Shaping the New Era of Systems-Based Medicine
Putting data in the hands of researchers, clinicians
A cornerstone of the systems medicine vision and a key priority for Howard J. Federoff, MD, PhD, executive vice president for health sciences at Georgetown University Medical Center, and Louis M. Weiner, MD, director of Georgetown’s Lombardi Comprehensive Cancer Center and co-chair of the systems medicine design team, G-DOC is a large-scale repository of cancer data, ranging from clinical information to genomic and proteomic data to tissue sample analyses. The hope is that researchers will be able to access enormous amounts of biomedical data from heterogeneous sources that have been integrated into a user-friendly portal.
The objectives are mainly two-fold: to enrich clinical practice according to systems medicine principles and to generate accessible and searchable information to seed Georgetown’s Drug Discovery Program, led by Milton Brown, MD, PhD.
Subha Madhavan, MS, PhD, who joined the Medical Center last year as its first director of clinical research informatics, is one of the key architects of the G-DOC infrastructure.
“Cancer statistics reveal that more than half a million cancer deaths occur annually; we need to put the tools in the hands of the decision makers — physician-scientists who are generating new hypotheses for their next clinical trial or study,” Madhavan says. “Not just tools, but user-friendly tools that do not have a steep learning curve.”
She and her team are working with researchers to coordinate data from three pilot studies: the Familial Cancer Registry; a translational breast cancer program combining two large data sets; and a colorectal cancer study involving roughly 100 samples provided by Indivumed.
“Biology is a very rich science and the ability to connect data sets will unquestionably enable some excellent research. Yet, as ambitious as our goals are, we want to be concrete and scope the project well,” Madhavan says. “G-DOC cannot be everything to everybody or else it will be a failure. We need to make sure that the pilots are used well so that G-DOC becomes an expandable systems medicine platform for other studies at GUMC.”
In the past, studies were rarely conducted in collaboration between various research groups. This means that until recently, data compiled by each researcher served as that group’s only resource hub.
Access to broad datasets and new research tools is part of a nationwide initiative advanced by the National Cancer Institute in the form of the Cancer Biomedical Informatics Grid, or caBIG. The mission is to develop a collaborative information network that shares research data across many investigators and institutions.
G-DOC will take advantage of standards and best practices from caBIG and other large-scale informatics projects to help integrate the wide variety of patient data it will hold.
The unification of large amounts of data is one of the largest challenges facing G-DOC. Madhavan’s team must diligently match fields in one database to fields in another, ensuring that units of measurement, timing, semantics and hundreds of other factors are consistent. This is in addition to the obstacles common to any other large-scale project, such as limited resources and a high learning curve.
For now, all of the data will reside in one main server – housed at Georgetown. Yet Federoff acknowledges that, as the systems medicine vision takes root, the volume of information that needs to be gathered, coordinated and then collapsed so that it might eventually be useful in a clinical setting is more than Georgetown can handle alone.
“The dimensionality of the data is staggering on an individual patient level. I don’t see Georgetown ever being a huge data warehouse. That will probably have to be offsite – either here or elsewhere in the country – as long as the connectivity and security is guarded,” he says.
Ethics of Systems Medicine
Patient privacy and data security are of paramount concern to the G-DOC team, according to Madhavan, and the pilot studies will assist her team with the implementation of the security infrastructure. She said the G-DOC working group, which meets every other week, includes experts from the Georgetown University Institutional Review Board and University Information Services who are particularly interested in privacy issues.
“G-DOC is a research database, and is designed to carry only completely de-identified information in the database,” she says.
The privacy protection issue is one of an array of ethical concerns that is frequently raised when Federoff discusses systems medicine – both within the university and to outside audiences.
Yet it is not the only issue, as Federoff readily acknowledges. Questions about bioethics, genetic discrimination and who would pay for genetic and other testing in a true systems medicine era are also quite common, although they are questions for which there are still no easy answers.
“We have realized over the past year that policy and ethics have to be integral and cannot be considered tangential or peripheral,” Federoff says. He notes that GUMC’s Kevin Fitzgerald, SJ, PhD, an expert on medical ethics, a biomedical researcher and a Jesuit priest, will be charged with working on these delicate issues with the legal, policy and legislative communities.
“That work is going to be so important to do well first because current genetic discrimination law is inadequate to address many of the things we envisage,” Federoff says.
As for who is going to pay to make these sweeping ideas a reality, Federoff says he believes the private sector must get involved. Given the rising cost of health care for employees and retirees, the for-profit sector has a financial interest in working with academic institutions such as Georgetown to fund projects that can demonstrate the utility of systems medicine, he explains.
The university is also hoping that federal funding – including money made available by the stimulus package – will play a key role in financing research and technological upgrades.
“These are unprecedented times financially because of the severity of the crisis and the rapidity with which it seems to be moving, but they are also unprecedented in terms of where opportunities lie,” Federoff says. “Those that emerge from this having a stronger business model are going to have an accelerated path to whatever the new [future] is.”
By Lauren Wolkoff, excerpted from the 2009 Spring/Summer issue of Georgetown Medicine Magazine.
