New Review: How Fuzzy and Confusing are FDA Drug Decisions?

See a paper from Stanford with several FDA authors on how FDA makes decisions when the evidence is close.   The paper screens drug applications from 2013 to 2018, finding 912, of which 22 faced multiple review cycles including a flat-out initial denial.  

 The authors conclude that "the FDA has no mechanism to find, or tradition to cite, similar cases when weighing evidence."   They argue that FDA decision pathways and evidence standards were "highly variable."   

The authors argue that a better tradition of "case studies" and systematic approaches would enhance the transparency and reliability of these decisions.

Find the Janiaud paper here.  Find the op ed here.

Dr. Janiaud is at the Meta-Research Innovation Center at Stanford; Dr. Goodman is professor of epidemiology there.   Goodman and John Ioannidis co-led the MRIC.  Dr. Russek-Cohen is retired FDA; Dr. Irony is former FDA, now with Janssen.

Although it's a 2021 decision, outside their scope of 2013-2018 decisions, the authors make several references to the 2021 approval of aducanumab (Aduhelm).  There is also an op ed from Washington University's Joel Perlmutter, who resigned in June from the FDA neurology committee.

Very Brief Blog: Comment by October 15 on the Cancellation of Medicare "Breakthrough Coverage"

In January 2021, the Trump administration finalized regulations that would provide 4 years of Medicare coverage to new devices if they were approved by the FDA Breakthrough Pathway - here.  The title is, "Medicare Coverage for Innovative Technology," or MCIT.

After several intermediate steps, the Biden administration announced on September 13 it intends to entirely cancel the Breakthrough coverage regulations - here.

       (See a listing of all the regulatory steps - here.)

In order to comment the MCIT cancellation, go to this webpage:

• Medicare Program: Medicare Coverage of Innovative Technology and Definition of Reasonable and Necessary (September 14, 2021)
• https://www.regulations.gov/document/CMS-2020-0098-0560

Click in the blue box "COMMENT" in the upper left to register your comment.  Final date is October 15, 2021.

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Note, the box in the upper right, "SUPPORT," is for technical support, not a button for making a PayPal donation to CMS or regulations.gov.

In Memoriam: Dr. Charles Root, Founder of CodeMap

On September 15, 2021, Dr. Charles Root passed away.  He was well-known throughout the laboratory community for his wisdom and expertise.   

Dr. Root, whose original training was in nuclear physics, was a founder of CodeMap, which provides policy guidance, analytics, and consulting for the laboratory industry.

See the In Memorium announcement at CodeMap, here.   See the CodeMap home page, here.

Very Brief Blog: Dr. Paul Gerrard Joins Veracyte as Medical Director, Managed Care

In an announcement posted on Link In (here), we learn that Dr. Paul Gerrard has joined Veracyte as the Medical Director for Managed Care.  

Dr. Gerrard previously served as a medical director for the MolDx program (here), and most recently, as a Vice President in the McDermott Plus consulting group affiliated with the McDermott Will & Emery law firm.

Online bio here.   Linked In here.  

In other news, Veracyte appointed Joshua Klopper MD as medical director of Endocrinology; he's been with both University of Colorado and Kaiser Permanente.  The executive medical director at Veracyte is Richard Klopper MD.

Very Very Brief Blog: Browse Comments on PFS Rule

Medicare published the proposed Physician Fee Schedule rule in July, with comments running to September 13.  Hot topics including valuation of AI services.

See the original rule here.

See and search the 35,000 comments receive  - here.  

CMS will publish the final rule circa November 1, effective January 1, 2022.

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AdvaMed always has strong comment letters that explain the problem before providing alternative solutions.  That's true again this year. See the 25-page AdvaMed general comment on codes and valuations here, and the special 14-page comment on issues like self-referral, here.

Very Brief Blog: Harvard Course on Molecular Diagnostics in Cancer

This past week, Harvard Medical School and partners ran a four-day course on molecular diagnostics in cancer.   I haven't researched this extensively, but it appears the full syllabi (in numerous powerpoints) are posted, along with a video archive which states it's online for two weeks.

See the home page here:

https://www.cmeinfo.com/harvard-molecular-diagnostics-syllabus/

click to enlarge

Click on each date row to unwind a listing of 8-10 powerpoints in PDF.  

Close to my heart, for example, on the fourth day, is a 20-slide deck by MGH's Dr Jochen Lennerz on reimbursement and regulatory issues.

https://www.cmeinfo.com/wp-content/uploads/2021/08/28.-Billing-and-Regulatory-Issues-Jochen-K.-Lennerz-MD-PhD.pdf

Lennerz and team have just released an article on insights from COVID policy towards regulation of LDTs in the future (trade press here, article here.)   

Click on the "video library" bar to open a calendar of the video files.  The website remarks, "Access to the Video Library is available for 2 weeks after the end of the conference and will expire at 5:00pm Central on October 1, 2021."

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For a 19-page,  2021 review of "clinical cancer genomic profiling," see Chackravarty & Solit, Nat Rev Genet, here.  The authors are at Memorial Sloan Kettering.

Very Brief Blog; HHS Releases Round 2 of Regulations on "Surprise Billing"

Last winter, Congress abruptly passed a Surprise Billing law, that will substantially regulate payments between insurers, patients, and out-of-network providers beginning in CY2022.  (Overview here.)

CMS issued the first round of implementing regulations for comment in July (here).  Article about the July rule here.  AHA letter on the initial surprise billing rule here.

On September 10, HHS released a second round of regulations, which appear to focus on topics like air ambulance, and ways that CMS itself can enforce surprise billing payment rules if states do not do so adequately.   It also addresses another corner of the law, in which consumers get transparency about how insurance brokers are compensated.

Press release here.

Regulation home page here.  Comment to October 18.

   (30 days comment; the earlier rule had 60 days.)

   PDF here (86 FR 71530, 9/16/21).

Air Ambulance fact sheet here.

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In September 2020, CMS announced a program that was controlling payments for air ambulance billing and had saved $650M in 4 years (acronym RSNAT).  Here.

In the new press release, HHS notes that the air ambulance industry is highly consolidated.  You would expect that; you wouldn't expect multiple competing firms to each have little market shares and high costs while maintaining aircraft and pilots on-call 24/7.   

Center for Medical Technology Policy to Close

 In a listserve marked, Update / For Immediate Release, the Center for Medical Technology Policy (CMPT) announces it will be closing in the near future.   

The change was announced by Donna Messner, PhD, the President and CEO of CMTP.  Advances in medical technology policy was a rarefied space 10-20 years ago, but now is "an active and vibrant space," including the federal PCORI (Patient-Centered Outcomes Research Institue), ICER (a high-visibility health outcomes institute), and others.  Messner holds a PhD in science and technology studies.

CMTP was founded by Dr. Sean Tunis 12 years ago.  Tunis had been Chief Medical Officer of CMS (2000-2005).   Tunis  has been a thought leader in evidence-based medicine and a prolific author (PubMed).

Find the CMTP website here.

Nerd Note: Lab Wins Legal Argument that LCDs Violate Statute; But Loses in Federal Appeals Court

 

Agendia Vs Azar; LCDs Ruled Invalid without notice & comment under APA; but Reversed at Appeals Court

Agendia, a molecular lab in California, has disputed denials of claims in 2012 and 2013 under an early MOLDX LCD and in a period when California was directly under Palmetto MAC LCDs.  

Agendia used constitutional arguments against LCDs.   They won at the federal court level in 2019 but the decision in their favor was reversed at the appeals level in July 2021.

Note - I am not an attorney and I am providing my best "English language" summary of the cases.

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The case was delayed due to ALJ backlog from 2014 to 2018.  An ALJ supported payment in 2018, finding the claims were "reasonable and necessary" despite the position of the MAC and QIC.   But it didn't end there. 

The Department Appeals Council overruled, saying the ALJ in this case had not clearly explained why he was overriding the LCD. (The judge is supposed to "grant deference" to LCDs and MAC medical directors, although he has the right to do overrule them, with justification.)

Agendia appealed to federal district course.  HERE.   Agendia v Azar, 10/29/2019.   Agendia argued that 

1. LCDs are an illegal delegation of responsibility from CMS to a private entity.  This is a constitutional issue, what the federal government can delegate.
2. LCDs violate the Administrative Procedures Act.  This is a statutory issue.
3. LCDs were arbitrary and capricious.  (Arbitrary is a judicial concept related to implementation of APA and other issues).

The district court ruled:

1. LCDs are not an illegal delegation, as CMS continues to supervise MACs and LCD claim decisions can be overturned (even if "deference" is paid to the LCD) and LCDs can be invalidated under a beneficiary's LCD challenge.
2. LCDs do violate the administrative procedures act.  They set operational CMS policy.  They may set CMS's initial policy.  Regardless of whether LCDs have a public comment period of sorts, there is no statutory basis for this to be different than APA notice and comment rulemaking.  (There IS, however, a separate statutory comment provided for NCDs.*)  
3. The judge need not address #3 because he has decided the case on #2.

For a discussion of the above district court ruling, Baker Donelson, here.

The judge remanded back to CMS for Department Appeals Board review, but instead, CMS appealed the case in federal appeals court.  

A video hearing is online from January 16, 2021.   YouTube, HERE.  (Autotranscript, here.) The appeals case was decided on July 16, 2021.   It determined that the federal court decision was incorrect, e.g. LCDs do not violate the APA.   HERE.  The decision was that the LCDs "do not establish or change a substantive legal standard" and therefore did not implicate APA.  One judge dissented.

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As discussed several times in the appellate case, the 21st Century Cures Act, which was passed in December 2016 before these cases, does create an explicit comment period framework for LCDs, so the 2019 judge's argument that there was no such explicit pathway, granted by Congress, separate from APA, would be moot today.

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For a Reuters article on the Appeals court case, July 2021, here.   

See back story on a similar, but prior, legal case supported by California Clinical Lab Association - May 2015 here (and see links to prior stories in April 2014, July 2014).  The prior case was eventually halted for "lack of standing," so a judgement on the issues was not reached.  There was no question in the current case that Agendia, having submitted claims, had standing.

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Separately, Agendia was involved in a corporate integrity agreement related to the 14 day rule - here.

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There are indexes for ALJ decisions, MAC (Medicare Appeals Council) decisions, and DAB (Departmental Appeals Board) decisions (here), but I wasn't able to find either the original 2018 ALJ decision for Agendia nor the 2019 MAC decision rescinding it.  What are linked above are, the federal district court case and the subsequent federal appeals case. Along the way I found a new 2018 guideline for appointing ALJ judges (here).

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* Since it is Congress that created the APA, it is Congress which can create alternatives to the APA for certain federal procedures, here, the NCD.

Very Brief Blog: CMS Blog on Plans for the MCIT, and Other Essays

 CMS has had several publications about innovation and new directions in the past few weeks.

MCIT #1

There's yesterday's announcement CMS plans to cancel the MCIT, Medicare Coverage for New Technologies, which was developed under the Trump administration last fall.  Here.

MCIT #2

On September 13, CMS revisited the MCIT topic in a long blog that parallels the release of the rulemaking.  Here.  Penned by Dr. Lee Fleischer, Chief Medical Officer.  

CMMI in Review

In August, CMS published a long blog at Health Affairs on CMMI, The First Ten Years.  Here.

CMS Administrator: Looking Ahead

September 9: Administrator Chiquita Brooks-LaSure pens an essay on her first several months and her outlook.  Here.

Flash: CMS Proposes to Cancel the MCIT Breakthrough Device Coverage Rule

CMS, under Biden, has now officially proposed cancellation of a suspended Trump administration rule.  The rule would have granted unconditional 4 year coverage to FDA breakthrough devices.  

See my four minute video on Youtube - Here:

https://www.youtube.com/watch?v=uFfHjfYXMWU

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In September 2020, CMS proposed to create immediate and unconditional automatic coverage, for four years, for all FDA breakthrough devices.  This is the "Medicare Coverage of Innovative Devices" or MCIT rule.

The FDA BT pathway is a review pathway for devices that do not have an FDA predicate or are novel in some other promising way.  It is issued early in the review process for promising devices, and is not contingent on the actual final performance of the device after clinical studies and FDA final review.

At least several hundred devices have entered the FDA BT pathway in the past several years.

In January 2021, CMS under President Trump finalized the MCIT regulation.  However, in March 2021, the Biden administration delayed it til May.  In May, they delayed it again, until December.

On September 13, 2021, after market close, CMS released a proposed rule that would exist simply to reverse the prior finalized rule, and would cancel the MCIT regulation.   CMS explains that public comment led it to reconsider problems with the MCIT rule.  For example, CMS now believes the MCIT rule would have resulted in erroneous coverage of devices even if they had no evidence specifically in the Medicare population, or coverage of devices whose manufacturers fail to complete post-marketing studies.   

Rather than unilaterally "cancelling" the rule, CMS must administratively "propose to cancel" the rule, take public comment for 30 days, and then issue its final position.   But the net policy is simply to retract the prior MCIT regulation.  

CMS published a "typescript" or inspection copy on September 13, and a full typeset publication will appear in Federal Register on September 15.  Comment runs until about October 11.

The rule can be read at the link:

https://public-inspection.federalregister.gov/2021-20016.pdf

Update:

CMS also released an essay on the MCIT topic which is penned by Dr. Lee Fleischer, Chief Medical Officer.  The main point is that MCIT is being canceled, but the general topic of adequate and timely coverage remains a priority of CMS administrators.

•    Here.   

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Coverage at Healthcare Dive here.  MHealthintelligence here.  AuntMinnie (radiology) here.  Fierce Healthcare here. Healthcare Finance News here.  RevCycleIntelligence here.

 AdvaMed press release here.  AdvaMed notes a favorable OpEd by Dr Anand Shah, who has worked at both CMS and FDA, here.   Others, like Tuft University's health policy expert Peter Neumann, opposed MCIT, here.  Some payers were critical - here.

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A Senate bill, S. 2416, introduced in 2019 and reintroduced in July 2021, asks CMS to accelerate coding and payment and coordinate better with FDA - here.  Senator Burr's press release here. Titled, "New Opportunities for Value to Extend Lives ("NOVEL") Act."  A different bill, HR4033, would specifically enforce coverage of breakthrough devices for 4 years through law, much as MCIT would have done (here).

Very Brief Blog: Medicare Coverage Database Will be "Down" 9-17 to 9-19.

Next weekend, you might as well go to the beach or the hills.   The Medicare Coverage Database, a national library of MAC coverage articles and LCDs, plus NCDs, will be out for the weekend of September 17-19.   They will migrate to a new hosting environment, hopefully, one that is more amenable to covering innovative new technologies.

https://www.cms.gov/medicare-coverage-database/search.aspx

MolDx Posts Advisory Committee for Upper GI Cancer, October 12, 2021

MolDx has posted an announcement that it will hold a Contractor Advisory Committee on October 12, 2021 (2-4 ET, 11-2 PT).  Registration is open until October 11.  The conference is listen-only mode for the audience.

The meeting will discuss the clinical literature related to MolDX: Molecular Testing for Risk Stratification of Upper Gastrointestinal Cancer and rate their confidence in a series of key questions.

What they mean is, tests that risk-classify Barrett's Esophagus (dysplasia).  The key question is, "Is there sufficient data to use molecular testing to risk stratify patients with BE to low or high grade dysplasia?"  Historically, this was done by tiny biopsy samples and simply rating the tissue on H&E slide for dysplasia.

They also ask, does the test preclude the need for more invasive procedures?  And/or, can biomarkers be sampled by less invasive means than traditional endoscopic biopsy?

• There's a recent open access review article by Grady et al., 2020, here.   
• There's an open-access article on managing Barrett's by Kamboj , 2021, here.  (One author, Iyer, is also featured on the Cernostics web site here.)
• There's a non-open-access review by Souza and Spechler, 2021, here.

The MolDx website is linked below, and the website includes additional documents like agenda and the complete text of key questions.  As well as registration.

https://www.palmettogba.com/palmetto/moldxv2.nsf/DID/9TXCRWTLD4

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Endnotes

I don't have a comprehensive roster of labs in this space but two with a focus on biomarkers in Barrett's would include Cernostics ("Tissue Cyper") and CDX ("WATS3D" testing).   Cernostics is backed by Pittsburgh/ UPMC (here).  

Unrelated to Barrett's, but also in the field of advanced pathology/immunohistochemistry, is ImmunoScore slide-based testing for colon cancer from HalioDx, recently acquired by Veracyte, in a circa $300M deal.  Their code 0X70U/0261U, was presented at the June 2021 CMS new test pricing meeting, with a request to crosswalk to 0108Ux1.2 (at $3015).   CMS will release pricing this fall.

For a July 2021 article by Liang et al. on digital pathology, here from the boutique consultancy Bionext.

The journal with the Grady review article mentioned above, published a long list of symposium articles on early detection of cancer with molecular testing in 2020 - here.  The articles spring from the 20 year NCI effort, Early Detection Research Network or NCI-EDRN. Overview of that, by Bast and Srivastava here.

Very Brief Blog: Last Two Days to Comment on Novitas Cardiology Genetics LCD

 There are numerous indications to test for genetic causes of cardiac diseases, including arrhythmias and cardiac hypertrophy.   Medicare coverage policies have sometimes been quite limited.

The NOVITAS MAC has had a draft LCD under comment from July 29 to September 11.  I think it has some good features, but it may be pretty quirky in other ways.   For example, it asks the risk of any gene testing to be 40% or more, which seems to high for normal medical practice.  They also seem a little unaware of the overlap of syndromes and thus, the use of panel based gene testing.  

Those with stronger content knowledge in cardiology genetics will want to comment by September 11 (yes, that's technically a Saturday.)  I've put the draft LCD DL39082 and article DA58795 in a zip file in the cloud here.   Comments are directed to, ProposedLCDComments@novitas-solutions.com .

I discussed some pro's and con's of this approach to writing LCDs - more vague LCDs - back on August 17 here.

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Core rules [partially quoted] include - 

Genetic testing for hereditary cardiovascular disease will be considered medically reasonable and necessary if:

1. The patient has rigorous disease-appropriate phenotyping to establish clinical diagnosis or suspected diagnosis for which the test results would directly impact the management of the patient’s condition, prior to ordering the test 

AND

2. The evidence for the gene-disease association is evaluated by the evidence-based, transparent, peer- reviewed process of the National Institutes of Health (NIH) sponsored Clinical Genome Resource (ClinGen) and is determined to demonstrate actionability in clinical decision making, meeting all bulleted metrics:

• Disease severity of sudden death, possible death or major morbidity, modest morbidity
• Substantial or moderate evidence of a >40% likelihood of disease
• Substantial or moderate evidence of a highly effective or moderately effective intervention
• The nature of intervention is either low risk/medically acceptable/low intensity intervention or moderately acceptable/risk/intensive interventions, 

AND

3. Clinical validity and qualitative descriptors from Moderate, Strong & Definitive with contradictory evidence NOT being reported as disputed or refuted.

Very Brief Vlog: Using Medicare's Physician & CPT Code Data, A Brief Video

This week, CMS released another year's worth of incredible granular data for how physicians and labs use CPT codes for all Part B patients.  There's 10M lines of data from CY2019.

My blog on the data release - find it here.   Would you like to explore the data yourself?  I've made a simple 5 minute video to help get you started.  Find the video here.

The Data Set in Use:

Who got paid for Category III codes in 2019?  Here.

Who got paid for PLA lab codes in 2019?  Here.

Who got paid for Unlisted Genomics code 81479, and where did it happen, in 2019? Here.

Who got paid for 81408, the "very unusual" and highest-paid lab code in 2019?  Here.