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Legislators Introduce Bill Seeking to Raise PGx Awareness, Adoption

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NEW YORK – Legislators on Monday introduced the Right Drug Dose Now Act, seeking to improve awareness of pharmacogenomics (PGx) among doctors and patients and facilitate the integration of drug response-related genomic information into patient care.

The bill, introduced by US House Reps. Eric Swalwell, D-Calif., and Tom Emmer, R-Minn., would advance PGx-related awareness campaigns for the general public and education programs for healthcare providers; provide funding for PGx implementation research; improve integration of PGx information into electronic health records (EHRs); and ensure that drug-gene interactions and drug-drug-gene interactions are more readily factored into the federal government's drug adverse events tracking system.

"The pharmacogenomics community is pretty excited about this bill," said Kristine Ashcraft, medical affairs director of pharmacogenomics at Invitae, which in 2020, acquired the PGx testing firm Genelex and the YouScript clinical decision support platform, hoping to accelerate the use of genetic information in drug prescribing. "If this moves forward," Ashcraft believes "it will positively impact any business that provides pharmacogenomics testing."

The bill, called the Right Act for short, so far is supported by several providers of PGx testing, including Invitae, Genomind, OneOme, GenXys, and Sanford Imagenetics. Personalized medicine advocacy groups, such as the Personalized Medicine Coalition and the GTMRx Institute, as well as the American College of Medical Genetics and Genomics, the Association for Managed Care Pharmacy, American Society of Pharmacovigilance (ASP) also back the bill.

Legislators have drafted the Right Act collaboratively, according to ASP President Sara Rogers, considering feedback from her own organization and other stakeholders across academia, industry, government, and patient communities. "Medication safety and personalized medicine is clearly a priority for [Reps. Swalwell and Emmer's] offices, and they've done a great job with outreach to stakeholders in [getting] support for this bill," Rogers said.

According to some reports, nearly 5 percent of deaths in the US are due to drug toxicities and the risk of drug-related harm is particularly high among older individuals who are on five or more medications, which can react badly with each other. The Medicare system could save an estimated $9.2 billion annually if preventive measures reduced the financial burden of adverse drug reactions by 5 percent.

Although more than half of drug adverse events are preventable, experts say doctors aren't using all the information they should, including PGx data, to avoid these toxicities in patients. Personalized medicine advocates have for years encouraged greater use of PGx testing to avoid costly drug adverse reactions and improve patients' outcomes, but uptake has been slow due to lack of public awareness, gaps in physician education, and limitations of health IT systems.

The US Department of Health and Human Services' Office of Disease Prevention and Health Promotion released a national action plan in 2014 to improve the government's ability to identify and prevent harms from commonly prescribed drugs, such as anticoagulants, diabetes drugs, and opioids. However, this report didn't necessarily consider how PGx information can help mitigate these adverse events, an oversight the Right Act wants to correct.

"The Right Act doesn't only require a report on the implementation and outcomes of the initial plan in 2014, but it would also ensure that new information is considered in updating the report, including drug-drug-gene interactions and pharmacogenetic testing and its role in preventing adverse events," Rogers said.

Since the 2014 plan was issued, there has been a lot more research establishing the role of genetics in modulating drug response, genetic testing has gotten cheaper, and PGx testing particularly has become more accessible through online consumer-facing companies like 23andMe and others. Even so, "patients aren't generally aware this type of testing exists," said Rogers, who is a pharmacist by training.

The legislation would provide $50 million to the National Human Genome Research Institute and other federal agencies to develop a multimedia awareness campaign in the US, especially for those living in rural and underserved communities. "There's a big opportunity with an awareness campaign to bring this information to the public in a way that hasn't been in the past," said Rogers, adding that ASP's pilot education efforts have shown that once people understand the role of PGx, they want access to it, especially individuals on many drugs.

Getting doctors on board

The bill would also advance training and education programs for the entire healthcare workforce, including doctors, administrators, pharmacists, nurses, and genetic counselors, so they can learn more about PGx and how to integrate it into patient care.

"Physicians don't learn about pharmacogenomics in their training, not usually in their didactic courses, and they have very little exposure to it when they're in their residences and even in fellowships," said Kelly Caudle, a co-principal investigator of the Clinical Pharmacogenetics Implementation Consortium (CPIC) at St. Jude Children's Research Hospital. "When they get out into clinical practice, because they don't really know much about it, they don't use it."

CPIC brings together PGx experts who curate evidence on the genetic changes that impact drug efficacy and safety and publish guidelines to help doctors use this information in patient care. Ultimately, what Caudle and other PGx experts believe will move the needle is more implementation research and support for the development of practice guidelines through efforts like CPIC. Doctors don't necessarily want to know how a gene is sequenced or the history of naming conventions for pharmacogenes, but they do "want to know which patients should be tested at which time and then what to do with the results," said Howard McLeod, an internationally recognized PGx expert.

The Right Act would provide $7 million to the National Institutes of Health from fiscal year 2022 through 2025 for PGx implementation research through the NHGRI-led Genomic Community Resources program, which maintains and distributes databases and informatics resources. The support would be welcome news for several efforts that have sprung up over the years to aid PGx implementation, such as CPIC.

"What a laboratory might provide is just the genotype result," Caudle said. "What CPIC does is we take that genotype, translate it into a phenotype, and we provide a recommendation that will help that physician. But without those guidelines, we can't move past that genotype."

Even in the face of substantial research, warnings about drug-gene interactions in drug labeling, and support for genetic testing in guidelines like CPIC, some doctors have been reluctant to incorporate PGx information in their practice. Cardiology is one example.

In 2010, the US Food and Drug Administration issued a black box warning to caution doctors against using Sanofi/Bristol Myers Squibb's blood thinner Plavix (clopidogrel) in CYP2C19 poor metabolizers and note the availability of genetic tests that can identify these patients. Plavix is commonly prescribed to reduce the risk of stroke in patients who've had a heart attack and undergone a stent procedure.

Since that boxed warning more than a decade ago, there has been increasing evidence supporting the use of CYP2C19 testing to identify acute coronary syndrome patients who may not benefit from Plavix. CPIC, from the first guidelines it issued in 2011 to the latest version this year, has recommended avoiding Plavix in ACS patients undergoing stent procedures who are CYP2C19 intermediate and poor metabolizers. And yet, since 2016, the American Heart Association and American College of Cardiology's guidelines recommend against routine genetic testing to guide Plavix treatment citing the absence of randomized-controlled trials.

Given the body of evidence supporting PGx testing in this setting, Caudle said a randomized-controlled trial would no longer be ethical to conduct. Even with all the available research, guidelines, and FDA recognition, some doctors still may not want to adopt PGx testing without their specialty group's support, and Caudle is unsure the extent to which the Right Act will help.

"CPIC will tell you how to use PGx information, and those [disease-specific] guidelines would tell physicians when to use that information," she said. "That right there is the huge gap. I am hoping that this additional funding [in the bill] might help support some of those initiatives as well, but I don't know if it will."

Tackling interoperability

EHR vendors have been slow to update health IT systems so doctors can easily access patients' test results from genetic testing labs. Within most EHRs patients' genetic test reports are still uploaded as PDFs. Furthermore, the lack of health IT interoperability makes it harder to share patients' health information, including genomic data, between providers in different health systems or practices.

All this limits integration of genetic information into clinical decision support systems, which guide doctors on what therapies to prescribe or avoid or what drug dose to give based on patients' genetic information. "Pharmacogenetics is such valuable information, but it's very difficult to implement without clinical decision support tools … [which help] take a genetic sequence all the way to that end action at the point of care," ASP's Rogers said.

The Right Act would tackle this problem in a number of ways. First, the bill asks the committee in charge of updating the 2014 national drug adverse event prevention plan to evaluate how the FDA Adverse Event Reporting System (FAERS) can be expanded to collect cases where patients experienced therapeutic toxicities due to genetic factors. This, several experts noted, could enhance the ability of the FDA to better identify when drugmakers would need to include PGx-related information in therapeutic labeling.

Next, the bill instructs HHS to develop certification criteria for updating electronic prescribing systems and pharmacy benefit checks, so these health IT systems can flag when patients need PGx testing before they receive a particular drug or when they have drug-gene or drug-drug-gene interactions that place them at risk for adverse events with prescribed drugs.

Finally, the Right Act requires HHS to report patients' genetically driven adverse drug reactions to FAERS and update the entire surveillance system to be more patient friendly and interoperable, so adverse events can be pulled automatically from health systems' EHRs and submitted to the government's tracking system.

Supporters and detractors

While this bill appears to have widespread support from personalized medicine and PGx testing advocates, it remains to be seen how certain influential groups in the healthcare community such as drugmakers, the health IT sector, and payors will react.

The Personalized Medicine Coalition, which has many pharmaceutical companies among its members, has provided feedback on the Right Act since early drafts began to circulate a year ago. "The PMC welcomes Reps. Swalwell and Emmer's focus on crafting legislation that would help educate providers and patients about the benefits of PGx and authorize additional funding for implementation research as part of a larger effort to encourage the use of PGx information in clinical settings," said Cynthia Bens, PMC's senior VP of public policy, adding that the organization has also suggested that the bill's sponsors consult with EHR vendors to ensure that the Right Act's health IT-related provisions don't have unintended consequences.

On the insurance front, Medicare contractors have in recent years expanded regional coverage for PGx testing, but there is likely more variability among commercial payors. Though in general, as spending on genetic testing has increased in step with utilization in recent years, the payor community has also become more vigilant about medically unnecessary spending and fraudulent billing practices. Legislation that seeks to raise more awareness of PGx testing could potentially also increase utilization, which payors may not like.

With or without this bill, however, genetic information is becoming more important in healthcare and doctors are finding it difficult to keep up with advances. Oncologists, for example, are particularly struggling to understand complex next-generation sequencing test reports and treat their patients based on the findings. Recognizing this need, McLeod founded Clarified Precision Medicine, which provides molecular tumor board and PGx testing services to oncologists around the country.

While expert support is one way to help doctors with genomic medicine, McLeod noted that the "portability issue" in health IT also needs to be urgently addressed so PGx information can be accessed at the point of care. "The big challenge is how to make this real in most doctors' offices, urgent care, pharmacies, and long-term care facilities," he said. 

"EHR vendors and insurance companies might prefer this [PGx testing adoption] happen slowly, but the deluge of information has caused a natural aversion to taking on new approaches, even if they make clinical and economic sense," continued McLeod, who also helped develop Pharmazam, which operates an app that flags adverse drug-drug or drug-gene interactions people may have to treatments they are taking.

If this bill advances, certainly the economics — the cost of implementing the Right Act compared to the downstream savings from implementing the bill's provisions — will be critical to garnering wider support among fiscally conservative legislators and from the broader healthcare community. Invitae's Ashcraft highlighted that the healthcare system wastes an estimated $528 billion annually on non-optimized medications, and in discussing the Right Act with stakeholders while it was being drafted, the idea of using PGx to reduce unnecessary spending seemed to resonate with Republicans and Democrats. 

"EMRs didn't see widespread adoption until there was a big legislative push," Ashcraft also reminded. Indeed, the Health Information Technology for Economic and Clinical Health Act in 2009 incentivized the transition to electronic medical records and provided resources to overcome adoption barriers. "Even if people thought it was a good idea to move from paper charts to the EMR, it just didn't happen" until there was legislative support, she recalled. "I'm hoping [the Right Act] does something similar. We know it's the right thing to do for patients."

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