Full collaborative trials

Validation attempts in tlie field of drug residue analysis have demonstrated that die requirement for a full collaborative trial at the ideal level, while desirable, is sometimes impractical. Limiting factors for completing ideal multilaboratory validation studies are usually the high cost, lack of sufficient expert laboratories willing to participate in such studies, and overall time constraints. Hence, a three-laboratory validation study is often applied (16). 

Provision of a unified and disciplined framework that covers all aspects of the validation process from sample and method selection to full collaborative trial. 

The overall process of method validation is illustrated in Figure I. However, the extent and scope of validation is governed by the applicability of the method. An in-house procedure requires a less exacting process than a method intended for multi-matrix and/or multi-laboratory use. For the latter methods, a full collaborative trial is necessary and is covered in Chapter 9. However, for many purposes validation is limited to either demonstrating that method performance criteria established during development are met under routine laboratory conditions and/or showing method equivalence (Figure 18). 

After many years of debate and discussion, there is now an international consensus about the statistical approach and method to be employed in full collaborative trials This topic is discussed further in Section 9.5. The lUPAC protocol referred to above requires the analysis of duplicate test samples of the same material (a minimum of five materials or, exceptionally, three) in eight or more laboratories. However, there are many occasions where inter-laboratory studies are needed which, for various reasons, cannot achieve the prescribed criteria. In instances where the lUPAC criteria cannot be achieved, it is recommended that the Youden Matched Pairs procedure is used. The statistics of the method have been recently updated and a new procedure described. 

Validation of a new analytical method is typically done at two levels. The first is the level of prevalidation, aiming at fixing the scope of the validation. The second level is an extensive, full validation performed through a collaborative trial or interlaboratory study. The objective of full validation, involving a minimum number of laboratories, is to demonstrate that the method performs as was stated after the prevalidation. 

Recommended procedures for comparing methods and for taking a single method through to a full lUPAC collaborative trial with the harmonised protocol are covered in Chapter 9. Chapter 10 is a bibliography of recommended books and papers that should be consulted for more details in specific areas. 

The literature contains examples of collaborative trials that only prove that the method was not fit for its intended purpose The full lUPAC harmonised protocol is by its very nature an extensive and expensive exercise. From an economic perspective such trials should only be undertaken when there is good and well-documented evidence that it is likely that the method under evaluation is sufficiently robust. Investment of time and intellectual effort in method selection and the other aspects of the user requirements specification will pay great dividends. Prevention is better and nearly always cheaper than cure. 

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