Health Equity and Access to COVID-19 Treatments Available through Emergency Use Authorizations.

Understanding and evaluating equity in access to care is a critical component to ensuring health equity for all individuals. During the COVID-19 pandemic, the U.S. Food and Drug Administration made unprecedented use of its regulatory authority by authorizing the use of unapproved products through Emergency Use Authorizations (EUAs). We use data from the U.S. National COVID Cohort Collaborative (N3C) to understand how access to therapeutic products authorized under EUAs has varied across COVID-19 patients and over time. We find that Black patients were more likely to receive early EUA drugs while White patients were more likely to receive monoclonal antibodies. Male patients were more likely to receive any EUA drug than Female patients. Patients in Metropolitan areas were more likely to receive EUA drugs than patients in other regions. Additionally, differences in the rates of exposure to EUA drugs by gender, rural-urban classification, and length of stay decreased over time while differences by race and ethnicity have generally persisted. Our project identifies inequities in the rate of access to EUA drugs across patient groups that can inform policy makers in future planning and decision making.

Utilization of long-acting injectable monthly depot buprenorphine for opioid use disorder (OUD) in Kentucky, before and after COVID-19 related buprenorphine access policy changes.

INTRODUCTION: Long-acting injectable buprenorphine (LAI-bup) formulations have advantages over transmucosal buprenorphine (TM-bup), but barriers may limit their utilization. Several policies shifted during the COVID-19 pandemic to promote buprenorphine access. The federal government expanded telemedicine treatment for opioid use disorder and Kentucky (KY) Medicaid lifted prior authorization requirements (PAs) for LAI-bup (i.e., Sublocade®). This retrospective cohort study evaluated changes in LAI-bup access, utilization, and retention before and after these policy changes in KY. METHODS: Individual-level TM-bup and LAI-bup dispensing record data from KY's prescription drug monitoring program examined LAI-bup utilization and retention, without a >30-day gap in coverage, for patients starting a new episode of LAI-bup treatment. Two key time periods were examined: pre-policy changes (Apr 1, 2019 - Dec 31, 2019) and post-policy changes (Apr 1, 2020 - Dec 31, 2020). Data on PA requests among Medicaid managed care organizations and availability of LAI-bup Risk Evaluation and Mitigation Strategy (REMS)-certified pharmacies were also obtained. A multivariable Cox proportional hazard regression model analysis compared pre- versus post-policy period treatment discontinuation. RESULTS: The number of patients initiating LAI-bup increased from 211 to 481 over the two periods. By the end of the post-policy period, 24.3 % of eligible patients were retained on LAI-bup, versus 12.5 % in the pre-policy change period. The adjusted hazard ratio, comparing discontinuation during the post- versus pre-policy change periods, was 0.70 (95 % confidence interval: 0.55-0.89). There were also more REMS-certified pharmacies and providers in the post-policy change period. CONCLUSIONS: LAI-bup access, utilization, and retention increased after several policy changes.

Comparison between European Medicines Agency and US Food and Drug Administration in Granting Accelerated Marketing Authorizations for Covid-19 Medicines and their Utilized Regulations.

BACKGROUND: Prompted by the Covid-19 pandemic and the need to ensure timely and safe access to medicines during a pandemic, the aim of this study was to compare and contrast the EU and US regulations, processes, and outcomes pertaining to the granting of accelerated Marketing Authorizations (MAs) for COVID-19 vaccines and treatments with a view to determining how effective these regulations were in delivering safe medicines in a timely manner. METHODS: MAs for medicines approved for Covid-related indications in the first two pandemic years (March 2020-February 2022) were identified using the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) websites. Authorization reports and utilized regulations were reviewed to determine and compare approval timelines, facilitated pathways, accepted clinical evidence, and effectiveness of the regulations by assessing them against time and safety standards. RESULTS: By the end of February 2022, the EMA and FDA had granted 12 and 14 MAs, respectively. Two EU and two US approvals were issued in relation to new indications for already-approved treatments; the remaining ones were first-time approvals of novel vaccines and treatments. The median time to approval was 24 days for the EMA's conditional MAs and 36 days for the USFDA's Emergency Use Authorizations (EUA) for all Covid-19 medicines. This is compared with 23 and 28 days, respectively, specifically for first-time novel vaccines and treatments authorized by both USFDA and EMA. The USFDA and EMA differed markedly in terms of the time taken to approve new indications of already-approved treatment; the USFDA took 65 days for such approval, compared with 133 days for the EMA. Where MAs were issued by both authorities, USFDA approvals were issued before EMA approvals; applications for approval were submitted to the FDA before submission to the EMA. Three EU and two US MAs were based on data from two or more phase 3 clinical trials; the remaining ones were based on single trial data. Only six EU and four US trials had been completed by the time of authorization. This was in line with regulations. While the applicable regulations shared many similarities, there were marked differences. For instance, the EU's conditional MA regulation pertains only to first approvals of new treatments. It does not cover new indications of already-approved treatments. This contrasts with the US, where the EUA regulation applies to both types of applications, something that may have impacted approval timelines. Overall, both EU and US utilized regulations were considered to be effective. For most cases, utilizing such regulations for Covid-19 MAs resulted in faster approval timelines compared to standard MAs. They were flexible enough to manage the process of granting emergency approvals while maintaining strict requirements and allowing comprehensive reviews of the supporting evidence. CONCLUSION: US and EU regulations were effective in ensuring timely accelerated market access to Covid-19 medicines during the pandemic without compromising the approval standards related to safety or efficacy. The population in both regions will receive comparable access to medicines during a pandemic if sponsors submit their applications to both authorities in parallel.

Automated versus manual prior authorization for diabetes mellitus drugs: A retrospective study from Israel.

Introduction: Drug prior authorization (PA) imposes a bureaucratic and economic burden on healthcare service providers and payers. A novel automated PA system may improve these drawbacks. Methods: An historical cohort study from a large health maintenance organization in Israel, comparing manual versus automated PA mechanisms for diabetes mellitus (DM) drugs: sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 analogs (GLP1-A). We compared patients with DM, whose first drug applications were approved using the automated system, with similar patients whose first drug applications were approved by manual PA. The primary endpoint was the time elapsed from application approval to prescription filling (accessibility time). Secondary endpoints included the prescription filling rate at 7 and 30 days. Results: In total, 1371 automated approved prescriptions and 1240 manually approved prescriptions were included in the analysis. Median accessibility time was one day (interquartile range (IQR) 0-5) with automated PA for both GLP1-A and SGLT2i, compared with four days (IQR 1-9) and three days (IQR 1-8), respectively, with the manual PA (p < 0.001). Eighty-four percent of GLP1-A automated PA approvals were filled within seven days compared with 70% with manual PA (p < 0.001). Similar results were seen with SGLT2i (80% vs. 72%, p < 0.008). No differences were observed at 30 days post-approval. Using logistic regression, odds for GLP1-A and SGLT2i prescription filling within seven days were 2.36 and 1.53 folds higher (respectively) with automated PA (p < 0.01). Conclusions: Automated PA system improved access time to SGLT2i/GLP1-A seven days post-approval compared to manual PA.

Emergency use authorization of medicines: History and ethical dilemma.

The regulatory approval process of the United States Food and Drug Administration and European Union is the most demanding and challenging worldwide. They have the provision of the expedited approval pathways, i.e., "Emergency use authorizations" and "Conditional marketing authorizations," respectively, to give approval to novel therapeutics agents during emergency situations. India, firstly formalized the accelerated pathway named "Accelerated Approval Process" as per the New Drugs and Clinical Trials rule 2019 to address unmet medical needs that was implemented by the Central Drug Standard Control Organization to approve the novel therapeutics agents during COVID-19. Hence, our aim is to understand and compare the different emergency approval processes in the world, their underlined claims and conditions with the list of approved products under this concept. All the information collected and analyzed from different official websites of regulatory bodies. In this review, we have enlightened on all these processes with their few approved products.

Is Time Spent on Prior Authorizations Associated With Approval?

Advanced practice providers increasingly assume responsibility for prior authorizations (PAs). We hypothesized that the time burden of PAs will be correlated with increased approval. We collected several variables (ie, type, method, time spent, use of peer to peer, and outcome) for all PAs completed by a departmental nurse practitioner in 1 region. Chi-square tests and 2 sample t tests were used to assess significance. There was no significant association between the method of request, the number of attempts, and the time spent to approved PA. Further research is needed to determine ways to decrease the time and opportunity cost associated with PAs.

Development and evaluation of a fluidic facemask for airborne transmission mitigation.

Recently, a fluidic facemask concept was proposed to mitigate the transmission of virus-laden aerosol and droplet infections, such as SARS-CoV-2 (COVID-19). This paper describes an experimental investigation of the first practical fluidic facemask prototype, or "Air-Screen". It employs a small, high-aspect-ratio, crossflow fan mounted on the visor of a filter-covered cap to produce a rectangular air jet, or screen, in front of the wearer's face. The entire assembly weighs less than 200 g. Qualitative flow visualization experiments using a mannequin clearly illustrated the Air-Screen's ability to effectively block airborne droplets (∼100 µm) from the wearer's face. Quantitative experiments to simulate droplets produced during sneezing or a wet cough (∼102 µm) were propelled (via a transmitter) at an average velocity of 50 m/s at 1 m from the mannequin or a target. The Air-Screen blocked 62% of all droplets with a diameter of less than 150 µm. With an Air-Screen active on the transmitter, 99% of all droplets were blocked. When both mannequin and transmitter Air-Screens were active, 99.8% of all droplets were blocked. A mathematical model, based on a weakly-advected jet in a crossflow, was employed to gain greater insight into the experimental results. This investigation highlighted the remarkable blocking effect of the Air-Screen and serves as a basis for a more detailed and comprehensive experimental evaluation.

COVID-19 Vaccines and Roles of the Health Regulatory Authority in Tunisia.

Given the unstoppable spread of coronavirus disease (COVID-19), the development of a vaccine was needed to contain the pandemic. In such a situation of global emergency, regulatory authorities ensured timely, safe, and equitable access to the vaccine.This article aims to outline the roles of the Tunisian regulatory authority, the Directorate of Pharmacy and Medicines (DPM) at the Ministry of Health, in registration and procurement of the COVID-19 vaccine.Requirement to grant the Exceptional Provisional Authorizations of Marketing (EPAM) for COVID-19 vaccines was 27 days versus 869 days for conventional marketing authorizations (MAs). The DPM has optimized its activity through: early dialogue with manufacturers, online submission, the use of distance communication technologies. It has demonstrated unprecedented flexibility through the continuous and rolling review approach.Regulatory authorities in Tunisia and around the world have partnered with manufacturers to speed up administrative procedures while ensuring the quality, safety, and efficacy of vaccines.

PCSK9 Inhibitors in Heart Transplant Patients: Safety, Efficacy, and Angiographic Correlates.

BACKGROUND: Statins are recommended in heart transplant patients, but are sometimes poorly tolerated. Alternative agents are often considered including proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i). We sought to investigate the use of PCSK9i after heart transplantation. METHODS AND RESULTS: We identified patients who received a heart transplant from 1999 to 2019 and were started on PCSK9i at our institution. Clinical, laboratory, and coronary angiography with intravascular ultrasound results were compared. Among 65 patients initiated on PCSK9i (48 for statin intolerance and 17 for refractory hyperlipidemia), the median time from transplant was 5.5 years (interquartile range [IQR], 2.8-9.9 years) with a median PCSK9 treatment duration of 1.6 years (IQR, 0.8-3.2 years) and 80% still on treatment. Evolocumab was used in 73.8%, alirocumab in 12.3%, and both in 13.8% owing to insurance coverage. All patients required prior authorization; initial denial occurred in 18.5% and 32.3% had denials in subsequent years. The median low-density lipoprotein cholesterol decreased from 130 mg/dL (IQR, 102-148 mg/dL) to 55 mg/dL (IQR, 35-74 mg/dL) after starting PCSK9i (P < .001), with 72% of patients achieving a low-density lipoprotein cholesterol of <70 mg/dL after treatment. There were also significant reductions of total cholesterol, non-high-density lipoprotein cholesterol, total/high-density lipoprotein cholesterol ratio, and triglycerides, with a modest increase in high-density lipoprotein cholesterol. These changes were durable at latest follow-up. In 33 patients with serial coronary angiography and intravascular ultrasound, PCSK9i were associated with stable coronary plaque thickness and lumen area. CONCLUSIONS: Among heart transplant recipients, PCSK9i are effective in lowering cholesterol levels and stabilizing coronary intimal hyperplasia with minimal side effects. Despite favorable effects, access and affordability remain a challenge.

The year's new drugs and biologics 2020.

2020 will go down in history as a year marked in every respect by the emergence and astonishingly rapid spread of the first major global viral pandemic in a century. It seems like nearly every event or story of the year was influenced in some way by COVID-19, and in that respect, the year ended on a high note with the authorization for emergency use of the first vaccines to prevent SARS-CoV-2 infection and drugs to treat COVID-19. Despite the pandemic's dominance of the 2020 headlines, productivity was at a record high level across all therapeutic areas, as seen by the number of products in this year's review: approximately 50% more than the previous year. Notable achievements include the launch of the first treatment for hepatitis D; regulatory decisions on a suite of biologics for the prevention and treatment of Ebola virus disease, fruit of the 2016-2018 outbreak in the Democratic Republic of Congo; the approval of the first-ever drug to treat Hutchinson-Gilford progeria syndrome, a rare genetic disorder that leads to premature aging; the first treatment developed specifically for thyroid eye disease, also known as Graves' ophthalmopathy; the first nonhormonal, on-demand, vaginal pH-regulating contraceptive; and the first oral allergen immunotherapy for peanut allergy.

Evaluating the effect of prior authorizations in patients with complex dermatologic conditions.

BACKGROUND: In dermatology, prior authorizations can delay treatment, decrease patient adherence, and deter providers from advocating for their patients. Patients with complex dermatologic conditions, often requiring off-label treatments, may face particularly significant insurance barriers. OBJECTIVE: Evaluate the effect of prior authorizations in patients with complex dermatologic conditions. METHODS: This prospective cohort study assessed patients treated by a dermatologist during 5 months who specialized in complex dermatology. Patients included were older than 18 years, treated at V.P.W.'s rheumatology-dermatology clinic, and prescribed a medication or ordered a diagnostic procedure that elicited an insurance prior authorization. Data on prior authorization outcome, administrative time, and delay to treatment were collected. RESULTS: Of 51 prior authorizations, 51% were initially denied, with systemic medications more likely denied than topical ones (P < .001). Total administrative time spent on 50 prior authorizations tracked was 62.5 hours (median time per prior authorization 30 minutes [interquartile range 17-105 minutes]). Time to access treatment was tracked for 80% of prior authorizations; median delay was 12 days [interquartile range 5.5-23 days]. LIMITATIONS: Single-center, single-provider patient panel. CONCLUSION: Patients with complex dermatologic conditions face a significant barrier to care because of prior authorizations. The administrative burden for provider practices to address these prior authorizations is substantial and may warrant a streamlined system in collaboration with insurers.

Micronutrient fortification of caffeinated energy drinks and supplemented foods marketed in Canada.

To examine the micronutrient content of discretionarily fortified products marketed under Canada's current regulations, we conducted an in-store and online search for products granted Temporary Marketing Authorizations in 2018. We located 129 caffeinated energy drinks and 98 other beverage products. Most were fortified at levels well below permitted maximums, but 82.2% of energy drinks and 35.7% of other beverage products contained nutrients above 100% of Daily Values, suggesting that current fortification practices are largely gratuitous. Novelty The micronutrients in a sample of discretionarily fortified products marketed under Canada's current regulations were generally below permitted maximum levels, but many greatly exceeded nutrient requirements.

[Conflicting recommendations between the French national authority for health (HAS) and clinical practice guidelines (CNGOF); focus on 200 late medical abortions, conducted outside marketing authorizations]. / Recommandations discordantes entre HAS et CNGOF ; le point avec 200 IVG médicamenteuses tardives, réalisées hors AMM.

OBJECTIVES: There are conflicting recommandations about late medical abortion: the French National College of Gynaecologists and Obstetricians (CNGOF) and the French Superior Health Authority are opposed. The aim was to assess misoprostol's efficiency in medical abortions at 9 to 14 weeks gestational age (GA) METHODS: This is an epidemiologic retrospective study led from March 2017 till January 2019, in Evreux's hospital, France, including all patients undergoing a medical abortion from 9 to 14 weeks GA. We followed the CNGOF's recommandations published in 2016. The main efficacy parameter was the failure rate of medical abortion at 9 to 14 weeks GA. The secondary efficacy parameters were the number of patients absent at the post-medical abortion examination, the consumption of misoprostol, the consumption of symptomatic treatment, the type of complication and the length of hospital stay. RESULTS: 200 patients were included: 19 patients had vacuum aspiration, so we report a 10.2 % failure rate (95% CI: 6.4%; 15.7%). 7 (3.5%) had vacuum aspiration for haemorrhage (2 (1%) receveived a blood transfusion) 9 (4.5%) had a vacuum aspiration for failure and 3 (1.5%) for retention. 71 (35.5%) patients were absent at the post-medical abortion examination. The mean consumption of misoprostol was 1234µg (441). The mean length of hospital stay was 12.2hours (8.28). CONCLUSIONS: The abortion failure rate is 10.2%. Our study didn't report any elements of bad tolerance of misoprostol in this indication.

Transgenic maize event TC1507: Global status of food, feed, and environmental safety.

Maize (Zea mays) is a widely cultivated cereal that has been safely consumed by humans and animals for centuries. Transgenic or genetically engineered insect-resistant and herbicide-tolerant maize, are commercially grown on a broad scale. Event TC1507 (OECD unique identifier: DAS-Ø15Ø7-1) or the Herculex®(#) I trait, an insect-resistant and herbicide-tolerant maize expressing Cry1F and PAT proteins, has been registered for commercial cultivation in the US since 2001. A science-based safety assessment was conducted on TC1507 prior to commercialization. The safety assessment addressed allergenicity; acute oral toxicity; subchronic toxicity; substantial equivalence with conventional comparators, as well as environmental impact. Results from biochemical, physicochemical, and in silico investigations supported the conclusion that Cry1F and PAT proteins are unlikely to be either allergenic or toxic to humans. Also, findings from toxicological and animal feeding studies supported that maize with TC1507 is as safe and nutritious as conventional maize. Maize with TC1507 is not expected to behave differently than conventional maize in terms of its potential for invasiveness, gene flow to wild and weedy relatives, or impact on non-target organisms. These safety conclusions regarding TC1507 were acknowledged by over 20 regulatory agencies including United States Environment Protection Agency (US EPA), US Department of Agriculture (USDA), Canadian Food Inspection Agency (CFIA), and European Food Safety Authority (EFSA) before authorizing cultivation and/or food and feed uses. A comprehensive review of the safety studies on TC1507, as well as some benefits, are presented here to serve as a reference for regulatory agencies and decision makers in other countries where authorization of TC1507 is or will be pursued.

Um olhar sobre as autorizações de permanência a estrangeiros no Brasil, entre 2005 e 2011 / A portray on foreigners authorized to come to Brazil, from 2005 to 2011 / Una mirada sobre los extranjeros autorizados a entraren en Brasil, entre 2005 y 2011

A proposta geral desse artigo é apresentar uma análise descritiva dos estrangeiros autorizados a se estabelecer temporária ou permanentemente no Brasil, durante o período de 2005 a 2011, bem como sua relação com a política migratória brasileira. Para isso, foram utilizados os microdados da Coordenação Geral de Imigração (CNIg) do Ministério do Trabalho e Emprego. Considerando a literatura apresentada, o intuito é identificar se há uma tendência de seletividade dos estrangeiros autorizados a entrarem no país. Apesar de tal fato não poder ser testado, pois não se dispõe de informações sobre o perfil dos candidatos que tiveram seus pedidos de autorizações negados, é possível inferir sobre tal questão a partir dos dados analisados. Os resultados mostram que as autorizações concedidas são majoritariamente para trabalhadores profissionais e investidores, homens, altamente qualificados e de países, em geral, mais desenvolvidos (norte-americanos, europeus e asiáticos), com destino para o Sudeste. Esse perfil dos autorizados pode ser explicado, em parte, pela política migratória brasileira, que continua a ser restritiva e seletiva. Embora não se possa identificar a origem da seletividade – se o governo brasileiro, o mercado de trabalho (de origem e/ou de destino), ou as próprias solicitações dos estrangeiros –, verifica-se que a política migratória brasileira assegura tal seletividade, independentemente de quem venha a ser o agente dessa ação...

The main purpose of this article is to bring a descriptive analysis about foreigners who are authorized to stay in Brazil in a temporary or permanent term, from 2005 to 2011; and to highlight its relation to Brazilian migration policy. As such, we worked with microdata from Brazilian Migration General Coordination (CNIg), at the Work and Employ Ministry. Based on the presented bibliography, our aim is to identify the existence of a selectivity tendency regarding the authorization of foreigners who accomplish to come to Brazil. Although, we cannot test this selectivity fact, as the information regarding the migrant profile, who had his/her authorization declined, is not available; we can infer this point from the data collected. The results show that the majority of issued authorizations refers to professional workers and investors, men, highly skilled, from developed countries (in general Americans, Europeans and Asians), and towards Brazilian Southeast. This profile of authorized migrants could be partially explained by Brazilian migration policy which remains restrictive and selective. Although it is not possible to identify the source of this selectivity – whether the Brazilian government, the labor market (for origin and destination), or just the specificities of foreigners' requests – Brazilian migration policy ensures this selectivity, regardless of whom could be the agent of this action...

La propuesta dese artigo es presentar un análisis descriptivo de los extranjeros autorizados a establecerse de manera temporaria o permanente en Brasil, por el período de 2005 a 2011, y su relación con la política de migración brasileña. Para eso, utilizamos los microdatos de la Coordinación General de la Migración (CNIg), del Ministerio del Trabajo y Empleo. Considerando la literatura presentada, nuestro intento es identificar si hay una tendencia a la selectividad de los extranjeros que entran en el país. Aunque no podamos testar tal facto, una vez que no tenemos las informaciones sobre los perfiles de los candidatos que tuvieron sus solicitudes negadas, es posible inferir tal cuestión por los datos analizados. Los resultados enseñan que los tipos de autorización concedidos son, en su mayoría, para trabajadores profesionales y inversores, hombres altamente cualificados, de países, en general, desarrollados (estadounidenses, europeos y asiáticos), y con destino al Sudeste del país. Este perfil de autorizados puede ser explicado, en parte, por la política de migración brasileña que continua a ser restrictiva y selectiva. Aunque no se pueda identificar la fuente de la selectividad - si el gobierno brasileño, el mercado de trabajo (origen y / o destino), o las propias solicitudes de los extranjeros - la política de inmigración brasileña asegura tal selectividad independientemente de quién sea el agente de esta acción...

Preparing medical legal reports and dealing with lawyers.

In preparing reports or records for patients in personal injuryThe term 'personal injury' includes cases involving automobile accidents, slip and falls, defective products and medical malpractice. litigation certain basic information will be necessary. Most of that information is often provided in the basic chart without the need for a written report. Ensure that when providing records or discussing the patient's care and treatment with an attorney that your are providing records in a timely manner to the attorney for the patient and that you are not discussing the case with counsel for your patient's opponent. When in doubt, call the patient's attorney and ask them what information is needed.