Why we need to unlock the full value of genome sequencing

Genome sequencing is rising in popularity, and for good reason. It can help identify the genetic cause of disease, guide more precise management and inform tailored treatment options. At The Hospital for Sick Children’s (SickKids), it’s a cornerstone of the Translational Genomics strategy, part of the Precision Child Health movement to more fully integrate genomic medicine into care.

But as genomics becomes more commonplace, supporting literature has been shy about measuring its value beyond yielding a diagnosis.

In a review recently published in Nature Medicine, an international team of researchers calls for more robust evaluation and implementation methods that can ensure genome sequencing becomes an equitable and sustainable tool for the future.

We asked two of the contributing researchers, Dr. Robin Hayeems, Senior Scientist in the Child Health Evaluative Sciences program and Dr. Michael Mackley, Resident Doctor in Medical Genetics at SickKids, for their insights.

Why do we need a more comprehensive approach to measuring outcomes in genomic sequencing?

Hayeems: Traditionally, the value of genomic technologies has been measured almost exclusively by their ability to deliver a diagnosis, known as diagnostic yield. This is because genetic testing and evaluation lived predominantly with laboratory scientists at first, whose expertise naturally centred on technical and diagnostic metrics. Diagnostic yield is important but doesn't tell the whole story. As these innovations mature and their clinical, social, and economic implications grow, the need for broader measurement becomes increasingly clear. Now we have multidisciplinary teams and new measurement tools that make it possible, and necessary, to measure the value of genomic technologies in a more holistic, meaningful way.

Mackley: Unlike treatments where impact can be easily quantified through improved survival or symptoms, genomic tools often provide diagnoses that have many different impacts, some immediate and some far off. This has made the value of it much harder to capture with traditional measures. Now we have the systems, workforces, and data in place to support broader evaluation, which allows us to collect the robust evidence that decision-makers need to make funding and policy decisions that ensure these technologies become a sustainable part of our health system.

What's the benefit for patients and families?

Hayeems: Genetic diagnoses can provide answers, guide therapy, and connect them to support and community. The latter is especially impactful for patients with rare disease who, with a diagnosis, can tap into a community who might share similar experiences. By broadening how we measure outcomes, we ensure that the value of genetic testing, from clinical impact to personal utility, is recognized and that patients and families are genuinely heard in the process. 

Mackley: With genome sequencing, patients are getting diagnosed sooner, which brings clarity and comfort and can reduce unnecessary procedures and additional testing. Even when there aren’t necessarily treatments available, you can see that feeling of relief with a patient and family when they gain an understanding of what’s going on.  

Why collaborate internationally?

Hayeems: When you’re in a rare disease world, you need to pool data to make statistically meaningful findings. That means we need systems that can share data and outcomes seamlessly. This is a challenging feat, but when we can do it, it makes a huge difference for our understanding of the value of genomics and allows us to respond effectively to the benefits and challenges new innovations can bring. The timing is right for this work. We now have, especially in Canada, emerging systems for data sharing and the attention of policy and funding decision makers who have an appetite for more comprehensive approaches to health-care technology assessment.

Mackley: If we don’t expand our understanding of the value of genomics, we risk undervaluing it on the whole, or investing in genomics in clinical domains where the value isn’t actually the greatest. Instead of doing sequential implementations and learning about issues one at a time, we can share our lessons with each other and condense our timeline around implementation. Essentially, we’re accelerating progress and ensuring that system changes happen faster and more effectively.

What is SickKids’ role in this work?

Hayeems: SickKids combines a legacy of innovation with a growing emphasis on outcome measurement, policy relevance, and collaborative research. With strategic investments and specialized research programs like Genometrics, within Child Health Evaluative Sciences program, we’re a strong voice on the world stage to help advocate beyond traditional discovery.

As part of these efforts, Hayeems’ lab developed C-GUIDE (Clinician-reported Genetic testing Utility InDEx) and P-GUIDE (Patient-reported Genetic testing Utility InDEx), validated tools that captures how genetic testing affects patient care. These tools are in use in many countries around the world.

Mackley: SickKids is not the kind of organization that focuses on the lowest hanging fruit; we’re always looking more holistically. The Precision Child Health movement is a great example of this. We’re looking at integrating personalized and precision care across our system, and a big part of that is acknowledging the impacts of genomics that go far beyond patients getting a diagnosis.

Hayeems and Mackley collaborated on the review with researchers from the Murdoch Children’s Research Institute in Melbourne, Australia; Harvard Pilgrim Health Care Institute in Boston, US; Great Ormond Street Hospital for Children in London, UK; La Ka Shing Faculty of Medicine in Hong Kong, China; BC Cancer Research Institute in Canada; and the RILD Wellcome Wolfson Centre in Exeter, UK.

Together, the research team aims to support the evidence base, implementation systems, cross-border collaboration, and measurement tools needed to evaluate the value of genetic testing in a rigorous, harmonized, and patient‑centred way.