Thursday, September 5, 2019

Jorge Conde and Logistics/Strategy of KNOME (Bioinformatics for Whole Genome)

A17Z Podcast
Software Company in Healthcare

(Extracted)


https://en.wikipedia.org/wiki/Knome  






JORGE CONDE - KNOME
                             So in our experience and know me, it was interesting because here, this is a company with the sole purpose of the company was to provide software capability to analyze genomic information. And so, you know, when you launched that, your assumption is, well this could be used to power all kinds of applications. It could be used for research, either in academia and industry. It can be used for, you know, clinical diagnostics, flexible. We thought it was very flexible and so challenge one is, you know, a solution looking for a problem is always a very, very dangerous thing. I think that's universally true. It's especially true in the healthcare space. And challenge two was understanding exactly where in the case of the clinical setting where this technology would be used in the workflow. So here we want it to go after the clinical labs.
Speaker 2:          That was your initial hypothesis.

Our initial hypothesis for an application in a clinical setting, you have technicians and docs that are inside of the laboratory setting, receiving samples, running a test, analyzing the results of that test, generating a report that gets signed off by lab director, that goes back to a physician.

Usually it's in the form of a diagnosis, right? And it gets signed off and it goes to the physician. The physician now takes that report and basically decides what to do based on that information. So our assumption was, well, if you have the ability to sequence DNA now in a way that you couldn't before, before you'd have to do all of these specific tests, you have to know what the test, and then you'd test it and then you'd get a report. You have to know what street lamp the keys were under, right?
Speaker 2:          Like they're in that case. Whereas once you had the full genome, you would just sequence everything and just run a bunch of software [careers.] So our thought going into this was, well, that's an incredibly powerful tool for clinical labs because first of all, you can sequence just once and analyze over time, right? You can again get like a totally legitimate, right. And it turns out that there was a lot of challenges with that assumption. The first one is every lab is different.
A lot of them didn't have the budget or the willingness to basically pay the upfront piece to buy the capability to use this technology, or they didn't have the ability to sequence everything upfront, even of all of the subsequent queries would be technically free later the way they're reimbursed. Oh, how fascinating. Too expensive. Basically it's too expense. So even the, theoretically there's an ROI, a return on the investment of sequencing up front, just the way the industry is structured, the way reimbursement flows, the way payments flow.
Speaker 2:          It just didn't make sense for a lot of labs to do this.

So how is that not just a complete roadblock at that point it was a big roadblock. So that would, that required us to do was to then focus on clinical labs that had the ability to make certain investments in up front cost and those tended to be very sophisticated labs that do a lot of research work in addition to patient care. Then they tended to be on this sort of on the bleeding edge and they wanted to incorporate new technology and they were great partners and all of that. But then it goes back to your N of one problem.

So you sell something into that lab and you go next door and next door. It has a totally different set of capabilities, a totally different set of constraints, a totally different set of expectations.
Speaker 2:          And so therefore all of a sudden the solution you created for lab a is not relevant or unattainable for lab B.

 Now to just add to the stepping in it, you know, when you're analyzing genomic data, there's a massive amount of computation required. And so we went in there assuming, well this is easy, we're just gonna shoot all of this up to the cloud, we'll run the analysis, we'll send the data back to the lab to the lab, could verify it, generate a report, and off we go. It turns out labs weren't comfortable sending data up into the cloud full stop at that time, at that time, arguably even today, arguably even today in 2019 but definitely at that time we probably should have known that earlier. That would have changed how we thought about going into the clinical lab space. How would you have done your homework?
Speaker 2:          I mean, what would that have actually looked like? It was frankly, I think just defining the specs of what would be required to bring in our technology because I think people intuitively know that genomic data is massive. But you know, I don't think they know sort of the level of computation required to run the interpretation. Right? So like really running the numbers, running the numbers for them. And by the way, we tried everything. I mean we brought representatives from AWS that could show them that they had a HIPAA compliant cloud, that they had received all the certifications and it came back to risk aversion. So someone in the lab director saying like, look, I'm sure all of that's true, but I'm not going to risk sending all of this data up into the cloud. So that was a big, big challenge for us. And it ended up being a major limitation for our ability to expand into the clinical setting because of all of those barriers.
Speaker 2:          So what did you do? We have to do a plan a and a plan B. And so the plan a was we assumed that there would be a couple of forward looking labs or forward thinking labs that would be willing to work in a cloud environment much easier to deploy there. The plan B was we had to create a box, we had a grid of box and the box had to have essentially the competition. Yeah, we had a normal plan. Remember that? Oh my God. Because they didn't want the data to go outside and it's for the reasons that we'd expect, you know, there, there's regulatory, there's risk associated with that today in 2019 in fact, the companies that have managed to use this technology have taken the sort of full stack service approach. So that sort of high, low strategy became the approach is get folks to deploy into the cloud when they were willing to, and in the case where folks needed an appliance, we basically had to go to labs that had enough of a sample volume that an appliance made sense for them and make basically the case there from an investment stand.
Speaker 1:          So again, multiple choice variety and like addressing in different ways. Okay.
Speaker 2:          Pure software company in healthcare is a really hard thing to do because on the one side you have this challenge that it's hard to create a sort of a solution that's going to fit everyone and therefore you need to have some level of services around that software that's on one extreme. So when you need to have humans in the process or in the loop, and in the other extreme of it, if it is pure software, then it's considered the, it should be free. So it's very hard to abstract value.
Speaker 1:          That's so interesting. Do you think that's shifting at all with the kind of understanding of the importance of data and some other,
Speaker 2:          yeah, look, I would argue with shifting on a couple of of axes. The first one is, is data is becoming more and more valuable. Historically data was viewed as being either too small in terms of its impact, too narrow, too dirty, et Cetera, et cetera. Too difficult. Yeah, to unstructured, you know, so that historically had been the case. So if you have ways to ingest data and clean it and make it meaningful, then I think that is valued. Probably the most public one is would flat iron was able to do and ultimately getting acquired by Roche for $2 billion. And that's viewed as using an electronic medical record to capture patient experiences, take that information and give researchers the ability to drive valuable insights from that. That's a relatively new thing. So I think there is the ability to create value there. So I think that's one axis. I think there's a general shift in the model that having a tech enabled service can be a valuable thing and if done well can be a scalable business. In other words, if you know what you're trying to build and if the software layer reduces sufficient friction in the system and allows you to add people not linearly as you scale, right, but in a leverageable way, then all of a sudden you can have tech enabled services that can grow and become large businesses.
Speaker 1:          So leaning into what it is that makes it difficult almost. And then scaling that, leveraging that. Exactly. Finding ways to make that scalable. Yeah, no, that's not easy to do, but

Medicare New Fraud Regulations: Locking the Revolving Door re Provider Enrollment of Fraudsters

Updates regulations in April 2006 and February 2011.
Includes minor updates based on general authorities 1102 and 1871 (here).
The proposed rule (Obama administration, 3/1/2016) received only 87 comments.

Trade journal Health Care Dive, here.
Dark Report covered in its October 14, 2019 issue.
Arent Fox at JD Supra, here.

CMS final rule at Federal Register here.  84 FR 47794-857 (64 pp), September 10, 2019.

CMS NEWS / FOR IMMEDIATE RELEASE
September 5, 2019
Contact: CMS Media Relations
(202) 690-6145 | CMS Media Inquiries



Inspection Copy:


CMS Announces New Enforcement Authorities to 
Reduce Criminal Behavior in Medicare, Medicaid, and CHIP
The Centers for Medicare & Medicaid Services (CMS) today issued a final rule that strengthens the agency’s ability to stop fraud before it happens by keeping unscrupulous providers out of our federal health insurance programs. This first-of-its-kind action – stopping fraudsters before they get paid – marks a critical step forward in CMS’ longstanding fight to end “pay and chase” in federal healthcare fraud efforts and replace it with smart, effective and proactive measures. Today’s action is part of the Trump Administration’s ongoing effort to safeguard taxpayer dollars and protect the core integrity of the critical Medicare and Medicaid programs that millions rely on. 

The final rule, Program Integrity Enhancements to the Provider Enrollment Process (CMS-6058-FC), creates several new revocation and denial authorities to bolster CMS’ efforts to stop waste, fraud and abuse. Importantly, a new “affiliations” authority in the rule allows CMS to identify individuals and organizations that pose an undue risk of fraud, waste or abuse based on their relationships with other previously sanctioned entities. For example, a currently enrolled or newly enrolling organization that has an owner/managing employee who is “affiliated” with another previously revoked organization can be denied enrollment in Medicare, Medicaid, and CHIP or, if already enrolled, can have its enrollment revoked because of the problematic affiliation.   

“For too many years, we have played an expensive and inefficient game of ‘whack-a-mole’ with criminals – going after them one at a time -- as they steal from our programs. These fraudsters temporarily disappear into complex, hard-to-track webs of criminal entities, and then re-emerge under different corporate names. These criminals engage in the same behaviors again and again,” said CMS Administrator Seema Verma.  “Now, for the first time, we have tools to stop criminals before they can steal from taxpayers. This is CMS hardening the target for criminals and locking the door to the vault. If you’re a bad actor you can never get into the program, and you can’t steal from it.” 
The rule also includes other authorities that will effectively improve CMS’ fraud-fighting capabilities. Similar to the affiliations component, these authorities provide a basis for administrative action to revoke or deny, as applicable, Medicare enrollment if:
  • A provider or supplier circumvents program rules by coming back into the program, or attempting to come back in, under a different name (e.g. the provider attempts to “reinvent” itself);
  • A provider or supplier bills for services/items from non-compliant locations;
  • A provider or supplier exhibits a pattern or practice of abusive ordering or certifying of Medicare Part A or Part B items, services or drugs; or
  • A provider or supplier has an outstanding debt to CMS from an overpayment that was referred to the Treasury Department.
The new rule also gives CMS the ability to prevent applicants from enrolling in the program for up to 3 years if a provider or supplier is found to have submitted false or misleading information in its initial enrollment application. Furthermore, the new rule expands the reenrollment bar that prevents fraudulent or otherwise problematic providers from re-entering the Medicare program. CMS can now block providers and suppliers who are revoked from re-entering the Medicare program for up to 10 years. Previously, revoked providers could only be prevented from re-enrolling for up to 3 years. Additionally, if a provider or supplier is revoked from Medicare for a second time, CMS can now block that provider or supplier from re-entering the program for up to 20 years.

These important new authorities and restrictions, effective November 4, 2019, ensure that the only providers and suppliers that will face additional burdens are “bad actors” — those who have real and demonstrable histories of conduct and relationships that pose undue risk to taxpayers, patients and program beneficiaries. This new rule ushers in an important new era of smart, effective, proactive and risk-based tools designed to protect the integrity of these vitally important federal healthcare programs we rely on every day to care for millions of Americans. 

This new rule builds on CMS’ previous successful efforts to protect beneficiaries and taxpayer dollars while limiting burden on our provider partners without whom we could not deliver high quality care to the millions of people we are honored to serve. “Every dollar that is stolen from federal programs is a dollar that will never contribute to paying for an item or service for seniors and eligible people who need them,” said Administrator Verma. 

The Trump Administration’s program integrity activities saved Medicare an estimated $15.5 billion in Fiscal Year (FY) 2017, for an annual return on investment of $10.8 to $1. The 2018 Medicare fee-for-service (FFS) improper payment rate was 8.12%, the lowest since 2010. This translates to about $4.5 billion less in estimated improper payments from 2017. For Medicaid, in FY 2018 CMS recovered $10.5 billion in FFS improper payments. An improper payment is any payment that should not have been made or that was made in an incorrect amount under statutory, contractual, administrative or other legally applicable requirements.

In addition to today’s rule, CMS has implemented several new initiatives to increase provider and supplier transparency and accountability while reducing burden in the Medicare and Medicaid programs. To learn more, click here.



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Get CMS news at cms.gov/newsroom

Tuesday, September 3, 2019

Imran Haque - LInked In, Interviews.

Imran Haque has had a series of top-tier bioinformatics jobs in Silicon Valley.  He holds an EE/CS degree from Berkeley and a PhD in CS from Stanford (2011).

LINKED IN
https://www.linkedin.com/in/imranshaque/

Positions have included Counsyl, Freenome, Recursion Bio.

TECH TONICS PODCAST (2019/07)
https://connectedsocialmedia.com/17582/tech-tonics-imran-haque-grounded-data-scientist/?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+ConnectedSocialMedia-TechTonics+%28Tech+Tonics%29

FORBES 201905
https://www.forbes.com/sites/davidshaywitz/2019/05/23/pharmas-desperate-struggle-to-teach-old-data-new-tricks/#726472f93434

FORBES 201901
https://www.forbes.com/sites/davidshaywitz/2019/01/03/data-scientist-explains-how-ais-seductive-power-can-mislead-biomarker-researchers/#294187d59594

JAMA 2016: 350,000 Genetic Profiles for Carrier Risk
https://jamanetwork.com/journals/jama/fullarticle/2544641


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Recursion Pharmaceuticals (SLC), CEO Chris Gibson PhD
https://www.recursionpharma.com/
$121M 201907
https://www.biospace.com/article/releases/recursion-pharmaceuticals-secures-121-million-in-series-c-financing/
201905 Fast Company
https://www.fastcompany.com/90345960/most-creative-people-2019-recursion-pharmaceuticals-chris-gibson

For another company focused on AI-driven drugs,
https://endpts.com/ai-study-led-by-insilicos-zhavoronkov-bolsters-case-for-faster-cheaper-drug-discovery/



Monday, August 26, 2019

ACA FAQ #12 re BRCA Testing Free of Copay

https://www.cms.gov/CCIIO/Resources/Fact-Sheets-and-FAQs/aca_implementation_faqs12.html


Affordable Care Act Implementation FAQs - Set 12

Set out below are additional Frequently Asked Questions (FAQs) regarding implementation of various provisions of the Affordable Care Act. These FAQs have been prepared jointly by the Departments of Labor, Health and Human Services (HHS), and the Treasury (collectively, the Departments). Like previously issued FAQs, these FAQs answers questions from stakeholders to help people understand the new law and benefit from it, as intended.

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Q6: Does the recommendation for genetic counseling and evaluation for routine breast cancer susceptibility gene (BRCA) testing include the BRCA test itself?
Yes. HHS believes that the scope of the recommendation includes both genetic counseling and BRCA testing, if appropriate, for a woman as determined by her health care provider.
PHS Act section 2713 addresses coverage for evidence-based items or services with a rating of “A” or “B” in the current recommendations of the USPSTF, as well as coverage for preventive care and screenings as provided for in comprehensive guidelines released by HRSA. The USPSTF recommends with a “B” rating that “women whose family history is associated with an increased risk for deleterious mutations in the BRCA1 or BRCA2 genes be referred for genetic counseling and evaluation for BRCA testing.”
The HRSA Guidelines, released by HHS in August 2011, incorporate by reference relevant portions of an Institute of Medicine (IOM) Report, released on July 19, 2011. In some instances, the IOM Committee Report provides additional interpretation of USPSTF recommendations. For the USPSTF BRCA recommendation, the IOM Committee interpreted the recommendation to include “referral for genetic counseling and BRCA testing, if appropriate.” Thus, genetic counseling and BRCA testing, if appropriate, must be made available as a preventive service without cost-sharing.

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Wednesday, July 31, 2019

President Trump References at HHS Website

This past week, I ran across several HHS/CMS press releases or quotations specifically praising President Trump's vision and leadership, and I wondered how this compared to the Obama era.

See for example:
“Hospitals would be required to post all their payer-specific negotiated rates, which are the prices actually paid by insurers,” CMS Administrator Seema Verma said on a conference call with reporters. “Hospital pricing has been a mystery, but thanks to the leadership of President Trump, those days are over.”
 At: MedCityNews, July 29, 2019, here.

Once in a while this may be OK, but if it ever becomes mandatory in each press release, it would be a little eerie (sort of like, "Thanks to Comrade Stalin's leadership, the wheat crop has increased by 2%.")

Searching CMS.gov

I used the built-in search function on the CMS website to search for citations to Trump, and there were 101 (that's 40 per year).   Searching for Obama, there are 270 (that's 33 per year).  But large numbers of the Trump citations are from public comments on rulemaking where "trump" is used as a verb (rule A trumps rule B), so at least with this simple quantitative measure, Trump occurs less at HHS than Obama, although the Trump citations are sometimes more bold and colorful, as in the Verma quote above.

"Trump" As Part of Headlines

While I haven't done a systematic review of press releases, I did notice that an October 7 press released "headlined" the Trump Administration on a policy update.  Here.  "Trump Administration Empowers Nursing Home Patients, Residents, Families, and Caregivers by Enhancing Transparency about Abuse and Neglect."  Opening sentence, "Today, the Trump Administration and the Centers for Medicare & Medicaid Services (CMS) announced a major enhancement of the information available to nursing home residents, families, and caregivers..."

Monday, July 29, 2019

FIT may be as good as colonoscopy

DARK REPORT
https://www.darkdaily.com/regenstrief-institute-finds-fecal-immunochemical-test-may-be-as-effective-as-colonoscopy-at-detecting-colorectal-cancers/

July 2019

ANNALS INTERN MED
https://annals.org/aim/article-abstract/2726664/performance-characteristics-fecal-immunochemical-tests-colorectal-cancer-advanced-adenomatous-polyps?searchresult=1

5 March 2019  Imperiale et al.

https://annals.org/aim/article-abstract/2726665/why-what-you-may-know-about-fecal-immunochemical-testing-matters

Op Ed: Allison

Some U.S. primary care physicians and many of their patients may be unaware that fecal immunochemical tests (FITs) are noninvasive, easy to prepare, and inexpensive and have effectiveness similar to that of colonoscopy when used in a consistent, programmatic fashion to screen for colorectal cancer (CRC) (1). The paucity of studies comparing FITs and colonoscopy in 2000 may have been why Podolsky advocated for insurers to cover colonoscopic screening in all average-risk persons aged 50 years or older (2). Shortly thereafter, Congress ordered Medicare to cover the procedure without requiring published evidence of its superiority over less invasive and cheaper tests. 

In 2019, although trials are under way, we still lack published results of randomized controlled trials showing that colonoscopy is superior to FITs.

Currently, only about 65% of U.S. adults aged 50 to 75 years have been screened for CRC, and most of them have been screened with colonoscopy (3).