Saturday, March 2, 2019

Portfolio of New and Recent Resources: Diagnostics in Sepsis

In the past few weeks, I ran across a range of resources on the importance of diagnostics in sepsis (and infection and antibiotics management), linking to some new policy perspectives and trends.  I provide links here.  Call it a portfolio...a cornucopia...a Pandora's box...a weblink compendium of open resources...

Topics Discussed re: Infectious Disease
  • The Importance of Diagnostics - Ginocchio, CAP Today, 2019
  • PAC CARB, 2019
  • 2020-2025: HHS Five Year Plan for CARB
  • Combating Antibiotic Resistance - Spellberg Book, Articles
  • Importance of Diagnostics - UK Report (O'Neill Report)
  • Importance of Diagnostics - US IDSA
  • Economics of Diagnostics - including BARDA
  • CMS Measures
  • JAMA Review of NGS in Microbiology
  • Costs, Causes of Sepsis
  • Zip file in cloud (open access sources)

Update: President's Advisory Council on Combating Antibiotic Resistance - PAC CARB - to hold special session on April 8, 2018, on whether it should throw its weight and prestige behind formally demanding that HHS should require CMS to finalize a postponed measure regarding hospital antibiotic stewardship requirements.  Here.  

Importance of Diagnostics - Ginocchio, CAP Today, 2019

In an article for CAP Today, Christine Ginocchio PhD (who has a long academic CV, currently at Biomerieux) provides an article titled, "No diagnostics, no stopping antibiotic misuse."   See it here.  Diagnostics can't be the poor stepchild of antibiotics & public health innovation.

PAC-CARB, 2019

Which is also a lead-in to the next topic,

Dr Ginocchio is, to the best of my knowledge, the first industry-based panelist at PAC-CARB, the President's Advisory Committee on Combatting Antibiotic Resistant Bacteria.

See the home page for PAC CAB, here.  It's become very active.

To get a feeling of the scope and value of the PAC CARB meetings, see the full agenda and decks for PAC-CARB's most recently meeting (January 30-31, 2019) are all online here.  (The webcast is also archived).   For some excerpts about T2 Diagnostics' presentation at PAC CARB, here.   PAC CARB has a special pop up meeting April 8 re: CMS seemingly dormant plan to require hospitals to have antibiotic stewardship committees, here.

2020-2025: HHS "Five Year Plan for CARB"

HHS is wrapping up its first five-year national plan to combat CARB (2015-2020).

In August 2018, Secretary Azar of HHS tasked PAC CARB with assisting HHS in creating a new five-year plan for CARB.   Here.

See the home page for the 5-year plan, including the original from 2015 and progress reports.  Here.  One of the arms of the five year plan directly involves improving diagnostics. 

See the 3-year interim review, dated October 2018, here.  Medicare watchers will note the CMS-based activities are pretty thin (see more below.)

Combating Antibiotic Resistance - Spellberg's Book and Articles

See Brad Spellberg's excellent nonfiction book on the global threat of antibiotic-resistant bacteria, "Rising Plague" (Prometheus, 2009; paper and ebook).  See his open access article on antibiotic policy dilemmas, Critical Care, 2014, here.

See also Spellberg's excellent open-access article on the difficulties of organizing strategic responses in hospitals, "How to Pitch an Antibiotic Stewardship Program to the Hospital C-Suite," Open Forum Infect Dis 3:ofw210, 2016, here.

(This free article should be required reading for anyone interested in how hospitals function.)

Importance of Diagnostics #1 - UK NHS, O'Neill Report (2015/2016)

UK has run a national "Review on Antimicrobial Resistance," aka the O'Neill Report. AMR home page here.  (This is cited in Ginocchio, above).

For work products, see the 2016 final UK white paper, which has a section on the importance of advancing diagnostics, here.

See also a special O'Neill commission report that is focused directly on rapid diagnostics, here.

Importance of Diagnostics #2 - IDSA (2013-2018)

In 2015, IDSA released an excellent 20 page white paper on the importance of diagnostics, and the role of LDTs in infectious disease.  Here

See also IDSA public policy paper Caliendo et al., "Better Tests, Better Care: Improved Diagnostics for Infectious Diseases," 2013, here.

See their 2018 IDSA guideline on "Utilization of the Microbiology Laboratory," Miller et al., entry point here, hopefully 94 page full document open access here.

IDSA has a home page for diagnostics policy here.  To reflect its policy positions, IDSA has written FDA and Hill to discourage over-regulation of LDT diagnostics which are vital for emerging infectious diseases, here.  IDSA has raised concerns about CMS infectious disease measures, here.

Economics of Developing New Diagnostics

There is a huge national and world literature on the economic challenges of developing new antibiotics, dis-investment by pharma in antibiotics, etc.  But: there are also substantial challenges to launching new diagnostics for infectious disease.  (See here and here and here for just three of countless possible examples.)

BARDA, the biodefense investments agency, has markedly upgraded its investments in infectious diease diagnostics in CY2018.  See website for BARDA/DRIVe investments in sepsis, here.

For an overview of some new BARDA investments, I highly recommend a trade press review article by Roth, HealthLeaders, February 2019, here.   Here, Roth summarizes the last 5-10 significant innovation investments by BARDA in this field.  Their goal is to help overcome market dysfunctions and valley-of-death problems for innovative microbiology diagnostics (and antibiotics).

In October 2018, Nature Reviews Microbiology published a truly superb review of the challenges of infectious disease diagnostics R&D and finance, Van Belkum et al, open access here.  This is the work product of an international team; I wrote about it here

(For a subscription-only article on PAMA and microbiology lab innovation, 360DX interviews Glenn George, here.  For a subscription-only article on how lab directors may skeptically view holistic arguments about test economics, here.)

For a comprehensive 2018 review of new and future antibiotic susceptibility testing systems (ASTs), Puttaswamy et al., open access, here.

FDA:  Antiobiotics, diagnostics, and resistance are FDA agency priorities.  For example, track back to a major address Dr Gottlieb gave at PEW Foundation in September 2018 here.   See also the FDA"s homepage for antibiotic resistance, here.

I highlight just one new item here.  In January 2019, FDA announced new efforts to help ensure that antibiotic susceptibility tests are available for new antibiotics, here and here.

CMS Measures for Infectious Disease Control and Prevention

In 2018, CMS proposed dropping a range of measures related to infectious disease, which stimulated concern in trade journals and public coments of the Association for Professionals in Infection Control.  Trade journal here, APIC letter here.

Dormant Requirement for Hospital ASP.  APIC has also asked CMS to finalize a proposed, but dormant, requirement for Medicare participating hospitals to have formal antibiotic stewardship committees (APIC policy page here with links to multiple letters to CMS, to PAC CARB, etc).   Note also that CMS has at best minimal roles and accomplishments in the 3-year review of the HHS Five Year Plan for CARB - here.

SEP-1.  I've written about CMS's important but controversial hospital quality measure, SEP-1, which is followed by less than half of US hospitals, entry point here.  SEP-1 was criticized in a 2018 article by NIH authors in Annals of Intern Med, Pepper et al., here.  See also a quite critical article by Faust & Weingart, 2017, here.

2019 - JAMA on Next-Gen Sequencing of Pathogens

Open access, review of advances in NGS sequencing and microbiology, by Gwinn et al., a two-page highlights article.  Here.

Coding of sepsis is difficult; CMS discusses this in its annual inpatient rulemaking each year, and there is a nice 6-page white paper from ACDIS (Assoc. Clinical Documentation & Improvement Specialists), here.

Costs and Causes of Sepsis - 2018 and 2019 Reviews

See a 2018 paper by Paoli et al, "Epidemiology and Costs of Sepsis in the United States," open access at Critical Care Medicine 46:1889-97.  Here.

Do see also a 2019 article that sepsis is a leading cause of hospital death, but nonetheless, in some proportion, acknowledge that it overlays other directly impending causes of death (terminal cancer, other terminal diseases).  Trade journal by Cheney, here, original article Rhee et al., here.

Not Cited in This Blog

I'll leave the citations there.  Not discussed - much effort at PEW Foundation, much effort at CDC.

Zip File in Cloud

Everything I've cited that is open access, find in a ZIP file in Cloud, here.  It's roughly 30 PDFs, 30 mb.