The MURDOCK Study: a long-term initiative for disease reclassification through advanced biomarker discovery and integration with electronic health records

Abstract

Background: Facing critically low return per dollar invested on clinical research and clinical care, the American biomedical enterprise is in need of a significant transformation. A confluence of high-throughput "omic" technologies and increasing adoption of the electronic health record has fueled excitement for a new paradigm for biomedical research and practice. The ability to simultaneously measure thousands of molecular variables and assess their relationships with clinical data collected during the course of care could enable reclassification of disease not only by gross phenotypic observation but according to underlying molecular mechanism and influence of social determinants.In turn, this reclassification could enable development of targeted therapeutic interventions as well as disease prevention strategies at the individual and population levels.

Methods/design: The MURDOCK Study consists of distinct project "horizons" or stages. Horizon 1 entailed the generation and analysis of molecular data for existing large,clinically well-annotated cohorts in four disease areas. Horizon 1.5 involves creating and maintaining a 50,000-person,community volunteer registry for biomarker signature validation and prospective studies, including integration of environmental and social data. Horizon 2 leverages and prospectively recruits Horizon 1.5 volunteers, and extends the study to additional disease areas of interest. Horizon 3 will expand the study through regional, national,and international partnerships.

Discussion: The MURDOCK Study embodies a new model of team science investigation and represents a significant resource for translational research. The study team invites inquiries to form new collaborations to exploit the rich resources provided by these biospecimens and associated study data.

Keywords: Stratified medicine; biomarkers; biorepository; community registry; disease reclassification; personalized medicine.

Figures

Figure 1

Distinct horizons of the MURDOCK Study. Horizon 1 entailed biomarker discovery in four existing cohorts. Horizon 1.5, launched concurrently with Horizon 1, creates a community registry of 50,000 subjects. Horizon 2 leverages the Horizon 1.5 Registry for validation studies, prospective studies, and to recruit targeted populations. Horizon 3 will expand the study with regional and national partnerships.

Figure 2

The MURDOCK Integrated Data Repository (MIDR). In addition to the clinical data stored in the current version of the MIDR, the next release will include subject consent data and structured metadata for study protocol, biospecimens, -omic, and imaging data. The resource will enable both administrative information retrieval and scientific discovery through hypothesis generation.