Clinical validation methodology

It has not yet been convincingly demonstrated that QALYs as currently measured Yc validity in mental health contexts (Chisholm et al, 1997), nor that the EQ-5D or similar should replace disorder-specific quality of life measures. However, the methodological rigour and transparency of the approach is impressive, and it is certainly true that few clinical effectiveness scales currently used in... 

Analytical methods are important not only in the development and manufacture of commercial biopharmaceutical drugs, they also play a vital role in the whole drug development life cycle. Drug discovery and preclinical research require development and application of analytical methodologies to support identification, quantitation, and characterization of lead molecules. It is difficult to perform a comparative potency assay on lead molecules if one does not know how much of each is going into the assay or how pure the molecule is. Analytical methods are typically developed, qualified, and validated in step with the clinical... 

Close cooperation for a year or more before the first administration to humans is likely to lead to a smooth transfer of the compound and the rapid movement of a compoimd out of preclinical into man. This lead time can be used to devise the ED plan, design the first studies and, when appropriate, to select and develop methodologies that will contribute to the drug s evaluation in man. This may include validation of pharmacod)mamic measures to be used in the clinical pharmacology unit, assessment of various imaging techniques, development of bioanalytical methods. Not infrequently, the assays that were perfectly adequate to support preclinical work are insufficiently sensitive, specific or accurate to quantify the comparatively low concentrations of parent... 

Once an application has been accepted for evaluation, the Pharmaceutical Chemistry Evaluation Section, Toxicology Section and Clinical Evaluation Units evaluate the Module 3, 4 and 5 data, respectively. For applications relating to products of biological origin, a second copy of the Module 3 data is also evaluated by the TGA Laboratories (TGAL) Branch, which evaluates aspects such as laboratory methodology, method validation and shelf-life. 

One of the more common criticisms of an evidence-based approach to clinical practice is that clinical trials and clinical practice are only weakly related. In research language, the external validity of many efficacy studies is suspect. External validity, which refers to the extent to which the results of the research are gener-alizable to clinical populations, is often contrasted to internal validity, i.e., the extent to which a study is methodologically sound. Without internal validity, it is hard to argue for the external validity of a study. Many internally valid studies are not fully relevant to clinical... 

Analytical testing (preformulation, stability, product release) is a core component of pharmaceutical operations from early R D through manufacturing of the commercial product. The original analytical methods are usually developed by the pioneer pharmaceutical firm and transferred to the provider. In some cases, the early methods are only preliminary methods and are not sufficiently robust to test the quality of downstream (clinical, commercial, and line extension) products and facility quality practices (cleaning validation). In those situations, the supplier is often asked to develop new methods, and in some cases those methods are transferred back to the client. In either scenario, the transfer of validated analytical methodology consists of the following four main tasks [52] ... 

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