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Thursday, September 21, 2017

Precision medicine update

My latest AAAS Science Magazine hardcopy arrived yesterday. Interesting (firewalled) article by veteran AAAS writer Jocelyn Kaiser therein:
NIH's massive health study is off to a slow start
Nearly 3 years after then-President Barack Obama laid out a vision for perhaps the most ambitious and costly national health study ever, the U.S. National Institutes of Health (NIH) is still grappling with the complexities of the effort, which aims to probe links between genes, lifestyle, and health. The study plan, or protocol, is ready, the biobank is taking samples, and the enrollment site is up, but study leaders are still in early “beta testing” of the 1-million-person precision medicine study.

The All of Us study, as it is now dubbed, had once expected that by early 2017 it would enroll at least 10,000 participants for a pilot testing phase; it is up to just 2000. Its national kickoff, envisioned for 2016 and then mid-2017, has been delayed as staff work out the logistics of the study, which is funded at $230 million this year and projected to cost $4.3 billion over 10 years. But study leaders say that for an endeavor this complex, delays are inevitable. “The pressure on our end is really about getting it right and doing this when we're ready,” says Joni Rutter, director of scientific programs for the project in Bethesda, Maryland...
Plans are to enroll a million consenting patients in the ambitious longitudinal research.

The study will recruit most volunteers through health care provider organizations (HPOs), or networks of clinics and physicians, and the rest directly from the general population. Volunteers age 18 or older will give blood and urine samples and undergo a few basic tests such as blood pressure, height, and weight during a 1-hour clinic visit, after which they will receive $25, the protocol says. They will complete three online surveys about their health and lifestyle. The study will also ask volunteers to allow access to their electronic health records so researchers can track their health over time.
They've dubbed it the "All of Us" study. From the NIH page:
"The All of Us Research Program is a historic effort to gather data from one million or more people living in the United States to accelerate research and improve health. By taking into account individual differences in lifestyle, environment, and biology, researchers will uncover paths toward delivering precision medicine."

Among the potentially daunting issues to be successfully traversed: "Self-selection bias" (though they claim to be mounting an intense disparities-mitigation recruitment effort on that front), "consent" issues (which can vary legally from state to state), particularly since they intend to delve into DNA analytics (oversold of late?), and "data quality"/EHR "interoperability" hurdles.

Other thoughts of mine: "A million?" Sounds great (but is it really "Big Data?"). When I was a bank credit risk analyst we ran highly effective credit underwriting modeling campaigns (pdf) using our internal customer data comprised of several million accounts (our team was astute; the bank had successive record profits each of the five years of my tenure).

But, it's one thing to do adroit CART and stress-tested correlation/regression studies using clean data comprising a relatively small number of independent variables. It's entirely another matter to do so where the databases have to house hundreds to thousands of (longitudinal) clinical variables per patient (of sometimes uncertain data origination pedigree). Study enrollee dropouts over time, and necessary stratifications (whether through subective "expert judgment" or data-driven via methods such as cluster analysis) may well make the "million" start to look pretty small in relatively short order.

The article concludes:
Others question whether the massive investment in DNA-based medicine will pay off. It may merely “confirm that for the vast majority of things, environment and behavior trump gene variants by a wide margin,” says physiologist Michael Joyner of the Mayo Clinic in Rochester, Minnesota. What's more, personalized medical care may not mean much for the millions of Americans who lack health insurance, says bioethicist Mark Rothstein of the University of Louisville in Kentucky. “We'd get a lot more bang for the buck by having everyone have access to the low-tech medicine that's available right now.”
Indeed. I forget the source at the moment, but I recall from one of my myriad books that I study and cite here the assertion that, for most clinical dx issues, "an old-fashioned, assiduously-taken SOAP note "FH" (Family History) spanning three generations still outperforms a genomic assay." Again, the applied "omics" are still in their analytical infancy and rife with challenges.

Also apropos, today's political "Repeal" fracas. From my iPhone this afternoon:

I also have to wonder about the security of the "All of Us" projected long-term $4.3 billion funding, given the Trump administration's zest for budget-cutting at every turn (Jocelyn does not share that concern, citing "congressional support." I guess we'll see).


Jocelyn Kaiser apprised me of this. I'd have seen it in any event, given that STATnews is one of my priority daily stops, but thanks!

By LEV FACHER @levfacher

The National Institutes of Health would like six vials of your blood, please.

Its scientists would like to take a urine sample, measure your waistline, and have access to your electronic health records and data from the wearable sensor on your wrist. And if you don’t mind sharing, could they have your Social Security number?
It is a big ask, the NIH knows, and of an equally big group — the agency eventually hopes to enroll over 1 million participants in the next step of what four researchers referred to in a 2003 paper as “a revolution in biological research.”

The appeals, however, are befitting the biggest-ever bet on precision medicine, now more than a decade in the making. The paper’s lead author, Dr. Francis Collins, has been devoted to the project from its inception, riding his vision for a more precise world of medical treatment to his current post as the NIH’s director.

The data-gathering experiment, dubbed “All of Us,” is an important stop on the way to making personalized medicine a reality around the world, Collins and others say. The NIH hopes that the trove of information could one day enable doctors to use increasingly precise diagnostic tests. Eventually, scientists could shape treatments based on an individual’s genetic characteristics.

But one of Collins’s stated goals is ensuring more than half of the participants come from communities that are historically underrepresented in biomedical research — and that’s a gamble…
Good article. A fairly long read. Worth your time. Nice examination of the ongoing logistical issues that will have to be surmounted.


The 11th Annual Health 2.0 Conference draws nigh. Be there. I will.


From The Incidental Economist, another of my daily stops.
The only option left to the Senate is to make health care reform someone else’s problem
…If it hasn’t become abundantly clear, the only thing left for Republican Senators to try is to kick the can down the road. Again. They’re going to try and pass a bill which gives less money overall to states, a lot less money to some states, and then tells them to “figure it out”. Later, they can claim that they gave the states all the tools they needed to fix the health care system, so now it’s THEIR fault things don’t work.

This is ridiculous.

There is no magic. There is no innovation. If there was a way to make the health care system broader, cheaper, and better, we would do it right now. We would have done it years ago…

The opening paragraph of my 2009 post "The U.S. health care policy morass."
Some reform advocates have long argued that we can indeed [1] extend health care coverage to all citizens, with [2] significantly increased quality of care, while at the same time [3] significantly reducing the national (and individual) cost. A trifecta "Win-Win-Win." Others find the very notion preposterous on its face. In the summer of 2009, this policy battle is now joined in full fury...
Eight years later, the can continues to be kicked.


Senator John McCain has announced that he will again vote against the latest GOP repeal bill. That will probably doom the effort.


More to come...

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