Introduction

Biomarkers have entered the drug development process with great fanfare, with the impression that this is the first time for a new approach. Projections of solving virtually all major issues faced in drug development, and the potential of new technologies revolutionizing medicine, have been promised by many specialists. In reality, biomarker assays represent the logical progression and integration of laboratory techniques already available within clinical pathology and biochemistry, with additional methods arising from new technologies such as molecular biology, genomics, proteomics, and metabonomics. The emphasis on biomarkers as a new approach often has lead to expectations that the ideal biomarker must be novel and/or exotic. To answer the pertinent questions during drug development, teams often embark on the quest for the "unicorn" of biomarkers, sometimes resulting in the best and most practical test being overlooked as the search progresses for elusive methods.

When working with drug development teams, especially those with limited hands-on experience in biomarker applications, it is imperative that the business need and scientific rationale for including a biomarker in the development plan be elaborated prospectively. By clearly defining both the question(s) to be answered and how a biomarker will advance the new drug 's development, the likelihood of successful implementation to advance the compound and save time and laboratory resources can be dramatic. In most instances the most expedient biomarker approach will be identified by focusing on what is necessary to advance the compound at its particular stage of development, independent of how that parameter will be measured. Establishing precisely what is needed versus what would be nice to have may reveal opportunities not initially obvious to all participants.

Building a new biomarker on an emerging technology generally should be a last resort. Acceptance, reproducibility, quality control, standards, automation, and assessing laboratory-to-laboratory differences become exponentially more complex to characterize with the novelty of technology and lower numbers of groups using those approaches. For translation of a potential biomarker from the bench to the bedside, simpler in all aspects is preferable. Simpler tests to administer and evaluate do not mean less scientifically sound or relevant, and can provide a more solid foundation for acceptance in clinical and regulatory environments. This is not to say that the new technologies aren't braving new territory and having a significant impact on drug safety and development [1]. The emphasis of this chapter is to show how casting a wide net for ideas and approaches can expedite a compound's progress and improve decision making, keeping in mind that even less novel technologies will often be the best choice.

Under ideal conditions, and in the instances where the quest is for a decision-making biomarker, there should be solid prospective agreement to actually affect the drug' s progress based on the biomarker results. To that end, scientists should keep in mind that the primary purpose of biomarkers is to enable better decisions. A better decision is one that can be made more confidently, earlier, less invasively, more efficiently, or the test is transferable to reference laboratories as the drug enters phase II or later. Therefore, it is essential that people supporting preclinical and clinical teams focus on the test(s) that aid in definitively graduating a compound to its next stage of development or to prove nonviability of the development efforts and compound attrition. This needs to be done without concern as to whether the biomarker derives from exciting new technology or is a new application of an established method using conventional science. In reality, if a team will not expedite, realign, or terminate a compound's development based on the bio-marker results, inclusion of a non-decision-enabling biomarker is unlikely to serve a purpose other than to increase costs or complicate study design.

Sometimes the appropriate biomarker is a "unicorn" (exciting, rare, and exotic), but more often it is a "horse" (understood, generally accepted, and available) or a "mule" (proven performance, hybrid, and versatile). In bio-

marker selection, the primary consideration must be whether the test(s) is the best solution for the situation at hand. As a part of the biomarker development package, the biological rationale and significance (as understood at that stage), in addition to confidence in the platform, have to be evaluated. Another important factor is time; the development of a novel biomarker can be as complicated and time consuming as developing a new chemical entity. This can be essential criteria in circumstances where multiple companies are working in the same areas or patent timelines are not ideal. Identification, development, testing, characterization, and scaling of a new biomarker, for any one stage of the drug development process, generally requires at least six to nine months. By looking beyond the experience base or capabilities of one group or laboratory, it may be that your search for unicorns ends most appropriately by locating a horse residing in the stable of someone else. This chapter highlights examples of unicorn, horse, and mule biomarker approaches.

Project Management Made Easy

Project Management Made Easy

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