Precision Medicine

Introduction

The National Institutes of Health (NIH) defines precision medicine as “an emerging approach for disease prevention and treatment that takes into account individual variability in genomics, environment, and lifestyle for each person.”¹ Historically, most medical treatments have been designed for the so-called “average patient.” As a result of this one-size-fits-all approach, treatments can be very successful for some but not for others.

Precision medicine gives clinicians tools to better understand the complex mechanisms underlying an individual patient’s health risks, disease or condition, and to better predict which treatments will be most effective.² It is hoped that this new “golden age” of medicine will lead to improved therapies and interventions to prevent and treat disease in a more efficient and effective way, thereby leading to decreased mortality and morbidity. Indeed, if the promises of precision medicine hold true, there will clearly be a significant impact on the life and living benefits insurance industry.

The Basis of Precision Medicine: Genomics

Genomics is the study of genes, their interactions with each other and the environment, and the resulting phenotype (physical manifestations and biochemical characteristics) of an individual. Genomic medicine is the emerging discipline that involves using genomic information and associated biomarkers to drive clinical care and create molecularly targeted therapies.³ The increased speed and decreased cost of gene sequencing over the last 15 years have resulted in larger and more refined databases from which personalized clinical applications can now be developed.

Understanding the enormous complexity of genomics requires multidisciplinary cooperation from both the government and private sectors. Not only is advanced high-throughput DNA sequencing necessary, but major developments in bioinformatics, cloud-based processing technologies and machine learning will be needed to analyze huge data sets to unlock the secrets of the genome.

Genomics has led to a growing number of clinical applications, including pre-disease risk assessment (and mitigation), refined disease diagnosis and prognostication, and the design of individualized treatment protocols. From an underwriting point of view, the impact of genomics cannot be understated, and from a medical point of view, is not even close to being fully realized. While essentially every branch of medical science has already been affected by genomic medicine, the primary areas where it is currently having its most visible impact are in the developing field of pharmacogenomics and the diagnosis and treatment of cancer.

Pharmacogenomics

The emerging field of study combining pharmacology and an individual’s genomic profile is known today as pharmacogenomics. Often, pharmacogenomics is described as “giving the right medicine at the right dose at the right time” in order to optimize favorable outcomes.

Much attention in precision medicine has been focused on pharmaceuticals and the great variability of effects on individuals. It has always been very difficult to predict who might benefit from a given medication, who might not respond at all, and who might experience adverse side effects.⁴ It is now known that genetic variations can impact how an individual absorbs, distributes, metabolizes and eliminates pharmaceuticals.⁵

Approximately 7% of medications approved by the US Food and Drug Administration (FDA) are affected by actionable inherited pharmacogenes. The FDA website specifically names approximately 165 medications with pharmocogenomic information in their labeling. Such information may include specific actions to be taken based on genetic biomarker information.⁶ Some of the listed medications are in common use, but rarely do clinicians actually order pre-treatment genomic testing for these medications.

Barriers to widespread use of pharmacogenomic testing include a lack of clear clinical guidelines and few controlled studies comparing genomically guided treatment with conventional therapy. In addition, professional societies and groups developing treatment guidelines can and do disagree on pharmacogenomic testing recommendations. There has, for example, been disagreement on pharmacogenomic testing recommendations for the blood thinner warfarin and the platelet aggregation inhibitor clopidogrel, drugs both commonly seen during underwriting.⁵

Analyzing an individual’s genomics is only part of the approach to precision drug treatment. While genomic studies can provide significant information, it is at the protein level that cellular processes are functionally regulated, and genomic results alone do not necessarily correlate with corresponding protein abundance and function. Thus, the proteome – the entire complement of proteins produced by an organism – must be studied along with the genome. This particular area of research is termed pharmacoproteomics.

Precision medicine must encompass both pharmacogenomics and pharmacoproteomics in order to provide true clinical utility. The personalized “omics” approach should improve understanding of disease and drug mechanisms and allow for greater discovery, detection and monitoring of novel biomarkers for a variety of complex diseases and their treatment.⁷ Success in this field of medicine should have a significant and favorable impact on mortality and morbidity outcomes, and potentially affect the approach to risk stratification in the future.

Precision Medicine and Cancer

The concept of applying genomics to cancer treatment is becoming one of the most clinically useful examples of precision medicine. Every cancer patient has a unique profile of inherited as well as tumor-specific genetic variants that influence the risk, onset and progression of their disease. Developing a personalized approach to individual patients with the aim of providing optimal outcomes is becoming a reality due to significant progress in the genomic characterization of tumors.⁸ In fact, in 2015 alone, the FDA approved 18 new agents for cancer, nearly all of which were based on the principles of precision medicine.⁹

One approach is to carry out whole exome sequencing (WES) of the tumor cells obtained at biopsy or surgical excision. (The exome is the portion of the genome which codes proteins.) By doing so, specific genetic abnormalities can be determined, which then may allow specific targeted treatment or immunotherapies to be prescribed. Additionally, WES of the patient’s somatic (body) non-cancerous cells can be done to compare with the tumor sequencing. One study discovered that there were a mean 17.3 cancer-relevant somatic mutations per patient in the study and that 91% had actionable variants. Moreover, the course of treatment was altered in approximately 10% of the study participants as a result of the testing. The study also demonstrated that the results of WES in diagnostic testing were superior to those of some commercially available targeted cancer panels in common use today.⁸

Other researchers are beginning to advocate for whole genome sequencing (WGS), rather the more limited WES.¹⁰ WGS, which sequences the entire genome including the non-protein coding regions, may reveal additional variations which could be relevant to understanding the development of cancer and designing targeted therapies.

Clinicians have been slow to adopt tumor sequencing as part of cancer treatment protocols. This is partly due to a lack of good clinical data (in many instances) supporting these novel approaches, unique differences in local and regional standards of practice, access to laboratories which can perform these high-tech analyses reliably, and reimbursement concerns. Attitudes toward such tests might also differ, depending upon whether the clinician is practicing oncology at a research institution or a community-based practice. To date, tumor sequencing has had the most impact on advanced or refractory tumor treatment. Universal tumor testing is more controversial. Two recent point-counterpoint opinion articles highlighted the division among clinicians.^11,12 Nonetheless, as significant advances are made and scientifically verified, the application of genomics in cancer treatment will certainly move forward.

Limitations and Challenges of Precision Medicine

The rapid development of genomics and precision medicine has generated genomic data at a rate that exceeds the ability of researchers and clinicians to adequately capture, fully analyze and properly interpret them. The extent to which doctors can apply genomic data in directing clinical treatments remains to be determined and is likely to vary over the short term. This is partly due to an absence of evidence-based standards for regulation, clinical decision-making and costs.

One of the main challenges of precision medicine is the requirement for new scientific methodologies to determine clinical utility in small target populations. Traditionally, clinical research is performed on large populations in order to establish statistical significance (i.e., validity). Developing personalized therapies will require new approaches to this paradigm and will introduce new uncertainties, at least for a while, in medicine. In fact, as precision medicine advances, the line between clinical research and clinical care may become blurred.9 In addition to establishing the accuracy and reliability of genomic medicine, social issues such as cost and access to care will need to be addressed by policymakers who direct the many diverse health care systems around the world.

Impact on the Insurance Industry

The use of genetic and genomic information in the insurance industry has historically been challenging and subject to significant regulatory restrictions. Insurers have always striven for fairness and symmetric access to information which is or may be predictive of risk. With genomics now becoming a mainstay of regular medical care, how that information is assessed for risk stratification purposes must be constantly assessed, as precision medicine and all of its offerings may significantly change the way applications are underwritten and also how claims are adjudicated.

The new discoveries in genomic and precision medicine offer opportunities for insurers to develop new products to benefit insured lives. Much recent discussion has centered on genetic testing’s wellness benefits post-issue, with the expectation that genomic information might help covered individuals mitigate their risk by making preventative alterations to lifestyle and undertake disease monitoring. Offering coverage for pharmacogenomic testing or WES (or even WGS) tumor testing as a living benefit to potentially improve client outcomes from both a morbidity and mortality point of view will also be given further research and consideration by the industry. It will be extremely important moving forward for insurers to continue the strict practice of treating an individual’s genomic information carefully and guaranteeing the insured’s privacy.

It is, to be sure, an exciting time in the history of clinical medicine and in insurance medicine as well. The changes now being witnessed and those to come will undoubtedly have long-lasting and potentially beneficial effects for both clients and the industry.