Evaluating cumulated research. I: The inadequacy of traditional methods.

Virtually all reviews of cumulated studies rely on statistical significance as a criterion for evaluating the reproducibility of the phenomenon under review. Despite its nearly universal application, that criterion is entirely inadequate: Its application is very likely to lead a reviewer to conclude that a phenomenon does not discriminate patients from controls when, in fact, it does do so. The reviewer is, paradoxically, more likely to draw this incorrect conclusion as more studies become available for review. It can lead a reviewer to conclude that one phenomenon is more discriminating than another when the opposite is actually true. Fortunately, procedures that do not distort the review process are available; some of these are briefly discussed.

The rationale and a computer evaluation of a gamma irradiation sterilization dose determination method for medical devices using a substerilization incremental dose sterility test protocol.

The experimental procedure described is designed to allow calculation of the radiation sterilization dose for medical devices to any desired standard of sterility assurance. The procedure makes use of the results of a series of sterility tests on device samples exposed to doses of radiation from 0.2 to 1.8 Mrad in 0.2 Mrad increments. From the sterility test data a 10(-2) sterility level dose is determined. A formula is described that allows a value called DS Mrad to be calculated. This is an estimate of the effective radiation resistance of the heterogeneous microbial population remaining in the tail portion of the inactivation curve at the 10(-2) dose and above. DS Mrad is used as a D10 value and is applied, in conjunction with the 10(-2) sterility level dose, to an extrapolation factor to estimate a sufficient radiation sterilization dose. A computer simulation of the substerilization process has been carried out. This has allowed an extensive evaluation of the procedure, and the sterilization dose obtained from calculation to be compared with the actual dose required. Good agreement was obtained with most microbial populations examined, but examples of both overdosing and underdosing were found with microbial populations containing a proportion of organisms displaying pronounced shoulder inactivation kinetics. The method allows the radiation sterilization dose to be derived from the natural resistance of the microbial population to gamma sterilization.