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 prema...

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Main Authors: Sravya B. Shankara, Yujia Liu, Qingfeng Zheng, Jing Guo, Guixia Wang, Bo Zhang
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2021/8812695
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author Sravya B. Shankara
Yujia Liu
Qingfeng Zheng
Jing Guo
Guixia Wang
Bo Zhang
author_facet Sravya B. Shankara
Yujia Liu
Qingfeng Zheng
Jing Guo
Guixia Wang
Bo Zhang
author_sort Sravya B. Shankara
collection DOAJ
description 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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series International Journal of Endocrinology
spelling doaj-art-e396fe004e4f48ea81e446ce3a3dc1952025-08-20T02:21:24ZengWileyInternational Journal of Endocrinology1687-83371687-83452021-01-01202110.1155/2021/88126958812695Study Design and Data Analysis of Artificial Pancreas Device Systems with Closed-Loop Glucose-Sensing Insulin DeliverySravya B. Shankara0Yujia Liu1Qingfeng Zheng2Jing Guo3Guixia Wang4Bo Zhang5Department of Medicine, School of Medicine, University of Massachusetts Medical School, Worcester, MA, USADepartment of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, ChinaDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Health Policy and Management, School of Public Health, Peking University, Beijing, ChinaDepartment of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, ChinaDepartment of Neurology and ICCTR Biostatistics and Research Design Center, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USAObjective. 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.http://dx.doi.org/10.1155/2021/8812695
spellingShingle Sravya B. Shankara
Yujia Liu
Qingfeng Zheng
Jing Guo
Guixia Wang
Bo Zhang
Study Design and Data Analysis of Artificial Pancreas Device Systems with Closed-Loop Glucose-Sensing Insulin Delivery
International Journal of Endocrinology
title Study Design and Data Analysis of Artificial Pancreas Device Systems with Closed-Loop Glucose-Sensing Insulin Delivery
title_full Study Design and Data Analysis of Artificial Pancreas Device Systems with Closed-Loop Glucose-Sensing Insulin Delivery
title_fullStr Study Design and Data Analysis of Artificial Pancreas Device Systems with Closed-Loop Glucose-Sensing Insulin Delivery
title_full_unstemmed Study Design and Data Analysis of Artificial Pancreas Device Systems with Closed-Loop Glucose-Sensing Insulin Delivery
title_short Study Design and Data Analysis of Artificial Pancreas Device Systems with Closed-Loop Glucose-Sensing Insulin Delivery
title_sort study design and data analysis of artificial pancreas device systems with closed loop glucose sensing insulin delivery
url http://dx.doi.org/10.1155/2021/8812695
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