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Clinical Sequencing: Beyond Exploration 

June 7, 2016

Often, the advances made in technologies for genome sequencing are cited as a pivotal achievement that will change medical practice in important and productive ways. In fact, I am often a person making such claims, and I stand by them. But that is not to say that I think the path forward will be easy - rather, there are many issues that need to be explored in bringing genome sequencing into medicine. NHGRI has a number of major research programs investigating those issues, a key one being the Clinical Sequencing Exploratory Research (CSER; pronounced 'caesar') Program.

In 2011, NHGRI launched CSER with co-funding from the National Cancer Institute. Two years later, additional research projects and a Coordinating Center were added, and nine projects formerly comprising the NHGRI-funded Return of Results Consortium and the NHGRI Intramural ClinSeq  project were brought into the fold. This impressive national consortium (comprising clinicians, scientists, bioinformaticians, economists, legal scholars, and ethicists) explores the use of genome sequencing to improve patient care.

CSER is capitalizing on NHGRI's long-standing experience in genome sequencing and analysis to explore the feasibility and best uses of genomic information for medical care. CSER's efforts have helped to guide the development and sharing of genomic approaches that work in clinical settings. CSER investigators have also made progress in exploring the ethical, legal, and psychosocial implications of bringing genomic data into patient decision-making processes.

In its first five years, CSER has made important contributions in identifying major opportunities and challenges with clinical genome sequencing. By recruiting over 5,700 research participants and by studying the interactions among patients, physicians, and clinical laboratories, CSER is helping define what we do and do not know about the clinical utility of genomic information (e.g., which genomic information is really useful to the patient and healthcare providers). CSER researchers have helped develop 'best practice' guidelines about how to increase consistency of genomic variant interpretation, how to disclose research findings in pediatric settings, how to display genomic information in electronic health records, and how to have doctors share tumor genome-sequencing results that may also be heritable. Even with these significant contributions, CSER's work is not done.

To examine the remaining challenges, NHGRI held a program planning meeting last year ("Integrating Genomic Sequencing into Clinical Care: CSER and Beyond") and issued a Request for Information ("Maximizing Impact of a Potential Future Program in Clinical Sequencing"). Both of these sought input from the research community about future research needs in the area of clinical genome sequencing. That input helped us to formulate a plan for a next phase of CSER, which will be called "Clinical Sequencing Evidence-Generating Research (CSER2)."

CSER2 aims to identify and analyze important consensus measures in 10,000 participants, thereby generating evidence about the utility of genome sequencing for clinical care. In doing so, CSER2 will strive to generate best practices that can be readily implemented, including for patients of diverse ancestries and socioeconomic situations. The program will investigate the most important interactions among patients, family members, health practitioners, and clinical laboratories that influence the use of clinical genome sequencing, as well as identify and address real-world barriers to integrating genomics into a wide range of healthcare systems.

CSER2 aims to improve how we collect and communicate information about a patient's health as findings from genome sequencing are generated, including understanding the impact of these findings on health-related outcomes. CSER2 will develop and test approaches to support clinical decision-making with genomic data, so that healthcare professionals have the tools for making the best clinical decisions about their patient and, potentially, their family members.

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CSER2 also plans to engage a variety of stakeholders (including professional societies, insurance payers, and regulatory agencies) for examining relevant genomic issues related to clinical practice, policies, regulations, and healthcare reimbursement. As with the initial CSER Program, CSER2 will have an ethical, legal, and social implications (ELSI) research component, in this case studying issues that arise uniquely in diverse populations (and in healthcare settings outside of academic medical centers) and those that are relevant to health disparities.

NHGRI, along with the National Cancer Institute and the National Institute on Minority Health and Health Disparities, plans to fund 3-6 clinical research sites to pursue the main CSER2 goals, 3-6 clinical sites with a focus on increasing the diversity of participants, and a coordinating center. In addition, NHGRI plans to fund 5-7 investigator-initiated novel research projects that address the general CSER2 goals. These CSER2 grants are expected to be awarded next year.

To access the CSER2 Requests for Applications, see Clinical Sites, Clinical Sites with Enhanced Diversity, Coordinating Center, and Investigator-Initiated Projects. Applications for each of these components are due by August 5, 2016. For more information about CSER, see genome.gov/27546194/clinical-sequencing-evidencegenerating-research-cser2//clinical-sequencing-exploratory-research// and cser-consortium.org/.

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Posted: July 5, 2016

Last updated: July 05, 2016