The US Food and Drug Administration (FDA) Amendments Act of 2007 authorized the FDA to require risk evaluation and mitigation strategy (REMS) programs for drugs with important safety concerns. REMS ...can have elements to assure safe use (ETASU), such as patient registries, dispensing restrictions, and physician training and certification requirements. We aimed to understand physician experiences with and perceptions of a selection of ETASU REMS.
Physicians prescribing 1 of 4 ETASU REMS-covered drugs: natalizumab, riociguat, sodium oxybate, and vigabatrin.
Descriptive phenomenological study based on semi-structured phone interviews.
Qualitative content analysis to summarize physician responses to open-ended questions.
Of 31 physicians (14 female), 6 prescribed riociguat, 6 vigabatrin, 7 sodium oxybate, and 12 natalizumab (5 for Crohn's disease, 7 for multiple sclerosis), most demonstrated good understanding of the rationale for and requirements of the ETASU REMS but believed that the programs had limited effect on clinical practice. Some physicians reported that the ETASU REMS made them more comfortable with prescribing covered drugs due to heightened oversight, facilitated discussions about treatment, and were likely more beneficial for non-specialists. Concerns were raised about the administrative effort needed to comply with the programs and the potential misuse of patient health information transmitted to manufacturers.
Physicians are generally aware of ETASU REMS and get reassurance from the additional oversight, but the programs can be better integrated into clinical workflows and can be designed to better protect patient health information.
In an analysis of risk evaluation and mitigation strategies for teratogenic drugs, Ameet Sarpatwari, Beatrice Brown and Aaron Kesselheim explore the variation in primary and secondary prevention ...measures.
The Food and Drug Administration (FDA) approves vaccines when their benefits outweigh the risks for their intended use. In this article we review the standard FDA approach to vaccine evaluation, ...which underpins its current approaches to assessment of vaccines to prevent coronavirus disease 2019 (COVID-19). The FDA has established pathways to accelerate vaccine availability before approval, such as Emergency Use Authorization, and to channel resources to high-priority products and allow more flexibility in the evidence required for approval, including accelerated approval based on surrogate markers of effectiveness. Among the thirty-five new vaccines approved in the US from 2006 through October 2020, about two-thirds of their pivotal trials used the surrogate outcome of immune system response, and only one-third evaluated actual disease incidence. Postapproval safety surveillance of new vaccines, and particularly vaccines receiving expedited approval, is crucial. This has generally been accomplished through such mechanisms as the Centers for Disease Control and Prevention (CDC) and FDA Vaccine Adverse Event Reporting System, the CDC Vaccine Safety Datalink, and the CDC Clinical Immunization Safety Assessment Project. Adverse events detected in this way may lead to changes in a vaccine's recommended use or withdrawal from the market. Regulatory oversight of new vaccines must balance speed with rigor to effectively address the pandemic.
The aim of this study was to investigate the relationship between glaucoma severity and perifoveal vessel density (pfVD), branching complexity, and foveal avascular zone (FAZ) size in normal tension ...glaucoma (NTG). 31 patients with NTG washed out of glaucoma medications were subjected to tests including; intraocular pressure measurement; standard automated perimetry; optical coherence tomography (OCT) measurement of macular ganglion cell complex (mGCC), inner macular thickness (IMT) and circumpapillary retinal nerve fibre layer (cpRNFL); and OCT angiography measurement of pfVD, FAZ perimeter and multispectral fractal dimensions (MSFD). Eyes with more severe glaucoma had significantly thinner mGCC and cpRNFL and lower pfVD. MD decreased by 0.4 dB (95% CI 0.1 to 0.6 dB, P = 0.007) for every 1% decrease in pfVD. Lower MSFD was observed in eyes with lower pfVD and in patients with systemic hypertension. Multivariable analysis, accounting for age and OCTA quality, found lower pfVD remained significantly associated with thinner IMT, thinner mGCC and worse MD but not with MSFD. pfVD was reduced in NTG and was diminished in eyes with worse MD. Macular vessel branching complexity was not related to severity of visual field loss but was lower in patients with systemic hypertension.
After the approval of a new drug, the Food and Drug Administration (FDA) may issue postmarketing requirements (PMRs), studies that the law requires manufacturers to conduct for drugs approved under ...certain conditions, and postmarketing commitments (PMCs), studies that the FDA and manufacturers agree should be conducted as a condition of approval.
With regulators' increasing reliance on gathering important evidence after initial product approval, we sought to assess the track record of PMRs and PMCs by synthesizing information about postmarketing study completion rates, timeliness, study types, and results reporting.
A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. Studies published in academic journals or government reports that reported original data about the characteristics of PMRs or PMCs were included. Studies of post-approval trial mandates issued by regulators outside the USA were excluded, as were those that addressed post-approval research without mentioning either PMCs or PMRs or a specific approval pathway associated with statutorily required PMRs. Two investigators independently screened and extracted data from studies and reports. Data sources included the Federal Register from 2003 to 2020, FDA backlog reviews from 2008 to 2020, PubMed from January 2006 to April 2021, and the US Government Accountability Office (GAO) database for reports from January 2006 to April 2021. PMR/PMC characteristics (e.g., completion rates, timeliness, results reporting, outcomes) were not meta-analyzed due to the heterogeneity in study designs.
Twenty-seven peer-reviewed articles from PubMed, five GAO reports, 17 annual Federal Register notices, and 12 annual backlog reviews were included. Among the 27 studies, 13 reviewed PMRs and PMCs, one reviewed only PMCs, and 13 reviewed only PMRs. A majority of new drugs were approved with at least one PMR or PMC. PMCs were completed at higher rates than PMRs, although delays were common and neither was found to be completed more than two-thirds of the time. Over two-thirds of PMRs and PMCs reported their findings in publications and trial registries. Over half of PMCs and PMRs produced novel information for clinical practice or leading to regulatory action, such as confirmation of benefit or a labeling change.
PMRs and PMCs are common for new drugs and can lead to worthwhile outcomes, but are often delayed or incomplete. Greater attention is needed to timely completion, improving transparency of findings, and ensuring that PMRs and PMCs produce optimally useful information for prescribers and patients.
To review the literature regarding the effects of caregiver depression on childhood asthma and integrate the findings into a multilevel model of pathways by which these effects occur to further the ...understanding of the complex biopsychosocial nature of childhood asthma and the key role that is played by caregiver depression.
PubMed was searched for articles published from 2007 to the present (10-year search), and Google Scholar was searched for articles published in 2017 and 2018 to identify the most recent publications.
Studies selected were recent, empirical, or meta-analytic, conducted in humans, and had specific relevance to one or more of the identified pathways. Articles published before 2007 were included if deemed essential because they addressed key pathways, for which there were no more recent articles.
Review of the literature substantiates that caregiver depression plays a key role in the socioeconomic, familial, psychological, and biological cascade of effects on childhood asthma. Childhood asthma outcomes are affected indirectly by socioeconomic status and family stress mediated by caregiver depression, which affects disease management, and/or stress and depression in the child, which, in turn, affect asthma through alterations in immune modulation and autonomic regulation.
Findings indicate that future research should concentrate on mediators and moderators to further clarify the complex interplay of these factors that affect childhood asthma. The findings also have substantial translational implications. Given that child stress and depression contribute to asthma disease activity and that treating caregiver depression improves child stress and depression, there is strong rationale for treating depressed caregivers of children with asthma as a component means of improving childhood asthma control.
Mifepristone, preemption, and public health federalism Zettler, Patricia J; Beckmeyer, Annamarie; Brown, Beatrice L ...
Journal of law and the biosciences,
2022 Jul-Dec, 2022-07-01, 20220701, Letnik:
9, Številka:
2
Journal Article
Odprti dostop
On June 24, 2022, the Supreme Court issued an opinion in which five justices voted to overturn
. Even before the final opinion issued, scholars and advocates had begun to consider legal strategies ...that might mitigate the decision's anticipated harmful consequences. One such strategy involves challenging state restrictions on Food and Drug Administration (FDA)-approved pregnancy termination drugs on preemption grounds. This article begins by exploring how these challenges might fare-considering both drug-specific restrictions and complete bans on abortion-arguing that there are compelling legal grounds on which courts should conclude that many state restrictions are preempted. Importantly, although these state restrictions have arisen within a larger debate about reproductive health care, this is far from the only area in which states seek to regulate prescription drugs. States have long regulated drugs in ways that diverge from FDA, arguably increasingly so in recent years. Accordingly, the article investigates the implications that preemption challenges in the abortion context may have for other areas of state drug regulation, making the case that the benefits of public health federalism need not be undermined by successful preemption challenges in the abortion arena.
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