Ending the Diagnostic Odyssey Act of 2019 (HR 4144, 116th Congress)

The Policy

What it does

Expands Medicaid coverage to include the use of whole genome sequencing for diagnosing some rare pediatric diseases.


The Ending the Diagnostic Odyssey Act of 2019 (HR 4144) would provide a state option to cover genome sequencing techniques under Medicaid. Specifically, the bill would provide access to whole genome sequencing, a technique which can be used to identify the genetic mutations underling a disease to improve diagnosis and treatment decisions.

Under this policy only a select group of “eligible individuals” would have access to whole genome sequencing under Medicaid. Eligible individuals would be children under the age of 21, unless otherwise dictated by the state. Additionally, prospective individuals must have been either admitted to an intensive care unit or seen by a specialist for a suspected genetic disease to be considered eligible. Finally, the disease symptoms in such individuals must have begun during infancy or childhood.

Under this proposed law the federal medical assistance percentage (FMAP) would be 75 percent. FMAP is the percentage of Medicaid services that are covered by the Federal Government, as opposed to a state’s contribution. The level of federal assistance varies per state; however, 75 percent is one of the highest federal assistance levels.

To facilitate state plan amendments, planning grants may be awarded to participating states. The state plan amendment would determine how eligible individuals are referred within the healthcare system, and where patients must receive genome sequencing services. In order to participate, states would have to submit a report following a three-year trial period. This report must include information about the extent to which whole genomic sequencing techniques reduced health disparities and improved the outcomes of patients using these services.


Medicaid and the Social Security Act Title XIX

This policy would amend Title XIX of the Social Security Act. First enacted in 1965, Title XIX of the Social Security Act created a directive and regulations for Medicaid, a program jointly run by Federal and State Governments. Under Medicaid, the Federal Government requires coverage for certain groups, including low-income families, disabled individuals, and qualified pregnant women and children. States can provide coverage to additional groups outside of those mandated by the Social Security Act and set some eligibility requirements. Nationally, 37 million children are covered by Medicaid. While genomic sequencing is considered reasonable and necessary under Medicare, coverage under state-based Medicaid programs varies.


Similarities between the Policy and Private Insurance

Under the definition provided, the proposed legislation would give patients access to whole genome sequencing, which gives a read-out of the entire genome, as opposed to whole exome sequencing, which provides a read-out of only the genes that instruct a functional product. Many prominent private insurance companies, including United Healthcare, Cigna, Aetna, and Blue Cross Blue Shield, provide some coverage for whole exome sequencing, but they do not provide coverage for whole genome sequencing on the basis that it is too experimental.

The Science

Science Synopsis

Genes are the hereditary unit of biology, allowing for traits to be passed through generations. Genes are dictated by a DNA sequence, and together compose a genetic code, known as a genome. Genes and DNA can be thought of as letters (DNA) that make up a word (a gene), which allow us to communicate a point (a trait).

Genomes include regions that provide either the instructions for specific traits or the regulation of those traits. More specifically, the regions that provide instructions for a specific trait are known as coding regions, or exons. These coding regions provide instructions for producing functional products, such as a protein that produces the pigment that results in green eyes. Noncoding regions, or introns, are less understood. However, introns have been shown to regulate exons. In practice, noncoding introns may be essential for insuring that genes are turned on and off as needed. The instructions provided by introns are, in part, the reason cells in your liver and cells in your brain can have the same genes but very different functions.  

The functional and regulatory abilities of the genome are why your body functions the way it does. Changes, or mutations, to the DNA sequence can prevent genes from properly completing their job. Mutations can cause genes to be turned off, stopping the production of their functional products. Other times, mutations can impact the regulation of a gene’s activity. For example, in a rare genetic disorder known as fibrodysplasia ossificans progressiva (FOP), a mutation causes bone to accumulate within a person’s muscles. As this example demonstrates, a tiny change in the genetic code can have catastrophic results leading to extremely debilitating diseases and/or death.

FOP is an example of a rare disease, impacting just one in two million people around the world. While each individual rare disease is uncommon, these conditions as a whole are not. In the US, 25-30 million Americans suffer from one of the 7,000 rare genetic disorders. Many rare genetic disorders have a fetal or pediatric onset, meaning that those affected begin to show symptoms while still developing in utero or during childhood, respectively. While newborns are screened for a small number of genetic disorders at birth, most rare disorders are not included in this screening.

Many rare genetic diseases present with a variety of nonunique symptoms, which makes them difficult to diagnose. Often it can take years for the underlying disease to be identified, resulting in serious emotional and financial stress. Within the rare disease community, the expensive burden and long timeframe from first symptoms to diagnosis is often referred to as a diagnostic odyssey.

Research suggests that genome sequencing can be used to address the diagnostic odyssey. Genome sequencing provides a read-out of a person’s DNA sequence. This sequence can be compared to a reference to identify mutations within an individual’s genome. Some mutations are pathogenic, meaning that they will cause diseases, while other mutations are harmless. There are two predominate classes of genome sequencing, whole genome sequencing and whole exome sequencing. Whole genome sequencing allows for a comprehensive examination of the DNA sequence, including both the coding and noncoding regions. In contrast, whole exome sequencing provides the DNA sequence for only the coding regions (exons) of DNA. Exons only account for about 2% of the DNA sequence. Unlike whole genome sequencing, whole exome sequencing does not examine the noncoding regions, which have a regulatory role. With that said, both techniques allow scientists to look for irregularities in a DNA sequence to identify abnormalities and underlying diseases.

Both whole genome sequencing and whole exome sequencing have clinical utility, with better diagnostic capabilities compared to other tests. Studies have shown that both whole genome and whole exome sequencing improve the ability to diagnose and care for sick infants on the basis that an understanding of the cause of a disease will facilitate better decision making during treatment or palliative care. One study found that genetic sequencing was clinically useful in the treatment of 65% of patients. Additional work has noted that whole genome sequencing may be particularly useful in neonatal intensive care units. This particular application is based on the reality that many rare genetic diseases present within the first month of life and other diagnostic methods are either too slow or ineffective to be clinically useful.

Scientific Assumptions

  • Diagnosing rare diseases is problematic and whole genome sequencing can help to address this issue. There are major difficulties in diagnosing children with rare diseases. Whole genome (and whole exome) sequencing can aid in diagnosis. However, while whole genome sequencing is much more effective than traditional diagnostic methods, it is not perfect. It does not provide a diagnosis 100% of the time due to technical limitations and because rare pediatric diseases do not always have a single genetic cause.

The Debate

Scientific Controversies / Uncertainties

Whole Genome Sequencing versus Whole Exome Sequencing

Within the medical and scientific field, there has been debate over whether whole genome sequencing is necessary to achieve a diagnosis or if whole exome sequencing is sufficient. Whole exome sequencing only examines approximately 2% of the genome. Both whole exome sequencing and whole genome sequencing are useful for diagnosis, but whole genome sequencing may be slightly more effective in diagnostics. With that said, whole exome sequencing is noticeably cheaper than whole genome sequencing because of its smaller scale. Therefore, the tradeoff between cost and increased efficacy is still up for debate.

The Cost of Whole Genome Sequencing

Whole genome sequencing has been available for many years, but its cost has made it difficult to justify using it clinically. However, the cost of genome sequencing has fallen precipitously in recent years, enabling its more widespread use. In fact, whole genome sequencing may be just as, or more, cost-effective than other traditional methods used in diagnosing and treating genetic abnormalities. With that said, whole genome sequencing is not cheap with prices in the thousands of dollars.

Ethnical Implications of Whole Genome Sequencing

One point of discussion has been how to handle incidental findings. In genomics, incidental findings are genetic abnormalities that can be identified but may not be the clinical source of an individual’s disease. Such findings may include genetic variations that are associated with behavioral and psychiatric disorders. These incidental findings may not be applicable to an individual’s disease in question but could be relevant to their overall health. Additionally, similar genetic variations may be carried by relatives or future children. Decisions on how and which incidental findings should be communicated, if at all, are still very much up for debate.

Endorsements & Opposition

  • One hundred and ten organizations issued a letter of support for this legislation. The letter stated, “This legislation has the potential to build upon the promises of the “21st Century Cures Act,” furthering the emerging field of precision medicine, and lowering health care costs by facilitating better diagnoses, and the consideration of preventive measures.”
  • The Prader-Willi Syndrome Association has endorsed this legislation. Stacy Ward, the Director of Family and Medical Support at the Prader Willi Syndrome Association (USA) noted, “For a child with Prader-Willi syndrome (PWS), an accurate and timely diagnosis can be the key to a longer, healthier life”.
  • Frances Collins, the director of the National Institutes of Health, has voiced his support for the widespread use of whole genome sequencing for diagnosing rare diseases stating, “Rapid diagnosis is critical for infants born with mysterious conditions because it enables them to receive potentially life-saving interventions as soon as possible after birth.”

Potential Impacts

If this policy were passed and adopted in all states the policy could expand access to whole genome sequencing to 37 million children, should they be an “eligible individual”. Expanding Medicaid coverage to include whole genome sequencing would decrease the time to diagnosis to combat the diagnostic odyssey faced by rare disease patients and their families. Research has contended that using genome sequencing as an early diagnostic test “rather than a last resort would be beneficial to many populations, especially critically ill neonates where rapid diagnosis is essential”. Decreasing the diagnostic odyssey would have clinical and financial implications. Clinically, it has been found that treatment adjustments as a result of genome sequencing have resulted in a lower number disease related issues in infants suffering from rare genetic disorders. Financially, decreasing the time to diagnosis can lower medical costs, making whole genome sequencing a cost effective option.