Comprehensive Genetic Sequencing in Clinical Care: How to Get it Right

By: Peter Nelson, Senior Business Analyst, Translational Sciences

At UPMC, we are committed to building a health system where the right patient gets the right care, in the right way, at the right time, every time. The “Rights” of clinical management are used to support quality health care decision-making and use of clinical resources. These Rights often include the Right Patient, the Right Rationale, the Right Care or Test, the Right Time, and the Right Response and Follow-Up. As UPMC moves to support innovation in medicine, it is critical that we constantly evaluate new technology and new therapies to deliver the highest level of clinical care.

Although the care management pathways are well established in many clinical situations, comprehensive genetic testing, such as Whole Genome Sequencing (WGS) and Whole Exome Sequencing (WES), remains new territory for many medical providers. Historically, these types of sequencing have been prohibitively expensive, hard to interpret, and without clear impact on clinical care, especially compared to the targeted multi-gene panels developed for distinct clinical cases such as oncology and rare diseases.

The cost of comprehensive genetic sequencing, however, has decreased dramatically over the last decade, making the use of sequencing in the course of clinical care more economically feasible. Furthermore, with specific reimbursement rates for WGS and WES established by the Centers for Medicare & Medicaid, there is increasing support for the use of comprehensive sequencing in specific clinical situations.

However, despite the decrease in costs and increase in clinical interest, there are still many challenges to understand the Rights of comprehensive genetic sequencing within clinical care.

Right Patient and Rationale

For those who don’t specialize in genetic testing, it might not be obvious when a patient could benefit from genetic testing. While WGS or WES can be critical for diagnosis and treatment of some patients, it should not be considered the “one size fits all solution.” Ultimately, the choice to perform WGS or WES lies with the patient and their clinician; however, it is important that testing serves to inform clinical decision-making or to change the course of care. Having a justifiable rationale for testing is also critical in order to obtain reimbursement and avoid undue economic and resource burden on patients and health systems. Although regulatory agencies and professional associations have released guidelines to suggest patients and indications that may benefit from comprehensive genomic testing, many groups acknowledge the need for clinicians to continuously seek the most up-to-date information given the rapid evolution of the field.

Right Test

For genomic sequencing, this consideration includes whether WGS or WES is most appropriate for the patient’s clinical presentation, or if a cheaper targeted panel can accomplish the same ends. In general, the benefit of testing like WGS or WES is the ability to cut through complex clinical diagnostic pathways by having all genetic information at once, rather than sequential use of individual or limited genetic tests. The decreasing costs of sequencing are quickly making comprehensive sequencing economically beneficial over traditional testing. Additionally, as sequencing becomes more common, better tools are being developed to assist with the interpretation of genetic data and the ongoing combination of phenotypic observations with genomic findings. In the right situations, with right test and the right interpretation, broad genetic testing can provide clinical and economic benefit over traditional targeted testing.

Right Time

Testing should be completed with enough time to impact clinical course of care. For situations involving the neonatal intensive care unit and oncology treatment, rapid turnaround of results is often critical for informed decision-making regarding patient care. With new advancements in sequencing technologies and bioinformatic interpretation, WGS or WES can have a similar turnaround time as traditional targeted gene panels. The added benefit of WGS and WES is that results can be reevaluated in the future to derive new insights as research evolves and clinical standards change, which is generally not possible with traditional testing.

Right Response and Follow-Up

Without the correct follow-up with the patient and corresponding change to care, comprehensive testing ultimately provides limited clinical value. A complete review of the data and appropriate patient follow-up or re-engagement is critical, especially given the changing landscape of actionable genetic variants. However, before patient follow-up can be established, health systems need to ensure that physicians are prepared and armed with the knowledge to inform, advise, and follow-up with their patients, either on their own or in collaboration with genetic counselors, especially if broad testing results in unintended, but impactful or actionable genetic findings.

Although there are many more considerations that contribute to the proper use of genomic sequencing in clinical care, getting these initial complexities right requires a collaborative and innovative approach that evolves with the changing genomic and clinical landscape. Evaluation of genomic technologies and adoption into regular practice becomes increasingly important as genomic sequencing continues to become faster, less expensive, and ubiquitous within clinical and direct-to-consumer markets. Through the Translational Sciences division of UPMC Enterprises and the UPMC Genome Center, we are dedicated to using genomic sequencing to enable innovative research and enhance cutting-edge clinical care.