In the rapidly advancing field of genomics, population-based screening for genetic conditions has gained significant attention from large, established healthcare organizations. Nearly ten years ago, the Centers for Disease Control and Prevention (CDC) designated three genetic disorders as Tier 1 for having strong evidence and notable potential to improve public health: Lynch syndrome, familial hypercholesterolemia (FH) and hereditary breast and ovarian cancer (HBOC) – each of which is associated with a high lifetime incidence of cancer or cardiovascular disease and has proven preventive interventions.

Despite this, a common question from providers and health system leaders is whether or not population-wide screening of CDC Tier 1 conditions is cost-effective and will make a difference. After all, while cost-effectiveness analyses have been conducted for each of the CDC Tier 1 conditions individually in the past, the impact of screening for all three together has been uncertain, until now.

In a recent study published in May 2023, researchers demonstrated the clinical and economic value of population screening by modeling a variety of use cases in an unselected U.S. population. The results show that, depending on test cost, this approach is cost-effective in US adults younger than 50 years if patients have access to preventive interventions.

Preventing Diseases and Enhancing Quality of Life

The researchers modeled various screening parameters to determine the effectiveness of population screening on preventing disease and increasing survival. They compared the cost-effectiveness in U.S. adults aged 20 to 60 years with usual care where those with high-risk family history would receive guidelines-based genetic or phenotypic testing.

A decision analytic model including 100,000 unselected 30 year olds resulted in the prevention of 101 cases of cancer and 15 cardiovascular events, yielding an incremental cost-effectiveness ratio (ICER) of $68,600 per Quality-Adjusted Life Years (QALY) gained, which is well under the commonly used US willingness-to-pay threshold of $100,000-per-QALY.

In other words, the additional cost incurred to gain a quality-adjusted life year for a patient from implementing population screening (in place of guidelines-based testing) suggests an effective use of resources.

The analysis yielded an incremental cost-effectiveness ratio of $68,600 per QALY gained.

In addition, screening adults aged 30-, 40- and 50-years old was cost effective in 99%, 88% and 19% of simulations, respectively, at the base-case test cost. The results also supported pairing cascade testing for first-degree family members with population screening to efficiently identify additional persons who could benefit from intensified screening or surveillance.

By identifying individuals at risk earlier, interventions can be implemented to prevent or mitigate the onset of severe disease associated with these highly penetrant and actionable genetic conditions. These findings underscore the significant impact of population genomic screening on public health and individual well-being.

Key Criteria for Success

While the results were robust, several criteria must be met to achieve cost-effective implementation, including:

Gene Selection

Population genomics programs should start with genes and variants with strong evidence of pathogenicity to ensure the highest level of accuracy and reliability in identifying at-risk individuals. This criterion is achieved by starting with CDC Tier 1 conditions.

Affordable Test Cost

Testing must be affordable to make population screening viable on a larger scale. To achieve this, health systems should select sequencing partners that have designed their labs like Helix, with the automation needed to achieve economies of scale and optimize costs to make quality, cost effective testing both feasible and sustainable.

Furthermore, genomic sequencing with Helix enables a Sequence Once, Query Often^® model. This means that once an individual has been sequenced, the data is available to be reanalyzed for additional use cases, without requiring another blood sample. This enables health systems to lower costs, while improving workflows and patient engagement.

Availability of Counseling and Recommendations 

High-risk individuals identified through screening require appropriate counseling and evidence-based recommendations. To avoid the risks of false reassurance, individuals with a negative result (which will be >98% of all who are tested) should also receive effective communication that standard cancer and cardiovascular screening tests are still recommended. Ensuring that your population genomics program has access to the infrastructure that will provide comprehensive support is an important consideration in order to provide individuals the guidance necessary to manage their genomic risks.

Access to Longitudinal Care 

Effective care management of genomic risks is crucial for ongoing prevention and early intervention. Enabling longitudinal care and ensuring individuals receive continuous support and monitoring tailored to their specific genomic risks throughout their entire lives is a critical part of programs partnered with Helix. Again, an individual’s genome can be queried as new genetic associations are made to support their clinical care over time.

Conclusion

A cost-effectiveness analysis of population genomic screening for CDC Tier 1 diseases has demonstrated its value in identifying at-risk individuals within the US population. By simultaneously testing for all three conditions, health systems can identify at-risk individuals earlier, reduce healthcare costs, and improve patients’ quality of life.

Through Helix’s real-world experience with Renown and the Healthy Nevada Project, we’ve seen that 1 in 75 patients screened carried pathogenic variants for the CDC Tier 1 diseases, 90% of which would have remained undetected through routine care. This new study's findings challenge the traditional approach of relying solely on family history for genetic testing and highlights the benefits of population screening in its ability to be both cost-effective and make a meaningful difference for patients, clinicians and health systems across the US.

Helix has implemented large-scale programs of 100K+ participants across 7 states and continues to expand as more systems recognize the value of adopting this approach to precision medicine. As a leading provider in this field, Helix offers support with gene selection criteria, affordable testing through our automated laboratory, access to comprehensive counseling, and longitudinal care management through its partners. In addition, all programs operate under a research program that supports the collection of real-world data to demonstrate the effectiveness of these programs and drive new translational discoveries that will continue to benefit these populations over time. By partnering with Helix and leveraging our end-to-end genomics infrastructure, health systems can unlock the full potential of population screening.