How the biopharmaceutical industry uses molecular imaging.

How the Biopharmaceutical Industry Uses Molecular Imaging O ver the past decade, biomarkers have been recognized as a critical element needed to improve predictability and efficiency in the process of developing more effective, more affordable, and safer therapeutics for patients. Biomarkers can provide information critical to both internal decision making (e.g., establish presence of target, evaluate biological/clinical populations, select dosages for later-phase trials, stratify study populations, and conduct interim analysis of efficacy and/or safety) and establishing efficacy and safety data for regulatory approval as a substitute for a clinical characteristic or variable reflecting patient feeling, function, or survival (i.e., as a surrogate endpoint). This presentation reviews the ways in which the pharmaceutical industry uses imaging as a biomarker, including what is needed from the molecular imaging community. The drug discovery and development process is more challenging today than ever before. Only a small fraction of agents pass successfully through the evaluation processes, and an even smaller fraction make it through the approval process and eventually to clinical applications. Of 10,000 compounds screened, only 100 are evaluated in animals, only 10–14 advance to studies in humans, and only 1 is likely to be marketed. This entire process can take 10–18 y and cost $800 million or more. The biggest needs in drug discovery today directly address the complexity and cost involved in the current pipeline. We need to find ways to shorten the overall timeline, reduce attrition, and decrease the cost. The U.S. Food and Drug Administration (FDA) addressed 1 approach to this triple need in documentation issued in 2004 on its Critical Path Initiative: ‘‘A new product development toolkit—containing powerful new scientific and technical methods such as. . .biomarkers for safety and effectiveness. . .—is urgently needed to improve predictability and efficiency along the critical path from laboratory concept to commercial product.’’ The FDA Critical Path language went on to describe the content of this toolkit: ‘‘The new tools will match and move forward new scientific innovations and will build on knowledge delivered by recent advances in science, such as bioinformatics, genomics, imaging technologies, and materials science.’’ Before discussing the ways in which the biopharmaceutical industry is approaching the development of biomarkers for medical imaging, it is important to define the terms we use. In a rapidly developing field, technical terms sometimes take on a life of their own and become laden with shorthand that is specific to a single field or interest group. The key terms for this discussion as defined in 2001 by the Biomarkers Definition Working Group are: • Biological marker (biomarker): Objectively measured indicator of biological/pathobiological process or pharmacologic response to treatment; • Clinical endpoint: Characteristic or variable that reflects patient feeling, function, or survival; and • Surrogate endpoint: Biomarker intended to substitute for a clinical endpoint (predict benefit or harm) based on epidemiologic, therapeutic, pathophysiologic, or other scientific evidence.