The Integration of Personalized Medicine Into Health Systems: Progress and a Path Forward

Tweetable abstract

Fueled by technological advancements and the integration efforts of many pioneer health systems, personalized medicine is now being clinically implemented at measurable but incomplete levels system-wide.

Keywords::

• clinical adoption
• clinical decision support
• data management
• diagnostic tests
• NorthShore University HealthSystem
• personalized medicine implementation
• population genomics
• targeted therapies

A landmark study published in March 2021 uses a quantitative multifactorial framework to assess the extent to which a representative sample of 153 US-based academic health systems, community health systems and integrated delivery networks are implementing personalized medicine in clinical care [1]. Most US healthcare delivery institutions (83%) scored a two or higher on the five-point scale used to examine their integration efforts. However, only 22% of the institutions studied scored a four or a five on the personalized medicine integration scale. By revealing a system-wide but incomplete push to implement personalized medicine in clinical settings, the study underlines both the momentum that the field has as well as the limitations associated with the utilization of new biomedical technologies and practices with extraordinary but understudied potential benefits. By providing a snapshot of progress in personalized medicine almost two decades after its introduction as a promising notion following the completion of the Human Genome Project in 2003 [2], these findings present an opportunity to reflect on how personalized medicine has evolved over the course of almost two decades.

Here, we document the scientific breakthroughs and clinical implementation challenges that have helped shaped the pace of progress in personalized medicine. We also spotlight the work of NorthShore University HealthSystem, an integrated healthcare delivery system serving patients throughout the Chicago metropolitan area. NorthShore’s pioneering integration efforts may point to clinical implementation strategies that could be broadly adopted to accelerate progress toward an era in which all patients benefit from the right interventions at the right time.

Scientific breakthroughs

The systemic move toward personalized medicine reflects scientific and technological breakthroughs that have been driving molecular diagnostics and personalized treatments to the market even in the midst of a global pandemic. In 2020, the US FDA approved 19 new personalized medicines, defined as those therapeutic products for which the label includes reference to specific biological markers, often identified by diagnostic tools, that help guide decisions and/or procedures for their use in individual patients [3]. Personalized medicines accounted for approximately 39% of the therapeutic new molecular entities the agency approved in 2020 and have now accounted for more than a third of new drug approvals for 3 of the last 4 years [3]. FDA’s Center for Biologics Evaluation has also approved six cell-based or gene therapies over the last half decade [4]. The advent of clinically approved cell-based and gene therapies, which involve the transplantation of genes into a patient’s cells for the treatment of an inherited or acquired disease, provides a significant breakthrough for this new class of personalized treatments that have been the focus of much research for many years.

The availability of an increasing number of diagnostic tests and platforms is also driving the integration of personalized medicine into healthcare [5]. Approximately 75,000 genetic tests were estimated to be available in 2018, with about 10 new tests entering the market daily [6]. New types of tests, such as those that measure non-genetic predictive biomarkers or those that measure multiple genetic markers in novel platforms, are also adding to the increasing complexity and predictive power of personalized medicine [7,8]. For example, the FDA approval of the first comprehensive pan-tumor liquid biopsy next-generation sequencing-based test may anticipate the earlier detection of multiple cancer biomarkers in cell-free DNA isolated from plasma specimens [9]. By guiding targeted treatment strategies with attention to the biological characteristics that influence how patients respond to certain drugs, the diagnostic tools that serve as the foundation of personalized medicine promise to make healthcare more effective and efficient for molecularly selected subsets of patients with cancer as well as those with certain rare, common and infectious diseases.

Improved digital and data management technologies are also playing an important role in advancing the adoption of personalized medicine. Emerging tools for digital data collection allow healthcare delivery systems to more rapidly generate, store, analyze and interpret data that previously would have taken many years to compile [10], and novel clinical decision support (CDS) software helps to efficiently sift through large amounts of data and deliver the information practitioners and patients need most [11,12]. Thus, by enabling improved data management, these tools allow for the kind of agility necessary to keep up with progress in a rapidly evolving field.

Clinical implementation challenges

Still, as the recent landscape analysis suggests [1], healthcare providers have a long way to go to realize the full potential of personalized medicine. Efforts to integrate novel personalized medicine technologies and practices are still in the early stages, and healthcare providers face challenges. For example, more than 30% of patients with non-small-cell lung cancer have tumors with actionable mutations [13], yet many patients do not undergo genetic testing [14]. Furthermore, a recent report estimates that 25–35% of patients with actionable mutations as determined by genomic testing still do not receive the targeted therapies for which they are eligible [15]. This practice gap may be attributed to implementation challenges such as limitations in the availability of diagnostic tests and interpretation of results; unstandardized biospecimen processing; limited access to targeted treatments; limited coverage and reimbursement for diagnostic tests and targeted therapies; and a need for greater awareness and education regarding rapidly emerging personalized medicine prevention and treatment strategies [16].

There have been many efforts to identify policy and practice barriers impeding the integration of personalized medicine into healthcare [17–22]. In a manuscript titled ‘Strategies for Integrating Personalized Medicine into Healthcare Practice,’ which was published in the journal Personalized Medicine in 2017, the Personalized Medicine Coalition, an educational and advocacy organization with a mission to advance personalized medicine, categorizes implementation barriers into five groups, including: awareness and education; patient empowerment; value recognition; infrastructure and information management; and ensured access to care [22]. As we have made progress toward addressing these challenges, we have seen a paradigm shift away from ‘one-size-fits-all’ healthcare and toward a more personalized and patient-centered approach.

Clinical implementation strategies

Indeed, many academic health centers, community hospital systems and integrated healthcare delivery systems across the US are adopting strategies and processes to overcome clinical implementation challenges [23]. By examining the experiences of these personalized medicine programs, the broader healthcare community is developing a better understanding of how to integrate personalized medicine into clinical practice [24]. This may be reflected in the high percentage of healthcare delivery institutions with measurable levels of integration as seen within the landscape analysis [1].

NorthShore University HealthSystem, for example, has made progress toward the clinical adoption of personalized medicine by using pharmacogenomics and a family history tool to build a foundation for stakeholder engagement; using a broader population genomics platform to enhance this foundation; and developing an in-house bioinformatics platform to address data challenges. At NorthShore, the Neaman Center for Personalized Medicine (NCPM) has implemented clinical programs to help overcome the barriers that come up during the ‘last mile’ of implementation of personalized medicine in a primary care network. The system is leveraging electronic health records (EHR) to drive CDS that can help overcome patient and clinician barriers to the incorporation of genomics into healthcare. To the extent that healthcare systems with similar characteristics are seeking to adopt personalized medicine within their own institutions, NorthShore’s experiences may be instructive.

Pharmacogenomics & family history

Through the implementation of direct access pharmacogenomics testing through primary care, NorthShore laid a crucial foundation of stakeholder engagement [25]. To build on this foundation, NorthShore launched a fully integrated family health history tool within the EHR called the genetic and wellness assessment (GWA). The GWA is deployed in advance of obtaining a patient’s annual history and physical exams. The GWA helps determine when genetic testing may be beneficial. It also helps primary care physicians identify patients who are at higher risk for inherited conditions, including cancer. Using embedded CDS tools, the GWA alerts physicians to order appropriate genetic tests and provides guidance regarding when to refer a patient to an appropriate specialist.

Population genomics

While primary care physicians valued the GWA’s clinical utility, they also recognized the limitations of an approach based solely on family history [26]. NorthShore therefore iterated and implemented a broader population genomics program, called DNA10K. More than 10,000 patients participated in the DNA10K genomic testing program. More than 8% of participants were found to have at least one actionable genetic risk variant (excluding pharmacogenomics) and approximately 2% of patients had a CDC Tier 1 genetic condition. Personalized medicine strategies were systematically implemented through the DNA10K program; thereby, streamlining processes and physician practices [27]. Patients rated their experiences with DNA10K as highly positive overall [28]. The GWA and DNA10K programs have now been merged to create a uniform primary care experience for patients.

Flype: an in-house bioinformatics platform

In order to meet the data challenges associated with the integration of personalized medicine, the NCPM developed Flype, an in-house web-based bioinformatics platform [29]. Flype allows NorthShore to securely accept data from a variety of third-party entities and perform secondary analysis and annotation of internally generated next-generation sequencing data, thus acting as a central repository for all genomic variants. Flype also maintains NorthShore’s clinical knowledge base and can be used to update variant annotations as new scientific knowledge emerges. This information can be integrated into patients’ EHRs and used to drive CDS that can, in turn, be implemented system-wide. The dynamic connection between EHRs and CDS can provide a mechanism to educate and inform patients and clinicians about clinical advances in the field.

Conclusion

Thus, despite myriad challenges, the US healthcare system is making progress toward translating the scientific and technological breakthroughs in personalized medicine into improved care for patients. Moving forward, additional multifactorial analyses of clinical adoption might capture this progress. In the meantime, leaders from each sector of the healthcare system can play a role in expanding the impact of personalized medicine by contributing to our collective understanding of strategies to overcome the outstanding clinical implementation challenges. Doing so will help advance a more rational healthcare system in which more effective treatments are targeted to those who are most likely to benefit from them.

Financial & competing interests disclosure

Peter Hulick is the Medical Director of the Mark R. Neaman Center for Personalized Medicine at NorthShore University HealthSystem. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.