Abstract
A
“On average, drug sponsors can spend over 13 years studying the benefits and risks of a new compound, and several hundred millions of dollars completing these studies before seeking FDA's approval. About 1 out of every 10,000 chemical compounds initially tested for their potential as new medicines is found safe and effective, and eventually approved by FDA, making the drug discovery and development process complex, time consuming, and costly.”
The current methodologies are not going to win the day anytime soon. Failures abound and the critical phase of translational medicine is sorely lacking any type of industrialization effort. At the same time there is a tsunami of new data that is drowning us: the sequencing of the human genome(s) and the cancer genome(s), the elucidation of disease-causing mutations and pharmacogenetics, and gene expression profiling. Additionally, genetic and genomic biomarkers and advanced molecular diagnostic tests are being developed at a growing rate. As the scientific community increases its capacity to process this type of data and to interpret this important information, the gap between biological knowledge and therapeutic product development increases each and every day.
This situation calls for new levels of leadership and a catalyzing force to advance a novel strategy to bridge the gaps between biomarkers, rational therapeutic development, clinical studies, and successful product development. This effort will require unprecedented collaborations of thought leaders from many fields, using cutting-edge tools through the creation of new processes by commoditizing and/or franchising various resources, and ultimately crafting new paradigms to reduce the systemic risk of drug development. Core to the paradigm shift will be the following:
A focus on systems change rather than individual diseases, both by scientists as well as disease advocates and industry; Novel partnerships grounded in resource sharing without regard for turf; making decisions on the basis of the goal, not on advancing one interest group, one technology, or one entity or another; and having permeable boundaries; Open access to methods and data, both positive and negative; New knowledge, in both process and content, that is evaluated regularly to iteratively retool the effort, with flexibility and timeliness.
Though there are numerous places within the current enterprise of drug development that must be re-imagined and renovated, genetic testing and molecular biomarkers are ripe candidates for being part of the solution. But there remains a significant cultural, scientific, and commercial divide between the biomarker and diagnostics community of practice and that of the biopharmaceutical and drug-manufacturing communities. Changing this dynamic is so fundamental to any reorganization of the system that aligning these disciplines to advance modern therapeutic development should be the first priority.
Well-characterized samples, clinical trial cohorts, and data registries are critical to the reformation of the drug development system. Innovation in this regard is coming from the growth of biorepositories, information technology, and the social network sector in nascent forms such as Inspire, PatientsLikeMe, the Love/Avon Army of Women, and i[2]y. These new communities will probably eventually supplant the brick and mortar disease-specific advocacy communities of the 20th century. These newly defined and self-organized communities will need technologies, tests, and biomarkers to transform themselves into valuable candidates for clinical trials for drug development. Some of the early linking technologies are already being built in entities such as ClinicalTrials.gov, EmergingMed (EmergingMed.com), Private Access (privateaccess.com), and 23andWe Research (23andwe.com).
The promise and evolution of biomarker development as well as the unique utility at each phase is critical to modern disease research, drug discovery, drug development, safety, surrogate endpoints, risk classification, event prediction, clinical diagnostics, companion diagnostic/therapeutic tests, and therapeutic monitoring are only a cursory example of the compelling importance of this applied science.
There are many types and roles for biomarkers:
Disease Safety Efficacy Toxicity Translational Mechanism Target Dosing/metabolism Staging Selection Surrogate Recurrence Prediction of therapeutic benefit Monitoring Adverse event evaluation
It remains to be seen if biomedical research, with its empha-sis on single disease and single molecule drug development, can capitalize on the emerging network solutions, standardized open data systems, and precision measurement technologies that other industries have successfully integrated to catapult themselves to new levels of adaptive effi-ciency. There is a tremendous amount of work to be done in biomarker and therapeutic development and there is a new sense of collective urgency to get this done right in the here and now.