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The most interesting healthcare news of this week was manifestly not Apple AAPL +3.06%’s new watch; I can only assume that the Cupertino-based company concluded, after meeting with the FDA and consulting with a range of experts, that it made far more sense to go down the path of nutritional supplements, and stay as far from regulators as possible — as many of their brethren here in the Valley have emphatically suggested.
No, the more substantive healthcare contribution of the week came from the latest issue of JAMA, where 2014 Lasker Award winner Mary-Claire King, writing with several colleagues from Israel, audaciously suggested that all adult women should be screened for defined categories of BRCA1 and BRCA2 mutations – specifically, on “unambiguously loss-of-function mutations with definitive effect on cancer risk.”
(Disclosure reminder: I work at a genomic data management company.)
Today, patients with a family history of breast or ovarian cancer may be referred for BRCA1 and BRCA2 testing, but King is suggesting something more: she wants every adult woman to receive this testing, based on recent research she and her colleagues have published suggesting that relying on family history may miss half of the families with relevant BRCA1 or BRCA2 mutations; these families without a known history of breast or ovarian cancer tend to be smaller, King says, but members carrying the mutations have roughly the same chances of getting cancer as carriers from families with an established history of the disease.
The questions to ask about screening are captured by the ACCE framework (which I recently highlighted in the context of data from wearables, but which was originally developed for genetic testing).
Analytic validity – do the tests reliably and consistently measure the mutations they say they measure?
Clinical validity – how well does a positive test predict the likelihood of a cancer due to BRCA gene dysfunction? To what extent can a negative test be relied on to conclude that a patient is not at elevated risk of cancer due to BRCA gene mutation?
Clinical utility – does a positive test provide actionable information? King writes that “Among women who carry mutations in BRCA1 or BRCA2, surgical intervention, in particular risk-reducing salpingo-oophorectomy, reduces risk of both ovarian and breast cancer and reduces overall mortality.”
Ethical, legal, and social implications: What are the implications of population-level screening? For example, might a negative screening test provide a false sense of security, resulting in reduced vigilance, and an ultimately an increase in non-BRCA-related breast cancers?
Is population-based testing for BRCA1 and BRCA2 mutations warranted? The New York Times discussed this with King:
“Critics may object that ‘women aren’t ready for this,’ [King] said. But she argued: ‘Why should women be protected from information that will empower them and allow them to control their lives? We don’t need that kind of protection.’”
This is really the essential challenge of the rapidly-growing field of genomic testing, and the question King is pressing all of us to contemplate: when are the data good enough to share with patients?
Set the bar too high, and it raises the ugly specter of paternalism (as King suggests), as well as the very real concern that regulators, with the best of intentions, may let the perfect be the enemy of the good, and make it more difficult (and more expensive) for patients to access important information that could impact their lives.
However, share too early (before analytic validity is established, for example), and you risk providing bad data to patients that could result in devastating, life-changing decisions; this is the logic behind the FDA’s drive to regulate high-risk laboratory developed tests, for example (nicely discussed on this Mendelspod podcast).
Similarly, if you share data you don’t understand (which is a fair characterization of many mutations that are found during genetic screening), you risk scaring patients without helping them. King, according to the Times, feels “ women should not be told about other rare mutations whose significance is unknown.” (Others feel even these data should be shared.)
As the molecular basis of cancer and other diseases becomes increasingly well-understood, and additional risk factors are identified and characterized, more and more genes are likely to enter the BRCA1 and BRCA2 category, and merit serious consideration for population screening.
Moreover, as the cost of sequencing plummets, and the amount of actionable data increases, we may start to ask (as some already have) whether it makes sense to offer newborn infants not a handful of biochemical tests, as we do today, but rather genetic screening – perhaps even sequencing of their complete genomes.
In an era where many parents already bank cord blood (as my wife and I did), based on the slight chance that it might be useful one day, is it such a stretch to imagine parents might want to obtain the complete genomic sequence of their kids, in hopes that over time, and with ever-increasing annotation, it might prove at least as beneficial as cord blood? Such testing would raise a host of thorny issues, as a group from McGill University discussed thoughtfully in Science Translational Medicine earlier this year.
In contemplating the astonishing complexity around bleeding edge medical technologies, including the very real operational challenges, and the attendant ethical issues that are appropriately raised, you can certainly appreciate why an incumbent consumer electronics company might elect to steer clear of controversy, and opt instead for a watch that occasionally reminds you to stand up.
But you can also see why Illumina ILMN +1.64%, the ascendant San Diego-based technology company that (as my colleague Matt Herper recently reported) makes most of the machines responsible for next-generation sequencing, has been experiencing such explosive growth. Over the last five years, Illumina stock has even outperformed Apple — no U2 giveaway required.
Evidently, technology moves in mysterious ways.
David Shaywitz, MD, PhD is the Chief Medical Officer of DNAnexus, and the co-author, with Lisa Suennen, of Tech Tonics: Can Passionate Entrepreneurs Heal Healthcare With Technology? (Hyperink Press, 2013). He is a co-founder of Center for Assessment Technology and Continuous Health (CATCH) in Boston and regular contributor to Forbes, where this post originally appeared. You can follow him on Twitter: @dshaywitz.