Drug development biomarker assays

REID E, HILL H M and Wilson ID (1998), Drug development assay approaches, including molecular imprinting and biomarkers — SP 226. London, Royal Society of Chemistry. 

Reid E, Hill HM, Wilson ID (1998) Drug Development Assay Approaches including Molecular Imprinting and Biomarkers. Methodological Surveys in Bioanalysis of Drugs. Vol. 25, The Royal Society of Chemistry Rogers KR, Mulchandani M (eds) (1998) Affinity Biosensors. Human Press, Totowa... 

A.G. Mayes and C.R. Lowe, In Methodological surveys in bioanalysis of drugs, vol. 25. Drug development assay approaches including molecular imprinting and biomarkers, E. Reid, H.M. Hill and I.D. Wilson Eds, p. 28 (1998). 

The value of biomarkers to establish the dose- and concentration response curves at the earliest stage of drug development cannot be overestimated. However, it should be recognised that the utility of any biomarker depends at least in part on the expertise of the experimentalists. Long before the study takes place a decision will need to be made about where the study will be placed and who precisely will perform the measurements. Whether assaying the concentrations of a hormone, performing respiratory function tests or measuring receptor occupancy... 

Lee, J.W., Nordblom, G.D., Smith, W.C., and Bowsher, R.R. (2003) Validation of bioanalytical assays for novel biomarkers practical recommendations for clinical investi gation of new drug entities. In Bloom J., and Dean R.A. (eds), Biomarkers in Clinical Drug Development. Marcel Dekker, New York, pp. 119 148. 

Many of the bioanalytical principles applied to drug development in the past arose from the diagnostics industry and clinical laboratory sciences. The application of biomarker assays and data in drug development often differs markedly from those approaches, particularly in the case of novel biomarker assays. It is important, therefore, to clarify definitions and use of terms. 

Assay acceptance criteria for biomarkers do not solely depend on the deliverable method accuracy and precision, as is the general rule in bioanalytical laboratories. Instead, the consideration should be on the assay suitability for the intended applications considering three major factors (a) the intended use of the data during various stages of drug development, (b) the nature of the assay methodology and the type of data that the assay provides, and (c) the biological variability of the biomarker that exists within and between populations. Thus, the first factor helps shape the assay tolerance or acceptance criteria for biomarkers. 

Lee, J.W., Figeys, D., and Vasilescu, J. (2007) Biomarker assay translation from discovery to clinical studies in cancer drug development quantification of emerging protein biomarkers. In Sikora, K. (ed.), Genomics in Cancer Drug Discovery and Development. Advances in Cancer Research Hampton GM, Elsevier, pp. 269 298. 

Many, if not all, of these procedures have evolved over many years and with continuous feedback within the scientific communities around the world. Much of this has been conducted within an organization called the Clinical Laboratory Standards Institute (CLSI) formerly known as the National Committee for Clinical Laboratory Standards (NCCLS). Many guidance documents are available from this organization s Web site (see below) that explain how some of the assay performance characteristics are established for the purposes of diagnostics. A number of these experiments are very similar to, or indeed the same as, experiments we conduct in validating biomarker assays for use in drug development and are listed in Table 7.1. 

This can really be seen as being an assessment of analytical methods in the presence of four different types of components. It is particularly important, and most often challenging, in ligand-binding methods, which do, of course, form the majority of biomarker assays used in drug development today. 

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