Two patients, both 73-year-old males with newly diagnosed congestive heart failure, are seen by the same provider and prescribed the same therapeutic regimen. Despite the similarities, the 2 patients experienced drastically different therapeutic outcomes. These divergent outcomes were not attributable to the clinical care they received but instead to non-clinical factors surrounding each patient’s circumstances. These non-clinical factors are also referred to as social determinants of health (SDOH). According to the Centers for Disease Control and Prevention (CDC) website, SDOH are conditions in the places where people live, learn, work, and play that affect a wide range of health risks and outcomes. Some key SDOH that may influence clinical outcomes include housing insecurity, food insecurity, lack of transportation, and lack of family or other social support.

It is widely known that social and economic factors have significant impacts on health outcomes of both individuals and communities. At a population level, it has been estimated that clinical care accounts for only 20% of a community’s health outcomes while the remaining 80% is related to a combination of health behaviors (e.g., diet and exercise), the physical environment (e.g., housing security), and socioeconomic factors (e.g., education and social support). Despite this insight, addressing SDOH has traditionally been the purview of government and charitable organizations rather than healthcare providers. However, with the shift toward value-based reimbursement and increased accountability for the costs and health status of patients, there is an incentive for health plans and providers to further consider the social and economic barriers that contribute to poor health outcomes. Models are being developed that link healthcare systems, providers, and community resources in an integrated fashion to address SDOH. These models are evolving from systems that rely on acute episodes of care to a coordinated system focused on prevention and care management.

As the largest payer for healthcare in the United States, Medicare has also recently begun to make accommodations in order to address SDOH in the privately administered Medicare Advantage (MA) program. MA is a capitated system placing health plans that administer MA benefits at risk for the cost of caring for each beneficiary. MA plans are permitted to offer supplemental benefits beyond traditional Medicare offerings as long as those benefits are “primarily health-related.” Historically, the most common supplemental benefits offered by MA plans have been services not traditionally covered by medical insurance such as vision exams, hearing tests, and preventative dental services.

The Centers for Medicare & Medicaid Services (CMS) have recently begun to implement regulatory changes allowing MA plans more flexibility with regard to these supplemental benefits. First, the definition of “primarily health-related” has been expanded. Examples of this expanded interpretation include providing in-home support for activities of daily living (ADLs) or installation of grab bars in the bathroom in order to prevent injuries and reduce avoidable emergency room utilization. In addition, supplemental benefits that may reduce exacerbations of existing illnesses, such as installing air conditioning units or providing carpet shampooing for patients with asthma, may be considered. Beginning in 2020, MA plans may offer chronically ill patients additional benefits that directly impact SDOH, such as expanded meal delivery options to address food insecurity and transportation for non-medical needs like grocery shopping. In announcing the expanded options for MA plans, CMS Administrator Seema Verma said the changes “give plans the ability to be innovative” and the changes permit “benefits and services that address SDOH for people with chronic disease.”

The shifts occurring in healthcare delivery, including the expansion of accountable care organizations (ACOs), the rise of capitated reimbursements, and penalties associated with hospital readmissions, incentivize healthcare systems to become increasingly focused on holistic care for beneficiaries. By addressing individual and population SDOH, healthcare systems, providers, and community support can be integrated to improve health outcomes and reduce unnecessary healthcare utilization.

While there may be some debate as to who deserves credit for originally developing insulin in the 1920s, there is no doubt that its serendipitous discovery had a life-saving impact. In an attempt to provide affordable treatment to the public, the researchers opted to sell the patent for insulin to the University of Toronto for $1. The researchers later collaborated with a pharmaceutical company to develop insulin due to limited ability of the university to develop it on its own. Once made primarily from animal sources in limited selection, several insulin options are now available, and each product differs slightly in manufacturing and design to better mimic the lacking endogenous insulin in patients with diabetes. Today, insulin is marketed primarily by three manufacturers, and counterintuitive to its length of time on the market as a primary treatment, insulin costs continue to increase. One assessment reported that annual spending per person with type 1 diabetes nearly doubled between 2012 and 2016, and the reported cost of one specific brand of insulin increased by 668% from 2001 to 2015. There are several purported reasons for the high costs of insulin, even resulting in lawsuits and a push for legislative involvement.

The high cost of insulin is a hurdle for many patients and the entire healthcare system, especially considering a reported 1.2 million Americans have type 1 diabetes and a portion of the nearly 30 million Americans with type 2 diabetes are insulin-dependent. So, what happens when a medication necessary for life continues to increase in price? Patients may resort to acquiring insulin from less expensive resources outside of the United States (US). In addition, some patients will continue to use insulin vials beyond their stable use (i.e., beyond 28 days once opened) or share insulin pens. Patients may ration their insulin for their own use or sell the remaining insulin to others, as the temptation for potential income may be too enticing for those with limited financial means. One study reported that the rise in costs has resulted in nearly 25% of patients not taking insulin as directed. Lack of blood glucose control resulting from these measures could be life-threatening.

Taking insulin access to another level, one project aims to develop a protocol for insulin production that would circumvent intellectual property concerns, enabling manufacturers to produce more affordable insulin. Theoretically, an open protocol for manufacturing of insulin could result in community biolab production or somewhat “home-brewed” insulin, but there would still be several costly regulatory hurdles for each product. Even if crowdfunding could support these “biohacked” insulin barriers, would the resulting product be the best treatment for all patients? Would it still result in a high-cost product?

Historically, the US Food and Drug Administration (FDA) has regulated insulins as small molecule drugs; thus, the few generics available are actually branded competitors and considered “follow-on” insulins. The FDA has announced insulins will be transitioned from the small molecule pathway to the biologics pathway effective in March 2020 as part of their Biosimilars Action Plan. According to acting FDA Commissioner, Dr. Ned Sharpless, after this transition, the FDA will be able to license biosimilar and interchangeable insulin products that may be substituted at the pharmacy, potentially leading to increased access and lower costs for patients.

While the idea for “generic” (cheaper) insulin is becoming more of a reality, what will patients do in the meantime for a disease state in which the treatment is not optional? Will interchangeable biosimilar insulin finally be the solution for reversing the constant upward trajectory of insulin prices?

Precision medicine describes an approach to treatment based on an individual patient’s unique genetic, environmental, and lifestyle factors. Genetic data, in particular, is central to the concept of precision medicine.

Perhaps more so than with any other disease state, precision medicine has had a definitive impact on the treatment of cancer. With the approval of imatinib (Gleevec®) to treat chronic myeloid leukemia (CML) nearly two decades ago, the concept of treating cancer based on underlying genetic anomalies was launched. In the case of CML, the underlying genetic abnormality is central to the diagnosis of the disease, but this is not the case for many other types of cancer. Specific genetic mutations may or may not be present in different patients with the same type of cancer. Identification of specific genetic mutations within cancer cells has led to the development and United States Food and Drug Administration approval of approximately 30 different “targeted” cancer treatments.

Tissue from the patient’s tumor is considered the gold standard for establishing the diagnosis and for identifying potential precision medicine targets. However, several challenges are associated with obtaining and interpreting information from tumor biopsies. Tumors may be located in areas of the body that are difficult to access and may require invasive procedures in order to obtain the needed tissue.

The use of liquid biopsies in place of tumor tissue biopsies is an emerging technology that may help to accelerate the use of precision medicine. The term liquid biopsy most commonly refers to the detection of tumor DNA fragments in the patient’s blood. This circulating tumor DNA (ctDNA) is the result of a dying cancer cell releasing fragments of DNA into the bloodstream. In addition to blood, liquid biopsies may also have utility with other bodily fluids, including urine, cerebrospinal fluid, and saliva, for example.

Liquid biopsies represent the potential for an easily retrievable source of information about a tumor’s genomic makeup, and they may have other advantages as well. Traditional tumor biopsies are often done on a single tumor lesion, which may inadvertently lead to sampling bias that does not capture the heterogeneity found in many tumors and/or different metastatic sites of the tumor. Conversely, ctDNA may provide a better “big picture” of the overall genetic makeup of the tumor cells. Another potential utility for liquid biopsies is the improved ability to monitor changes in the tumor’s genetic profile over time. Serial liquid biopsies can detect when a tumor acquires resistance to the current therapy before other manifestations of tumor progression are established. Liquid biopsies may also be able to spare patients more intensive treatments that offer limited added benefit. For example, in some types of cancers, the detection of microscopic residual disease remaining after surgery may identify patients who will benefit from further systemic therapy. Conversely, patients without this detectable residual disease by ctDNA may be spared from further toxic therapy that would not increase their chance of cure. TPerhaps the most hopeful use of ctDNA technology is the ability to screen and identify asymptomatic patients who are at a very early stage of their cancer when the possibility for cure is much higher.

For now, tumor tissue biopsies remain the standard of care in the majority of clinical situations; however, if the promise of liquid biopsies is validated through further study, more patients may be able to benefit from the promise of precision medicine.

In January, the Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) published Advancing Health through Innovation: 2018 New Drug Therapy Approvals. This report provides a benchmark for approvals and highlights the game-changers approved in 2018. Compared to 2016 and 2017, in which CDER approved 22 and 46 new drugs, respectively, in 2018 a total of 59 novel agents were approved. This number does not even include new and expanded uses of already approved drugs, new formulations, new dosage forms, or the seven biosimilar approvals. This marks the largest number of novel approvals in over two decades and far exceeds the average of 33 novel approvals per year in the past 10 years, surpassing the record setting approvals in 2017. Figure 1 outlines approvals and filings over the past 10 years.

Several potential explanations may account for this uptake in approvals in the past couple years. The FDA’s leadership, with its continued strategic initiatives, may be partly responsible for the increase. In early 2017, the FDA was criticized following the lower than average approvals seen in 2016. Public interest in opioid abuse and dependence treatment, access to drugs for rare diseases, drug shortages, and competition potentially affecting pricing have also put the FDA at the forefront of the public’s mind, further challenging the FDA to demonstrate action in the public’s interest. Finally, additional defined methodology for evaluating data in rare diseases, such as real-world and patient reported outcomes, may also have played a role.

Last year, all 59 novel drug approvals met their Prescription Drug User Fee Act (PDUFA) goal dates. In 2018, 32% were considered first-in-class and 58% were approved for rare diseases (Orphan Drugs). Priority Review was granted to 73% of new drugs, 7% received Accelerated Approval, 24% were designated as Breakthrough Therapy, and 41% garnered Fast Track designation. Furthermore, 95% were approved in the first review cycle, and 71% were approved in the US prior to approval in other countries. A breakdown of the types of drugs approved in 2018 is illustrated in Figure 2, with drugs in the expansive oncology spectrum once again dominating the approvals.

Some of the notable 2018 approvals included the first non-opioid drug approved to reduce opioid withdrawal symptoms, a new antiretroviral for multidrug resistant human immunodeficiency virus-1, a new class of drugs for migraine (calcitonin gene-related peptide receptor antagonists), the first FDA-approved drug derived from marijuana, the first treatment approved for multiple sclerosis in children, expanded options for cystic fibrosis, and the first antibiotic approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs.

Among the several Orphan Drugs approvals were drugs for Fabry disease, phenylketonuria, X-linked hypophosphatemia, Lennox-Gastaut syndrome, Dravet syndrome, hemophagocytic lymphohistiocytosis, adenosine deaminase deficiency, and Lambert-Eaton myasthenic syndrome.

Although 2019 approvals have begun more slowly, given the substantial number of approvals in 2018, it appears that the large number of approvals from 2017 was not an anomaly but, perhaps, the continuation of a trend.