Screening, statistics applied

Kuentz, M., Nick, S., Parrott, N. and Rothlisberger, D. (2006) A strategy for preclinical formulation development using GastroPlus as pharmacokinetic simulation tool and a statistical screening design applied to a dog study. European Journal of Pharmaceutical Sciences, 27, 91-99. 

Kuentz M, Nick S, Parrott N, and Roethlisberger D. A Strategy for Preclinical Formulation Development Using GastroPlus as Pharmacokinetic Simulation Tool and a Statistical Screening Design Applied to a Dog Study.i MrJ Pharm Sci 2006 27 91-99. 

In the first step, a screening process will be applied to separate the major potential hazards these will be addressed in more detail. QRA techniques are used to evaluate the extent of the risk arising from hazards with the potential to cause major accidents, based on the prediction of the likelihood and magnitude of the event. This assessment will be based on engineering judgement and statistics of previous performance. Where necessary, risk reduction measures will be applied until the level of risk is acceptable. This of course is an emotive subject, since it implies placing a value on human life. 

The main objective of the In-Plant Reliability Data System (IPRDS) was to develop a comprehensive and component-specific data base for PRA and other component reliability-related statistical analysis. Data base personnel visited selected plants and copied all the plant maintenance wor)c requests. They also gathered plant equipment lists and plant drawings and in some cases interviewed plant personnel for Information on component populations and duty cycles. Subsequently, the maintenance records were screened to separate out the cases of corrective maintenance applying to particular components these were reviewed to determine such things as failure modes, severity, and, if possible, failure cause. The data from these reports were encoded into a computerized data base. 

A number of commercial expert systems have been applied to screen drug libraries. For instance, DEREK, TOPKAT, MultiCASE, and many other systems all have possibilities in this regard. However, it should be noted that for broad screening only compounds with toxicity associated with them can be identified, and hence these are very crude measures of hazard assessment. The use of expert systems to screen libraries is fraught with dangers, not least that no performance statistics are available for these systems being used for such an application. It is also highly probable that the vast majority of predic-... 

Franz et al. [42] reviewed these techniques completely, along with statistical screening techniques and other experimental methods, with an excellent list of publications. A few selected publications from the recent literature demonstrate the wide variety of formulation and processing problems to which these techniques can be applied and the varying methods selected for optimization. 

The traditional acute, subchronic, and chronic toxicity studies performed in rodents and other species also can be considered to constitute multiple endpoint screens. Although the numerically measured continuous variables (body weight, food consumption, hematology values) generally can be statistically evaluated individually by traditional means, the same concerns of loss of information present in the interrelationship of such variables apply. Generally, traditional multivariate methods are not available, efficient, sensitive, or practical (Young, 1985). 

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