What's Your Sequence?

DNA sequencing -- genetic testing -- is in the news.  As it has been, and as it is increasingly going to be.

Whether we're really ready or not.

Geisinger President and CEO David Feinberg announced at HLTH Conference that it would make DNA sequencing part of its preventive care protocol, stating: "Understanding the genome warning signals of every patient will be an essential part of wellness planning and health management."

As Dr. Feinberg had said in a previous article:

The way we look at it, that's millions of Geisinger family members who no longer have to rely on the law of averages to forecast their health and make plans about their life and how they live it."  

Geisinger already had enrolled 200,000 participants in MyCode Comunity Health Initiative, its precision medicine initiative.  The new effort will expand on the efforts to identify genetic risks early.  "We’re going to start doing it the same way we would talk to patients about getting a cholesterol check," Dr. Feinberg told reporters.

And they're putting their money where their mouth is: patients won't pay for the sequences -- estimated at $300 - $500 per participant.  According to Forbes, Geisinger will pay for the sequencing via donor funds and insurance company quality initiative payments.  Dr. Feinberg is confident it is the right thing to do: "We think by scaling it we’ll hopefully more quickly show the cost-effectiveness of it, and it will become pretty obvious that everybody should be getting this.”

Geisinger is far from the only believer.  A report from the Garvin Institute for Medical Research declares that genomics is "already driving a remarkable paradigm shift in health practices and outcomes."  Its lead author, Dr. Thomas Barlow, says: "Genomics is changing healthcare – now and for future generations. We’re no longer merely forecasting change: instead, we’re watching it happen.” 

The above would be plenty of news to digest on its own, but Health Affairs had an issue devoted to Precision Medicine that generated some news of its own.

One of the articles that has generated a good deal of attention is one by Katherine A. Phillips and colleagues looking at the growth of genetic testing, with particular focus on 2014-2017.   They found that there are already over 75,000 genetic tests on the market, with 10 new ones coming on the market each day.

Absorb that for a second.  I'm trying to decide which number is the more startling.

Many of these tests are redundant, with only an estimated 10,000 unique test types.  Testing for pediatric and rare diseases are increasing fastest, followed by prenatal, cancer, hematology, and neurology, although spending on prenatal and hereditary cancer tests were highest.  They predict this will be a $7.7b market by 2020. 

Adding all these tests to clinicians' tool-set would seem like a good thing, but it may not be.  Those 75,000 variations of 10,000 test types makes picking the right version, from the right vendor, challenging.  And this is a challenge that most physicians are not ready for.

Another article, by Diane Hauser, et, alia, reported on the results of a survey of primary care providers on genetic testing.  The good news is that most had formal genetic education, and most had a positive opinion about the value of genetic testing; 70% thought it would be improving outcomes within 5 years. 

The worrisome news, though, is that only 14% had any confidence in their ability to interpret genetic test results, especially for patients at high risk for genetic conditions.  Only about a third had ever ordered a genetic test -- and previous experience with genetic testing did not increase their confidence. 

As the authors pointed out, this was not a hypothetical issue: the physicians surveyed were about to have their patients with African ancestry enroll in genetic testing designed to identify risk for kidney failure.  They were soon going to get results that they would have to explain and possibly do something about.

"Ten new tests a day — no one can be expected to master that," Ms. Hauser told The Washington Post, referring to Dr. Phillips' results.  "How are we going to help primary-care providers, who are barraged with all these genetic tests — some of which are very actionable and important, and some of which are not.”

Dr. Phillips shares the concern:

If I were a provider trying to figure out what to order, that's where this is in some way the Wild West, because we have so many tests out there.  Trying to sort out what to use, when and how much to pay for a test is pretty complicated.

The NIH urges consumers to be aware of three things when thinking about genetic tests: analytical utility, clinical validity, and clinical utility.   I.e.,

• does the test accurately detect the gene variant?
• how strongly is the gene variant related to a specific risk?
• are there diagnoses/treatments for the identified risk?

Meanwhile, the market for home testing is booming.  For example, in March the FDA announced 23andMe could market a test for gene mutations associated with risk for breast and ovarian cancer, which 23andMe CEO Anne Wojcicki called "a major milestone in consumer health empowerment."  

The FDA noted, though, that most mutations that would increase an individual's risk are not detected by the test.  A negative result doesn't mean you aren't at risk, nor does a positive one necessarily mean you are.  

Keep in mind as well that a recent report found a 40% false positive rate in variants reported by direct-to-consumer genetic tests (no words on other genetic tests).  "Bad" results may just be faulty results.  The authors caution that genetic tests need to be interpreted by qualified health care professionals, in the context of other risk factors.  Ms. Hauser might warn that those might not be so easy to find. 

DNA sequencing is not going away.  Nor should it.  Our DNA will soon become an integral part of our health history, and, sometime after that, of our treatment decisions.  The trouble is going to be the gap between those two. 

We will almost certainly know what genetic results might be a problem sooner than when we'll know what is likely to be a problem, and, in most cases, we'll probably know both of those before we'll know what to do about those problems.   Precision medicine is going to remain frustratingly imprecise for some time. 

So, go ahead and get your DNA sequenced.  Just don't expect it to be a magic bullet...yet.