Thursday, February 05, 2015

It IS more precise, argues Shaywitz

David Shaywitz and some others at Twitter have had some not so nice things to say about this recent post I wrote quoting an article by Michael Millenson.  While I've urged them to post comments here (where you get more than 140 characters), they haven't yet.  So I'll try to summarize the major points while the issue is still ripe here on the blogosphere.  (David is very clear to disclose that he's with DNAnexus, a company in the genomic and health data management space.)

The general premise is that Michael and I shouldn't be so negative about a new government program designed to support "Precision Medicine."

David links first to an article in which he expressed the excitment of being present for the President's East Room announcement.

As an executive at a relatively young and decidedly ambitious company, it’s hard to describe the excitement and sense of remarkable possibility you experience sitting in the East Room hearing the President of the United States emphasize the fundamental importance of exactly what it is you believe you and your colleagues are doing.   Entrepreneurs are perennially encouraged to follow hockey great Wayne Gretzky’s advice, and skate to where you think the puck will be going.  Now, imagine feeling that the President has just fired the puck in your direction.

In short, he frames the issue this way (you can read the details):

It’s difficult not to be struck by both the audacity and the difficulty of the President’s initiative.  Developing effective cures for complex disease is generally far more complicated than identifying a single causative gene. 

Nevertheless, there are conspicuous examples of progress.  

After further back-and-forth on Twitter, David notes: "My point is ACCE framework central to personalized medicine," and cites this article he wrote at

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?

Comments welcome! 


nonlocal MD said...

Reminds me of Nixon's War on Cancer. Before we understood much of what causes cancer.

Initial Truth said...

I like David Shaywitz's writing on, where we both post, and respect his work as an entrepreneur. However, for the scientific reasons he cites, clinical genomics is only modestly useful today precisely because we don't have very many precise diagnostic solutions and even fewer therapeutic ones.

In the white paper I wrote that I link to in my industry. The three competing breast cancer article, I cite many other examples of hype by the recurrence tests is not an anomaly.

Dr. Khoury's work at CDC carefully treads the line. Others are enthusiasts. That's fine -- we need enthusiasts to make progress, and I wish Shaywitz nothing but success. At the same time, Americans with cancer and other diseases need realistic information about what genomic therapy can do for them today and in the near future.

Can you imagine Steve Jobs publicly admitting the failings of Apple computers? Me, neither. But that doesn't mean all the Apple products were always wonderful. The same applies to the current products of the talented folks bring you not "personalized" or "precision" medicine, but clinical genomics.