Defect analysis methodology

Risk assessment for a given drug is highly dependent on the methodology used and in all cases must not rely solely on an analysis of data from clinical trials. It must be recalled that for AED, underreporting of adverse effects appears to be a chronic defect. In addition, it can sometimes be difdcult to attribute cause to a specidc dmg due to the frequency of comedications and the absence of the habimal mechanistic explanation of the observed phenomena. 

Selection of a health outcome for study depends in part upon the exposure of interest and methodological considerations such as the ability to define, measure, and validate adverse outcomes, especially if self-reported. Operational definitions for outcomes can be general or specific in nature (e.g., all birth defects versus spina bifida, respectively), and will affect the type of statistical analysis which can be performed and the interpretation of results. Statistical power may be limited if restrictive operational definitions are used for rare outcomes, or if other important covariates cannot be fully addressed. 

Nanomechanics of Defects in Solids by M. Ortiz and R. Phillips in Advances in Applied Mechanics, Vol. 36, edited by E. van der Giessen and T. Y. Wu, Academic Press, New York New York, 1999. This article provides a thorough analysis of several of the methodological advances described in this chapter. 

This LC-MS-based methodology can be automated to fit specialized needs within drug discovery based on throughput [62], The recent application of mass defect filtering [90] and high-resolution accurate mass analysis [33] provides further automated protocols for metabolite identification (see Chapters 5 and 6 for more on this topic). 

---