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PGx-Guided Depression Treatment Could Save Canadian Province C$956M Over 20 Years, Study Suggests

Prescription capsules and tablets of various shapes and colors arranged in the shape of DNA on a green background

NEW YORK – Incorporating pharmacogenomic testing to inform routine care of patients with depression could save the public health system in Canada's British Columbia province C$956 million over 20 years, according to a study published in the Canadian Medical Association Journal on Tuesday.

There are more than 35 antidepressants available to patients in Canada; however, patients often have to try multiple drugs and doses before finding the treatment that works for them.

According to previous research, patients may try up to four antidepressants before symptoms subside, with only one-third staying with the first medication they're prescribed. Pharmacogenomics offers a possible solution by tailoring prescription choices according to how an individual patient will metabolize antidepressants based on variations in their genes. Supporters of PGx testing in this setting believe it can shorten the time it takes for a patient to find a best-fit treatment and reduce their chances of experiencing adverse events from inappropriate medications. Variants in the CYP2C19 and CYP2D6 genes, in particular, are associated with how patients metabolize antidepressants.

However, the provincial authorities within Canada's public health system currently don't fund PGx testing to personalize treatment with antidepressants.

In an effort to estimate the impact to the Canadian province should it offer such testing, researchers led by co-senior authors of the new paper, Stirling Bryan, a professor at the University of British Columbia's school of population and public health, and Jehannine Austin, a professor in the psychiatry and medical genetics departments at the University of British Columbia, modeled outcomes and the associated cost of treating thousands of patients with and without PGx testing.

Researchers projected the healthcare journey, from diagnosis to after treatment, of nearly 200,000 adult patients with moderate to severe depression in British Columbia with and without PGx-guided treatment over a 20-year period. In their modeling, they factored in patients' demographics, the progression of their depression, treatments, adverse events, hospitalizations, and mortality by drawing on healthcare administrative data, outcomes from clinical trials, and input from a panel of clinical experts. The model accounted for 40 different medications and other treatment options, such as individual psychotherapy and electroconvulsive therapy (ECT). Notably, investigators also included two patients in the model design process, who weighed in on modeling assumptions and limitations.

Using this model, researchers estimated costs, years of life, and quality-adjusted life-years (QALYs) for the projected patients over two decades, to ensure the results incorporated downstream outcomes. They found that a program offering PGx testing to adult patients with depression could save the health system in British Columbia C$956 million overall over 20 years and, on a per-patient basis, save C$4,926, add 0.064 years of life, and add 0.381 QALYs compared to treatment without PGx. The savings were primarily due to the fact that PGx-guided treatment was associated with 37 percent fewer patients with treatment-resistant depression. Additionally, the model showed that PGx-informed treatment could decrease the use of more resource-intensive options like psychotherapy by 22 percent and ECT by 28 percent. In the paper, PGx-guided treatment was also estimated to result in 1,869 fewer deaths and 21,346 fewer hospital admissions over 20 years.

"All people with major depression deserve to feel hopeful about their life," Linda Riches, one of the patient partners in the study and a patient who has lived with major depression for more than 30 years, said in a statement. "Genetic testing may give them the opportunity to know what treatment they need," and not what 10 they don't need.

PGx-guided care added C$121 million in test-related costs and C$524 million in increased episodic care; however, this additional spending would be offset by decreasing the cost of treatment-resistant depression by C$1.6 billion, the model showed. Based on this, the researchers predicted that the healthcare system would recoup its initial investment to establish a PGx testing program after two years.

"These findings not only point to major cost savings for healthcare systems, but also to alleviation of some of the current human resource challenges in healthcare," Bryan, Austin, and colleagues wrote in their paper. "Through the adoption of pharmacogenomics, the opportunity likely exists to reallocate limited resources to other parts of the health system and deliver further benefits to other patient groups."

The study was funded by the nonprofits Genome BC and Genome Canada, and Michael Smith Health Research British Columbia, the Canadian province's health research agency. Genome BC wanted to develop an "unbiased review and analysis of the clinical effectiveness and cost-effectiveness of pharmacogenomics for depression," given rapid advancements in PGx research, said Shahzad Ghanbarian, first author on the paper and a mathematical modeler and health economist at the Vancouver Coastal Health Research Institute's Centre for Clinical Epidemiology and Evaluation. That's one reason why the research involved investigators across multiple disciplines, including public health, genetics, and mathematics.

This is the first time the team has conducted a cost-effectiveness analysis for PGx testing, but Ghanbarian said they are open to conducting similar analyses on the impact of testing in other medical areas or in other geographies.

Ghanbarian and coauthors also recognize that additional work is needed to understand and establish how to best implement such PGx testing into care, including how to store data and determine which clinicians are best suited to administer testing and deliver results.

"Our study offers valuable insights that can guide public funding for pharmacogenomic testing for depression in B.C.," she said. "Moving forward, it is crucial to develop effective implementation strategies and identify the most qualified individuals to provide pharmacogenomic-guided care."