The Demise of Islet Allotransplantation in the US: A Call for an Urgent Regulatory Update The ISLETS FOR US Collaborative

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and more than minimally manipulated human cell and tissue products (HCT/Ps). Across the world, human islets are appropriately defined as minimally manipulated tissue which has led to islet transplantation becoming a standard-of-care procedure for patients with type 1 diabetes mellitus and problematic hypoglycemia. As a result of the outdated US regulations, only eleven patients underwent allo-ITx in the US between 2011-2016 and all in the setting of a clinical trial. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both, better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and “more than minimally manipulated” human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as “minimally manipulated tissue” and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States

Control Rights, Network Structure and Vertical Integration: Evidence from Regional Airlines

This paper investigates the relationship between vertical integration and the importance of control rights under incomplete contracts. Our setting is the U.S regional airline industry. Regional airlines operate flights for major carriers under the major’s brand. The majors market the regionals’ flights as their own. There is substantial heterogeneity in whether or not regionals are owned by the major for which they operate. Furthermore, several majors own some of their regional partners while also contracting with others. We develop a simple framework that illustrates the benefits and costs of vertical integration between a major and regional. We argue that when unforeseen disruptions create the need for schedule adjustments – as frequently occurs in the airline industry - the major will internalize the impact of the disruption on its entire network, while the regional will not. Ownership of a regional mitigates this incentive problem by giving the major rights of control over how the regional’s physical assets and labor force are used. However, by bringing the regional’s labor force “in-house”, ownership of a regional may erode some of the labor cost savings that are very reason why majors subcontract certain flights to regionals. Using data on majors’ use of regionals in the second quarter of 2000, we test whether majors’ choice of organizational form reflects this tradeoff between greater control and lower labor costs. Our results provide support for our analytical framework. We find that owned regionals are more likely to serve city pairs that are (1) more integrated into the major’s network, where externalities not internalized by the regional will be the greatest; and (2) that owned regionals are more likely to serve city pairs with adverse weather conditions, where unforeseen schedule disruptions will be more common

Quality Disclosure Programs and Internal Organizational Practices: Evidence from Airline Flight Delays

Disclosure programs exist in many industries in which consumers are poorly informed about product quality. We study a disclosure program for airline on-time performance, which ranks airlines based on the fraction of their flights that arrive less than 15 minutes late. The program creates incentives for airlines to focus their efforts on flights close to this threshold. We find that firms in this industry are heterogeneous in how they respond to these incentives. Moreover, this heterogeneity correlates with internal firm characteristics. Our findings highlight the importance of interactions between incentives created by a disclosure program and firms' internal organizational practices. (JEL D22, L15, L25, L93)Forbes gratefully acknowledges financial support from National Science Foundation (NSF) grant SES-1124154. Lederman gratefully acknowledges financial support from the Social Science and Humanities research Council of Canada. Tombe gratefully acknowledges financial support from Social Sciences and Humanities Research Council (SSHRC) grant IDG 430-2012-421