The Sequence 11/7-11/13
Treatment Implications for Epilepsy, Genetic Testing Labs Are Unprofitable, Broader Newborn Screening Expands to Greece, Genomic Dataset of Multi-population Asian Individuals with Bipolar Disorder
Treatment implications for genetic forms of epilepsy
McKnight et al. studied 418 patients with epilepsy who received a genetic diagnosis at Invitae to understand treatment implications for their genetic diagnoses.
Tell me more.
In a study of 418 patients with epilepsy who were found to have a genetic cause of epilepsy, i.e. they had mutations, or harmful changes in the DNA, that caused epilepsy, almost half had clinical management changes.
That’s a lot. What kind of changes?
It is. The most common clinical management changes were the addition of a new medication, the initiation of medication, the referral of a patient to a specialist, additional awareness of extraneurological disease features, and the stopping of a medication.
Now for the outcome of those changes: For the 167 patients with follow-up clinical information available, 74.9% reported positive outcomes, 64.7% reported reduction or elimination of seizures, 22.2% had decreases in the severity of other clinical signs, and 6.6% had reduced medication adverse effects. A few patients reported negative outcomes, including a decline in their condition (12.0%), increased seizure frequency (3.6%), and adverse medication effects (1.8%).
What’s the takeaway?
Although genetic testing for epilepsy is not yet standard of care, some professional societies have recently published guidelines that advocate genetic testing after other types of diagnostic tests and referrals to specialists. Recent advances in medicine based on specific genetic etiologies (i.e. precision medicine) have made things like enzyme replacement therapies and gene therapies available, or if not available then in clinical trials. As additional gene-specific therapies become available for epilepsy, I expect genetic testing will become standard of care in order to identify eligible patients for treatment.
Why are genetic testing labs so unprofitable?
We’ve all heard that the cost of genetic testing is going down. As technology gets better and processes are more streamlined, the cost has decreased. The Human Genome Project, the research project that first sequenced all of the genes of the human genome, required $2.7 billion. The cost to generate a high-quality 'draft' whole human genome sequence in late-2015, by contrast, was below $1,500. If the cost of sequencing is so ‘cheap’ in comparison to a decade ago, why are commercial genetic testing companies so unprofitable?
Here we explore an article by By Katie Stoll, MS, Jessie Conta, MS, and Michael Astion, MD, PHD, breaking this down.
Yes, genetic testing has become cheaper, but it’s still expensive at a large scale.
Compared to more common lab tests, genetic testing is more labor-intensive and time consuming, involves higher-wage staff, and involves technology that has a higher cost per test. Think the additional tasks of genetic variant analysis and genetic counseling, which are not generally seen with other common tests.
Genetics and insurance companies are not really friends.
Insurance plans control genetic test reimbursement by using ‘medical necessity policies’ (i.e. guidelines on when genetic testing is needed) tied to preauthorization systems, which use software to electronically aid in the decision-making of whether a test will be covered. The electronic decision-making is usually in collaboration with a combination of genetic counselors, nurses, and physicians to help make the decision. However, the software tends to be overly tuned to block fraud, waste and abuse, and is often delayed in keeping up with scientific evidence. Therefore, insurance systems may block genetic testing that is in fact medically necessary.
So not only are tests not being covered by insurance, but then it gets more expensive for genetic testing labs when they need to hire staff in order to manage all of the tests that insurance denies coverage for. Think submitting appeals, and customer support when test coverage is denied.
Genetics testing companies spend A LOT on marketing.
Like, way more than other types of clinical laboratories. It is not unusual for genetic testing companies to have marketing and sales budgets around 40-50% or more of revenue.
Genetic testing companies have very highly-paid executives.
Another contributor to financial losses in genetic testing labs is the high pay of executive leadership. Interestingly, executive pay seems to be inversely correlated with net profits. Think, the longer that a company lasts, the more executives are paid, even as losses grow deeper.
Interesting. What’s the takeaway?
Well, as the genetics community has already seen commercial genetic testing labs having massive lay-offs of genetic counselors as well as other clinical providers, the fear is that if genetic testing companies are not profitable, they may not be able to support essential services in genetic testing, like genetic counseling.
Think you should talk to a genetic counselor about genetic testing? Find one here.
Research study aimed at studying the utility of broader newborn screening expands to Greece
Earlier this year, Rady Children's Institute for Genomic Medicine published a study detailing their results from BeginNGS, a pilot program to screen newborns for hundreds of genetic diseases with known treatment options using rapid whole-genome sequencing (rWGS). This should sound a lot like the GUARDIAN study, which stands for Genomic Uniform-screening Against Rare Diseases in All Newborns, that I wrote about last week.
The news here, though, is that Rady Children's Hospital and Health Center has teamed up with healthcare data company PlumCare RWE to expand its whole-genome sequencing-based newborn screening program to Greece.
Cool. What does that mean?
It means that the program, which looks at the utility of screening newborns for up to 388 rare genetic conditions, was successful enough to expand to Greece!
Results from the pilot study had showed that simulated rWGS newborn screening for 388 disorders identified 104 of 119 previously reported diagnoses, i.e. 87% of findings it definitely should have, as well as 15 findings not previously reported, i.e. 15 extra findings that weren’t picked up before by standard newborn screening.
Of more critical importance? In 43 of the 104 children in which this study identified diagnoses that were previously reported, symptoms could have been avoided completely had those diagnoses been made earlier (like as a newborn).
Tell me more about the program in Greece
Together, PlumCare and the Greek National Public Health Organization plan to recruit at least 1,000 families at academic sites, such as the EKPA-Alexandra Hospital in Athens, AUTH-Papageorgiou Hospital in Thessaloniki, and the University of Thessaly-University Hospital in Larissa. As with the program in the US, BeginNGS Greece will collect blood spot samples at birth for rWGS analysis. BeginNGS will not replace, but complement, current biochemical newborn screening.
For more information on how newborn screening works now and why 388 genes is in fact a lot, also see my post from last week.
What’s the takeaway?
Theoklis Zaoutis, president of the National Public Health Organization in Greece, said
"This is an important initiative that we fully support because it brings actionable treatments for individuals to improve outcomes for our children, delivers the latest translational medical science to Greek families, and it places Greece in a foundational position to further newborn genomic screening".
Advancing newborn screening in light of newer discoveries in precision medicine is important in ensuring babies have access to treatments that can have a critical impact on their lives.
Major partnership to create the largest genomic dataset of multi-population Asian individuals with bipolar disorder
Researchers from Broad Institute of MIT and Harvard, Virginia Commonwealth University, Johns Hopkins University, National Institute of Mental Health and NeuroSciences in India, Indian Institute of Science, Institute of Mental Health in Singapore, Korea University College of Medicine, and National Taiwan University are working together to recruit participants from India, Pakistan, Singapore, South Korea, and Taiwan into a study called the Asian Bipolar Genetics Network (A-BIG-NET). The study will be the largest cohort of Asian individuals with bipolar disorder to date.
Great. Why is this important?
There’s a lack of representation of the Asian population in genetic datasets. In fact, although nearly 60 percent of the world’s population resides in Asian countries, only 10 percent of participants of genetic studies are of Asian descent.
See my post about this when I reported on another new large genomic dataset from Asia here.
Got it. How exactly will this help?
By sequencing this population’s genomes and analyzing the data, the researchers hope to identify whether there are certain changes in the DNA that are linked with bipolar disorder in the Asian population.
Interesting. What’s the takeaway here?
We’re not all the same, and so the genetic testing offered to us all should not be the same either. This study supports focusing on different genes that cause bipolar disorder in individuals with Asian background.