By Alex Bisignano

Familial Hypercholesterolemia – An Opportunity for Real Precision Medicine in the U.S. Thwarted by Odd Incentives

Lives can be saved by a straightforward genetic test, yet our healthcare ecosystem is falling behind due to incentives that value frugality over preventative care and patient outcomes.

According to the National Institutes of Health, Precision Medicine is defined as “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person.” The goals are 1) to identify predictors of disease in individual patients before onset and to prevent these diseases, and 2) to identify predictors of how best to treat individual patients’ diseases. Familial hypercholesterolemia is one such disease that represents an excellent opportunity to accomplish both patient-specific diagnosis and treatment of serious, life-altering disease. Yet, despite the capacity of the U.S. healthcare ecosystem to implement life-saving measures protecting against this illness, economic complexities are keeping a solution at bay. Understanding these complexities is a first step in resolving the situation and engineering a plan to give more people control of their health.

What is Familial Hypercholesterolemia, and what risks does it present?

Familial Hypercholesterolemia, colloquially referred to as ‘FH’, is a disease caused by mutations in genes responsible for cholesterol metabolism; most commonly, mutations in the Low Density Lipoprotein (LDL, or “bad” cholesterol) Receptor protein (LDLR). FH is typically diagnosed based on an LDL count in excess of 200 mg/dL, along with family pedigree analysis. While diseases of genetic origin may seem to be rare occurrences, FH is estimated to have a prevalence as high as 1/500 in the United States, with some estimates of an even higher prevalence of 1/200 in the overall population.1

The consequences of FH are quite severe. In affected individuals, a buildup of plaque along the arteries begins to occur much earlier in life due to an inability to properly process and metabolize LDL cholesterol. As a result, more than half of females affected with FH will experience a heart attack before the age of 60. Prognosis for males is even bleaker, with more than half experiencing a heart attack by the age of 50.2

FH is inherited in an Autosomal Dominant fashion, meaning an affected parent carrying one mutation will, on average, pass the disease to 50% of his or her children. However, despite the high prevalence and rate of transmission, FH is notoriously underdiagnosed in the United States. While an estimated >600,000 Americans are at risk, less than <1% of affected individuals are diagnosed.3

Okay, so FH is bad; FH is common. But what can we do about it?

Believe it or not, a simple, well-known type of drug is shown to have a significant impact on life expectancy for patients afflicted with FH: statins. A study published in 2013 by Børge Nordestgaard and colleagues, working for the European Atherosclerosis Society Consensus Panel, showed that early and aggressive statin treatment of individuals diagnosed with FH resulted in a significantly reduced incidence of coronary heart events relative to untreated individuals. On average, statins reduced the chance of a heart attack by >40% following 15 years of treatment!

With such clarity in diagnosis and treatment, why is early screening and intervention so uncommon in the United States?

The Netherlands and other single-payer healthcare economies recognize that the upfront screening costs to identify individuals with FH are negligible compared to the savings in both heart disease cost and patient lifespan. Unfortunately, the United States has been sluggish and almost resistant to establishing a screening paradigm. Why is this?

While there are likely a plethora of contributory factors, one of the main problems with covering FH screening and intervention is clarifying incentives for third-party payers, since investing in the early diagnosis and treatment of FH is making a very long-term bet on a patient population. For example, imagine diagnosing a male 20-year-old with genetic FH and recommending aggressive prophylactic statin treatment. The benefit to this patient is unlikely to be tangibly realized until their mid-forties. That’s a 25 year timeline investment for an insurance company. Yet on average, patients can be expected to stay on a plan for 2 – 3 years depending on their employment status. Herein lies the problem – the gain from this upfront investment will likely be realized by a completely different insurer.

In the U.S., investment in long-term health outcomes such as FH prevention are difficult due to what economists call the “Tragedy of the Commons”

In economic theory, the Tragedy of the Commons occurs when a public ‘resource’ or common ‘good’ is lost due to the actions of individual agents behaving only in their own self-interest. In this case, the common ‘good’ can be viewed as ‘better population health outcomes due to prevention of FH.’

Theoretically, any insurance company can produce this good by paying for the precision diagnosis and treatment of FH as discussed above. The resource ultimately leads to better outcomes and lower costs in the future. However, due to the frequency of patients cycling in and out of insurance plans, theoretically all payers benefit from any investment in FH prophylaxis. For that reason, each payer becomes demotivated to pay for this type of care, since it makes more sense to let their competitor pay for it: a concept known as the Free Rider Problem.

With the incentives so misaligned, how can we move the needle for better coverage of precision, preventative medicine when it comes to FH? Typically, Free Rider Problems are addressed by government regulations. In the case of our single-payer European counterparts, a government agency was able to step in and mandate coverage for these valuable, life-saving medical technologies.

Challenging insurer dynamics in precision medicine are not just limited to the diagnostic world. Amgen’s Repatha, a drug which inhibits PCSK9 in order to lower LDL cholesterol, is having trouble gaining coverage for its annual $14,000 price tag. Despite a marked 15% decrease in the likelihood of bad outcomes (heart attacks, strokes, death, etc.) in a study of over 27,000 individuals, insurers claim they still want to see more.

Optimism for the Longer-Term Future of Precision Medicine

While the current healthcare-economic ecosystem is less supportive of genomic-based precision medicine initiatives, there is hope for the future on three key fronts:

  • Value-Based Reimbursement: Over the past 8 years, a model for Value-Based Reimbursement for the delivery of healthcare, based on clear improvements in patient outcomes, has been successfully implemented across a number of areas of medicine. This approach attempts to shift payer financial incentives away from short-term cost reduction and in the direction of longer term patient outcomes.
  • Continued Reduction in Sequencing Costs: While not applicable to clinical genomics just yet, Illumina claims to soon be able to deliver the $100 genome. At some point in the process of bringing down the cost of sequencing, either the patients will be willing to pay for early diagnosis of genetic diseases or the upfront cost of investing for payers will be small enough to be intangible relative to the longer-term benefits.
  • Patient and Employer Demand: Self-insured employers, proactive patients, and other players at the intersection of U.S. healthcare economics are starting to take matters into their own hands. Companies like Progyny are pioneering novel solutions for employers to be able to deliver coverage for precision medicine directly to their employees. This trend will hopefully motivate the larger payors to create similar offerings to stay competitive.

Ultimately, the healthcare-economic landscape of the U.S. is shifting to accommodate the need for precision medicine, but as with many larger cultural changes, investments of time and effort are required to make the vision become a reality. At Phosphorus, we are doing our part to usher in a new era in the state of modern healthcare, and with determination, we believe that the dream of ubiquitous precision medicine will become a reality.

References:
1Mendelson, M. M. et al. (2015). Circulation, Vol. 123, Issue Suppl 3
2Pears, R et al. (2015). Current Opinion in Lipidology, 26(3), 162–168. http://doi.org/10.1097/MOL.0000000000000173
3Nordestgaard B G et al. European Heart Journal 2013 eurheartj.eht273

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  • Jack Mar 24, 2017 Reply

    The need for publicly traded insurers to keep pace with investor quarterly earnings expectations may exacerbate this problem by driving a short term and short sighted decisions. Material savings from covering FM tests would result in a relatively small short term increase in cost with a material but longer term ROI. Of course they could offset their costs by raising the cost of plans that cover FM testing but premiums and out of pocket costs are already growing in double digits.