US Food Research Articles

Novel Approaches for the Management of Type 2 Diabetes Mellitus: An Update.

Diabetes mellitus is an irreversible, chronic metabolic disorder indicated by hyperglycemia. It is now considered a worldwide pandemic. T2DM, a spectrum of diseases initially caused by tissue insulin resistance and slowly developing to a state characterized by absolute loss of secretory action of the β cells of the pancreas, is thought to be caused by reduced insulin secretion, resistance to tissue activities of insulin, or a combination of both. Insulin secretagogues, biguanides, insulin sensitizers, alpha-glucosidase inhibitors, incretin mimetics, amylin antagonists, and sodium-glucose co-transporter-2 (SGLT2) inhibitors are the main medications used to treat T2DM. Several of these medication's traditional dosage forms have some disadvantages, including frequent dosing, a brief half-life, and limited absorption. Hence, attempts have been made to develop new drug delivery systems for oral antidiabetics to ameliorate the difficulties associated with conventional dosage forms. In comparison to traditional treatments, this review examines the utilization of various innovative therapies (such as microparticles, nanoparticles, liposomes, niosomes, phytosomes, and transdermal drug delivery systems) to improve the distribution of various oral hypoglycemic medications. In this review, we have also discussed some new promising candidates that have been approved recently by the US Food and Drug Administration for the treatment of T2DM, like semaglutide, tirzepatide, and ertugliflozin. They are used as a single therapy and also as combination therapy with drugs like metformin and sitagliptin.

Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon-like peptide 1.

Sotagliflozin is the first dual SGLT1/2 inhibitor antidiabetic drug approved by the US Food and Drug Administration for the management of heart failure. SGLT1/2 inhibition is observed to potentiate the secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1). The current preclinical research sought to investigate the effect of sotagliflozin on the secretion of fat-regulating peptides such as GLP-1, glucagon and fibroblast growth factor 21 (FGF21) and their prospective association with sotagliflozin's potential beneficial effects on dyslipidaemia. During an oral fat tolerance test in mice, sotagliflozin substantially increased GLP-1 and insulin concentrations. Although sotagliflozin alone did not ameliorate postprandial lipemia, its combination with linagliptin (DPP-IV inhibitor) significantly improved lipid tolerance comparable to orlistat (lipase inhibitor). In a triton-induced hypertriglyceridemia model, sotagliflozin, along with other medications (fenofibrate, exenatide and linagliptin) reduced fat excursion; however, co-administration with linagliptin provided no extra advantage. Furthermore, sotagliflozin stimulated glucagon secretion in the alpha TC1.6 cells and healthy mice, which resulted in an increased circulating FGF21 and β-hydroxybutyrate concentration. Finally, chronic treatment of sotagliflozin in high-fat diet (HFD)-fed obese mice resulted in reduced body weight gain, liver triglyceride, cholesterol, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) levels compared with the placebo group. However, the addition of linagliptin did not provide any additional benefit. In conclusion, sotagliflozin was found to have an effect on GLP-1 and also stimulate the release of glucagon and FGF21, which are important for regulating fat metabolism. Therefore, sotagliflozin might represent a potential therapeutic approach for the treatment of diabetic dyslipidemia and steatohepatitis.

Rural American farmers’ perceptions of crime, safety and policing

PurposeThe purpose is to understand how farmers in rural American communities perceive crime, safety and policing.Design/methodology/approachAn online survey, adapted from a version used in Victoria, Australia (Harkness, 2017), was modified and administered through social media and farming organizations throughout three US states. The survey covers topics relating to crime and victimization, feelings of safety or fear in rural areas, policing practices and trust in police in their areas and any crime prevention practices that respondents use.FindingsWith nearly 1,200 respondents and four scales investigated, results indicate that those respondents with more favorable views of law enforcement and the criminal justice system had the highest fear of crime, those who had been prior victims of crime had a higher fear of crime than those who did not, those with higher community involvement had higher fear of crime, and those from Nebraska compared to Colorado had higher fear of crime.Research limitations/implicationsA better understanding of the agricultural community’s perceptions of crime, safety and policing will aid law enforcement in community policing efforts and in farm crime investigation and prevention. Limitations of the study, including the distribution method will be discussed.Originality/valueFarm- and agriculture-related crimes have serious financial and emotional consequences for producers and local economies. Stereotypes about rural areas being “safe with no crime” are still prevalent. Rural American farmers’ perceptions of crime, safety and police are largely absent from the literature and are important for improving farm crime prevention.

Targeting KRASG12C in Non-Small-Cell Lung Cancer: Current Standards and Developments.

Among the most common molecular alterations detected in non-small-cell lung cancer (NSCLC) are mutations in Kristen Rat Sarcoma viral oncogene homolog (KRAS). KRAS mutant NSCLC is a heterogenous group of diseases, different from other oncogene-driven tumors in terms of biology and response to therapies. Despite efforts to develop drugs aimed at inhibiting KRAS or its signaling pathways, KRAS had remained undruggable for decades. The discovery of a small pocket in the binding switch II region of KRASG12C has revolutionized the treatment of KRASG12C-mutated NSCLC patients. Sotorasib and adagrasib, direct KRASG12C inhibitors, have been approved by the US Food and Drug Administration (FDA) and other regulatory agencies for patients with previously treated KRASG12C-mutated NSCLC, and these advances have become practice changing. However, first-line treatment in KRASG12C-mutated NSCLC does not differ from NSCLC without actionable driver genomic alterations. Treatment with KRASG12C inhibitors is not curative and patients develop progressive disease, so understanding associated mechanisms of drug resistance is key. New KRASG12C inhibitors and several combination therapy strategies, including with immune checkpoint inhibitors, are being studied in clinical trials. The aim of this review is to explore the clinical impact of KRAS, and outline different treatment approaches, focusing on the novel treatment of KRASG12C-mutated NSCLC.

Antibiotics-associated pseudomembranous colitis: a disproportionality analysis of the US food and drug administration adverse event reporting system (FAERS) database

ABSTRACT Background Evaluating antibiotics most commonly associated with pseudomembranous colitis (PMC) based on the real-world data is of great significance. Research design and methods We used the data from FAERS to evaluate the potential association between antibiotics and PMC by disproportionality analyzes. Results Eighty-one antibiotics which met the three algorithms simultaneously were enrolled. There were 1683 reports of PMC associated with the enrolled antibiotics. In the top 24 antibiotics, cefoxitin, streptomycin, fosfomycin, and micafungin had a high risk of PMC, but there were few reports in the literature. Conclusions This study was of great significance for healthcare professionals to realize the potential PMC risks of antibiotics.

A real‑world pharmacovigilance study of FDA adverse event reporting system events for daratumumab

ABSTRACT Background Daratumumab, a first-in-class humanized IgG1κ monoclonal antibody that targets the CD38 epitope, has been approved for treatment of multiple myeloma by FDA. The current study was to evaluate daratumumab-related adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Research design and methods Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were employed to quantify the signals of daratumumab-associated AEs. Results Out of 10,378,816 reports collected from the FAERS database, 8727 reports of daratumumab-associated AEs were identified. A total of 183 significant disproportionality preferred terms (PTs) were retained. Unexpected significant AEs such as meningitis aseptic, leukoencephalopathy, tumor lysis syndrome, disseminated intravascular coagulation, hyperviscosity syndrome, sudden hearing loss, ileus and diverticular perforation were also detected. The median onset time of daratumumab-related AEs was 11 days (interquartile range [IQR] 0–76 days), and most of the cases occurred within 30 days. Conclusion Our study found potential new and unexpected AEs signals for daratumumab, suggesting prospective clinical studies are needed to confirm these results and illustrate their relationship.

Impact of renal denervation on quality of life how does renal denervation contribute to improving hypertension treatment affected by poor medication adherence?

The US Food and Drug Administration has approved renal denervation (RDN) as a new treatment option for hypertension (HT) because it not only has antihypertensive effects but also improves the quality of blood pressure (BP) reduction. RDN is expected to be increasingly used in clinical practice in the future. This review summarizes the impact of RDN on quality of life (QOL). Although the treatment of HT aims to improve life prognosis, the use of antihypertensive agents can impair QOL because of adverse effects and lifestyle changes associated with long-term medication use. Consequently, poor adherence to antihypertensive agents is a common problem and may be the most important issue affecting patient QOL. In RDN trials in patients taking antihypertensive agents, approximately 40% of patients had poor adherence to the drugs. Poor adherence is often the cause of resistant hypertension. Therefore, RDN should be well suited to treating HT and improving QOL. Studies have shown that approximately 30% of HT patients prefer RDN to drug treatment. Patients who prefer RDN are typically male and younger and have high BP, poor adherence, and a history of adverse effects of antihypertensive agents. We hope that RDN will improve not only life prognosis but also QOL in HT patients because of its benefits for adherence. Furthermore, we expect that in the future, RDN will be used in other sympathetic nervous system-related diseases, such as heart failure, atrial fibrillation, and sleep apnea syndrome.

Bolstering FDA Pathways for Reducing Death and Disease from Tobacco

This JAMA Forum discusses the US Food and Drug Administration’s efforts to implement the 2009 Family Smoking Prevention and Tobacco Control Act through approval of products that demonstrate evidence to help smokers quit and to reduce their risk of relapse.

Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea in a Young Child With Down Syndrome.

Obstructive sleep apnea (OSA) is common in children with Down syndrome (DS). Adenoidectomy and/or tonsillectomy are the usual first interventions employed to treat OSA in children with DS but sometimes do not achieve adequate resolution of clinical signs. Positive airway pressure treatment is often used next, but this treatment is poorly tolerated by this population. Persistent OSA can adversely affect a child's health and cognitive development. Hypoglossal nerve stimulation (HGNS), previously shown to be safe and effective in adults with OSA, has been used in children as young as 10 years old with DS and has achieved measurable neurocognitive benefits. The US Food and Drug Administration recently lowered the age for HGNS implantation to 13 years for children with DS. However, questions remain regarding treatment of refractory OSA in younger children. Here, we report the case of a 4-year-old boy with DS and treatment-refractory OSA who underwent successful HGNS implantation. The decision to proceed with HGNS implantation in such a young child involved discussions about anatomic feasibility and potential neurocognitive benefits. The device was implanted without complication and with minimal postoperative bulk. This case suggests a possible treatment option that can be discussed in the course of shared decision-making between clinicians and families of young children with DS and treatment-refractory OSA.

Guselkumab for Pityriasis Rubra Pilaris and Dysregulation of IL-23/IL-17 and NFkB Signaling: A Nonrandomized Trial.

There is no US Food and Drug Administration-approved treatment for pityriasis rubra pilaris (PRP), and it is common for patients to fail to experience improvement with several systemic options. Involvement of interleukin (IL) 23 suggests a potential therapeutic target. To determine whether guselkumab, an IL-23p19 inhibitor, provides clinical improvement for participants with PRP and better understand gene and protein dysregulation in PRP. This single-arm, investigator-initiated nonrandomized trial was conducted from October 2019 to August 2022 at a single-center academic university with participants from 8 states in the US. In total, 14 adults with moderate to severe PRP were enrolled; 12 completed the trial. Age-matched and sex-matched healthy controls provided skin and blood for proteomic and transcriptomic studies. The primary outcome was observed at 24 weeks, and additional follow-up occurred at 36 weeks. Guselkumab is a fully human immunoglobulin G1 λ monoclonal antibody that selectively binds and inhibits the p19 subunit of IL-23. Subcutaneous injections were given at the US Food and Drug Administration-approved dosing schedule for psoriasis over a 24-week period. The primary outcome was the mean change in the Psoriasis Area Severity Index (PASI) score at week 24. Secondary outcomes included pruritus, Dermatology Life Quality Index score, clinical response at week 36, and association with transcriptomics and proteomics expression. A per-protocol analysis was performed for the cohort of 4 female and 8 male patients who had a mean (SD) age of 56.5 (18.7) years. The mean improvement in PASI score, pruritus, and Dermatology Life Quality Index score was 61.8% (P < .001), 62.3% (P = .001), and 60.2% (P < .001), respectively. Nine participants (75%) achieved a 50% improvement in PASI. Among these clinical responders, at week 36, 8 of 9 achieved PASI75, and 6 of 9 achieved PASI90. No participants had pathogenic CARD14 gene variations. There was 1 serious adverse event that was not associated with the study drug. Proteomics and gene expression profiles identified dysregulation of a predominance of inflammatory pathways (such as T helper 17 and nuclear factor κ B) in participants with PRP who later responded well to treatment with guselkumab and stronger dysregulation of keratinocyte development pathways in individuals who did not respond to guselkumab. The results of this nonrandomized trial suggest that guselkumab has efficacy in treating refractory moderate to severe adult PRP. ClinicalTrials.gov Identifier: NCT03975153.

Method development and validation for the estimation of gedatolisib in mouse plasma by tandem mass spectrometry and its application to pharmacokinetics studies.

A simple and a sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of gedatolisib in mouse plasma. The extraction technique involved a simple precipitation method to extract gedatolisib and idelalisib (internal standard) from mouse plasma. A clean chromatographic separation of gedatolisib and the internal standard was achieved on an Atlantis dC18 column using an isocratic mobile phase (10mm ammonium formate and acetonitrile; 30:70% v/v, both supplemented with 0.1% formic acid) delivered at a flow rate of 0.7ml/min. The total run time was 2.0min, and gedatolisib and idelalisib were eluted at 0.80 and 0.95 min, respectively. Gedatolisib was monitored at m/z 616.40 → 488.20 and idelalisib at 416.05 → 176.10. All the required parameters for the method validation were performed as per US Food and Drug Administration guidelines, and the results were within the acceptance criteria. The method was accurate and proved to be precise at a linearity range of 1.33-2667 ng/ml. The accuracy for gedatolisib in mouse plasma was in the ranges 0.99-1.06% (intra-day) and 0.96-1.04% (inter-day). Gedatolisib appeared to be stable in a series of stability conditions. Gedatolisib showed a good intravenous profile when administered through a solution formulation.

Public Health Response to SARS-CoV-2 in Assisted Living Facilities in New York State: March 2020-December 2022.

Assisted living facility (ALF) residents are especially vulnerable to SARS-CoV-2 infection due to the age and comorbidities of the resident population and the social nature of these facilities. To collate all New York State Department of Health guidance and regulations to control transmission of SARS-CoV-2 infection within ALFs from March 2020 through December 2022 and to include US Food and Drug Administration COVID-19 testing and vaccine authorizations. A narrative chronological review of all New York State Department of Health guidance. Documents and associated guidance and regulations are divided into 4 sections: (1) lockdown until COVID-19 vaccine emergency use authorization; (2) COVID-19 vaccine authorization until phased reopening; (3) phased reopening, vaccination requirements, and booster vaccination; (4) the period of the bivalent booster. Controlling the spread of SARS-CoV-2 within ALFs required a multifactorial approach that included stringent infection control measures, testing, and vaccination and careful attention to the social structure and support systems within ALFs. The SARS-CoV-2 pandemic highlighted the complexity of controlling spread of an easily transmissible respiratory pathogen in assisted living communities and the need to structure infection control programs within the diverse ALFs that provide care for our aging population.

Investigating bleeding adverse events associated with BTK inhibitors in the food and drug administration adverse event reporting system (FAERS)

ABSTRACT Background This study analyzed the bleeding adverse events (AEs) resulting from the treatment of B-cell lymphoma with Bruton tyrosine kinase (BTK) inhibitors, according to reports in the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) Methods Bleeding AEs associated with BTK inhibitors (including ibrutinib, zanubrutinib, and acalabrutinib) from the first quarter of 2013 to the third quarter of 2023 were extracted. Reporting odds ratio (ROR) and proportional reporting ratio (PRR) were reported. Preferred Terms (PTs) of Medical Dictionary for Regulatory Activities (MedDRA) terms were mapped to System Organ Class terms (SOC) terms and analyzed bleeding AEs associated with three BTK inhibitors. Results A total of 463 cases of bleeding AEs were included. Contusion, subcutaneous hemorrhage, hematuria, and cerebral hemorrhage were included in PTs. Blood urine was present and subdural hematoma were also reported. The incidence of bleeding AEs was higher with ibrutinib (Case number = 10,696) than with zanubrutinib (Case number = 213) and acalabrutinib (Case number = 314). Conclusion Our findings indicate that bleeding AEs linked to BTK inhibitors in various conditions underscore the need for cautious clinical decision-making, particularly in nervous system disorders, injuries, poisoning, surgical complications, vascular disorders, and others.

Enhancing the action of serotonin by three different mechanisms prevents spontaneous seizure-induced mortality in Dravet mice.

Sudden unexpected death in epilepsy (SUDEP) is an underestimated complication of epilepsy. Previous studies have demonstrated that enhancement of serotonergic neurotransmission suppresses seizure-induced sudden death in evoked seizure models. However, it is unclear whether elevated serotonin (5-HT) function will prevent spontaneous seizure-induced mortality (SSIM), which is characteristic of human SUDEP. We examined the effects of 5-HT-enhancing agents that act by three different pharmacological mechanisms on SSIM in Dravet mice, which exhibit a high incidence of SUDEP, modeling human Dravet syndrome. Dravet mice of both sexes were evaluated for spontaneous seizure characterization and changes in SSIM incidence induced by agents that enhance 5-HT-mediated neurotransmission. Fluoxetine (a selective 5-HT reuptake inhibitor), fenfluramine (a 5-HT releaser and agonist), SR 57227 (a specific 5-HT3 receptor agonist), or saline (vehicle) was intraperitoneally administered over an 8-day period in Dravet mice, and the effect of these treatments on SSIM was examined. Spontaneous seizures in Dravet mice generally progressed from wild running to tonic seizures with or without SSIM. Fluoxetine at 30 mg/kg, but not at 20 or 5 mg/kg, significantly reduced SSIM compared with the vehicle control. Fenfluramine at 1-10 mg/kg, but not .2 mg/kg, fully protected Dravet mice from SSIM, with all mice surviving. Compared with the vehicle control, SR 57227 at 20 mg/kg, but not at 10 or 5 mg/kg, significantly lowered SSIM. The effect of these drugs on SSIM was independent of sex. Our data demonstrate that elevating serotonergic function by fluoxetine, fenfluramine, or SR 57227 significantly reduces or eliminates SSIM in Dravet mice in a sex-independent manner. These findings suggest that deficits in serotonergic neurotransmission likely play an important role in the pathogenesis of SSIM, and fluoxetine and fenfluramine, which are US Food and Drug Administration-approved medications, may potentially prevent SUDEP in at-risk patients.

Leave the Milk for the Calf and Spread the Word: Exploring Factors Determining US Consumers’ Willingness to Try Plant-Based Milk Alternatives and Their Word-of-Mouth Sharing about Plant-Based Milk Alternatives

Plant-based milk alternatives are important beverages in US consumer markets. Sustainability, consumer awareness, lifestyle changes, and other value-based reasons are why these beverages are increasing in popularity. The present study is focused on plant-based milk alternatives. It builds on an online consumer survey that explores the factors explaining US consumers’ willingness to try plant-based milk alternatives and their word-of-mouth sharing about these beverages. Animal welfare concerns, environmental concerns, health consciousness, and dairy preferences are the factors under investigation. Results show that animal welfare, dairy preference, environmental concerns, and plant-based milk enthusiasm are significant predictors for willingness to try plant-based milk alternatives. Dairy preferences, environmental concerns, and plant-based milk enthusiasm predict the word-of-mouth factors. Overall, plant-based milk enthusiasm is the strongest driver for both consumer behaviours. Best practice recommendations address marketers in the US food and beverage industry and provide suggestions on how to target different consumer groups based on nutritional preferences and needs and on value-based product characteristics.

Cost-Effectiveness of Lecanemab for Individuals With Early-Stage Alzheimer Disease.

Little is known regarding the cost-effectiveness of lecanemab (Leqembi), a monoclonal antibody approved by the US Food and Drug Administration in January 2023 for the treatment of mild cognitive impairment (MCI) or mild dementia due to Alzheimer disease (AD). This study aims to quantify the cost-effectiveness of lecanemab and how it varies based on the accuracy of AD testing and individuals' APOE ε4 status. Seven alternative test-treat-target strategies defined by combinations of testing approaches (PET, CSF, or plasma assay), treatment choices (standard of care [SoC] alone or lecanemab in addition to SoC), and targeting strategies (targeting APOE ε4 noncarriers or heterozygous patients or not) were compared. A hybrid decision tree-Markov cohort model was constructed with 5 states: (1) MCI (Clinical Dementia Rating-Sum of Boxes [CDR-SB] 0-4.5); (2) mild dementia (CDR-SB 4.6-9.5); (3) moderate dementia (CDR-SB 9.6-16); (4) severe dementia (CDR-SB >16); and (5) death. Effectiveness was measured by quality-adjusted life years and costs from third-party and societal perspectives were estimated in 2022 US dollars over a lifetime horizon. Among the 7 test-treat-target strategies, SoC alone was the optimal strategy from a cost-effectiveness perspective. Neither targeted lecanemab treatment nor treatment unrestricted by APOE ε4 genotype was cost-effective vs SoC alone, regardless of the test used to diagnose patients with early-stage AD. However, CSF assay followed by targeted treatment would become cost-effective if lecanemab is priced below $5,100 per year. These results were robust to the accuracy of diagnostic testing and rates of lecanemab discontinuation and adverse events. Neither targeted lecanemab treatment nor treatment unrestricted by APOE ε4 genotype is cost-effective vs SoC alone for patients with MCI or mild dementia due to AD. Lecanemab would be cost-effective in some settings if priced below $5,100 per year.

Prevalence of menthol cigarette use among adults who smoke from the United States by census division and demographic subgroup, 2002–2020: findings from the International Tobacco Control (ITC) project

BackgroundTargeted marketing of menthol cigarettes in the US influences disparities in the prevalence of menthol smoking. There has been no analysis of sub-national data documenting differences in use across demographic subgroups. This study estimated trends in the prevalence of menthol use among adults who smoke in the nine US census divisions by sex, age, and race/ethnicity from 2002 to 2020.MethodsData from 12 waves of the US ITC Survey were used to estimate the prevalence of menthol cigarette use across census divisions and demographic subgroups using multilevel regression and post-stratification (n = 12,020). Multilevel logistic regression was used to predict the prevalence of menthol cigarette use in 72 cross-classified groups of adults who smoke defined by sex, age, race/ethnicity, and socioeconomic status; division-level effects were fit with a random intercept. Predicted prevalence was weighted by the total number of adults who smoke in each cross-classified group and aggregated to divisions within demographic subgroup. Estimates were validated against the Tobacco Use Supplement to the Current Population Survey (TUS-CPS).ResultsOverall modeled prevalence of menthol cigarette use was similar to TUS-CPS estimates. Prevalence among adults who smoke increased in each division from 2002 to 2020. By 2020, prevalence was highest in the Middle (46.3%) and South Atlantic (42.7%) and lowest in the Pacific (25.9%) and Mountain (24.2%) divisions. Prevalence was higher among adults aged 18–29 (vs. 50+) and females (vs. males). Prevalence among non-Hispanic Black people exceeded 80% in the Middle Atlantic, East North Central, West North Central, and South Atlantic in all years and varied most among Hispanic people in 2020 (Pacific: 26.5%, New England: 55.1%).ConclusionsSignificant geographic variation in the prevalence of menthol cigarette use among adults who smoke suggests the proposed US Food and Drug Administration (FDA) menthol cigarette ban will exert differential public health benefits and challenges across geographic and demographic subgroups.

From access toward sovereignty: A scoping review of municipal land access policies for urban agriculture in the United States

Accessing land—and protecting that access—for the purpose of growing food and other agricultural products is a significant challenge in urban agriculture (UA), an issue exacerbated by racial and wealth disparities and high land values in cities. While local policies and programs supporting the use or sale of public land for UA have increased steadily since the early 21st century, limited research has examined the diversity, accessibility, and permanency of mechanisms facilitating land access and tenure. To address this gap, we compared the availability and characteristics of land access mechanisms across the 40 most populous U.S. cities. While 75% of cities employed at least one mechanism to facilitate land access, few (20%) offered multiple options. Mechanisms facilitating temporary use of public land for UA such as Adopt-A-Lot programs and city-run farms and gardens were more common than those enabling more secure tenure through long-term leases, land trusts, and simplified sales processes. Most policies and programs explicitly focused on local residents and nonprofit/community groups rather than for-profit entities. Nearly half (45%) of cities designed their land access mechanisms with a focus on equity or supporting underserved populations. Less than a quarter of cities offered subsidized water access, liability insurance, soil testing, or funding to complement public land access. The diversity of available mechanisms for facilitating land access underscores how different cities are enabling UA for different goals. Additionally, the incongruence between advocates’ demands for land sovereignty and the mechanisms currently offered raise questions about the extent to which cities are advancing permanent land reforms or provisional interventions at risk of revocation. Our findings may be of use to policymakers and advocates who are creating, comparing, and adapting land access policies and programs to best address growers’ needs and advance sustainable and equitable food transformations.

Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval

The US Food and Drug Administration's (FDA) accelerated approval pathway allows approval of investigational drugs treating unmet medical needs based on changes to surrogate measures considered "reasonably likely" to predict clinical benefit. Postapproval clinical trials are then required to confirm whether these drugs offer clinical benefit. To determine whether cancer drugs granted accelerated approval ultimately demonstrate clinical benefit and to evaluate the basis of conversion to regular approval. In this cohort study, publicly available FDA data were used to identify cancer drugs granted accelerated approval from 2013 to 2023. Demonstrated improvement in quality of life or overall survival in accelerated approvals with more than 5 years of follow-up, as well as confirmatory trial end points and time to conversion for drug-indication pairs converted to regular approval. A total of 129 cancer drug-indication pairs were granted accelerated approval from 2013 to 2023. Among 46 indications with more than 5 years of follow-up (approved 2013-2017), approximately two-thirds (29, 63%) were converted to regular approval, 10 (22%) were withdrawn, and 7 (15%) remained ongoing after a median of 6.3 years. Fewer than half (20/46, 43%) demonstrated a clinical benefit in confirmatory trials. Time to withdrawal decreased from 9.9 years to 3.6 years, and time to regular approval increased from 1.6 years to 3.6 years. Among 48 drug-indication pairs converted to regular approval, 19 (40%) were converted based on overall survival, 21 (44%) on progression-free survival, 5 (10%) on response rate plus duration of response, 2 (4%) on response rate, and 1 (2%) despite a negative confirmatory trial. Comparing accelerated and regular approval indications, 18 of 48 (38%) were unchanged, while 30 of 48 (63%) had different indications (eg, earlier line of therapy). Most cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within 5 years of accelerated approval. Patients should be clearly informed about the cancer drugs that use the accelerated approval pathway and do not end up showing benefits in patient-centered clinical outcomes.

Clinical Value of Molecular Targets and FDA-Approved Genome-Targeted Cancer Therapies

The number of new genome-targeted cancer drugs has increased, offering the possibility of personalized therapy, often at a very high cost. To assess the validity of molecular targets and therapeutic benefits of US Food and Drug Administration-approved genome-targeted cancer drugs based on the outcomes of their corresponding pivotal clinical trials. In this cohort study, all genome-targeted cancer drugs that were FDA-approved between January 1, 2015, and December 31, 2022, were analyzed. From FDA drug labels and trial reports, key characteristics of pivotal trials were extracted, including the outcomes assessed. The strength of evidence supporting molecular targetability was assessed using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT). Clinical benefit for their approved indications was evaluated using the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS). Substantial clinical benefit was defined as a grade of A or B for curative intent and 4 or 5 for noncurative intent. Molecular targets qualifying for ESCAT category level I-A and I-B associated with substantial clinical benefit by ESMO-MCBS were rated as high-benefit genomic-based cancer treatments. A total of 50 molecular-targeted drugs covering 84 indications were analyzed. Forty-five indications (54%) were approved based on phase 1 or phase 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials, and 48 (57%) were approved on the basis of subgroup analyses. By each indication, 46 of 84 primary end points (55%) were overall response rate (median [IQR] overall response rate, 57% [40%-69%]; median [IQR] duration of response, 11.1 [9.2-19.8] months). Among the 84 pivotal trials supporting these 84 indications, 38 trials (45%) had I-A ESCAT targetability, and 32 (38%) had I-B targetability. Overall, 24 of 84 trials (29%) demonstrated substantial clinical benefit via ESMO-MCBS. Combining these ratings, 24 of 84 indications (29%) were associated with high-benefit genomic-based cancer treatments. The results of this cohort study demonstrate that among recently approved molecular-targeted cancer therapies, fewer than one-third demonstrated substantial patient benefits at approval. Benefit frameworks such as ESMO-MCBS and ESCAT can help physicians, patients, and payers identify therapies with the greatest clinical potential.