Every individual responds differently to medications, and their reactions can vary greatly. While a specific drug may be effective for one person with no adverse effects, another individual may experience a negative reaction to the same medication. Pharmacogenomic (PGx) testing enables the identification of patients who are prone to adverse drug reactions, individuals who are more likely to benefit from specific medications and those who may require adjusted dosages. As adverse drug reactions rank as the fourth leading cause of death in the United States, pharmacogenomics plays a crucial role in patient care by utilizing genetic information to optimize medication strategies. By applying this knowledge, healthcare providers can tailor medication plans to individual patients, maximize treatment outcomes and minimize potential risks.
The PREPARE Study
A landmark study conducted in Europe coined the PREPARE study (Pre-emptive Pharmacogenomic Testing for Preventing Adverse Drug Reactions) has furthered the discussion regarding the large-scale deployment and value of PGx testing, precision medicine, and preventative healthcare around the world. The PREPARE study was a randomized, international, multi-facility study with 7,000 patients across the healthcare industry. The results were impressive, showcasing significant harm reduction to patients who benefited from PGx testing through a 30% decrease in clinically significant adverse drug reactions. Among other data, the PREPARE study’s results were consistent with existing and expected data from other published PGx studies, showing a repeatable finding from the implementation of PGx testing in real-world practice.
One major genetic marker included in the PREPARE study, DPYD, has been a focus for PGx testing more recently, as it is associated with a higher risk of adverse drug reactions from common chemotherapy treatments. The study’s findings showed that the prevalence of DPD deficiency, a condition related to this gene, was as expected, emphasizing the need for oncologists to include testing for DPYD before prescribing therapy to their patients.
Applied PGx
In the United States, some hospitals have already started implementing proactive testing measures. For example, they test for DPYD genetic variations in any patient diagnosed with a solid tumor. For organizations who use PGx testing for chemotherapy, it makes sense for those tests to also include other clinically actionable pharmacogenes in a single, wide-spectrum PGx test. By starting with an all-encompassing test, providers can get all genomic biomarkers at once rather than re-testing every time a new prescription is considered for the patient.
Other hospitals have taken their testing a step further and include additional pharmacogenes, such as UGT1A1, in the same PGx test, covering two genes with one sample. This is beneficial because many “chemo cocktails” used in solid tumor treatment protocols rely on medications affected by both the DPYD and UGT1A1 genes. By testing for both genes in one overarching test, physicians can better prevent negative reactions to drugs and improve patient safety. This pre-emptive multi-gene panel testing has already started developing in several institutions, like UCSF, which recently launched its PGx program to proactively aid patient care.
For oncology, while pre-chemotherapy testing is vital to proper treatment and protection for the patient, there are other aspects of PGx testing that can benefit both the organization and the patient. For example, it’s well known that many patients undergoing cancer treatment will also be prescribed other medications, such as analgesics, antidepressants, and anti-nausea agents. By incorporating PGx testing into the treatment plan, healthcare providers can optimize the selection and dosage of these medications, ensuring better overall patient outcomes and minimizing potential drug interactions or adverse effects.
Implementing Large-Scale Testing
The PREPARE study demonstrated that international healthcare systems can successfully implement and use technologies and programs that support the real-world addition of PGx testing into daily operations and patient care. With therapeutic areas like oncology already using PGx testing and precision medicine in standard practice, this is paving the way for other industries to follow suit. As institutions begin to implement precision medicine, it is important to focus on finding a solution that provides programs and technologies tailored to their end users while still being able to support delivery at scale.
In addition, the PREPARE study proved that PGx testing and precise prescribing are ready and feasible at large scale, operationally and logistically. The current healthcare infrastructure can provide efficient testing logistics, quality tests that cover clinically relevant genetic markers, understandable and impactful data analysis, and proper decision support tools that lead to positive results for patients. However, it is now up to the healthcare industry to embrace precision medicine, broaden the use of PGx testing modalities, and utilize the available tools to support their preventative healthcare programs.
Empowering Our Health Systems
We need to empower physicians with programs and systems that support their workflow, inform which genomic markers to test based on clinically actionable data, adjust the data accordingly to various patient variables, and provide results consistently packaged in a way that can remain permanently within the healthcare provider’s systems for ease of access throughout the care continuum. For institutions, simply adding the ability to order a PGx test is the first step. Institutions need access to technologies that integrate within the prescribing workflow, give insights that are understandable to the healthcare team, and provide actionable information so steps are taken to protect the patient before prescriptions are written, or treatments are changed. As supported by the PREPARE study results, the creation of a comprehensive precision medicine program will lead those institutions to significant harm reduction for their patients.
A Shift to Proactive Care
As the healthcare industry continues to shift from a focus on reactive care to one of proactive healthcare, the results from general PGx testing will continue to play a more important role in diagnosis and care. Results of the PREPARE study reinforce the overwhelming benefit of proactive testing and the proven ability to apply these practices across health systems. Bolstered by these clinically proven results, as well as the general availability of the technology needed to support healthcare teams and patient understanding and utilization, our health systems are now ready to begin the process of proactive treatment optimization using patient genetic signatures.
Houda Hachad, PharmD, M. Res., Vice President of Clinical Operations, Aranscia
Houda is a widely recognized leader in the field of pharmacogenomics and has spearheaded multiple efforts to translate scientific requirements into practical technology-based solutions. Houda serves on the Clinical Pharmacogenetics Implementation Consortium (CPIC) Scientific Advisory Board and is an active member of the Pharmacogene Variation Consortium (PharmVar). She is also involved with several pharmacogenomics working groups and committees aimed at standardizing pharmacogenomic testing modalities and at facilitating their adoption by the clinical community.
