McKinsey Discussed 81408

 

https://www.mckinsey.com/industries/life-sciences/our-insights/genetic-testing-opportunities-to-unlock-value-in-precision-medicine

Genetic testing opportunities

October 2018

 Thanks to a number of technological, scientific, and frontline operational advances, the cost of deciphering the entire human genome has dropped by an order of magnitude, from $10,000 in 2011 to about $1,000 today.

Genetic tests are reimbursed at relatively high rates (Exhibit 2): for example, CPT code 81416 for exome sequencing analysis (added early this year) has a national maximum allowable limit of $12,000. Reimbursements for pharmacogenomics, which assesses the way gene variants affect individual responses to drugs, generally cover the sequencing of multiple genes and vary a good deal, from $100 to $2,000. An interesting example—81408, a CPT code at the higher price end, $2,000—covers 24 genes for various disease conditions (Exhibit 3). 

Quantitative analysis of private-payer reimbursements from 2014 to 2016 indicates that the average level of reimbursement for 81408 has declined, to $1,080 per test, from $1,545. This suggests that higher-priced genetic tests may stabilize at a lower price range.

click to enlarge

SUMMARY AI

Genetic testing and precision medicine have significant growth potential in the healthcare industry. The market for personalized medicine is projected to reach $140 billion by 2026. The cost of genetic sequencing has significantly decreased, and next-generation sequencing (NGS) is becoming a widely adopted technology. Diagnostic-test-service providers can generate tangible revenue from selling tests and intangible value from the insights gained from collected data. Data integration and analytics, increasing cost pressures on payers, and evolving reimbursement landscape are three major trends in the genetic testing market.

Facts

• 💰 The global market for personalized medicine is expected to grow from $44 billion in 2016 to $140 billion by 2026.
• 🧬 The cost of deciphering the human genome has dropped from $10,000 in 2011 to about $1,000 today.
• 🧪 Next-generation sequencing (NGS) is replacing the Sanger method and is widely adopted in research and clinical practice.
• 💡 Diagnostic-test-service providers create value through tangible revenues from tests and intangible value from collected data.
• 👥 Companies like 23andMe aggregate genetic information, generating revenue from selling tests and partnering with pharmaceutical companies.
• 🏥 Roche's acquisition of Flatiron Health and Foundation Medicine accelerates precision medicine progress in oncology.
• 📊 Three major market trends in genetic testing: data integration and analytics, increasing cost pressures on payers, and evolving reimbursement landscape.

I asked GPT4 to summarize my own long blog about TCET.

Summary of my long blog on TCET.

Part 1:

The Centers for Medicare & Medicaid Services (CMS) has released a 37-page proposal for comment outlining the Transitional Coverage for Emerging Technologies (TCET) pathway. The TCET pathway is designed to provide Medicare coverage for breakthrough medical devices that have the potential to significantly improve patient outcomes. It aims to expedite coverage decisions while generating additional evidence to support long-term coverage determinations.

The document introduces the purpose of the TCET pathway and provides links to 

• the TCET document, 
• the press release, 
• the Chief Medical Officer's blog, 
• and the agency's new evidence review guidance document. 
• 
  

It states that the TCET proposal does not seem to include formal legal changes but rather changes in attitude or process for coverage decisions.

The TCET pathway involves a premarket "nomination" and FDA-CMS review phase, followed by a 2-5 year period of "transitional coverage" under a National Coverage Determination (NCD), with updates provided to CMS. 

The coverage options under the TCET pathway include more Coverage with Evidence Development (CED), non-coverage, coverage under NCDs, or coverage under Local Coverage Determinations (LCDs).

Part 2:

Part 2 of the text provides further details on the TCET pathway and its components. It mentions that breakthrough devices, as designated by the FDA, are eligible for consideration under the TCET pathway. Manufacturers are required to provide evidence of substantial clinical improvement, address an unmet medical need, and commit to collecting additional evidence through post-market studies.

The document explains the process of nomination for the TCET pathway, which involves manufacturers submitting comprehensive information about the device, evidence supporting its breakthrough status, and a detailed plan for evidence development. It highlights the importance of clear communication between manufacturers and CMS during the nomination process.

After a nomination is submitted, there are steps involved, including prompt submission of nominations by manufacturers to facilitate alignment among CMS benefit category determination, coverage, coding, and payment considerations. Manufacturers are encouraged to provide specific information to facilitate benefit category and coding determinations.

The document describes the review and coverage process under the TCET pathway, including the timeline for reviewing nominations, conducting evidence previews, and developing evidence development plans (EDPs). It emphasizes the importance of stakeholder input in shaping coverage policies and discusses the duration of transitional coverage under the TCET pathway.

The roles of different participants in the TCET pathway are highlighted, including manufacturers, CMS, FDA, and the Agency for Healthcare Research and Quality (AHRQ). It mentions the availability of other expedited coverage mechanisms like Parallel Review and the need to prioritize innovative medical devices with the potential to benefit Medicare beneficiaries.

In summary, the TCET pathway aims to expedite Medicare coverage for breakthrough devices while generating additional evidence for long-term coverage determinations. It involves a nomination process, evidence development plans, and a transitional coverage period. The document emphasizes stakeholder engagement, the roles of various entities, and the importance of evidence generation and timely coverage decisions.

I hope this summary provides you with the main points of Part 1 and Part 2 of the text.

FOIA: JOA Noridian/MolDx

 Based on a February 3, 2020 letter, on June 1, 2023, I received a redacted MAC MOLDX JOA from CMS.   It was redacted only for personnel names.   It's a pretty dry document, stipulating business responsibilities and negotiation rules.   There are several remarks that at various points, Noridian requested edits [not shown], which MolDx rejected.  It's document 020320207041 at CMS FOIA.

There has been debate whether MolDx includes only DNA RNA.  The legal JOA clearly refers to a reference document, the MolDx Manual, and that (public at MolDx) clearly defines the scope of the program as including DNA, RNA, proteins, and metabolites.  That would seem to be the end of debate.

The MolDx Manual also states the program includes "MDTs and LDTs" defined as molecular diagnostic tests and laboratory developed tests.   It frequently refers to MDT and LDT, but the meaning by using both is obscure; as defined, MDT seems to include relevant LDTs.

A auto generated Chat GPT 4 summary is here:

This document describes an operating agreement, also known as Joint Operating Agreement (JOA), between Palmetto GBA's MolDX team and Noridian Jurisdiction F 75FCMC18C0029 Medicare Administrative Contractor (MAC). The agreement concerns the joint responsibilities of both parties to effectively administer services within the scope of the MolDX program.

Key takeaways from the document include:

This agreement is designed to regulate the delivery of services in the MolDX program, which involves molecular diagnostics testing. Providers of these services operate across multiple jurisdictions, thus necessitating clear and consistent processes.

The agreement specifies that the parties are not partners or joint ventures, and no party has the power to bind the other.

The agreement is set to continue until either party's contract with CMS for related services terminates or until CMS provides other instructions.

Both parties have committed to adhere to the Freedom of Information Act, HIPAA, and Privacy Act requirements.

The roles and responsibilities of both the MolDX team and Noridian MAC have been clearly laid out.

Key roles and responsibilities of the MolDX team include:

1. Administering the MolDX program as defined in the MolDX manual, which includes managing registered tests, assisting MAC with implementing MolDX registration, providing technical assessments on submitted dossiers for new tests, and being the primary interface with lab providers.
2. Providing technical assistance and educational material to MAC.
3. Developing and maintaining a model Molecular Diagnostic Testing (MDT) LCD and a network of clinical and academic experts.  [*]
4. Supporting MAC MDT LCD and MolDX LCD publication and administration. [*]

Key roles and responsibilities of the Noridian MAC include:

1. Coordinating publication of the MDT policy elements as a Jurisdictional Local Coverage Determination (LCD) and maintaining the policy per MolDX guidelines.
2. Identifying and directing unregistered tests to the MolDX program for registration and technical documentation requirements.
3. Participating in monthly MolDX processing meetings with Palmetto and other MAC contractors.

Dispute

A dispute resolution process is in place that involves escalating the dispute to higher levels if not resolved within certain timelines.

Non-compliance issues are addressed by submitting the matter in writing to the relevant contracting officers and representatives.

Change requests and interim changes to the JOA can be made via a Memorandum of Understanding (MOU) until the next scheduled revision.

The JOA amendment process stipulates quarterly updates in the first year and semiannual updates thereafter.

The JOA includes a glossary section and details on JOA amendments, noncompliance issues, dispute resolution, change requests, and interim JOA changes.

##

MolDx Manual Clips

https://www.palmettogba.com/Palmetto/moldx.Nsf/files/MolDX_Manual.pdf/$File/MolDX_Manual.pdf?Open&

[*] Points 3 and 4 refer to the MDT, a "master LCD" written at the beginning of the MolDx program, sort of like the Constitution supports all other laws.  However, the MolDx MDT is an unusually document as it primarily says that anything not made payable by MolDx is deniable [with no further facts, evidence, or details].  Therefore, it is unlikely that an LCD Challenge to the MDT would fail.

__________________

What do the parties want to accomplish:

Palmetto GBA's MolDx program:

The Molecular Diagnostic Services (MolDx) Program, run by Palmetto GBA, seeks to bring clarity and consensus to the coding and coverage of molecular diagnostic tests (MDx tests). Its goal is to improve the availability and quality of molecular diagnostics, facilitate coverage of testing services that provide a tangible benefit to patient care, and support advancements in personalized medicine. They would likely want to continue to advance in these areas, potentially through partnerships that enhance their technological capabilities, improve their service offerings, or increase their market share.

Noridian:

Noridian is a healthcare solutions and services company with a focus on administration and customer service for government and private healthcare programs. Noridian's primary goals typically involve improving healthcare delivery through efficient administration, reducing costs, and enhancing patient experience. They could seek to accomplish more efficient claims processing, improved fraud detection, better customer service, and expanded offerings through partnerships

AI looks at JNCCN Case Study of Lynch/Ovarian Syndrome

 Here is the article:

https://jnccn.org/view/journals/jnccn/21/6/article-p588.xml

Laboratory Selection in Germline Genetic Testing:

 Laboratory Science Matters

Author: Suzanne M. Mahon

 J NCCN Volume/Issue: Volume 21: Issue 6  Online Publication Date: Jun 2023

 AI GPT4

Summarize what actually happens to the patient?  Who is the patient?  What is her problem?  What happens to her?  What goes wrong?  How does it get fixed?

ChatGPT

Absolutely. Let's delve into the details:

Who is the patient?

The patient is a woman who has a family history of Lynch Syndrome, an inherited disorder that increases the risk of many types of cancer, particularly colorectal cancer and endometrial cancer.

What is her problem?

The patient's mother was found to have a pathogenic MLH1 variant, a genetic mutation often associated with Lynch Syndrome. The patient was also tested for this mutation to determine if she had inherited the risk.

What happens to her?

Initially, the patient was tested using a 25-gene panel, and she tested negative for the MLH1 variant. However, this was due to an error: the initial test did not cover the exact location of her mother's mutation. Therefore, it falsely indicated she did not have the genetic risk for Lynch Syndrome.

What goes wrong?

The negative result of the initial test led to a false sense of security for the patient, as she believed she had not inherited the risk. Guidelines for preventative measures and early detection strategies typically implemented for people with a pathogenic MLH1 variant were not put into place, potentially putting her at risk for developing cancer.

How does it get fixed?

The error was discovered after a genetic professional was consulted. The professional recommended an appropriate test that covered the exact location of the mother's mutation, which was carried out by a reputable laboratory. The new test results confirmed that the patient did indeed have the MLH1 variant. With this accurate information, the appropriate preventative and surveillance measures could be initiated. Despite the initial distress caused by the revelation of her actual genetic risk, the patient was provided with the opportunity to mitigate this risk with surgery and intensive surveillance.

This case illustrates the critical role of genetic professionals in choosing the right tests, ensuring accurate interpretation of results, and mitigating potential medical and legal consequences of incorrect genetic testing.

KEY POINTS VIEWPOINT

This is discussing the importance of appropriate genetic testing and the roles of healthcare providers and genetics professionals in this process. This is indeed a significant subject, particularly in the context of cancer prevention and early detection. The use of genetic testing for identifying pathogenic variants, such as MLH1, can guide clinicians in determining the best course of treatment and preventative measures for patients and their families.

Key points brought up in this discussion include:

Need for Expertise in Genetic Testing: A lot can go wrong with genetic testing if it's not carried out correctly. Selection of the right test, correct interpretation of the results, and the choice of the best laboratory for testing require specialized knowledge. Thus, involving a genetics professional can be a cost-effective strategy and potentially reduce the risk of error.

Recommendations for Patients with Pathogenic Variants: For patients with identified pathogenic variants, such as MLH1, preventative measures are usually recommended starting from early adulthood. Failure to implement these guidelines due to inaccurate genetic testing results can put patients at unnecessary risk.

Liability Concerns: Medical practitioners who order genetic testing should be aware of the associated liabilities if the wrong test is ordered. Some institutions have taken steps to minimize such risks by requiring systematic review of test appropriateness by a molecular pathologist or a genetics professional.

Importance of Family Communication and Care Coordination: If a clinician orders genetic testing, they must also take responsibility for communicating potential risks to other family members and coordinating care for them. This is not just a matter of professional duty; it can also be a legal issue, with case law recognizing negligence for failure to warn family members of potential risk.

The Power of Germline Genetic Testing: Done correctly, germline genetic testing can be a powerful tool for cancer prevention and early detection in patients and their families. However, it is essential that the assessment is complete, testing is correctly ordered, and results are correctly interpreted.

It's clear that a team-based approach involving both medical and genetic professionals can greatly improve the accuracy and efficacy of genetic testing for cancer-related genes. This, in turn, can lead to better patient outcomes, earlier cancer detection, and more effective prevention strategies.

AI Looks at Trosman 2023

 Purely AI computerized view point on TROSMAN 2023.

http://www.discoveriesinhealthpolicy.com/2023/06/ucsf-papers-on-liquid-biopsy-1-payor.html

#### GPT4  June 20, 2023

Thank you for sharing Trosman et al. Now that I have all parts of the text, I understand that this article is discussing Multi-Cancer Early Detection (MCED) tests from the perspective of private insurance payers in the U.S.

This text outlines various considerations and concerns of private insurance payers when it comes to MCED tests. These tests have the potential to detect a wide array of cancers in their early stages, and they may be particularly useful for those cancers which don't have established early detection methods. However, insurers express several concerns, including:

1. The benefit of early detection: There may be cancers that don't have a confirmed benefit from early diagnosis. Early detection could lead to overtreatment and unnecessary stress for patients if these cancers are slow-growing and not life-threatening.
2. Accuracy of the tests: The high false-negative rate could lead to missed diagnoses. Also, false positives could result in additional, unnecessary testing and related costs.
3. Lack of protocols: There is currently a lack of follow-up protocols for cases where a MCED test detects potential cancer, but it cannot be confirmed with existing diagnostic methods. This lack of clarity can lead to challenges in patient management and treatment.

The private insurance payers also provided insights on the kind of evidence they need to justify the cost of MCED tests. They indicated a preference for real-world data and surrogate endpoints, even in the absence of mortality evidence.

The paper concludes that private payers should be stakeholders in the national MCED policy agenda, as they play a significant role in determining coverage and therefore access to these tests. Future policies and efforts should also focus on equity and address workforce capacity for cancer detection and care.

Note that the study has its limitations, mainly due to its reliance on in-depth interviews with a limited number of payers. Future studies could examine the views of public payers, including Medicare and state Medicaid plans, as their coverage will be essential for equitable access to MCED tests. The impact of MCED tests on patient out-of-pocket costs and insurance premiums should also be explored.

Does this paper contribute new insights to our understanding

 of how payors will make policy decisions about multi cancer early detection MCED.

ChatGPT

Yes, this paper does contribute valuable insights into how private payers, or insurance providers, may approach policy decisions regarding Multi-Cancer Early Detection (MCED) tests. Here are the key contributions:

1. Payer Concerns: The paper outlines specific concerns private payers have regarding MCED tests, including uncertainty over the benefit of early detection for certain cancers, the accuracy of these tests, and the lack of established protocols for managing cases where cancer is detected but not confirmed.

2. Evidence Requirements: The study sheds light on the type of evidence that payers find convincing for coverage decisions. This includes rigorously generated real-world data and surrogate endpoints, even in the absence of direct mortality evidence.

3. Role of Payers in Policy Agenda: The paper emphasizes the need for private payers to be part of a national MCED policy agenda. Their involvement is crucial in addressing equity efforts and initiatives around workforce capacity for cancer detection and care.

4. Need for Collaboration: The paper suggests that there may be opportunities for health systems to collaborate with private payers, setting up pilot programs to address the latter's concerns.

5. Limitations and Future Research Directions: The paper also highlights the limitations of the study and suggests directions for future research, such as including the perspectives of public payers and investigating the impact on patient out-of-pocket costs and insurance premiums.

In conclusion, the paper provides new information and a unique perspective on how private payers view MCED tests. This perspective can inform both developers and health systems as they refine tests and care protocols, as well as policymakers as they design comprehensive and equitable healthcare strategies.

Payers are a diverse group of private companies. 

How could they form "a national policy agenda?" 

Or even as a group be part of one? 

Would their be collusion risks for example.

ChatGPT

Your question raises important considerations about the logistics and potential risks of private payers collectively forming or being part of a national policy agenda.

First, it's important to note that when the study suggests private payers should be part of a national MCED policy agenda, it doesn't necessarily mean that payers should form a unified front or operate as a singular entity. Instead, it underscores the importance of including their perspectives, concerns, and insights in shaping the national agenda for MCED testing. Here's how it could work:

1. Through Industry Associations and Representative Bodies: Private payers can participate in national policy discussions through industry associations or other representative groups. For instance, in the U.S., the America's Health Insurance Plans (AHIP) is a national association that represents insurance providers. Associations like this can provide a platform for collective input without direct coordination between individual companies, thereby mitigating collusion risks.

2. Through Public Comment and Consultation Processes: Policymakers often seek input from various stakeholders during the policy formulation process. Private payers could provide their views and expertise during these stages to influence the policy.

3. Through Direct Engagement with Policymakers and Regulators: Private payers can also engage directly with policymakers and regulators, providing feedback on proposed regulations, offering expert testimony in legislative hearings, or participating in advisory committees.

However, you correctly point out that there are potential risks to such collaboration, including collusion. To avoid this:

• Interactions would need to comply with antitrust laws, which are designed to prevent unfair business practices including price-fixing, bid-rigging, or market allocation.
• The discussions would need to focus on policy and public health issues, not on commercial, pricing, or competitive strategies.
• Where necessary, the involvement of third parties (like industry associations or independent facilitators) can help ensure that discussions remain within legal and ethical bounds.

In conclusion, while it may not be feasible or appropriate for private payers to form a national policy agenda by themselves, they could certainly contribute to one in several ways, provided that their involvement is carefully managed to avoid any legal or ethical issues.

During the review process,

 what do you think peer reviewers would have focused on

 in their critique of this paper for the editor?

ChatGPT

Peer reviewers typically evaluate a research paper based on its scientific rigor, originality, relevance, clarity, and ethical compliance. In the case of this paper, reviewers might have focused on the following aspects:

1. Study Methodology: Reviewers would evaluate the methodology used in interviewing private payers and assessing their perspectives. They would scrutinize the rigor and reproducibility of the approach, the appropriateness of the questions asked, and how the responses were recorded and analyzed.

2. Representativeness of the Sample: Reviewers may assess whether the cohort of private payers was truly representative of the broader group of payers in the country. They might question the selection process and the criteria for inclusion in the study.

3. Interpretation of Results: The reviewers would closely look at how the authors interpreted the results and whether their conclusions were justified based on the data collected. They would consider whether the authors addressed all the potential implications and limitations of their findings.

4. Addressing Potential Biases: The reviewers might examine how the study addressed potential biases, such as selection bias (the possibility that the private payers who agreed to participate were those most interested in MCED) or response bias.

5. Utility and Relevance of Findings: The reviewers may evaluate the relevance and applicability of the study's findings to the broader field of cancer screening and healthcare policy. They might consider whether the study fills a significant gap in knowledge and if the findings could impact policy discussions about MCED tests.

6. Ethical Compliance: Reviewers would ensure that the study complied with relevant ethical standards, such as maintaining the anonymity and confidentiality of the interviewees.

Remember, the specific points of focus might vary depending on the expertise and perspectives of individual reviewers, the specific field of the research, and the guidelines of the journal in which the research is being submitted.

Quotes: Harvard's Avorn in WaPo on FDA intermediate approvals. Paul T Kim responds.

 

 

From: Bruce Quinn <bruce@brucequinn.com> 

Subject: Harvard's Jerry Avorn Advice for NCD Reform. Foley Hoag's Paul Kim Responds.

Below, I clip a new Washington Post op ed by Harvard's Jerry Avorn, arguing for major NCD process reform.

Below that, I clip a response by a former colleague (recently left Foley Hoag LLP) Paul T Kim.

####

https://www.washingtonpost.com/opinions/2023/06/15/fda-conditional-approval-alzheimers-drug-leqembi/

New Alzheimer’s drug is a problem for FDA’s pass-fail approach

By Jerry Avorn

Jerry Avorn is a professor of medicine at Harvard Medical School and co-director of the Program on Regulation, Therapeutics and Law (PORTAL) at Brigham and Women’s Hospital in Boston.

The Food and Drug Administration is slated to soon give full approval to Leqembi, a new medicine for Alzheimer’s disease that offers only modest benefit, could pose worrisome risks and stands to cost the nation $2 billion to $5 billion per year. But the agency has an all-or-nothing problem. Even when evaluating a drug that’s minimally effective or could carry considerable risks, the FDA’s decision nearly always comes down to accept or reject.

Under this pass-fail system, a drug that the FDA disapproves remains mostly unavailable, except to subjects in research studies, while one that is approved can generally be prescribed to anyone. Certain risks may be described in the official product labeling, which few physicians read, or in educational risk management programs that are not designed to measure a drug’s effectiveness. But the decision is almost always a binary one that is ill-suited to the way science works — and to the needs of patients.

The Leqembi decision illustrates the problem. In clinical trials, the drug did not improve patients’ memory, but it slightly reduced their rate of cognitive decline — a small change that might be welcome to some patients but unnoticeable to many others and their families. 

Yet the drug didn’t do nothing clinically, and that makes it nearly impossible for the FDA to disapprove.

The treatment requires ongoing intravenous infusions every two weeks, it can cause cerebral swelling and bleeding, and it will be priced at $26,500 a year, not including physician charges. This raises the question: How much minimal improvement in dementia is worth what level of patient burden and risk of complications?

Similar questions come up for other drugs to treat muscular dystrophy and ALS (amyotrophic lateral sclerosis). For these medicines, the FDA has granted “accelerated approval” based not on patients’ clinical improvement but merely on small changes in lab tests. After accelerated approval, drugmakers are asked to do follow-up studies to prove that their drugs actually help patients. But the government may allow many years to complete such studies, and they are often started late or done poorly, my research group has found.

 

The FDA faces enormous pressure from patients and their families — and from drug companies — to grant full approval to these drugs with thin credentials, and many others like them, including cancer treatments. But what happens if the medicines don’t fulfill their promise, or their side effects turn out to be worse than expected? It has proved difficult to get such products out of circulation. In 2011, a medication meant to prevent premature birth, Makena, was approved on an accelerated basis, but then was never clearly shown to work. Getting it off the market took until this past April.

Medicine has been dealing with tough benefit-risk trade-offs for well over a century. 

The FDA’s simple all-or-none decision framework is a poor fit for this evolving scientific reality. The agency should instead create a new status for some drugs that is neither full approval nor outright rejection — a conditional approval that would allow a new drug with ambiguous credentials to be used only in a limited way until better evidence is collected. This would let doctors and patients learn how well it works in typical use outside of trials.

Then, in two or three years, the FDA could evaluate a richer portfolio of evidence to decide whether to make the drug available to all patients without restrictions. This would save tens of millions of dollars wasted on ineffective or unnecessarily risky drugs — and thousands of preventable adverse events.

The Medicare program has said it will create registries to track Leqembi use and outcomes. But it will not require that any untreated comparison patients be enrolled in these registries, rendering this approach nearly useless in measuring whether the slight reduction in decline that was seen in the drug’s single clinical trial is borne out in typical use.

A more nuanced approach to final approval could also influence the price of a new medicine, though cost is not the FDA’s direct responsibility. The Medicare and Medicaid programs are usually required to buy most FDA-approved drugs at whatever price the manufacturer sets, regardless of any questions about their relative value, efficacy or safety.

At an industry conference in Boston this month, FDA Commissioner Robert M. Califf admitted that companies that receive accelerated approval for their drugs often fail to complete the needed follow-up studies promptly to fully define their actual benefits and risks. He suggested that it might make sense for the prices of such drugs to be set lower until their true worth is better established.

Medical science is not an all-or-none, once-and-for-all endeavor: Knowledge evolves as evidence and experience accumulate, and that’s wonderful. But the FDA’s all-no or all-yes framework doesn’t fit the way our understanding of prescription drugs develops. For some drugs, the agency needs to become nonbinary to better reflect this reality.

https://www.linkedin.com/feed/update/urn:li:activity:7075166708155478017/

PAUL T KIM ON LINKED IN

Jerry Avorn is an insightful scholar, but stumbles in this #washingtonpost op-ed on the pending #FDA review of Leqembi to treat Alzheimer’s disease.

Avorn wants to fundamentally alter FDA's "pass-fail" review of new drugs because it "is ill-suited to the way science works — and to the needs of patients," and that "FDA’s simple all-or-none decision framework is a poor fit for ... evolving scientific reality."

His solution? "The agency should instead create a new status for some drugs that is neither full approval nor outright rejection — a conditional approval that would allow a new drug with ambiguous credentials to be used only in a limited way until better evidence is collected."

This is a deceptively risky idea, one that—

• ignores how "conditional approval" would create unprecedented confusion -- changing a global "gold standard" into a "green? No, more like yellow?" standard;

• doesn’t recognize the enormous risks that off-label prescribing would swamp the "conditionally" in "conditionally approved" drugs - and that manufacturers would exploit the new pathway to market as a shortcut to a drug’s sale for more lucrative but unproven uses; and

• is highly dependent on labeling that Avorn says "few physicians read" (!) to ensure conditionally-approved drugs are "used only in a limited way".

Most surprising, Avorn never acknowledges the enormous flexibility FDA exercises regularly - and sometimes creatively - under current law to dictate the specifics - indeed, the minutiae - of approved uses, labeling, and other conditions for new drugs.

That creativity is why, using current authorities, FDA reviews drugs with astonishing efficiency - deciding on the latest, most novel and challenging medicines in six months or less! - and why the most important new drugs are approved here in the US before the rest of the world. "Conditional approval" promises little to improve that record, and may instead threaten to complicate regulatory pathways to market and patient access to new treatments.

Finally, I find it strange that Avorn dismisses the power of #CMS, private payers, and PBMs to control or restrict coverage, reimbursement and prescribing of new drugs. Rather than have Congress undertake risky major surgery to FDA’s statutory authorities, we should instead be scrutinizing how these entities play their own roles, fulfill their responsibilities, and exercise their contractual or statutory authorities to manage prescription drug utilization. PBM reform, anybody?

IRF PA Review Choice Program

 It's a cliche' that generally, Parts A and B don't involve prior authorization.  CMS has recently instituted new guardrails around Medicare Advantage prior authorization (and coverage policies) and Congress has toyed with legislation on insurers and PA.  It's also a big topic for AMA.

There's a program for inpatient rehab hospitals (IRFs) to have EITHER prior auth or post pay review of all their claims, in a number of large MACs.  It's called "IRF Review Choice Demonstration" or IRF RCD.

https://www.cms.gov/files/document/r12080otn.pdf

https://www.cms.gov/research-statistics-data-systems/medicare-fee-service-compliance-programs/prior-authorization-and-pre-claim-review-initiatives/review-choice-demonstration-inpatient-rehabilitation-facility-services#:~:text=The%20Review%20Choice%20Demonstration%20(RCD,compliance%20with%20Medicare%20IRF%20rules.

https://www.aapmr.org/members-publications/member-news/member-news-details/2021/10/12/aapm-r-submits-comments-to-cms-opposing-review-choice-demonstration-for-irf-services#:~:text=The%20IRF%20review%20choice%20demonstration,several%20Medicare%20Administrative%20Contractor%20jurisdictions.

https://calhospital.org/cms-announces-start-of-irf-review-choice-demonstration/