CSER consortium ends after twelve years of groundbreaking research

Since 2011, the Clinical Sequencing Evidence-generating Research (CSER) consortium has worked to offer patients and their families, healthcare systems, and policymakers a clearer understanding of the opportunities and challenges of implementing genomic medicine in diverse populations and settings. After twelve years of groundbreaking research about advancing genomics in the clinic, the CSER program ended in June 2023.

Over the past two decades, the power of genome sequencing has become evident in disciplines like biology, evolution, forensics, and ancestry. But one of the most relevant areas for humanity is the use of genome sequencing in medicine; that is, genomic medicine (a growing medical discipline that involves using a person's genomic information as part of their clinical care). However, there are many potential barriers to implementing genomic medicine, and the CSER program has conducted research aiming to overcome these barriers.

The first phase of CSER, then called the Clinical Sequencing Exploratory Research program, began when NHGRI partnered with the National Cancer Institute (NCI) to fund six research sites to ease the adoption of genome-sequencing methods in medicine, guide the development and dissemination of best practices for the integration of genomic information in clinical care, and examine the ethical, legal, and psychosocial implications of bringing genomic data into clinical decision-making. This included, for example, evaluation of the risks and benefits associated with the return of incidental findings and information on genomic variants of uncertain effect.

In mid-2013, the CSER consortium added three more clinical sites and one coordinating center in addition to incorporating the nine projects formerly comprising the ELSI Return of Results Consortium. Investigators from the NHGRI intramural ClinSeq™ project also participated. In August 2017, NHGRI partnered with NCI and the National Institute on Minority Health and Health Disparities (NIMHD) to launch the second phase of CSER, renamed the Clinical Sequencing Evidence-Generating Research consortium. CSER researchers moved from "exploratory" research to "evidence-generating" research, focusing on accelerating the diagnostic process and investigating what is effective in improving outcomes and patient care. To broaden the applicability of the generated evidence, CSER researchers emphasized the inclusion of diverse populations (i.e., populations that traditionally experience health disparities) and populations that receive clinical care outside of specialized academic medical centers.

The second phase of CSER included six clinical sites, the NHGRI intramural ClinSeq™ project, and a coordinating center. As of June 2022, CSER phase 2 had recruited < 5,200 participants, 75% of whom were from underserved populations.

Although funding for CSER is now over, investigators are still working to write manuscripts addressing several topics that represent well the overall goals of the program. These topics include clinical utility of returning genomic testing results, experiences with family communication of genomic test results, challenges with reporting incidental findings for pediatric patients, resources required to implement new genetic testing tools, pediatric neurodevelopmental phenotypes, and engaging underrepresented stakeholders in genomic research.

After its dozen years of productive work, CSER's legacy includes many notable accomplishments. The program embedded multiple disciplines in the implementation of genomic medicine and engaged diverse patients and healthcare settings. It helped to create standardized genome sequencing practices and increased knowledge of how genomic variation influences health. It examined how clinical management changes based on new genomic information and how such information leads to improved health outcomes.

Since its inception, CSER has aimed to generate evidence supporting the clinical utility of genome sequencing, with a major emphasis on diverse patient populations and healthcare settings. It is largely regarded as an exemplar among the genomic medicine research programs funded by NHGRI. While the funding for CSER has ended, the type of research it conducted and the clinical practices it advocated for continue to be widely disseminated.