Scite.AI: MRD Studies in Lung Cancer

 There seem to be many fewer studies for Minimal Residual Disease monitoring (MRD) in lung cancer, compared to colorectal cancer. What are the best studies of MRD in lung cancer (circulating tumor DNA) and if possible discuss why this field lags behind MRD studies in colorectal cancer.

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SCITE.AI

Minimal Residual Disease (MRD) monitoring in lung cancer, particularly through the analysis of circulating tumor DNA (ctDNA), has garnered attention, yet it remains significantly less explored compared to colorectal cancer. This disparity can be attributed to several factors, including the complexity of lung cancer biology, the historical focus on colorectal cancer in MRD studies, and the challenges associated with ctDNA detection in lung cancer.

 Recent studies have begun to elucidate the potential of ctDNA in monitoring MRD in lung cancer. For instance, demonstrated that longitudinally undetectable MRD in localized non-small cell lung cancer (NSCLC) patients correlates with a high likelihood of remaining disease-free, suggesting a potential for identifying a "cured" population within this cohort (Zhang et al., 2022). Furthermore, highlighted the efficacy of ctDNA profiling in early detection of MRD, emphasizing its role in guiding treatment decisions (Chaudhuri et al., 2017). These findings indicate that while the prognostic value of ctDNA in lung cancer is promising, the body of research is still developing.

 In contrast, colorectal cancer has seen a more robust integration of ctDNA in MRD monitoring. Studies such as those by have established ctDNA as a reliable biomarker for recurrence in resected colorectal cancer, demonstrating its superiority over traditional imaging methods in certain contexts (Fakih et al., 2022). The comparative abundance of studies in colorectal cancer can be attributed to its well-defined treatment pathways and the established role of biomarkers like carcinoembryonic antigen (CEA) in clinical practice (Fakih et al., 2022). This has facilitated a more extensive exploration of ctDNA applications, leading to a wealth of data supporting its use in MRD monitoring.

 The lag in lung cancer research can also be linked to the inherent biological complexities of lung tumors. noted that most studies have focused on single qualitative markers in ctDNA, such as specific mutations (e.g., EGFR and KRAS), rather than adopting a comprehensive multi-marker approach that has proven effective in colorectal cancer (Szpechcinski et al., 2015). This limitation in study design may hinder the broader applicability of ctDNA as a reliable MRD marker in lung cancer.

 Moreover, the technical challenges associated with ctDNA detection in lung cancer cannot be overlooked. The sensitivity of ctDNA assays can be affected by the tumor's heterogeneity and the low levels of ctDNA present in the bloodstream, particularly in early-stage disease (Yan & Liu, 2022). This contrasts with colorectal cancer, where ctDNA levels are often higher and more consistent, facilitating easier detection and monitoring.

 In summary, while there are promising studies indicating the potential of ctDNA for MRD monitoring in lung cancer, the field lags behind colorectal cancer due to a combination of historical focus, biological complexity, and technical challenges in ctDNA detection. Continued research and the development of more sensitive and comprehensive ctDNA assays may bridge this gap in the future.

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Could you focus on 2023 and 2024 studies of circulating tumor dna to detect minimal residual disease (MRD) or recurrence, in lung cancer.

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In recent years, the application of circulating tumor DNA (ctDNA) for monitoring minimal residual disease (MRD) and recurrence in lung cancer has gained traction, with several notable studies emerging in 2023 and 2024. These studies highlight the potential of ctDNA as a non-invasive biomarker for assessing disease status post-treatment and guiding clinical decisions.

 One significant study by Kang et al. (2023) introduced a dynamic methylation-based analysis of cell-free DNA for postoperative monitoring in lung cancer patients. The study found that patients with low MRD scores were unlikely to experience relapse within four months, suggesting that such a methylation-based approach could personalize postoperative management and reduce unnecessary imaging (Kang et al., 2023). This finding underscores the utility of ctDNA in providing timely insights into patient status, potentially leading to more tailored treatment strategies.

 Another important contribution is from (Franzi, 2023), who conducted a meta-analysis on the role of liquid biopsy in non-small cell lung cancer (NSCLC). The authors noted that dynamic changes in ctDNA levels correlated with therapeutic responses, indicating that ctDNA could be effectively used for early detection of MRD and recurrence in early-stage lung cancer (Franzi, 2023). This study reinforces the idea that ctDNA monitoring can enhance the management of lung cancer by identifying patients at risk for relapse.

 O'Sullivan et al. (2023) further explored the challenges and future directions of MRD monitoring in radically treated NSCLC. They emphasized that the variant allele frequency (VAF) of ctDNA is prognostic, particularly in early-stage patients. Those with detectable ctDNA prior to resection exhibited a higher risk of recurrence compared to those without detectable ctDNA, highlighting the potential of ctDNA as a predictive tool in clinical practice (O’Sullivan et al., 2023). This study illustrates the critical role of ctDNA in stratifying patients based on their risk of relapse, which could inform follow-up and treatment decisions.

 Desai (2024) also contributed to this field by discussing the integration of ctDNA into clinical practice for managing EGFR-mutant NSCLC. The study highlighted ctDNA's role in risk stratification and treatment decision-making, particularly for patients undergoing curative-intent treatment (Desai, 2024). This aligns with the growing recognition of ctDNA as a valuable tool for monitoring MRD and guiding therapeutic interventions.

 Moreover, Morgensztern (2024) emphasized the expanding role of ctDNA in resectable NSCLC, suggesting that its detection could facilitate personalized treatment approaches. By identifying patients at high risk for relapse, clinicians may opt for more aggressive therapies, while those at low risk could avoid overtreatment (Morgensztern, 2024). This personalized approach is crucial in improving outcomes for lung cancer patients.

 In summary, the studies from 2023 and 2024 collectively demonstrate the promising role of ctDNA in detecting MRD and predicting recurrence in lung cancer. The ability to provide real-time insights into disease status and risk stratification positions ctDNA as a vital component of modern oncological practice, particularly in the management of NSCLC.

 References:

Chaudhuri, A., Chabon, J., Lovejoy, A., Newman, A., Stehr, H., Azad, T., … & Diehn, M. (2017). Early detection of molecular residual disease in localized lung cancer by circulating tumor dna profiling. Cancer Discovery, 7(12), 1394-1403. https://doi.org/10.1158/2159-8290.cd-17-0716

Desai, A. (2024). Ctdna for the evaluation and management of egfr-mutant non-small cell lung cancer. Cancers, 16(5), 940. https://doi.org/10.3390/cancers16050940

Fakih, M., Sandhu, J., Wang, C., Kim, J., Chen, Y., Lai, L., … & Kaiser, A. (2022). Evaluation of comparative surveillance strategies of circulating tumor dna, imaging, and carcinoembryonic antigen levels in patients with resected colorectal cancer. Jama Network Open, 5(3), e221093. https://doi.org/10.1001/jamanetworkopen.2022.1093

Franzi, S. (2023). Liquid biopsy in non-small cell lung cancer: a meta-analysis of state-of-the-art and future perspectives. Frontiers in Genetics, 14. https://doi.org/10.3389/fgene.2023.1254839

Kang, G., Lizaso, A., Beck, S., Lyskjær, I., Chervova, O., Li, B., … & Wang, J. (2023). Individualized dynamic methylation-based analysis of cell-free dna in postoperative monitoring of lung cancer. BMC Medicine, 21(1). https://doi.org/10.1186/s12916-023-02954-z

Morgensztern, D. (2024). The expanding role of circulating tumor dna in resectable non–small cell lung cancer. Cancer, 130(10), 1730-1732. https://doi.org/10.1002/cncr.35268

O’Sullivan, H., Feber, A., & Popat, S. (2023). Minimal residual disease monitoring in radically treated non-small cell lung cancer: challenges and future directions. Oncotargets and Therapy, Volume 16, 249-259. https://doi.org/10.2147/ott.s322242

Szpechcinski, A., Chorostowska‐Wynimko, J., Struniawski, R., Kupis, W., Rudziński, P., Langfort, R., … & Orłowski, T. (2015). Cell-free dna levels in plasma of patients with non-small-cell lung cancer and inflammatory lung disease. British Journal of Cancer, 113(3), 476-483. https://doi.org/10.1038/bjc.2015.225

Yan, X. and Liu, C. (2022). Clinical application and prospect of mrd evaluation in lung cancer based on ctdna level: a review. Tumori Journal, 109(4), 356-362. https://doi.org/10.1177/03008916221101927

Zhang, J., Liu, S., Gao, W., Liu, S., Yan, H., Ji, L., … & Wu, Y. (2022). Longitudinal undetectable molecular residual disease defines potentially cured population in localized non–small cell lung cancer. Cancer Discovery, 12(7), 1690-1701. https://doi.org/10.1158/2159-8290.cd-21-1486

Chat GPT: CLIA Verification vs Validation.

 You are an expert on CLIA and clinical laboratory Policy.  What is the difference between "Verification" and "validation" in this context.  I think that verification has to do with bring up a complex IVD FDA-approved test for use, while validation has to do with validating an inhouse lab developed test (LDT).  However, don't assume I have that correct.

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You are on the right track with your understanding of verification and validation in the context of CLIA (Clinical Laboratory Improvement Amendments) and clinical laboratory policy, but let's clarify these terms in more detail.

Verification refers to the process of confirming that a laboratory can accurately perform a test according to the specifications provided by the manufacturer of an FDA-approved or cleared test (typically an in vitro diagnostic [IVD] device). When a lab brings an IVD test into use, they must verify that they can replicate the test’s performance characteristics (e.g., accuracy, precision, sensitivity) as specified in the product labeling. This step ensures that the test performs as expected in the laboratory's specific setting but does not involve altering the test methodology.

Validation, on the other hand, is a more comprehensive process used primarily for laboratory-developed tests (LDTs), which are not FDA-approved or cleared. Validation involves establishing the test’s performance characteristics from the ground up, as there are no manufacturer specifications to verify. This includes defining and confirming accuracy, precision, sensitivity, specificity, and other relevant performance characteristics for the test in question. The lab essentially proves that the test is reliable for its intended use.

In summary:

Verification: Performed for FDA-approved/cleared tests (IVDs) to ensure the lab can run the test properly.

Validation: Required for in-house LDTs, where the lab must fully establish the test's performance characteristics.

Let me know if you need more details on either process!

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Assume I am preparing to be hired for a lab director role, and I need to answer an oral question contrasting and comparing the two processes.   Provide a more detailed answer suitable for someone interviewing to be a lab director.

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Verification and validation are critical processes under CLIA, but they differ in scope, purpose, and regulatory requirements. Let’s start by defining each process:

1. Verification is required when a laboratory implements an FDA-approved or cleared test—typically an in vitro diagnostic (IVD) device. Since the test has already undergone rigorous validation by the manufacturer as part of the FDA approval process, the lab is not required to perform a full validation. Instead, the lab must verify that it can perform the test within its own environment and achieve the same performance characteristics specified by the manufacturer. The key parameters verified include:

   • Accuracy: Does the test provide results that match known standards?
   • Precision: Is the test reproducible, with minimal variation between runs?
   • Reportable Range: Does the test accurately report values across the intended range?
   • Reference Range: Do results fall within the expected normal ranges for the patient population?

   The process typically involves running controls and samples to confirm that the lab’s staff, equipment, and environment can maintain the test’s intended performance. Verification is especially focused on ensuring consistent application of a pre-established test in a new setting.

2. Validation, by contrast, applies to laboratory-developed tests (LDTs) or modified FDA-approved tests. Since LDTs are not FDA-reviewed, the lab must take full responsibility for proving that the test performs as intended. This process is more involved and includes:

   • Establishing Performance Characteristics: The lab must generate data to support accuracy, precision, sensitivity, specificity, and analytical range. 
   • Unlike verification, which confirms performance against an existing standard, validation requires building the evidence to define those standards.
   • Risk Assessment: As part of validation, the lab also conducts a thorough risk analysis, considering factors such as potential cross-reactivity, matrix effects, and robustness in various operating conditions.
   • Clinical Utility: The lab must demonstrate that the test’s results provide meaningful clinical information that can be used for patient care decisions, ensuring the test is fit for its intended clinical purpose.

Key Differences:

• Scope: Verification focuses on confirming performance characteristics established by the manufacturer, while validation involves defining and establishing these characteristics for a new or modified test.
• Regulatory Requirements: For verification, the lab is bound to follow the FDA-approved test's guidelines. 
• For validation, the lab takes on the responsibility for all aspects of test performance, requiring a higher degree of scrutiny and documentation.
• Complexity: Verification is a more straightforward process with predefined benchmarks, while validation involves more extensive, data-driven analysis to ensure the test is fit for its intended use.

Key Similarities:

• Both processes are crucial for ensuring that any test used in the clinical laboratory meets the necessary quality standards under CLIA and applicable regulatory guidelines.
• Both require careful documentation and adherence to the lab’s quality management system, including the monitoring of ongoing performance through quality control (QC) measures.

In summary, while verification is generally limited to confirming that an FDA-cleared test works as expected in the lab’s environment, validation is a more comprehensive process used when developing new tests or significantly modifying existing ones. As a lab director, it's important to oversee both processes to ensure compliance, maintain high-quality patient care, and mitigate risks associated with testing."

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This answer highlights your knowledge of both processes, while also demonstrating your leadership capabilities in maintaining quality and regulatory compliance in the lab.

Order of Bullets in van Shaik, CGP Value

Original blog:   https://www.discoveriesinhealthpolicy.com/2024/09/journal-club-broad-tech-assessments-of.html 

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SIDEBAR: Why the Order?

 

1. Actionable Mutations Were Common, but Impact Was Unclear: I put this first because finding actionable mutations is the core promise of CGP. But if these findings don't consistently lead to better outcomes, then the whole premise of CGP becomes questionable. This felt like the most important point to address upfront.

2. Limited Diagnostic Impact: After actionable mutations, I wanted to highlight the diagnostic value of CGP. If it's not significantly improving or refining diagnoses, it calls into question whether CGP is doing enough to justify its use. So, I placed this right after the actionable mutations discussion.

3. Matched Treatments Had Inconsistent Results: This comes next because the idea behind CGP is to guide personalized treatment. If matched treatments are inconsistent across studies, it’s a major limitation. I felt that once we’ve talked about actionable mutations and diagnostic impact, discussing treatment outcomes naturally follows.

4. Clinical Utility Limited by Treatment Access: Even if CGP finds actionable mutations, if patients can’t access the treatments due to insurance or logistical issues, then the real-world utility is limited. This is a practical barrier that felt important to address early on, right after the more theoretical points about mutations and diagnostics.

5. No Randomized Controlled Trials (RCTs): I placed this high on the list because RCTs are considered the gold standard for proving efficacy. The absence of RCTs really weakens the conclusions about CGP’s clinical utility, so it seemed important to mention early.

6. Turnaround Time Variability: Turnaround time directly affects patient care, and if it’s inconsistent or too slow, CGP’s practical value in clinical settings diminishes. I thought this was an operational issue that needed to be addressed before moving on to more abstract concerns like study design.

7. Lack of Standardization in Outcomes: This is a big frustration because it makes it hard to compare results across studies. Without standardized outcomes, we can’t draw solid conclusions about CGP’s effectiveness, so it felt like a key limitation to highlight after the discussion on practical and clinical issues.

8. Difficulty in Assessing Long-Term Benefits: I wanted to emphasize that CGP’s potential long-term benefits, like hereditary findings, are often overlooked. This is a missed opportunity, and I thought it was important to mention before moving on to methodological and cost-related issues.

9. Observational Study Design Challenges: Since observational studies are the main source of data for CGP, their limitations have to be acknowledged. But I placed this a bit lower because it’s more of a methodological issue, which feels secondary to clinical outcomes and real-world utility.

10. Lack of Cost-Effectiveness Data: Cost-effectiveness is critical when deciding whether to implement a technology like CGP, but without strong data here, it’s hard to justify its use. I placed this lower because while it’s important, clinical and operational factors seemed more pressing.

11. Limited Empirical Evidence: There’s a lack of empirical evidence for some factors, like laboratory organization and scientific spillover. This is a significant gap, but I placed it lower because it’s not as immediately impactful as the clinical and financial concerns.

12. Need for Real-World Evidence and Comprehensive Assessments: Finally, I wanted to end with a forward-looking recommendation. The need for more real-world evidence and comprehensive assessments summarizes what’s missing and where future research should go. It felt like a natural conclusion after discussing all the limitations.

This order begins with the most pressing clinical findings and gradually moves toward methodological, operational, and future research concerns, creating a logical flow that prioritizes patient-centered utility before broader or systemic issues.

OPPS Comment Radiopharm Competitive Settings

 TOPIC: Payment for diagnostic radiopharmaceuticals.   

III.V.B.c. 89 Fed Reg 59213-9.

I support the separate billing of certain costly radiopharmaceuticals.  This supports the fact that OPPS is a prospective payment system sensitive to major levels (APCs for Radiology 1, 2, 3 etc).  This use of packaging plus levels is also found in DRGs as are MS-DRGs (w/MCC, etc).

CMS does not mention in this context incentives or perverse incentives regarding location of service.  Currently, diagnostic radiopharmaceuticals in Part B non-facility settings are paid separately (e.g. $600 scan, $2000 tracer).   This provides a current incentive to use these tracers only in part of the nuclear scan places of service, creating a segmented and therefore less competitive market.  By paying for costly tracers separately in both freestanding and facility outpatient settings, there will be a more level playing field and more potential for competition.

Thank you! Your comment has been submitted to Regulations.gov for review by the the Centers For Medicare & Medicaid Services.   Comment Tracking Number: m0s-l837-lcz4

HHS Folds Cards After Judge Vacates Regulation "AGAINST" Web-Tracking Visitor Behavior

 Example of a judge in Texas VACATING an HHS regulation that "over reaches."

https://www.fiercehealthcare.com/regulatory/hhs-reverses-course-will-no-longer-appeal-federal-courts-hospital-web-tracker-decision

The white flag came 10 days after the administration had filed its appeal to the Fifth Circuit.

The case had been brought in late 2023 by the American Hospital Association (AHA) the Texas Hospital Association, Texas Health Resources and United Regional Health Care System, which had argued that HHS’ Office for Civil Rights (OCR) overstepped its authority with guidance it had issued in 2022.

That bulletin warned providers that online trackers to monitor user traffic and behavior, such as the Meta Pixel or Google Analytics, could be at odds with the Health Insurance Portability and Accountability Act (HIPAA). Such tools are widely employed by hospitals, triggering a spate of class-action lawsuits and settlements.

The lawsuit, which enjoyed the support of numerous state hospital groups and individual health systems, argued that the trackers are a key tool for providers tailoring their service offerings to meet the needs of their communities. The hospitals also argued that HHS had exceeded its statutory authority by expanding HIPAA’s definition for its bulletin and noted that many of the government’s own healthcare websites actively use the tools HHS OCR was restricting.

Despite a March adjustment to the bulletin, Judge Mark Pittman of the U.S. District Court for the Northern District of Texas vacated the guidance. He wrote in the ruling that the department’s bulletin “was promulgated in clear excess of HHS's authority under HIPAA."

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CHAT GPT 4o

The case "American Hospital Association, et al. v. Xavier Becerra, et al." before the United States District Court for the Northern District of Texas, Fort Worth Division, involves the American Hospital Association (AHA) and other plaintiffs challenging the Department of Health and Human Services (HHS) over its interpretation and enforcement of the Health Insurance Portability and Accountability Act (HIPAA) in the context of online tracking technologies.

Background

The case centers on the application of HIPAA’s Privacy Rule, particularly concerning “individually identifiable health information” (IIHI). HHS issued guidance documents, first in December 2022 (the “Original Bulletin”) and then a revised version (the “Revised Bulletin”), which attempted to address privacy concerns related to the use of online tracking technologies by healthcare providers. The Bulletins posited that the combination of a user’s IP address with visits to health-related webpages could constitute IIHI, thereby invoking HIPAA protections.

The plaintiffs, which include two hospital associations and a regional healthcare system, argue that the Bulletins impose new substantive obligations not supported by HIPAA's statutory framework. They contend that HHS overstepped its authority by expanding the definition of IIHI without going through the proper rulemaking processes, thereby violating the Administrative Procedure Act (APA).

Legal Arguments and Ruling

The court ruled in favor of the plaintiffs on several key points:

1. Jurisdiction: The court determined it had jurisdiction over the case, rejecting HHS’s argument that the Bulletins were not a “final agency action” and therefore not subject to judicial review. The court found that the Revised Bulletin represented the consummation of HHS’s decision-making process and imposed new legal obligations on covered entities, making it a final agency action.

2. Substantive Overreach: The court found that the Bulletins improperly expanded the definition of IIHI beyond what HIPAA’s statutory language permits. The Revised Bulletin’s attempt to include online tracking data (the “Proscribed Combination”) as IIHI was seen as an overreach because it imposed new obligations not grounded in the statutory text of HIPAA.

3. Legal Consequences: The court concluded that the Revised Bulletin created new legal obligations by prescribing specific conduct to ensure compliance with the Privacy Rule, effectively making the guidance document enforceable as law. The court rejected HHS’s argument that the Revised Bulletin was merely a policy statement without binding legal force.

Conclusion

The court granted summary judgment in part to the plaintiffs, finding that HHS had exceeded its statutory authority under HIPAA by attempting to regulate online tracking technologies through guidance documents without going through the proper rulemaking process. This case underscores the sensitivity of Texas federal courts to perceived agency overreach and their willingness to curtail what they see as executive agencies exceeding their statutory bounds.

This ruling is particularly significant in the broader context of administrative law and health policy, as it reaffirms the limits of agency authority in interpreting and enforcing complex regulatory frameworks like HIPAA. It also highlights the ongoing tension between federal agencies and the courts regarding the proper scope of regulatory power, especially in a jurisdiction like Texas, known for its skepticism of federal overreach.

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The judge makes a reference to the Bible, specifically the Book of Luke, in a whimsical manner to emphasize a point. In discussing the expansive reach of the federal bureaucracy and the potential consequences of allowing agencies to overstep their authority, the judge alludes to Luke 19:26, which says, "to everyone who has, more will be given, but from the one who has not, even what he has will be taken away."

This citation is used to underline the idea that once an agency like HHS begins to expand its authority beyond its statutory limits, it tends to accumulate more power, often at the expense of the freedoms or rights initially protected by the law. The judge uses this biblical reference to critique the tendency of federal agencies to self-perpetuate and expand their influence, which is a central theme in his argument against the overreach of HHS in this case.

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Towards the end of the opinion, the judge broadens the scope of the case beyond just the specific issues surrounding HIPAA. He characterizes the case as being fundamentally about the limits of agency power and the broader implications of unchecked executive authority.

This rhetorical flourish serves to highlight the judge's perspective that this case is not merely a legal dispute over the technicalities of HIPAA, but rather a part of a larger narrative concerning the role of federal agencies and the importance of maintaining a balance of power. By framing it this way, the judge is emphasizing the potential dangers of allowing agencies to interpret and enforce laws in ways that may extend beyond the authority granted to them by Congress.

The comment can be seen as somewhat gratuitous because it steps away from the specifics of the case to make a broader philosophical point about the nature of government power. It reflects the judge's concern with the potential for agency overreach to undermine the principles of limited government and the rule of law, making a case that this decision has implications beyond the immediate legal context.

This closing remark underscores the judge's view that cases like this are critical in preserving the constitutional boundaries of agency authority, ensuring that executive agencies do not exceed the powers delegated to them by Congress. It's a way of stressing the significance of the ruling in the broader context of American governance and legal principles.

Arenas-Gallo and the MolDx Transthyretin policy and Race.

 A July 2024 article in NEJM (Arenas-Gallo) questions use of race-based concepts in medicine.

What might they say about the inclusion of "African-American descent" as a Medicare policy?

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Camilo Arenas-Gallo and his co-authors argue against the use of race as a biologic category in clinical decision-making, emphasizing that race is a social construct rather than a scientifically valid basis for clinical algorithms. They express concerns that race-based recommendations in medical guidelines could perpetuate health disparities, reinforce unconscious biases, and obscure the impact of socioeconomic factors that more accurately explain differences in health outcomes.

Given these views, Arenas-Gallo might be critical of the MolDx policy's use of African American descent as a criterion for coverage in the context of molecular diagnostics for hereditary transthyretin amyloidosis (hATTR). The inclusion of race as a factor in the policy could be seen as problematic for several reasons:

1. Biologic Determinism vs. Social Construct: Arenas-Gallo would likely question the scientific validity of using "African American descent" as a criterion, given that race does not have a clear biologic basis. He might argue that this approach risks attributing genetic or disease predispositions to race, when in reality, these should be understood through a combination of genetic, environmental, and socioeconomic factors.

2. Potential for Reinforcing Bias: The policy’s focus on race could unintentionally reinforce biases among healthcare providers, leading them to make assumptions about patients based on racial categories rather than individualized assessments. Arenas-Gallo might argue that this could exacerbate existing health disparities rather than addressing them.

3. Neglect of Socioeconomic Determinants: By focusing on race, the policy might overlook more significant determinants of health outcomes, such as access to care, education, and income levels. Arenas-Gallo and his co-authors suggest that socioeconomic factors often have a more substantial influence on health disparities than race itself.

4. Inconsistency and Confusion: The use of race as a criterion could lead to inconsistencies and confusion, both for patients and healthcare providers. Arenas-Gallo would likely advocate for more universal and unbiased criteria that do not rely on race, thereby reducing ambiguity and ensuring that all patients receive equitable care based on scientifically sound factors.

In summary, Arenas-Gallo might argue that the MolDx policy should reconsider the use of race as a criterion and instead focus on more precise, non-racial factors that influence health outcomes. He would likely advocate for an approach that emphasizes individual patient characteristics and broader social determinants of health, rather than relying on race as a proxy for risk.

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But if a gene is more common in "African American" populations and therefore in guidelines, is that difference in gene frequency really an economic side effect?  Seems unlikely. 

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You're right to point out that if a particular gene or genetic variant is more prevalent in a specific population, such as African Americans, this difference isn't simply an economic side effect but rather a matter of genetic epidemiology. When a gene is more common in a certain population, this can have significant implications for disease prevalence and, consequently, for clinical guidelines.

Distinction Between Genetic Differences and Race as a Social Construct

Arenas-Gallo and his co-authors would likely acknowledge that genetic differences can indeed exist between populations, which might explain why certain diseases or conditions are more prevalent in specific groups. However, they would also emphasize the importance of not conflating these genetic differences with the concept of race, which is often used as a social and not a strictly biological construct.

The Role of Genetic Epidemiology

• Gene Frequency: If a genetic variant associated with a condition like hereditary transthyretin amyloidosis (hATTR) is more common in African American populations, it makes sense from a medical perspective to consider this in screening and diagnostic guidelines. The frequency of such variants in a population can justify targeted genetic testing strategies.

• Population-Specific Guidelines: The challenge, as Arenas-Gallo might see it, is to develop guidelines that recognize these genetic realities without reinforcing the idea that race itself is a biologic determinant. This requires careful language and a focus on genetic risk rather than race per se.

Balancing Precision and Equity

Arenas-Gallo might argue for a more nuanced approach that separates genetic risk factors from racial categories. This could involve:

• Clarifying the Language: Instead of using "African American" as a shorthand, guidelines could specify that certain genetic variants are more common in people of West African ancestry, for example. This would make it clear that the focus is on genetics, not race.

• Genetic Testing Based on Risk: Guidelines could recommend genetic testing based on known risk factors, including ancestry, rather than broadly applying racial categories. This approach would ensure that individuals at higher genetic risk are identified and treated appropriately, without implying that all members of a racial group share the same risk.

Arenas-Gallo's Likely Perspective

Arenas-Gallo might still be cautious about the use of race in guidelines, even if it's justified by genetic differences, because of the risk of reinforcing stereotypes or overlooking the social determinants of health. He would likely advocate for guidelines that are precise, focusing on genetic risks specific to certain ancestries or populations, while avoiding the pitfalls of race-based medicine. This could involve a shift towards more personalized approaches in medicine, where genetic testing and ancestry information are used to tailor care, rather than relying on broad racial categories.

MolDx TA's and Retroactive Coverage

We hear about MolDx tech assessments and retroactive coverage; here is an example.

Publicly-held Personalis released its 2Q (June 30, 2024) financials as an SEC 10-Q on about August 7, 2024.

They remark,

In January 2024, we announced that we received a final Medicare coverage determination for our NeXT Dx offering, extended retroactively to August 29, 2023. While we estimate that approximately half of new solid tumor cancer cases will be diagnosed in patients covered by Medicare...

https://investors.personalis.com/static-files/1b727c36-7351-4f6f-ab2b-d3a252287e54