Personalized medicine's goal is to optimize treatment based on genetic variations. Due to recent technological advances, information can now be collected on individual genetic variation quickly enough to allow practical use of the data in clinical practice. Personalized medicine is already known to be beneficial in medication and chemotherapy tailoring. Now, finally, we can screen patients for genetic variations that predispose them to disease, and intervene proactively with preventive treatment and lifestyle adjustments to delay or prevent the onset of disease.

At Northwestern in Chicago, we are actively pursuing this new and exciting field. Our Feinberg School of Medicine works with Northwestern Memorial Hospital (NMH), an 897-bed inpatient and ambulatory care facility, in tight affiliation with the 650-physician Northwestern Memorial Faculty Foundation (NMFF), a specialty faculty practice plan. The school also has a close relationship with Children's Memorial Hospital (CMH) and the Rehabilitation Institute of Chicago (RIC).

We are taking several approaches to incorporate personalized medicine into clinical practice, and to use translational medicine to deliver the benefits of increased genetic knowledge to patient care.

At NMH, a variety of genetic laboratory tests are currently being used. Many of the tests are performed in-house, particularly in the areas of coagulation and hematology/oncology. We send other tests to external reference labs. NMH has an inbound interface from Genzyme (Cambridge, Mass.) to capture those results in a structured fashion, but results from Athena (athenahealth, Watertown, Mass.) and Prometheus (San Diego, Calif.) are scanned into PowerChart (Cerner, Kansas City, Mo.). Ideally, all results would be obtained in electronic structured format through an interface, but since considerable time and expense are required for each interface to an external lab, there is a strong incentive to conduct as many tests as possible in-house.

In the transplant division, the transplant immunology laboratory is using genetic tests to screen for compatibility between patients and donors. For bone marrow stem cells, patients and living unrelated donors are characterized with a high-resolution DNA sequencing assay. With related donors, a genetic test is first conducted, which allows multiple samples to be characterized at low cost. A genetic test is also used prior to solid organ transplantation to characterize the compatibility of the patient and donor.

Genetic typing data from these assays will typically be stored in HistoTrac (SystemLink, Washington, D.C.) and the Online Transplant Tracking Record (OTTR) computer systems used in the transplant lab, and is not sent to the Cerner or Epic EMRs. Raw instrument data is stored locally with the instrument software.

The Northwestern campus is developing and utilizing an Enterprise Data Warehouse (EDW), which is intended to function as a consolidated and standardized clinical data repository of all Northwestern patients. The EDW combines patient data from the NMH, the Feinberg School of Medicine, and NMFF, and currently stores details on over 2 million patient records. The EDW has given us a secure and efficient means of using clinical data in translational research.

In addition to other uses, the EDW is used to create standardized disease registries. These registries will play an increasingly important role in phenotyping and genotyping patients before they manifest symptoms of a particular disease. The EDW will also soon be used to create medication registries to track patients' specific reactions to medications that are known to have a strong genetic influence.

The NUgene Project (http://www.nugene.org) is a biobank of several thousand DNA data samples coupled to EMR data from participating patients at Northwestern's affiliated medical centers. Study participants' DNA samples are combined with data from a one-time questionnaire and health data from participants' EMRs for their ongoing care at the medical center.

This NUgene project is being used to help identify genetic mechanisms underlying common diseases, with the intention that information gained will ultimately help integrate genetics into clinical care. The NUgene database securely stores the data representing the genotype and questionnaire data, while the EDW stores medical record information representing the phenotype generated through routine clinical care. An additional system, NOTIS, Northwestern's clinical trial information system, contains the participants' protected health identifiers and is used to link the NUgene and EDW databases via an encrypted connection. A combination of EDW data and self-reported questionnaire data is used to select subpopulations of NUgene participants for individual research studies.

Research use of NUgene requires approval by a sample access committee, in addition to the typical IRB approvals.

Leveraging the campus-wide NUgene resource, Northwestern has joined the national Electronic Medical Records and Genomics Network (eMERGE). The goal of eMERGE (http://www.gwas.net) is to test the ability to leverage EMRs and DNA biobanks for the conduct of genomic research. Northwestern's eMERGE efforts currently focus on type 2 diabetes. Using the EDW as an EMR-mining platform, an algorithm has been developed that allows selection of EMR records from individuals with and without type 2 diabetes for the study. Corresponding DNA samples from NUgene biobank participants will then be used to characterize the genetic variations present in the selected study populations.

It is hoped that this and other studies from the eMERGE network will not only contribute to our understanding of disease, but that lessons learned from the consortium will also begin to set the stage for integration of genomics into EMRs to achieve the long-term vision of personalized medicine.

For a number of pediatric studies, CMH has begun to use the Xenobase software system, which is produced by the Van Andel Research Institute (Grand Rapids, Mich.). The Xenobase software integrates directly with data from EMR providers like Cerner and Epic, and provides an external translational research computing environment. Xenobase can directly accept data from genetic microarray experiments and includes its own statistical processing capability. It is being used in a brain tumor study to help identify genetic markers that might identify patient subpopulations and predict drug resistance.

Another study at CMH is utilizing Xenobase to identify environmental, genetic, and other factors that might be related to food allergies. And another project is using Xenobase to identify factors that affect outcomes in critical care.

Currently, the use of genetic information in direct patient care is primarily limited to individual genetic tests, with a resulting minimum amount of genetic data to store and process. The primary focus at present is to have all genetic test results produced in structured format for ease of storage and analysis, rather than using data in text format, or scanned images. Structured data will be necessary to allow the use of decision support systems that can properly utilize genetic data in combination with medication lists and patient medical history.

In the next three years, the cost of determining an individual's complete genetic content will probably drop to around $1,000. At that price, significantly more genetic data could be used for prevention and diagnosis. Northwestern is in discussions with commercial DNA screening services to endorse and offer these commercial services to Northwestern patients who are “early adopters” in the quest for better understanding the relationship between their health and their personal genetic biases.