Study Design and Data Analysis of Artificial Pancreas Device Systems with Closed-Loop Glucose-Sensing Insulin Delivery

Objective. The objective of this article is to provide a high-profile review and discussion on the study design and statistical analysis of pivotal clinical trials conducted to demonstrate the safety and effectiveness of closed-loop investigational artificial pancreas device systems (APDSs) in premarket approval applications. Methods. The United States Food and Drug Administration (FDA) guidance on the content of investigational device exemption and premarket approval applications for APDSs is reviewed with special emphasis on study design and statistical analysis of the pivotal clinical trials. The two pivotal studies for the MiniMed 670G hybrid closed-loop system by Medtronic in their premarket approval application are summarized and discussed. Results. The United States FDA established detailed recommendations on the study design and statistical analysis of pivotal clinical trials for the industry that seek market investigational APDSs and for FDA scientific reviewers that regulate the device applications. The recommendations cover specifics regarding patient population, clinical endpoints, and strategies for data analysis. However, the two pivotal studies that demonstrated the effectiveness of the FDA-approved MiniMed 670G hybrid closed-loop system were not typical randomized controlled trials as per FDA recommendations. Conclusion. The development and regulation of investigational APDSs require careful and sophisticated clinical study designs and data analysis in premarket approval applications. The regulatory evaluation process of the APDSs is rather complicated since the devices consist of multiple components that collaboratively function to mimic human pancreases.

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Anaerobic Digestion Creating Renewable Energy-The Ultimate Closed Loop System

International Journal of Innovative Technology and Exploring Engineering - Special Issue ◽

10.35940/ijitee.b1046.1292s219 ◽

2019 ◽

Vol 9 (2S2) ◽

pp. 197-199

Keyword(s):

Waste Water ◽

United States ◽

Renewable Energy ◽

Anaerobic Digestion ◽

Closed Loop ◽

The United States ◽

Power Source ◽

Closed Loop System ◽

The Press ◽

Sustainable Power

This paper clarifies the significance of Anaerobic Digestion (AD) process. Sustainable power source from anaerobic assimilation gets little evaluation in the press when contrasted with other standard inexhaustible power age advances. It has not been so well known a sustainable power source when contrasted with hydropower sustainable power source or wind sustainable power source in the course of the most recent couple of years. Be that as it may, Renewable vitality from anaerobic processing is boosted the innovation will turn out to be increasingly mainstream in the coming years. Sustainable power source from anaerobic assimilation is amassed in America and Europe and eminently famous in India. Each 1 ton of sustenance waste discarded unnecessarily is in charge of 4.5 huge amounts of CO2 proportionate emanations. Advertisement gives a neighbourhood reasonable secure vitality source free of worldwide financial vitality changes and accessibility, where income is kept in the nearby economy as opposed to going to oil rich nations and multinationals. Sustainable power source from anaerobic processing is created by the consuming of methane. Sustainable power source from anaerobic assimilation is created in storehouses where specific microbes are added to natural waste. Sewage, vegetation, excrement, slaughterhouse waste and waste water would all be able to be separated in an anaerobic assimilation storehouse. At times, specific silage yields are developed for decay. The microbes are added to the waste and the disintegration happens without oxygen. The methane delivered during decay is scorched nearby, driving turbines and making inexhaustible power. Anaerobic processing isn't especially reasonable for little scale local sustainable power creation, to a great extent because of the space prerequisites for the storehouses and the sheer measure of waste required to delivering methane. Notwithstanding, sustainable power source from anaerobic assimilation can be delivered on a huge business scale, a training regular in the United States, taking waste from a wide area.

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Developing a Clinical Trials Infrastructure in the United States

NAM Perspectives ◽

10.31478/201205g ◽

2012 ◽

Vol 2 (5) ◽

Author(s):

Paul Eisenberg ◽

◽

Petra Kaufmann ◽

Ellen Sigal ◽

Janet Woodcock ◽

...

Keyword(s):

United States ◽

Clinical Trials ◽

The United States

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Global Power Shift

10.1093/oso/9780190697518.003.0002 ◽

2017 ◽

Author(s):

Roberts Cynthia ◽

Leslie Armijo ◽

Saori Katada

Keyword(s):

United States ◽

South Africa ◽

Data Analysis ◽

The United States ◽

Rising Powers ◽

Extensive Data ◽

Power Shift ◽

Multiple Dimensions ◽

Global Power ◽

Rise Of China

This chapter evaluates multiple dimensions of the global power shift from the incumbent G5/G7 powers to the rising powers, especially the members of the BRICS (Brazil, Russia, India, China, and South Africa). Taking note of alternative conceptualizations of interstate “power,” the text maps the redistribution of economic capabilities from the G7 to the BRICS, most particularly the relative rise of China and decline of Japan, and especially Europe. Given these clear trends in measurable material capabilities, the BRICS have obtained considerable autonomy from outside pressures. Although the BRICS’ economic, financial, and monetary capabilities remain uneven, their relative positions have improved steadily. Via extensive data analysis, the chapter finds that whether one examines China alone or the BRICS as a group, BRICS members have achieved the necessary capabilities to challenge the global economic and financial leadership of the currently dominant powers, perhaps even the United States one day.

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690 Are participants in obstetrical randomized clinical trials representative of the United States pregnant population?

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2020.12.714 ◽

2021 ◽

Vol 224 (2) ◽

pp. S433

Author(s):

Cynthia Coots ◽

Stephen Wagner ◽

Matthew J. Bicocca ◽

Megha Gupta ◽

Hector Mendez Figueroa ◽

...

Keyword(s):

United States ◽

Clinical Trials ◽

Randomized Clinical Trials ◽

The United States

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EPID-07. ACCESS TO GLIOBLASTOMA CLINICAL TRIALS FOR RURAL PATIENTS IN THE UNITED STATES FROM 2010–2020

Neuro-Oncology ◽

10.1093/neuonc/noaa215.325 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii79-ii79

Author(s):

Kathryn Nevel ◽

Samuel Capouch ◽

Lisa Arnold ◽

Katherine Peters ◽

Nimish Mohile ◽

...

Keyword(s):

United States ◽

Clinical Trials ◽

Rural Communities ◽

The United States ◽

Interventional Treatment ◽

Phase Ii Trials ◽

Treatment Trials ◽

Rural Sites ◽

Rural Patients ◽

Urban Sites

Abstract BACKGROUND Patients in rural communities have less access to optimal cancer care and clinical trials. For GBM, access to experimental therapies, and consideration of a clinical trial is embedded in national guidelines. Still, the availability of clinical trials to rural communities, representing 20% of the US population, has not been described. METHODS We queried ClinicalTrials.gov for glioblastoma interventional treatment trials opened between 1/2010 and 1/2020 in the United States. We created a Structured Query Language database and leveraged Google application programming interfaces (API) Places to find name and street addresses for the sites, and Google’s Geocode API to determine the county location. Counties were classified by US Department of Agriculture Rural-Urban Continuum Codes (RUCC 1–3 = urban and RUCC 4–9 = rural). We used z-ratios for rural-urban statistical comparisons. RESULTS We identified 406 interventional treatment trials for GBM at 1491 unique sites. 8.7% of unique sites were in rural settings. Rural sites opened an average of 1.7 trials/site and urban sites 2.8 trials/site from 1/2010–1/2020. Rural sites offered more phase II trials (63% vs 57%, p= 0.03) and fewer phase I trials (22% vs 28%, p= 0.01) than urban sites. Rural locations were more likely to offer federally-sponsored trials (p< 0.002). There were no investigator-initiated or single-institution trials offered at rural locations, and only 1% of industry trials were offered rurally. DISCUSSION Clinical trials for GBM were rarely open in rural areas, and were more dependent on federal funding. Clinical trials are likely difficult to access for rural patients, and this has important implications for the generalizability of research as well as how we engage the field of neuro-oncology and patient advocacy groups in improving patient access to trials. Increasing the number of clinical trials in rural locations may enable more rural patients to access and enroll in GBM studies.

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Ports and Environmental Justice in the United States: An Exploratory Statistical Analysis

Risk Analysis ◽

10.1111/risa.13697 ◽

2021 ◽

Author(s):

Michael R. Greenberg

Keyword(s):

United States ◽

Statistical Analysis ◽

Environmental Justice ◽

The United States

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The United States’ Regulatory Environment Is Evolving to Accommodate a Coming Boom in Gene Therapy Research

Applied Biosafety ◽

10.1177/1535676019854866 ◽

2019 ◽

Vol 24 (3) ◽

pp. 147-152 ◽

Cited By ~ 2

Author(s):

Daniel Eisenman

Keyword(s):

United States ◽

Gene Therapy ◽

Clinical Trials ◽

The United States ◽

Regulatory Environment ◽

Evidence Based ◽

Regulatory Structure ◽

Regulatory Changes ◽

Current State ◽

Therapy Field

Introduction: A dramatic increase in the number of clinical trials involving gene-modified cell therapy and gene therapy is taking place. The field is on the verge of a boom, and the regulatory environment is evolving to accommodate the growth. Discussion: This commentary summarizes the current state of the field, including an overview of the growth. The United States (US) regulatory structure for gene therapy will be summarized, and the evolution of the oversight structure will be explained. Conclusion: The gene therapy field has recently produced its first FDA-approved therapeutics and has a pipeline of other investigational products in the final stages of clinical trials before they can be evaluated by the FDA as safe and effective therapeutics. As research continues to evolve, so must the oversight structure. Biosafety professionals and IBCs have always played key roles in contributing to the safe, evidence-based advancement of gene therapy research. With the recent regulatory changes and current surge in gene therapy research, the importance of those roles has increased dramatically.

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Considerations for Tissue-Engineered and Regenerative Medicine Product Development Prior to Clinical Trials in the United States

Tissue Engineering Part B Reviews ◽

10.1089/ten.teb.2009.0449 ◽

2010 ◽

Vol 16 (1) ◽

pp. 41-54 ◽

Cited By ~ 91

Author(s):

Mark H. Lee ◽

Judith A. Arcidiacono ◽

Anastacia M. Bilek ◽

Jeremiah J. Wille ◽

Caitilin A. Hamill ◽

...

Keyword(s):

United States ◽

Clinical Trials ◽

Regenerative Medicine ◽

Product Development ◽

The United States ◽

Medicine Product

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Enrollment disparities in cancer clinical trials leading to FDA approvals between 2008 and 2020.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18501 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18501-e18501

Author(s):

Ryan Huu-Tuan Nguyen ◽

Yomaira Silva ◽

Vijayakrishna K. Gadi

Keyword(s):

Prostate Cancer ◽

United States ◽

Clinical Trials ◽

Drug Approval ◽

The United States ◽

Cancer Clinical Trials ◽

Cancer Prevalence ◽

Fda Approval ◽

The Us ◽

Enrollment Data

e18501 Background: Cancer clinical trials based in the United States (US) have lacked adequate representation of racial and ethnic minorities, the elderly, and women. Pivotal clinical trials leading to United States Food and Drug Administration (FDA) approval are often multi-national trials and may also lack generalizability to underrepresented populations in the United States. We determined the racial, ethnic, age, and sex enrollment in pivotal trials relative to the US cancer population. Methods: We reviewed the FDA’s Drug Approvals and Databases for novel and new use drug approvals for breast, colorectal, lung, and prostate cancer indications from 2008 through 2020. Drugs@FDA was searched for drug approval summaries and FDA labels to identify clinical trials used to justify clinical efficacy that led to FDA approval. For eligible trials, enrollment data were obtained from FDA approval summaries, FDA labels, ClinicalTrials.gov, and corresponding journal manuscripts. Enrollment Fraction (EF) was calculated as enrollment in identified clinical trials divided by 2017 SEER cancer prevalence. All data sources were publicly available. Results: From 2008 through 2020, 60 drugs received novel or new use drug approval for breast, colorectal, lung, or prostate cancer indications based on 66 clinical trials with a total enrollment of 36,830. North America accounted for 9,259 (31%) enrollees of the 73% of trials reporting location of enrollment. Racial demographics were reported in 78% of manuscripts, 66% of ClinicalTrials.gov pages, and 98% of FDA labels or approval summaries. Compared with a 0.4% enrollment fraction among White patients, lower enrollment fractions were noted in Hispanic (0.2%, odds ratio [OR] vs White, 0.46; 95% confidence interval [CI], 0.43 to 0.49, P< 0.001) and Black (0.1%, OR 0.29; 95% CI 0.28 to 0.31, P< 0.001) patients. Elderly patients (age ≥ 65 years) were less likely than younger patients to be enrollees (EF 0.3% vs 0.9%, OR 0.27; 95% CI 0.26 to 0.27, P< 0.001) despite accounting for 61.3% of cancer prevalence. For colorectal and lung cancer trials, females were less likely than males (EF 0.7% vs 1.1%, OR 0.66; 95% CI 0.63 to 0.68, P< 0.001) to be enrolled. Conclusions: Black, Hispanic, elderly, and female patients were less likely to enroll in cancer clinical trials leading to FDA approvals from 2008 to 2020. Race and geographic enrollment data were inconsistently reported in journal manuscripts and ClinicalTrials.gov. The lack of appropriate representation of specific patient populations in these key clinical trials limits their generalizability. Future efforts must be made to ensure equitable access, representation, and reporting of enrollees that adequately represent the US population of patients with cancer.

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