NEW YORK (GenomeWeb) – A new consortium aims to bring pharmacogenomic testing into routine clinical practice in Europe within the next few years. Backed by €15 million ($16.1 million) in EU Horizon 2020 funding, the Ubiquitous Pharmacogenomics Consortium (U-PGx) seeks to implement preemptive pharmacogenomic testing at seven healthcare systems across the continent by 2020.
"The EU has emphasized that for them this is a showcase project on how pharmacogenomics can really be implemented in actual day-to-day patient care," Jesse Swen, an associate professor of pharmacogenetics at Leiden University Medical Center, said in an interview.
According to Swen, LUMC is coordinating U-PGx together with investigators at institutions from 10 European countries. The project commenced last year and is slated to run through the end of the decade.
As part of the effort, U-PGx members will genotype 8,100 patients at sites in Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK with a panel of genes relevant to drug dosage. Half of those patients will have their genetic data stored in local electronic medical systems to help physicians advise on drug selection and dosage, while the other half will serve as controls.
By the end of the study, the U-PGx consortium members hope to show a decline in adverse drug reactions and improvement in drug efficacy among genotyped participants. They also hope the results will spur healthcare systems across Europe to adopt pharmacogenetic testing as part of routine patient care.
"Of course what we hope to show by completing this project is that if you use preemptive pharmacogenomics, by using a panel of pharmacogenes in your patient care, that can really help to improve the outcome of drug treatments," Swen said.
The roots of U-PGx lie in the activities of the Royal Dutch Pharmacists Association's Dutch Pharmacogenomics Working Group, which initiated its activities in 2005 and eventually rolled out guidelines for drug use and dosage while undertaking a pilot study that saw Dutch patients genotyped and their relevant data entered into local electronic healthcare records. When a call for a European-wide study was put out, LUMC and collaborators from across the continent answered it with the new project, officially entitled, "Ubiquitous Pharmacogenomics (U-PGx): Making actionable pharmacogenomic data and effective treatment optimization accessible to every European citizen." It commenced on Jan. 1, 2016, and consists of four main components, according to Swen.
The first, overseen by Matthias Samwald, an investigator at the Medical University of Vienna in Austria, was to create a suitable environment to run the trial component of the study.
"One of the major goals of my work is to develop new paradigms of how information technologies can improve global health care and I see pharmacogenomics as such a new paradigm," Samwald said in an interview. According to Samwald, the implementation of pharmacogenomics has been hindered by "trivial problems" related to making treatment recommendations accessible to clinicians and pharmacists.
"These questions are not easily answered in a world where clinicians have little knowledge about pharmacogenomics, where interconnected health IT systems are still far from perfect or even unavailable in many regions, and utilization of genetic data is impeded by regulatory concerns," said Samwald.
In response to these issues, Samwald's group developed a so-called safety code card. Genotyped patients are given a card that contains their genetic makeup as well as a scannable code. Any physician with a smartphone is then able to scan the card and access a website containing the relevant dose for a particular patient. "The idea of the safety code system is that patients themselves are given control of their pharmacogenomic data," said Samwald. "They get tested for a panel of all currently well-researched genes, and their results get printed on a card they can carry in their wallets," he said.
This way, Samwald noted, pharmacogenomic data, decision support, and treatment optimization can be implemented everywhere, regardless of local hurdles and lacking infrastructure.
According to Swen, much of U-PGx's first year has been spent implementing the smart code card system and other systems to support the envisioned genotyping trial. "One of the challenges is to make this work at sites where [electronic records] are less developed," Swen said. "In Greece or Slovenia, electronic health records are less common, and we have other systems in place to use our dosing guidelines," he said. With smart code cards, "they can still make use of the system," said Swen.
Swen is overseeing the second component of U-PGx, the large genotyping study, which is referred to as Preemptive Pharmacogenomic Testing for Prevention of Adverse Drug Reactions (PREPARE).
This component of U-PGx calls for the genotyping of 8,100 patients with a panel of 50 variants of 13 pharmacogenes used to guide drug and dose selection for 43 drugs, using LGC Group's SNPline platform, a PCR-based genotyping assay that will be adopted at all sites taking part.
Swen said that U-PGx selected the SNPline platform because it was "flexible" and enabled users to run individual repeats without consuming microarrays and "producing far more data than needed."
According to Swen, the primary aim of PREPARE is to assess the impact of pharmacogenomics implementation on adverse event incidence. He predicted a 30 percent reduction in such adverse reactions, as well as an accompanying rise in drug efficacy, though he cautioned that would be harder to gauge given the variety of variants and drugs surveyed in the study. Additional results of PREPARE will include data on cost-effectiveness, as well as process indicators for implementation and provider adoption of pharmacogenomics.
It is the use of a multi-gene panel across seven different healthcare systems that U-PGx participants believe sets the new effort apart from earlier studies, which were often limited to specific, individual drug-gene pairs, Swen noted. "Our program is unique in its multi-center, multi-gene, multi-drug, multi-ethnic, and multi-healthcare system approach," he said.
While PREPARE is certainly at the heart of U-PGx's effort to demonstrate the clinical utility of implementing pharmacogenomic testing into day-to-day care, two other components of the project will focus on marker discovery as well as communicating the benefits of pharmacogenomic testing to major stakeholders.
"The project is not only about testing in a preemptive way," noted Swen.
A third component of U-PGx is called "A Next Step in the Future," and revolves around applying next-generation sequencing, pharmacokinetic modeling, and systems pharmacology to discover additional variants associated with drug response and to elucidate drug-drug-gene interactions.
Matthias Schwab, head of the Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology in Stuttgart, Germany, is leading this component of the project.
"I feel it is important to note that U-PGx will not only implement currently existing knowledge but will consider visions and future directions," Schwab said in an interview. "Since I am not only a clinical pharmacologist but also a clinician, I highly appreciate that U-PGx is generally a strong translational project but gives us the opportunity also to do innovative up-to-date research work."
This work will include implementing pharmacogenomic markers discovered at Schwab's institution in the context of PREPARE, as well as carrying out sequencing of candidate genes to identify new variants. Schwab's group will also employ a systematic pharmacokinetic modeling approach to study information from the U-PGx trial.
"Of course, pharmcogenomics must include not only genetic information but requires clinical pharmacological information like co-medication, drug-drug interaction, and environmental factors that contribute to drug response, as well," said Schwab.
Christina Mitropoulou, director of the Golden Helix Foundation, a London-based biomedical research organization, is overseeing the fourth component of U-PGx, which is called "Dissemination and Communication," and is focused on the ethical issues of the project, including outreach to stakeholders and creating educational materials for physicians.
Mitropoulou said in an interview that U-PGx will engage in training activities to increase pharmacogenomics knowledge among healthcare professionals, and is planning activities to raise awareness about the potential of pharmacogenomics among patients and the general public, healthcare professionals, policy makers, and regulators.
Mitropoulou said that her aim is to spread awareness of pharmacogenomic testing among "various stakeholders of the EU member states," including patients, healthcare professionals, regulatory agencies, politicians, and policy makers as well as healthcare insurers, both public and private providers.
Dissemination activities, according to Mitropoulou, mainly include single-day events and a scientific symposium aimed for healthcare professionals, as well as events to raise pharmacogenomic awareness in patients and the general public.
In connection with these outreach activities, U-PGx hosted its first Personalized Medicine Day in Granada, Spain, last month, with a focus on pharmacogenomics for the treatment of vascular diseases. In September, Golden Helix also hosted an event in Greece called "Cancer Genomics and Individualized Therapy," where U-PGx members participated.
Mitropoulou said that U-PGx so far has been "fruitful" in its efforts, which she argued are unique among pharmacogenomic studies to date.
"Such an approach will be implemented for the first time in seven different healthcare systems in Europe, providing immediate knowledge of one's personalized pharmacogenomic profile, without any disruption of his or her routine clinical care," said Mitropoulou. "This way, a theoretical concept will find its way into clinical practice."