2020 Value Health 23_3 Loblova Soc Sci of HTA (ha).pdf
2023 PLOS ONE Parker Decision impact studies zDIS 0280582 22p Toronto.pdf
2022 SSM Holloway Consultants Role in MDX (Ha).pdf
2022 SSM Hogarth Regulatory Niches for UK DX 1990 2018.pdf
2022 SSM Dupras NIPT Delphi Future.pdf
2022 SSM Framing Regulatory Utility Genet 1989 2000 Sturdy.pdf
2020 REG GOV Hogarth Video to Data FDA Pers Med promissory (ha).pdf
2012 SHI 34_234 Hogarth HPV Cervical MONOPOLY.pdf
2004 Clin Chem 50_473 Moons Test vs Diagnostic Res.pdf
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PARKER PLOS Decision Impact Studies
The article titled "Decision impact studies evidence of clinical utility for genomic assays in cancer: A scoping review" by Parker et al., published in PLOS ONE, is a scoping review that aims to characterize decision impact studies (DIS) and their role in assessing the clinical utility of genomic assays in cancer care. The study conducted a comprehensive database search, resulting in 87 studies meeting inclusion criteria, most of which pertained to breast cancer. The review observes a significant increase in DIS publications in recent years, indicating a growing acceptance of these studies as evidence of clinical utility in genomic medicine.
The review finds that DIS are largely focused on breast cancer and proprietary assays and have been used to support reimbursement decisions across multiple countries. DIS are positioned to provide surrogate evidence of clinical utility due to the contested nature of clinical utility definitions and underdeveloped robust clinical outcomes for genomic assays.
The studies included in the review reported 22 discrete clinical utility measures across four levels of clinical utility as defined by the Fryback and Thornbury model. However, less than half of the studies reported changes in actual treatment, highlighting the debate over what constitutes valuable outcomes for assessing clinical utility. The review suggests that while DIS report changes in clinical decision-making, changes in actual treatment may be more indicative of clinical utility.
Outcomes related to costs and savings are also critical, as most genomic assays are expensive, and DIS that included cost analyses typically demonstrated that the savings from reduced adjuvant treatment outweighed the assay costs.
The review concludes that DIS represent a new and expanding research area within genomic medicine and cancer care, providing evidence for clinical and reimbursement decision-making. It suggests that further research is needed to understand the specific impact of DIS on reimbursement processes and the extent to which DIS are used in decision-making.
In essence, this review underscores the importance of DIS in providing evidence for the clinical utility of genomic assays and their influence on clinical practice and reimbursement decisions in cancer care.
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HOLLAWAY Consultants and Genomics in the USA
"The Consultant's intermediary role in the regulation of molecular diagnostics
in the US"
The paper by Holloway et al., published in Social Science & Medicine, delves into the complex regulatory landscape governing molecular diagnostics in the United States, with a focus on the role of consultants as intermediaries. As molecular diagnostics become integral to personalized medicine, the authors investigate how consultants help companies navigate and influence the polycentric regulatory regime, particularly in gaining broad clinical uptake for their products.
The study utilizes a web-based search, analysis of online materials, and interviews with consultants to understand their role in coverage and reimbursement of novel diagnostics. It finds that consultants act as crucial links between manufacturers and regulatory entities, shaping evidentiary standards for payment decisions that benefit their clients.
The paper highlights that while molecular diagnostics can often bypass stringent FDA regulations by being marketed as laboratory-developed tests (LDTs), securing reimbursement and insurance coverage is critical for their commercial success. This is because the definition of clinical utility—a key determinant for coverage decisions—is not well-established and is subject to interpretation.
Consultants provide expertise and strategic navigation through this complexity, advocating for definitions of clinical utility that favor their clients. They assemble networks of actors, including Key Opinion Leaders (KOLs), to generate evidence of a test's clinical utility, which can be based on its use in clinical practice or its impact on patient outcomes.
In summary, Holloway et al.'s study reveals that consultants play a formative role in the regulatory processes that determine the success of molecular diagnostics in the market. Their work raises questions about whose interests are prioritized in the regulation of diagnostic innovation and its implications for public health policy. The authors call for a reorientation of public policy discussions to critically evaluate the safety, efficacy, and clinical utility of these diagnostics, highlighting the need for more robust statutory regulation
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HOGARTH on FDA's "enthusiasm for genomics." Case study, relabeling genetics of warfarin, which generated disputes.
The paper "The ratio of vision to data: Promoting emergent science and technologies through promissory regulation the case of the FDA and personalised medicine" by Hogarth and Martin, published in Regulation & Governance, explores the FDA’s role in regulating pharmacogenetic tests, which are used to tailor drug treatments based on genetic data. It details the FDA's efforts to advocate for pharmacogenetic testing in the mid-2000s and the resulting disputes over the evidence needed for the adoption of such testing, focusing on the case of warfarin, a blood-thinning medication.
The authors argue that the FDA's actions represent a form of "promissory regulation," where regulatory policy is shaped by the transformational potential of emergent science and technologies (ESTs). The paper discusses the FDA’s use of genomic science as a means to shift from being a gatekeeper of drug approval to an enabler of innovation. This shift is part of a broader deregulatory trend in which scientific advances are used to justify loosening regulatory standards.
Hogarth and Martin provide a critical examination of the FDA's role in creating markets for ESTs, the political economy of regulation, and the modification of scientific standards to accommodate ESTs. The case of warfarin relabeling is used to illustrate the tension between the FDA’s traditional role in protecting public health and its newer role as a promoter of personalized medicine.
The paper suggests that while the FDA sought to promote pharmacogenetics as a transformative approach to drug dosing, there were significant challenges due to the lack of consensus on clinical utility and the evidentiary standards required for widespread clinical adoption. The FDA’s advocacy faced skepticism from healthcare payors and clinicians who demanded more robust evidence of the tests’ benefits, particularly through randomized control trials.
In conclusion, Hogarth and Martin’s paper examines the intricate balance the FDA must maintain between promoting innovation and ensuring public safety. It calls for a critical assessment of how the interests of different stakeholders, including regulators, industry, and the public, are served in the regulation of diagnostic innovations, especially in the context of genomic medicine and personalized healthcare.
Hogarth cites his own 2015 paper with a similar title.
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The paper "The Emerging Social Science Literature on Health Technology Assessment: A Narrative Review" by LOBLOVA et al. examines the growing body of social science research on Health Technology Assessment (HTA). The narrative review focuses on sociology and political science, highlighting how these disciplines contribute to understanding HTA's implementation and practice.
The review identifies three main themes within the social science literature on HTA: the reasons behind the establishment and design of HTA bodies; the impact of institutionalized HTA on pricing, reimbursement, and the broader society; and the social and political influences on HTA decision-making processes. Social scientists scrutinize the role of institutions and actors involved in HTA, using qualitative research methods to provide critical perspectives that challenge previously unquestioned assumptions about HTA.
Loblova et al. reveal that while HTA is often presented as a tool for efficient healthcare resource distribution, its adoption and institutionalization are subject to varying local pressures and interests. Differences in the institutional and methodological aspects of HTA bodies reflect diverse national healthcare systems and political preferences. The review argues that political and strategic choices by governments and key actors play a significant role in shaping HTA practices, which, in turn, influence reimbursement outcomes.
Additionally, the paper discusses the complexities of evidence-based policy in the context of HTA, where the definition of evidence is contested. The social scientists argue that HTA processes tend to prioritize quantitative evidence over the lived experiences of practitioners and patients, revealing a negotiation process that grapples with complexity and uncertainty.
In conclusion, the review by Loblova et al. underscores the need for closer collaboration between social scientists and HTA practitioners. It suggests that integrating social science perspectives into HTA research could improve understanding of the role of culture, values, and institutions in HTA practices. This could help answer larger questions about the actual benefits of HTA for healthcare systems, policy-making, and societal health outcomes.blova: Studying the Literature around HTAs. HTAs as a subject, how it is studied.
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STURDY reviews the growing emphasis on Clinical Utility in FDA and Payor regulation of genomics in the 1990s. Risks of genetic tests, eg. BRCA, were increasingly seen as a risk benefit balance.
The paper "Framing utility: Regulatory reform and genetic tests in the USA 1989–2000" by Steve STURDY traces the shift in regulatory focus for genetic tests in the United States during the 1990s. It seeks to understand why, specifically in relation to genetic tests, there was a move to assess their "clinical utility" – whether they benefit those undergoing testing. The paper situates the debate within the historical context of medical genetics and its efforts to distance itself from associations with eugenics in the 1970s.
Throughout the 1990s, a series of policy committees, including the NIH-DOE Task Force and the Secretary’s Advisory Committee on Genetic Testing (SACGT), were convened. These committees were instrumental in framing the idea that genetic tests should not only meet standards of analytic and clinical validity but also demonstrate clinical utility before being adopted in clinical practice. This framing reflected a shift from geneticists' traditional reliance on genetic counseling as a communicative tool to a growing call for regulatory measures ensuring that tests used in practice were beneficial.
Sturdy's analysis illuminates how the concept of clinical utility emerged as a regulatory requirement for genetic tests. It reflects a period when medical geneticists were adjusting their approach to mitigate the potential harms of genetic testing amidst new technical capacities and regulatory opportunities. The paper concludes that the framing of genetic tests in terms of clinical utility relates to current debates on "genetic exceptionalism" and recent articulations of clinical utility in testing governance.
This detailed focus on the history of clinical utility as a regulatory concept reveals the evolving nature of the debate surrounding the regulation of genetic tests. It highlights how the interplay between technical innovation, regulatory opportunities, and the medical genetics community's response to past controversies over eugenics shaped the trajectory of genetic test regulation.
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In a second paper by HOGARTH, regulatory "nices" for genomic testing are discussed focusing on 30 years in UK, 1990-2018. The second author LOBLOVA was first author on a paper above.
The paper "Regulatory niches: Diagnostic reform as a process of fragmented expansion. Evidence from the UK 1990-2018" by Stuart Hogarth and Olga Löblová explores the evolution of the regulatory landscape for diagnostics within the UK National Health Service (NHS). It addresses the shift from an informal, clinician-led model of diagnostic innovation to a more structured regulatory environment driven by new governance mechanisms.
Historically, the introduction of new diagnostic tests within the NHS was an evolutionary process without significant external controls. This informal system was challenged by the emergence of regulatory niches—discrete spaces within the overarching clinical pathology regime that introduced new evaluation frameworks, organizational structures, and epistemological boundaries.
The study identifies five key drivers that triggered the formation of these niches: public scandals, technological changes, marketization, institutional isomorphism, and transnational policy transfer. These drivers catalyzed a fragmented regulatory expansion, characterized by the establishment of specific governance mechanisms, such as the UK National Screening Committee (NSC), NICE’s Diagnostics Assessment Programme (DAP), and the UK Genetic Testing Network (UKGTN).
Each niche is differentiated by its outcomes and origins, reflecting the various responses to the increasing complexity and significance of diagnostic tests in healthcare. The authors argue that the rise of evidence-based medicine and centralized regulatory impulses from the state have progressively encroached on clinical autonomy, leading to a power contest increasingly mediated by influential non-governmental organizations.
Hogarth and Löblová's paper contributes to a deeper understanding of the regulation of diagnostics, highlighting the nuanced and multi-faceted nature of regulatory change within the healthcare system. The paper calls for a re-examination of the balance between innovation facilitation and public safety assurance in the context of genomic medicine and personalized healthcare policy.
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DUPRAS 2022 reviews "alternate futures" for NIPT testing (NIPS).
The paper "Governing the futures of non-invasive prenatal testing: An exploration of social acceptability using the Delphi method" by Dupras et al. investigates the social acceptability of current and future uses of non-invasive prenatal testing (NIPT) in Canada. Using a three-round Policy Delphi study involving experts from healthcare, social sciences, patient advocacy, and cultural/religious communities, the research seeks to understand the perspectives on NIPT.
The study finds that NIPT, while non-diagnostic, has considerably altered prenatal care due to its low-risk profile and early timing in pregnancy. It has triggered ethical, legal, and social concerns, particularly regarding its routinization, potential to pressure women into testing and termination of pregnancies, and the erosion of counseling and consent processes.
The paper addresses the technology's rapid development and global dissemination, noting how its use has expanded from trisomy 21 screening to detecting a wide array of conditions, raising questions about responsible governance. The participants in the Delphi study reached consensus on the social acceptability of NIPT depending on the conditions tested and the motives for testing. There was broad agreement on public coverage for conditions leading to severe pain or early death, as well as trisomies and sex chromosome abnormalities. Conversely, there was agreement that direct-to-consumer NIPT and testing for non-medical reasons should be banned or discouraged.
Key points of consensus include the need for appropriate consent procedures, patient counseling, education of health professionals, and regulation reflecting the society's inclusive values. The study also reveals divergent views on governing whole-genome sequencing and testing for late-onset conditions with low penetrance, highlighting the complexity of NIPT's social acceptability and governance.
In conclusion, the paper underscores the intricacies of NIPT governance and the importance of considering a diverse range of expert and public opinions in policy-making. It illustrates the need for robust regulation and public education to navigate the ethical landscape shaped by advances in prenatal testing technology.
2012 Hogarth paper on Digene HPV patents and FDA approval and reimbursement and policy processes built around this.
"A molecular monopoly? HPV testing, the Pap smear and
the molecularisation of cervical cancer screening in the
USA"
The paper "A molecular monopoly? HPV testing, the Pap smear, and the molecularisation of cervical cancer screening in the USA" by Hogarth et al. delves into the development and commercialization of molecular diagnostic testing for human papillomavirus (HPV), particularly its integration with and potential replacement of the Pap smear in cervical cancer screening.
The study examines the intricate process of 'molecularisation' where the shift from traditional cytology-based to molecular-based screening practices in the U.S. is portrayed as a gradual, contentious, and commercially driven process rather than a straightforward scientific progression. Digene Corporation's role is central to this narrative, as it developed the Hybrid Capture 2 (HC2) test, which emerged as a significant competitor to the Pap smear.
Key themes from the paper include the exploration of Digene's strategic use of patents and marketing to establish a foothold in the screening market, the reliance on clinical studies to build credibility, and the company's efforts to redefine the concept of clinical utility to prioritize molecular diagnostics. The paper also touches on how the regulatory landscape, particularly FDA approval, played a critical role in legitimizing the HC2 test, leading to its adoption in clinical guidelines and its establishment as the dominant HPV test in the U.S.
The article reflects on the broader implications of the molecularisation of cervical cancer screening for healthcare policy, particularly concerning the commodification of healthcare and the potential consequences of prioritizing corporate interests in public health decisions. It suggests that the entrenchment of molecular diagnostics in screening programs is not only a scientific and medical issue but also a sociopolitical one, where regulatory, clinical, and commercial interests intersect and compete.
In conclusion, Hogarth et al.'s analysis provides a nuanced view of the transition toward molecular diagnostics in cervical cancer screening, highlighting the complex interplay between technological innovation, market dynamics, and regulatory frameworks. It calls for a critical assessment of the impact of commercial strategies on the quality and accessibility of healthcare, particularly in the context of life-saving screening programs.
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2004 Clin Chem 50_473 Moons Test vs Diagnostic Res.pdf
Moons, Karel G.M., Biesheuvel, Cornee J., and Grobbee, Diederick E. Test Research versus Diagnostic Research. Clinical Chemistry, 2004, Vol. 50, No. 3, pp. 473-476. https://doi.org/10.1373/clinchem.2003.024752
This article argues that most published research on diagnostic test accuracy has limited relevance for clinical practice. The authors make a distinction between "test research" which focuses on quantifying test characteristics like sensitivity and specificity, and "diagnostic research" which examines how much a test adds to the probability of disease presence beyond existing information.
They contend test research has little practical utility because:
- It focuses on quantifying test characteristics rather than determining the test's contribution to estimating disease probability, which is more relevant clinically.
- Test characteristics like sensitivity/specificity are not fixed properties as often assumed, but can vary across and within patient populations depending on other factors related to the disease.
- Test research often suffers from verification bias in patient selection by choosing those with known disease status rather than a relevant clinical population.
The authors propose that diagnostic research should reflect actual clinical practice by: selecting patients based on suspicion of disease, modeling disease probability based on typical test sequence, using multivariable analysis to determine which tests independently add information, and presenting results as multivariable prediction models or rules. They argue this approach better captures the multivariable and probabilistic nature of diagnostic reasoning.
In summary, the authors make a strong case that diagnostic test research needs to shift focus from reporting performance measures of individual tests toward quantifying the incremental value of tests within the clinical context and flow of diagnostic decision-making. This better serves the end goal of improving estimation of disease presence and guiding appropriate treatment.
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