Precision medicine is still finding its footing, caught between the excitement around its promise and the challenges of its realization, as Stat reporter Sharon Begley has just chronicled in the Boston Globe, in the context of oncology. A similar pattern of hope and disappointment was seen after the completion of the original Human Genome Project – also memorably captured by Begley in an oncology story, this one for Newsweek.
In a recent podcast, Marc Andreessen (citing economist Carlota Perez) described how technology adoption characteristically goes through just this sort of cycle, from enthusiasm to disappointment to impact. Most strikingly, though, is that the time when the technology tends to be written off by the market is often precisely the period when the new technology starts to work – though it can take the market a bit of time to figure this out.
Phrased differently, Andreessen is suggesting that if you examine a technology during the disappointment phase, you may find the seeds of its eventual success.
In the case of precision medicine, I don’t see disappointment as much as I perceive impatience, a sense that it’s time for precision medicine to “show me the impact.” (Usual disclosure/reminder: I work at DNAnexus, a cloud genomics company in Mountain View.)
This moment may be close at hand in reproductive health, where the impact of genetic testing is experienced by many couples in a decidedly non-abstract fashion.
Genetic testing is increasingly employed for carrier screening (to evaluate if both parents carry specific deleterious mutations that can result in lethal conditions such as Tay-Sachs disease) and for non-invasive prenatal testing, or NIPT (a screening test to evaluate, via a routine blood draw from a pregnant woman, whether her fetus carries certain genetic abnormalities, such as an extra chromosome). (Disclosure: some DNAnexus partners work in this space.)
By obviating the need for more invasive procedures like an amniocentesis (if the screening test comes back negative), NIPT evaluation has proved sufficiently robust and economically beneficial that some payors, like Anthem, now authorize use of this test in pregnant women carrying a single fetus, regardless of risk status (previously, only women in a high-risk category would see NIPT covered).
Payors have generally resisted the widespread use of genetic testing, determined not to “test for testing’s sake.” Consequently, reimbursement of NIPT represents a strong endorsement of the economic value of genetic testing, when deployed in an appropriate clinical context.
On the carrier screening front, many insurers cover the cost of testing only in cases where there’s a suspicious family history. Otherwise, carrier screening has tended to be regarded as a fishing expedition, likely to add cost but not benefit.
However, recent work by Imran Haque, director of research at the Silicon Valley genetics testing company Counsyl, suggests that payors may want to rethink these assumptions. (Disclosure: neither I nor DNAnexus has a financial relationship with Haque or Counsyl.)
Haque’s company (like some others in the space) tests a range of select genes for mutations by evaluating the sequence of each of them. Using the mutation frequencies collected by the company, Haque asked what is the theoretical likelihood that a couple with a given ethnic background would have a child with a “profound” disease (like Tay-Sachs) or a “serious” disease (like cystic fibrosis). He then computed how many parents would need to be screened in order to identify a single afflicted fetus.
Haque’s result: while severe mutations (resulting in “profound” or “serious” disease if a child receives a mutation from each parent) individually are extremely rare, collectively, they are common enough to afflict more fetuses than trisomy 21 (Down Syndrome), which is routinely screened for in pregnancy (increasingly by NIPT as discussed above). The implication is that if payors are willing to reimburse for trisomy 21 screening, shouldn’t they willing to pay for carrier screening, which theoretically might impact more pregnancies?
While intriguing, Haque’s computational study will presumably need to be evaluated in a real-world setting to see how well the assumptions (many of which were actually fairly conservative) translate, both scientifically and financially.
Even so, time seems to be on Haque’s side; as more potentially deleterious mutations are identified and added to carrier screening tests, their diagnostic utility will continue to grow.
The implications of identifying an increasing number of at-risk couples (i.e. couples each carrying a recessive deleterious mutation in the same gene) will obviously raise profound ethical, social, legal, and financial questions.
If couples respond to the discovery that each parent carries a severe mutations in the same gene by pursuing pre-implantation genetic diagnosis (PGD), where a single cell of an early-stage embryo produced by IVF is removed and subject to genetic testing, this could be enormously expensive compared to the status quo – to say nothing of the ethical questions it would raise for some.
On the other hand, the cost of PGD may turn out to be less than the costs associated with the care of a child with a serious affliction; will this lead to unwanted pressure on such parents to pursue PGD?
The ability to screen parents – and fetuses – for rare genetic disease can raise vexing questions for patient communities. Some families strongly endorse screening, and feel they wouldn’t want others to undergo what they’ve experienced. Yet others worry about the effect on a patient community if there are fewer patients, concerns that can reflect both humanistic (see here) and pragmatic considerations; for instance, pharma companies might choose not to pursue a drug for a rare disease if screening seems likely to eliminate most future cases.
The profound questions raised by genetic testing in the context of carrier screening and NIPT evaluation reminds us that instead of lamenting the pace of precision medicine’s journeys, perhaps we had better figure out what to do once it arrives. The time for planning grows short.
