Food And Drug Administration Oversight Research Articles

Assessing Post-Marketing Requirements for Orphan Drugs: A Cross-Sectional Analysis of FDA and EMA Oversight.

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) oversee pharmaceutical regulations, including orphan drugs targeting rare diseases with limited patient populations. Post-marketing studies are crucial for monitoring safety and efficacy, with post-marketing requirements (PMRs) mandated by the regulatory agencies to ensure compliance. This study aims to compare PMR statuses, objectives, and pivotal trial characteristics of orphan drugs approved by the FDA (n = 154) and EMA (n = 79) from 2008 to 2018, shedding light on regulatory differences and their impact on drug development. Contrary to expectations, our analysis found no significant disparity in the proportion of orphan drugs with and without PMRs approved by both the FDA (48.1%) and EMA (55.7%). Safety concerns surrounding orphan drugs post-approval, attributed partly to pivotal trial design, underscore the need for robust post-marketing surveillance. While the FDA primarily focuses on post-marketing safety (36.1%), the EMA places a higher emphasis on both efficacy and safety (47.1%), reflecting distinct approaches to PMR management between the two regulatory bodies. The observed trend of delayed PMRs at the EMA (47.1%) highlights the importance of effective cooperation between regulators and pharmaceutical companies to ensure the timely completion of PMRs and enhance drug safety.

Sugammadex Use for Reversal in Nonobstetric Surgery During Pregnancy: A Reexamination of the Evidence.

Sugammadex Use for Reversal in Nonobstetric Surgery During Pregnancy: A Reexamination of the Evidence.

Safe Technical Innovation: Development and Implementation of a Robotic Breast Operation Program.

Safe Technical Innovation: Development and Implementation of a Robotic Breast Operation Program.

Prescribing unproven cancer drugs: physician perspectives on expanded access and right to try.

For gravely ill patients who have no treatment options and who are ineligible for clinical trials, the US Food and Drug Administration (FDA) established the Expanded Access Program (EAP). Motivated by efforts to weaken FDA regulation and sold as providing greater access to experimental drugs, the federal Right to Try Act (RTT) was passed in 2017. It reduces FDA oversight by not requiring physicians to report safety data and foregoes approval of protocols by local institutional review boards. This study explored the views of 17 neuro-oncologists from 15 different academic medical centers with varying experience with EAP and RTT using convenience sampling. We conducted semi-structured interviews and qualitative analysis to identify emerging themes. Most oncologists were confused between the two pathways, had little familiarity with RTT, and had little knowledge about experimental medicine available through either pathway. Oncologists reported a preference of enrolling patients in clinical trials over off-trial preapproval pathways with scant data. As a result, oncologists revealed concerns over properly evaluating risks for their patients. Our findings suggest that neuro-oncologists need better resources and clearer mechanisms at their institutions to help navigate EAP and RTT in order to counsel patients interested in experimental medicine.

Do You Know How to Assess Risks Posed by Over-the-Counter Vitamin A Supplements?

Dietary supplements are regulated as foods by the US Food and Drug Administration (FDA) and, despite their potentially harmful effects, are not subject to labeling rules that apply to prescription medications. This commentary responds to a case about vitamin A supplement safety. The commentary compares regulation of vitamin A-derivative prescription medications, such as isotretinoin, to regulation of high-dose vitamin A supplements, illuminating both products' potential for causing birth defects. Label analysis is key to educating patients about risks of vitamin A-containing supplements. The commentary also suggests the need for more FDA oversight of the dietary supplement industry.

Abstract P043: A Framework For The Evaluation Of Digital Tools

Digital health tools encompass a wide range of technologies that have been used in healthcare services including mobile applications, health information technology, smart wearable devices, remote monitoring and treatment, and health platforms. These tools walk a fine line between lifestyle consumer products and medical devices. Sleep applications can be used by consumers as a fun gadget to track sleep, but it may also be used as a medical tool to collect information concerning serious sleep disorders. The fast proliferation of these tools has put pressure on concerned stakeholders to make sense of this group of technologies. Various questions have been raised within this realm: What counts as medical as opposed to a lifestyle device? Which devices require regulation and under what standards? Which devices are allowed to be used in the medical context? And which are not? And under what conditions? Social scientists have highlighted the complexity of digital health tools that (include both medical and lifestyle characteristics and the difficulties accompanied with classifying these tools for regulatory purposes. In an attempt to do so, several regulatory bodies including the US Food and Drug Administration (FDA) have revised their existing standards to accommodate the regulation of digital health tools. As such, the FDA published a guidance document on Mobile Medical Applications; this led to various concerns questioning the boundaries between lifestyle and medical digital technologies that were defined by the FDA guidelines, which left a significant number of technologies that were considered to be low-risk, completely out of the FDA oversight and with no required compliance/quality control/effectiveness checks. This prompted many companies to develop hundreds of products that belong to the low-risk category, granting them the ability to ignore FDA regulations. Consequently, there remains considerable concern regarding the quality and safety of these digital health technologies that are being used within the medical context. Clear and well-defined regulation processes are needed to control the development and design of these tools, especially that many lack scientific evidence and data privacy. The framework ought to include a risk-based approach to classify devices for regulation in a way to ensure the safety and effectiveness of all digital health tools throughout their life cycle, even those classified as low-risk. The framework and regulatory process also need to take into consideration the rapid change in digital product development, as processes that extend for a long period of time may become obsolete in supporting decisions about these tools. As these digital health tools become more sophisticated, accessible, widespread, and cheaper, the need for classifying and regulating the sector becomes important, especially with the rapid evolution of these technologies.

Off-Label Use of Ketamine: A Challenging Drug Treatment Delivery Model With an Inherently Unfavorable Risk-Benefit Profile.

Off-Label Use of Ketamine: A Challenging Drug Treatment Delivery Model With an Inherently Unfavorable Risk-Benefit Profile.

A Proposal for FDA Oversight of Tear Gas

Tear gas is designated a chemical weapon by multiple treaties that prohibit its use in war. However, despite mounting reports suggesting that tear gas may endanger targets beyond transient discomfort, its domestic use as a crowd control mechanism has not been adequately studied, nor is its use regulated by any United States government agency. Without comprehensive and demographically-representative epidemiological studies, the continued use of tear gas on civilian protesters poses an unknown and potentially severe threat to public safety. Chemical substances employed on civilians for a desired effect are more akin to drugs than to weapons. We, therefore, propose that legislation be introduced to place tear gas under the regulatory purview of the Food and Drug Administration (FDA) in order to understand its effects on the health of all members of the public and to better regulate its deployment.

How to Get Away with Immunity: FDA's Emergency Use Authorization Scheme and PREP Act Liability Protection in the Context of COVID-19

The U.S. Food and Drug Administration (FDA) plays a vital role in our country’s response to biological agents that threaten public health and safety. On December 31, 2019, officials in Wuhan, China confirmed dozens of cases of pneumonia caused by an unknown pathogen. Chinese officials later identified that pathogen as severe acute respiratory syndrome coronavirus (SARS-CoV-2), which causes the disease COVID-19. The COVID-19 pandemic has created a perfect storm for unprecedented and litigation-provoking health harms in the United States. As the country’s death toll rises and states seek to reopen, many Americans are assessing their COVID-19-related health status based on the results of diagnostic and antibody tests, which have been cleared through the FDA’s emergency use authorization scheme notwithstanding their concerning inaccuracy rates. This paper argues that the unacceptably high inaccuracy rates of these COVID-19 tests are a direct result of lax FDA regulation and oversight under current federal law. The Public Readiness and Emergency Preparedness Act of 2005 (PREP Act) established a framework that extends blanket immunity from liability to the manufacturers of medical products, including blood assays and serology tests, that are used to diagnose and treat COVID-19. The breadth and scope of the statute’s immunity make it nearly impossible for an injured plaintiff to recover from injuries sustained from their use of or reliance on diagnostic tests. This paper details and critiques PREP Act immunity and proposes several PREP Act reforms aimed at enhancing public health and safety during a infectious disease pandemic. As special interest groups ramp pressure of the federal and state legislatures to enact additional immunity protection as the states reopen, the quality of COVID-19 related care and treatment is likely to continue to worsen unless and until the country implements reforms that authorize meaningful medical device regulation and oversight.

The Role of Antibody Testing for SARS-CoV-2: Is There One?

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) brought with it rapid development of both molecular and serologic assays for identification of COVID-19 infections. While Food and Drug Administration (FDA) emergency use authorization (EUA) is required for clinical application of SARS-CoV-2 molecular tests, submission for EUA is currently a voluntary process for manufacturers of serologic assays. The absence of FDA oversight of serologic tests is concerning given that the commercially available serologic assays are highly variable, differing in their format, the antibody class detected, the targeted antigen, and the acceptable specimen types. An added complication is the lack of a clear understanding for how such assays should be utilized and what the reported results ultimately indicate or, perhaps more importantly, what they do not indicate. Here, we provide a brief summary of the performance of a number of serologic assays reported in the literature, comment on what we do and do not know regarding our immune response to SARS-CoV-2, and provide a number of scenarios for which serologic testing will play a role during our global response to this pandemic.

Consumer understanding of the scope of FDA's prescription drug regulatory oversight: A nationally representative survey.

Misperceptions of how the US Food and Drug Administration (FDA) regulates prescription drugs may affect how consumers assess the safety and efficacy of prescription drugs. The study objective was to survey the public on their knowledge of FDA oversight regarding prescription drug approval and advertising. In 2017, we conducted a nationally representative mail-push-to-web survey with 1,744 US adults. Although most respondents (86%) knew that FDA approves prescription drugs, we found misperceptions about what that approval means. In addition, few respondents understood FDA oversight of prescription drug advertising, with approximately half of respondents reporting that they did not know whether FDA approved these ads or components of the ads, and several mis-reporting that FDA approves these ads (31%) or components of the ads (22%-41%). Enhanced collaboration and communication with the public by key stakeholders in this space could increase public understanding of the roles and responsibilities of FDA.

FDA's Unimproved Enforcement of Postmarketing Requirements and Commitments: Implications for Providers and Patients

The 2007 reauthorization of the Prescription Drug User Fee Act empowered the Food and Drug Administration (FDA) to require and enforce postmarketing studies to monitor the safety of prescription drugs, an increasing number of which are approved under expedited development or review programs. However, compliance rates for postmarketing requirements are low, and the FDA has not exercised its enforcement authority, allowing the very safety concerns that prompted the expansion of its power to continue. Prior evaluations have found that the FDA lacks reliable, timely, and readily accessible data for tracking postmarket safety issues, and that it has failed to enforce the postmarket surveillance measures it requires of the pharmaceutical industry. This study provides an updated evaluation of FDA oversight of postmarketing requirements and commitments and assesses whether there have been improvements since 2010. This study utilized data from the FDA's annual Report on the Performance of Drug and Biologics Firms in Conducting Postmarketing Requirements and Commitments. It evaluated studies opened in FY 2011-2014 and tracked their status through the FDA's FY 2018 report (data as of September 30, 2018), thereby allowing the pharmaceutical industry 4-7 years to complete a given PMR/PMC. Descriptive statistics were calculated, and differences in the status of postmarketing requirements and postmarketing commitments between FYs 2011-2014 and FY 2009-2010 were evaluated. During fiscal years 2011-2014, there was little difference in the FDA's oversight of postmarketing studies compared to fiscal years 2009-2010. While there were some year-to-year significant differences, the overall trend indicated no change. The FDA's oversight of postmarketing studies has not improved since 2010. This paper discusses implications for providers and patients who unduly assume the responsibility of postmarketing surveillance due to the lack of FDA oversight.

Coming changes to mammography standards: With its proposed amendments to update mammography rules, the US Food and Drug Administration hopes to empower patients and health care providers.

Coming changes to mammography standards: With its proposed amendments to update mammography rules, the US Food and Drug Administration hopes to empower patients and health care providers.

United States regulatory approval of medical devices and software applications enhanced by artificial intelligence

In the United States, regulatory oversight of medical devices has evolved with the changing technology. With the introduction into routine clinical practice software applications and computer-based devices, the U.S. Food and Drug Administration (FDA) has further defined categories of risk and intended use to better uphold patient safety, while encouraging innovation in medical technology. However, as new software technologies such as artificial intelligence (AI) are developed, refined, and introduced into the healthcare sector, there will be a need for regulatory bodies to rapidly respond. In the current review, we discuss the evolution of US FDA oversight of medical devices, initially of hardware, and the present stance on medical software applications, including devices augmented with artificial intelligence.

Texas H.B. 810: Increased Access to Stem Cell Interventions or an Increase in Unproven Treatments?

Born of the expectations and hype associated with regenerative medicine, there are now numerous clinics around the world selling stem cell-based interventions (SCBI) that have yet to be proven effective or safe, with little to no accounting of the outcomes being collected. In the United States, SCBI are overseen by the U.S. Food and Drug Administration (FDA), but several SCBI clinics have been pushing for policies to expand access and circumvent FDA oversight. Related to this effort, in 2017, Texas passed a bill, HB 810, which allows clinics to provide "investigational stem cell treatments to patients with certain severe chronic diseases or terminal illnesses." In this article, we describe how the new law relates to another deregulation movement, state and federal, the Right to Try laws, the content of HB 810, and the state legislators' intent in passing HB 810.

Consumer Sleep Technology: An American Academy of Sleep Medicine Position Statement.

Consumer sleep technologies (CSTs) are widespread applications and devices that purport to measure and even improve sleep. Sleep clinicians may frequently encounter CST in practice and, despite lack of validation against gold standard polysomnography, familiarity with these devices has become a patient expectation. This American Academy of Sleep Medicine position statement details the disadvantages and potential benefits of CSTs and provides guidance when approaching patient-generated health data from CSTs in a clinical setting. Given the lack of validation and United States Food and Drug Administration (FDA) clearance, CSTs cannot be utilized for the diagnosis and/or treatment of sleep disorders at this time. However, CSTs may be utilized to enhance the patient-clinician interaction when presented in the context of an appropriate clinical evaluation. The ubiquitous nature of CSTs may further sleep research and practice. However, future validation, access to raw data and algorithms, and FDA oversight are needed.

Challenges in the Regulation of Autologous Stem Cell Interventions in the United States.

The direct-to-consumer marketing of stem cells for unproven therapeutic uses has grown rapidly in the United States in recent years. This development is surprising since the marketing and distribution of human cell-based medical products is stringently regulated in the US. This essay describes ambiguities, gaps, and inconsistencies in the current regulatory system that have enabled such businesses to thrive. In addition to directly challenging the authority of the Food and Drug Administration (FDA) over autologous cell-based products in the courts, stem cell marketing firms have also identified and exploited regulatory loopholes, such as the same surgical procedure exception, which exempts from FDA oversight human cell-based products that are harvested and reimplanted in a single procedure. Many businesses also advertise stem cell clinical studies on a pay-to-participate basis, which requires patients to pay large sums to enroll in clinical research. This business model not only shifts many of the cost and risks of medical experimentation from providers to patients but may also indemnify sellers from fraud litigation. Lastly, stem cell advertisers borrow heavily from the language and concepts of science-based medicine in their marketing. The inaccurate promotion of autologous stem cell injections as a form of "personalized" medicine lends a veneer of credibility and precision that may encourage patients to undergo procedures of uncertain effectiveness and to sympathize with stem cell businesses in their efforts to evade oversight.

Regulating Black-Box Medicine

Data drive modern medicine. And our tools to analyze those data are growing ever more powerful. As health data are collected in greater and greater amounts, sophisticated algorithms based on those data can drive medical innovation, improve the process of care, and increase efficiency. Those algorithms, however, vary widely in quality. Some are accurate and powerful, while others may be riddled with errors or based on faulty science. When an opaque algorithm recommends an insulin dose to a diabetic patient, how do we know that dose is correct? Patients, providers, and insurers face substantial difficulties in identifying high-quality algorithms; they lack both expertise and proprietary information. How should we ensure that medical algorithms are safe and effective? Medical algorithms need regulatory oversight, but that oversight must be appropriately tailored. Unfortunately, the Food and Drug Administration (FDA) has suggested that it will regulate algorithms under its traditional framework, a relatively rigid system that is likely to stifle innovation and to block the development of more flexible, current algorithms. This Article draws upon ideas from the new governance movement to suggest a different path. FDA should pursue a more adaptive regulatory approach with requirements that developers disclose information underlying their algorithms. Disclosure would allow FDA oversight to be supplemented with evaluation by providers, hospitals, and insurers. This collaborative approach would supplement the agency's review with ongoing real-world feedback from sophisticated market actors. Medical algorithms have tremendous potential, but ensuring that such potential is developed in high-quality ways demands a careful balancing between public and private oversight, and a role for FDA that mediates--but does not dominate--the rapidly developing industry.

An Investigation of Consumer and Doctor Regulatory Beliefs and Regulatory Knowledge about Pharmaceutical Drug Promotions

AbstractPharmaceutical drug companies engage in numerous promotional activities—from advertising to sales calls. Yet little is known about whether consumers or doctors believe these activities are regulated by the Food and Drug Administration (FDA) or whether their beliefs are accurate. We refer to these constructs as regulatory beliefs and regulatory knowledge, and we introduce and partially test a conceptual model including them. Specifically, we surveyed 311 consumers and 104 doctors about 24 different marketing-type activities undertaken by pharmaceutical drug companies, and assessed their persuasion knowledge, regulatory beliefs, and regulatory knowledge. We found that both groups, but especially doctors, had high persuasion knowledge, whereas doctors had weaker regulatory beliefs about FDA oversight; on regulatory knowledge both groups manifested comparable and substantial deficits. This research contributes theoretically by introducing the constructs of regulatory beliefs and regulatory knowledge, ...

FDA's draft guidance on laboratory-developed tests increases clinical and economic risk to adoption of pharmacogenetic testing.

The US Food and Drug Administration (FDA) notified Congress July 31, 2014,1 of its intent to regulate laboratory developed tests. These encompass thousands of clinical assays currently used in medical practice including most pharmacogenetic tests. This guidance has the potential to impact the innovation and sustainability of pharmacogenetic research and its clinical implementation.