FDA Regulation and Approval of Medical Devices: 1976-2020.

Importance: US law generally requires testing of high-risk medical devices prior to approval, as well as premarket evaluation of moderate-risk medical devices, with the goal of ensuring that the benefits of these products exceed their risks. The US Food and Drug Administration (FDA) attempts to balance the need for evidence generation with an approval process that facilitates access and encourages innovation. Objective: To review the development of laws and standards affecting the evaluation and oversight of medical devices by the US regulatory system and the outcomes of this system from 1976 to 2020. Evidence Review: Laws enacted by US Congress and regulations promulgated by the FDA through 2020; databases maintained by the FDA of device authorizations from 1976 to 2020; and annual reports of user fees paid to the FDA by industry. Findings: Since Congress and the FDA initiated premarket review of medical devices in 1976, some fundamental innovations in the device regulation system have included special pathways to accelerate availability of investigational devices, more flexible evidence and review requirements, and increased funding to the FDA through industry-paid user fees. From 1987 to 2020, the annual number of novel devices granted premarket approval (which excludes supplements) ranged from 8 to 56 (median, 32), and the number of clearances for 510(k) devices (those that are "substantially equivalent" to marketed devices) ranged from 2804 to 5762 (median, 3404). User fee funding for devices was established in 2002 and annual fees collected increased from $30 million in 2003 (in 2019 dollars) to more than $208 million in 2019; this represented 43% of FDA funding related to the review of medical devices. Although many new devices have led to considerable patient benefit, such as hypodermic needles and magnetic resonance imaging machines, important adverse events caused by some devices, such as an implanted device for birth control and a surgical mesh implant for pelvic organ prolapse, have led to calls to reexamine the regulatory system for such products. Conclusions and Relevance: Over the last 45 years, medical device regulation has become more complex, with more regulatory pathways and greater variations in the evidence and controls required for authorization. Increased FDA support from industry and concern about flexible authorization requirements reflect the tension between efficient access and the need for assurances that products will safely benefit patients.

Genes, cells, and biobanks: Yes, there's still a consent problem.

From a research perspective, the interest in biobanking continues to intensify. Governments and industry have invested heavily in biobanks, as exemplified by initiatives like the United Kingdom Biobank and United States' Precision Medicine Initiative. But despite this enthusiasm, many profound legal and ethical challenges remain unresolved. Indeed, there continues to be disagreements about how best to obtain consent and the degree and nature of control that research participants retain over donated samples and health information. Emerging social trends-including concerns about commercialization and perceived rights of continuing control ("biorights")-seem likely to intensify these issues.

The Impact of Breast Density Notification Laws on Supplemental Breast Imaging and Breast Biopsy.

BACKGROUND: Dense breast tissue increases breast cancer risk and lowers mammography sensitivity, but the value of supplemental imaging for dense breasts remains uncertain. Since 2009, 37 states and Washington DC have passed legislation requiring patient notification about breast density. OBJECTIVE: Examine the effects of state breast density notification laws on use of supplemental breast imaging and breast biopsies. DESIGN: Difference-in-differences analysis of supplemental imaging and biopsies before and after notification laws in 12 states enacting breast density notification laws from 2009 to 2014 and 12 matched control states. Supplemental imaging/biopsy within 6 months following an index mammogram were evaluated during four time periods related to legislation: (1) 6 months before, (2) 0-6 months after, (3) 6-12 months after, and (4) 12-18 months after. PARTICIPANTS: Women ages 40-64 years receiving an initial mammogram in a state that passed a breast density notification law or a control state. INTERVENTION: Mandatory breast density notification following an index mammogram. MAIN MEASURES: Use of breast biopsies and supplemental breast imaging (breast ultrasound, tomosynthesis, magnetic resonance imaging, scintimammography, and thermography), overall and by specific test. KEY RESULTS: Supplemental breast imaging and biopsy increased modestly in states with notification laws and changed minimally in control states. Adjusted rates of supplemental imaging and biopsy within 6 months of mammography before legislation were 8.5% and 3.1%, respectively. Compared with pre-legislation in intervention and control states, legislation was associated with adjusted difference-in-differences estimates of + 1.3% (p < 0.0001) and + 0.4% (p < 0.0001) for supplemental imaging and biopsies, respectively, in the 6-12 months after the law and difference-in-differences estimates of + 3.3% (p < 0.0001) and + 0.8% (p < 0.0001) for supplemental imaging and biopsies, respectively, 12-18 months after the law. CONCLUSIONS: As breast density notification laws are considered, policymakers and clinicians should expect increases in breast imaging/biopsies. Additional research is needed on these laws' effects on cost and patient outcomes.

The continuing saga of patents and non-invasive prenatal testing.

OBJECTIVE: This paper examines the Intellectual Property (IP) landscape for non-invasive prenatal testing (NIPT) in three key regions: the United States; Europe, with particular focus on the United Kingdom; and Australia. METHOD: We explore the patent law issues against the commercial and healthcare environment in these regions and consider the implications for development and implementation of NIPT. RESULTS: There are many patents held by many parties internationally, with litigation over these patents ongoing in many countries. Importantly, there are significant international differences in patent law, with patents invalidated in the USA that remain valid in Europe. Despite the many patents and ongoing litigation, there are multiple providers of testing internationally, and patents do not appear to be preventing patient access to testing for those who can pay out of pocket. CONCLUSION: The patent situation in NIPT remains in a state of flux, with uncertainty about how patent rights will be conferred in different jurisdictions, and how patents might affect clinical access. However, patents are unlikely to result in a monopoly for a single provider, with several providers and testing technologies, including both public and private sector entities, likely to remain engaged in delivery of NIPT. However, the effects on access in public healthcare systems are more complex and need to be monitored.

Medical-Legal Partnership Impact on Parents' Perceived Stress: A Pilot Study.

Stress has adverse effects on health, and prolonged stress exposure is a risk factor for several mental and physical illnesses. 1 Families living in poverty face many stressors created and maintained by economic hardship and unaddressed legal and social needs. Medical-Legal Partnerships (MLPs) aim to improve health and well-being by addressing health-harming legal and social needs of patients. This pilot study examined whether MLP-involved parents perceived themselves as stressed; to what they attributed their stress; and whether they reported a reduction in stress when their MLP cases were closed. The study shows improvements in perceived stress following receipt of MLP interventions.

A decade of marketing approval of gene and cell-based therapies in the United States, European Union and Japan: An evaluation of regulatory decision-making.

There is a widely held expectation of clinical advance with the development of gene and cell-based therapies (GCTs). Yet, establishing benefits and risks is highly uncertain. We examine differences in decision-making for GCT approval between jurisdictions by comparing regulatory assessment procedures in the United States (US), European Union (EU) and Japan. A cohort of 18 assessment procedures was analyzed by comparing product characteristics, evidentiary and non-evidentiary factors considered for approval and post-marketing risk management. Product characteristics are very heterogeneous and only three products are marketed in multiple jurisdictions. Almost half of all approved GCTs received an orphan designation. Overall, confirmatory evidence or indications of clinical benefit were evident in US and EU applications, whereas in Japan approval was solely granted based on non-confirmatory evidence. Due to scientific uncertainties and safety risks, substantial post-marketing risk management activities were requested in the EU and Japan. EU and Japanese authorities often took unmet medical needs into consideration in decision-making for approval. These observations underline the effects of implemented legislation in these two jurisdictions that facilitate an adaptive approach to licensing. In the US, the recent assessments of two chimeric antigen receptor-T cell (CAR-T) products are suggestive of a trend toward a more permissive approach for GCT approval under recent reforms, in contrast to a more binary decision-making approach for previous approvals. It indicates that all three regulatory agencies are currently willing to take risks by approving GCTs with scientific uncertainties and safety risks, urging them to pay accurate attention to post-marketing risk management.

Selection of and Evidentiary Considerations for Wearable Devices and Their Measurements for Use in Regulatory Decision Making: Recommendations from the ePRO Consortium.

BACKGROUND: Wearable devices offer huge potential to collect rich sources of data to provide insights into the effects of treatment interventions. Despite this, at the time of writing this report, limited regulatory guidance on the use of wearables in clinical trial programs has been published. OBJECTIVES: To present recommendations from the Critical Path Institute's Electronic Patient-Reported Outcome Consortium regarding the selection and evaluation of wearable devices and their measurements for use in regulatory trials and to support labeling claims. METHODS: The evaluation group was composed of Critical Path Institute's clinical outcome assessment (COA) scientists and COA specialists from pharmaceutical trial eCOA solution providers, including COA development and validation specialists. The resulting recommendations were drawn from a broad range of backgrounds, perspectives, and expertise that enriched the development of this report. Recommendations were developed through analysis of existing regulatory guidance relating to COA development and use in clinical trials, medical device certification/clearance regulations, literature-reported best practice, and practical experience of wearable technology application in clinical trials. RESULTS: We identify the essential properties of fit-for-purpose wearables and propose evidence needed to support their use. In addition, we overview the activities required to establish clinical endpoints derived from wearables data. CONCLUSIONS: Using this framework, we believe there is enough current understanding to promote the appropriate use of wearables in study protocols. We hope this will provide a basis for discussion among clinical trial stakeholders and catalyze the development of more robust regulatory guidance.

[Psychologically/Psychosomatically Relevant Aspects in the German Medical Association's Guidelines for Transplant Medicine]. / Psychologisch bzw. psychosomatisch relevante Aspekte in den Richtlinien zur Transplantationsmedizin der Bundesärztekammer.

Transplant medicine in Germany is regulated by mandatory guidelines of the German Medical Association, the transplant law passed in 1997 serving as the legal basis. In 2012 a comprehensive modification of the guideline procedure was initiated. Since then, all guidelines are subject to an elaborate revision process. The present contribution initially depicts relevant background information and explains the formal aspects of the guideline procedure. Subsequently, the psychologically/psychosomatically relevant contents of the guidelines for organ transplantation are presented. With regard to this matter, first of all the state of the guidelines prior to the current revisions is described. Afterwards, already adopted revisions as well as published drafts are explicated, followed by the authors' evaluation of the revisions and recommendations for further revisions to be pursued. In addition, recommendations on psychosocial aspects regarding the evaluation and follow-up in living organ donation are presented, which have been submitted in similar form to the German Medical Association for a currently drawn up guideline.

[STRENGTHENING OF CONTRACTUAL PRINCIPLES WITHIN LEGAL RELATIONS BETWEEN A PATIENT AND A MEDICAL INSTITUTION WHILE REFORMING THE HEALTH CARE SYSTEM IN UKRAINE].

The objective of the article is to study the main theoretical and practical problems arising within the introduction of contractual regulation of legal relations between a patient and a medical institution, which is connected with the reform of the health care system in Ukraine. In the process of writing a scientific article, the authors have used general scientific, special and legal methods. For example, in July-September 2017, there was a study in Ukraine, when 1,200 people aged 18 and over were interviewed using a formalized interview method. The studies of 82% of surveyed Ukrainians confirmed that Ukrainian medicine does not properly function and needs to be reformed. The beginning of the medical reform in Ukraine was marked by the development of new bills and introduction of innovations into the current legislation, one of which is the conclusion of a declaration with a doctor for the primary medical care. Thus, the legislator tried to introduce organizational and legal ways to improve the functioning of medical workers, to raise the efficiency and development of the medical services market, and also to guarantee the protection of patients' rights. Taking into account the analysis of contractual regulation of legal relations between a doctor and a patient in other countries, the authors of the article have suggested to apply positive experience of reforming the health care system in England, which is the most optimal and effective for introduction in Ukraine. The analysis of the data, obtained results during the study of the initial stage of the medical reform shows that there are gaps in the legislation and about the need to reform the health care system in Ukraine.

Two steps forward, one step back: current harm reduction policy and politics in the United States.

Harm reduction policies and attitudes in the United States have advanced substantially in recent years but still lag behind more advanced jurisdictions in Europe and elsewhere. The Obama administration, particularly in its last years, embraced some harm reduction policies that had been rejected by previous administrations but shied away from more cutting edge interventions like supervised consumption sites and heroin-assisted treatment. The Trump administration will undermine some of the progress made to date but significant state and local control over drug policies in the US, as well as growing Republican support for pragmatic drug policies, motivated in part by the opioid crisis, ensures continuing progress for harm reduction.

Quota in specialty and super-specialty courses: What does the judiciary say?

Reservations in super-specialty courses have been controversial for decades. A number of practising doctors, medical students and others in society have wanted to do away with reservations in specialty and super-specialty courses, while there are others in favour of persisting with reservations. Article 15 (4) of the Constitution of India states that nothing shall prevent the State from making any special provision for the advancement of any socially and educationally backward classes of citizens or for the Scheduled Castes/Tribes. However, Article 14 of the Indian Constitution should also be considered. The judiciary, particularly, the Supreme Court of India, in its judgments has strived to strike a balance between the two constitutional provisions. The Supreme Court, on various occasions, has observed that reservations in super-specialty courses should be done away with, as such reservations would be detrimental to the advancement of medical science and research and will also not serve national interest. We present the observations of the Supreme Court of India through its various judgments, with a focus on the recent case of Dr Sandeep versus Union of India, where the honourable court stated that the government should do away with reservations in super-specialty courses.

From sanctioning culture to safety culture: Let's stop making errors on error.

The punitive culture continues to prevail in health care organizations that rely primarily on functional systems hierarchies based on conformity. This type of culture is recognized as a major source of an unacceptable number of medical errors. The safety culture has emerged as an imperative to improve the quality and safety of patient care, but also as a shield against the judgments targeted towards the caregivers (doctor and / or nurse) involved in an undesirable event. The safety culture allows a broader view of the error by analyzing both system failures and staff incompetence. Therefore, it places caregivers in their workplace with mutual interactions and protects them from "second victim" status. It is imperative to have a reflection on the safety culture that constitutes a proof of transparency and openness towards society about the mistake that remains taboo. This attitude will avoid the risk of "judicialization of health".

The EU Clinical Trials Regulation: key priorities, purposes and aims and the implications for public health.

The replacement of the European Union (EU) Clinical Trials Directive by the new Clinical Trials Regulation (CTR), which entered into force on 16 June 2014 but will not apply before 28 May 2016, provides an opportunity to review the legal and political context within which this important aspect of research law and policy sits and to reflect on the implications for public health. My aim in this article is to relate the context to the key purposes and aims of EU law and policy on clinical trials in order to explain and clarify its orientation. On that basis, I argue that the CTR and the changes it introduces to the law on clinical trials are part of the EU's continued focus on market optimisation. It is this focus that orients and directs the wider pharmaceutical development pipeline, but that undermines the achievement of key public health objectives.

Legal and Ethical Considerations in Allowing Parental Exemptions From Newborn Critical Congenital Heart Disease (CCHD) Screening.

Critical congenital heart disease (CCHD) screening is rapidly becoming the standard of care in the United States after being added to the Recommended Uniform Screening Panel (RUSP) in 2011. Newborn screens typically do not require affirmative parental consent. In fact, most states allow parents to exempt their baby from receiving the required screen on the basis of religious or personally held beliefs. There are many ethical considerations implicated with allowing parents to exempt their child from newborn screening for CCHD. Considerations include the treatment of religious exemptions in our current legal system, as well as medical and ethical principles in relation to the rights of infants. Although there are significant benefits to screening newborns for CCHD, when a parent refuses for religious or personal beliefs, in the case of CCHD screening, the parental decision should stand.

Should We Reject Donated Organs on Moral Grounds or Permit Allocation Using Non-Medical Criteria?: A Qualitative Study.

Conditional and directed deceased organ donations occur when donors (or often their next of kin) attempt to influence the allocation of their donated organs. This can include asking that the organs are given to or withheld from certain types of people, or that they are given to specified individuals. Donations of these types have raised ethical concerns, and have been prohibited in many countries, including the UK. In this article we report the findings from a qualitative study involving interviews with potential donors (n = 20), potential recipients (n = 9) and transplant staff (n = 11), and use these results as a springboard for further ethical commentary. We argue that although participants favoured unconditional donation, this preference was grounded in a false distinction between 'medical' and 'non-medical' allocation criteria. Although there are good reasons to maintain organ allocation based primarily upon the existing 'medical' criteria, it may be premature to reject all other potential criteria as being unacceptable. Part of participants' justification for allocating organs using 'medical' criteria was to make the best use of available organs and avoid wasting their potential benefit, but this can also justify accepting conditional donations in some circumstances. We draw a distinction between two types of waste - absolute and relative - and argue that accepting conditional donations may offer a balance between these forms of waste.

The Double Helix: Applying an Ethic of Care to the Duty to Warn Genetic Relatives of Genetic Information.

Genetic testing reveals information about a patient's health status and predictions about the patient's future wellness, while also potentially disclosing health information relevant to other family members. With the increasing availability and affordability of genetic testing and the integration of genetics into mainstream medicine, the importance of clarifying the scope of confidentiality and the rules regarding disclosure of genetic findings to genetic relatives is prime. The United Nations International Declaration on Human Genetic Data urges an appreciation for principles of equality, justice, solidarity and responsibility in the context of genetic testing, including a commitment to honoring the privacy and security of the person tested. Considering this global mandate and recent professional statements in the context of a legal amendment to patient privacy policies in Australia, a fresh scrutiny of the legal history of a physician's duty to warn is warranted. This article inquiries whether there may be anything ethically or socially amiss with a potential future recommendation for health professionals or patients to universally disclose particular cancer predisposition genetic diagnosis to genetic family members. While much of the discussion remains applicable to all genetic diagnosis, the article focuses on the practice of disclosure within the context of BRCA1/2 diagnosis. An 'ethic of care' interpretation of legal tradition and current practice will serve to reconcile law and medical policy on the issue of physician disclosure of genetic results to family members without patient consent.

[Current legislation in the healthcare system 2015/2016]. / Aktuelle Gesetzgebung im Gesundheitswesen 2015/2016.

The energy of the legislator in the healthcare system was barely stoppable in 2015. Many new laws have been brought into force and legal initiatives have also been implemented. The Hospital Structure Act, the Treatment Enhancement Act, amendments of the official medical fee schedules for physicians, the Prevention Act, the E-Health Act, the Anti-corruption Act, the hospital admission guidelines and amendments of the model specialty training regulations are just some of the essential alterations that lie ahead of the medical community. This article gives a review of the most important new legislative regulations in the healthcare system and presents the fundamental consequences for the practice.

[Current legislation in the healthcare system 2015/2016]. / Aktuelle Gesetzgebung im Gesundheitswesen 2015/2016.

The energy of the legislator in the healthcare system was barely stoppable in 2015. Many new laws have been brought into force and legal initiatives have also been implemented. The Hospital Structure Act, the Treatment Enhancement Act, amendments of the official medical fee schedules for physicians, the Prevention Act, the E-Health Act, the Anti-corruption Act, the hospital admission guidelines and amendments of the model specialty training regulations are just some of the essential alterations that lie ahead of the medical community. This article gives a review of the most important new legislative regulations in the healthcare system and presents the fundamental consequences for the practice.

[Paradigm shift in the legislative approach of vulnerable people in Belgium]. / Changement de paradigme dans l'approche législative des personnes vulnérables en Belgique.

The application since September 2014 of the new 17 March 2013 law «reforming disability schemes and introducing a new protection status in accordance with human dignity¼, restates the legal approach to helping vulnerable people. The changes are complex and wide-ranging. This article describes the key elements of the reform, focusing particularly on the role of the medical doctor.

L'entrée en vigueur, début septembre 2014, de la loi du 17 mars 2013 «réformant les régimes d'incapacité et instaurant un nouveau statut de protection conforme à la dignité humaine¼, reformule l'approche juridique de l'aide aux personnes vulnérables. Les changements introduits sont complexes et de grande ampleur. Le présent article expose les éléments clés de la réforme, en se focalisant plus particulièrement sur le rôle du médecin.