of experiments for probability of detection (DOEPOD) has been developed to provide an efficient and accurate methodology that yields estimates of POD and confidence bounds for both Hit-Miss or signal amplitude testing, where signal amplitudes are reduced to Hit-Miss by using a signal threshold Directed DOEPOD uses a nonparametric approach for the analysis or inspection data that does require any assumptions about the particular functional form of a POD function. The DOEPOD procedure identifies, for a given sample set whether or not the minimum requirement of 0.90 probability of detection with 95% confidence is demonstrated for a minimum flaw size and for all greater flaw sizes (90/95 POD). The DOEPOD procedures are sequentially executed in order to minimize the number of samples needed to demonstrate that there is a 90/95 POD lower confidence bound at a given flaw size and that the POD is monotonic for flaw sizes exceeding that 90/95 POD flaw size. The conservativeness of the DOEPOD methodology results is discussed. Validated guidelines for binomial estimation of POD for fracture critical inspection are established.