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.

"It's about how much we can do, and not how little we can get away with": Coronavirus-related legislative changes for social care in the United Kingdom.

The coronavirus pandemic, referred to here as Covid-19, has brought into sharp focus the increasing divergence of devolved legislation and its implementation in the United Kingdom. One such instance is the emergency health and social care legislation and guidance introduced by the United Kingdom Central Government and the devolved Governments of Wales, Scotland and Northern Ireland in response to this pandemic. We provide a summary, comparison and discussion of these proposed and actual changes with a particular focus on the impact on adult social care and safeguarding of the rights of citizens. To begin, a summary and comparison of the relevant changes, or potential changes, to mental health, mental capacity and adult social care law across the four jurisdictions is provided. Next, we critique the suggested and actual changes and in so doing consider the immediate and longer term implications for adult social care, including mental health and mental capacity, at the time of publication.several core themes emerged: concerns around process and scrutiny; concerns about possible changes to the workforce and last, the possible threat on the ability to safeguard human rights. It has been shown that, ordinarily, legislative provisions across the jurisdictions of the UK are different, save for Wales (which shares most of its mental health law provisions with England). Such divergence is also mirrored in the way in which the suggested emergency changes could be implemented. Aside from this, there is also a wider concern about a lack of parity of esteem between social care and health care, a concern which is common to all. What is interesting is that the introduction of CVA 2020 forced a comparison to be made between the four UK nations which also shines a spotlight on how citizens can anticipate receipt of services.

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.

[A new end-of-life law? An Italian detour]. / Une nouvelle loi pour la fin de vie ? - Détour par l'Italie.

On January 31, 2018, advance directives law has come into effect in Italy. It is a law that grants the right to any individual of full age to express his or her preferences regarding treatment in anticipation of the days when he or she might be unable to do so. In France, however, two years after its entry into effect, the Claeys-Leonetti law is increasingly under attack. Some are even calling for a new end-of-life legislation altogether. A discussion of the Italian case, focused on the debates that led to the approval of this new legislation, can help us re-contextualize the French case. While there are many similarities between the two laws, their differences in terms of practices and intellectual frameworks may suggest additional avenues of thinking and help improve end-of-life conditions.

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.

[CRIMINAL RESPONSIBILITY OF MEDICAL AND ITS CASE LAW EVOLUTION. LEGAL AND ECONOMIC PROFILES].

The article deals with the regulatory and jurisprudential evolution of medical criminal responsibility from the 70s to the Gelli-Bianco law of 2017. Subsequently it winds through the contribution of the last important judgments of the subject up to the decisions of the Supreme Court with United Sections of 2018, finally to conclude with an economic analysis on the increasement of the legal disputes registered in recent years.

Diminished Responsibility: Law Reform in the United Kingdom and Personal Perspective on Forensic Psychiatric Practice in Hong Kong.

This commentary discusses law reform on diminished responsibility in the United Kingdom and provides a personal perspective on forensic psychiatric practice relating to diminished responsibility in Hong Kong.

Are the Italian ethics committees ready for Europe? Commentary.

The Law of 3 January 2018 established in Italy the "National Centre for the Coordination of Regional Ethics Committees for Clinical Trials of Medicines and Medical Devices for Human Use" and reduced the number of ethics committees in the country to 40. This Act should, amongst other things, facilitate Italy's compliance with the provisions set forth in European Regulation (EU) 536/2014. Hopefully, in addition to the provisions set forth in the Law, the National Centre will strive to foster the harmonisation of ethics committee procedures, in order to reform Italian legislation on the evaluation of clinical trials and, more generally, biomedical studies.

2018 White Paper on Recent Issues in Bioanalysis: focus on immunogenicity assays by hybrid LBA/LCMS and regulatory feedback (Part 2 - PK, PD & ADA assays by hybrid LBA/LCMS & regulatory agencies' inputs on bioanalysis, biomarkers and immunogenicity).

The 2018 12th Workshop on Recent Issues in Bioanalysis took place in Philadelphia, PA, USA on April 9-13, 2018 with an attendance of over 900 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, week-long event - a full immersion week of bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small- and large-molecule bioanalysis involving LCMS, hybrid LBA/LCMS and LBA/cell-based assays approaches. This 2018 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2018 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations for PK, PD and ADA assays by hybrid LBA/LCMS and regulatory agencies' input. Part 1 (LCMS for small molecules, peptides, oligonucleotides and small molecule biomarkers) and Part 3 (LBA/cell-based assays: immunogenicity, biomarkers and PK assays) are published in volume 10 of Bioanalysis, issues 22 and 24 (2018), respectively.

[Endocrine disrupters: Towards an unsatisfying regulation]. / Perturbateurs endocriniens : vers une régulation insatisfaisante.

Endocrine disruptors commonly make the headlines of newscasts and magazines, which is not without generating questions, even anxieties, with the general public. In a recent survey, 90% of French people considered it desirable to set up regulations concerning endocrine disruptors. However, under pressure from the lobbies of the chemical industry, and also due to scientific conflicts, the European Union is slow to legislate and has even been condemned before the European Court for failing to fulfill its obligations. This article does not intend to be exhaustive on the issue of endocrine disrupters, but rather to give the reader a certain number of keys enabling him to understand why national or European regulators are slow to establish specific regulation.

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.