Patient population target validation

The team members should provide an exposition of the logic governing the identification of the target patient population and the statistical validity of the intended sample study population. 

Initial Test of Matrix Effects Assay matrices are typically the most troublesome component in LBA. There should be careful consideration of this variable during method validation. Two types of tests are used to address the two major concerns surrounding matrix effects. These are performed in consideration of (1) whether there is a matrix difference between the standards and anticipated study samples that impacts the relative accuracy of an assay and (2) whether there are inter-individual or disease-specific differences in matrix in the target patient population. Two types of tests are used to evaluate such matrix effects spike recovery, where known amounts of analyte are mixed ( spiked ) into characterized matrix, and parallelism in patient samples. However, limited availability of patient samples may prevent the latter testing during the method feasibility phase. 

Proof of principle of target validation can be demonstrated in the relevant patient population, usually in phase Ila clinical trials. 

The other important consideration is which patient popnlation to select. Again, it is ideal to validate a POCT method using samples that are taken from the target patient group in whom the test is to be used, as there may be patient-specific interference or matrix considerations. For example, a POCT that measures blood ketones may perform differently in extremely dehydrated patients admitted with ketoacidosis to a healthy diabetes out-patient population. However, it may also be valuable to undertake the test in a different population. At the very least, users undertaking a method validation, should consider which sample matrix to test and which sample population to study (see Box 2.2 for a case example). 

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