A Worldwide Survey of Activities and Practices in Clinical Islet of Langerhans Transplantation

It has almost become commonplace to state that islet transplantation has become an established beta-cell replacement therapy since the seminal publication of the Edmonton protocol. The significant improvement of outcomes reported has led to a multiplication of islet transplant centers and transplant procedures. In comparison to the 237 procedures performed during the 1990–1999 decade and reported to the now defunct International Islet Transplant Registry (ITR), 2,150 islet allotransplants have been reported to the Collaborative Islet Transplant Registry in the 1999–2015 period alone.

High-quality prospective clinical trials have been conducted in the past 2 decades and have demonstrated the value of islet transplantation in controlling complicated type 1 diabetes. Despite these achievements, islet transplantation still doesn't benefit from third party health care coverage, most conspicuously, in the United States. Although this has not yet been studied, it is likely that reimbursement and activity should be correlated.

Another notable difference is the organization in islet transplant consortia, albeit with variations in the types and levels of interaction, that has been embraced in Europe, Australia and Japan, but not in North America. National, or even regional (GRAGIL, Nordic Network), networks, with transplant centers located around a centralized islet production laboratory, facilitate access to islet transplantation and ease the burden of traveling to a distant islet center for the patients. These models undoubtedly have a positive impact on finances and equity of access, and national health policymakers should consider promoting and implementing their construction in countries where they do not exist.

In the survey period, allogeneic islet transplantation activity has been mostly performed in Europe, and the differences have accentuated in the past 7 years. High activity levels have progressively shifted from North America to Europe, both in terms of patients transplanted, but also active islet transplant centers. It is striking that more than half of North American transplants have been performed in Canada (833 transplants in 360 patients, versus 642 in 255 for the United States). This is an unsurprising and expected result of the regulatory framework in the United States, in which allogeneic islets are considered a biologic drug, with the ensuing difficulties met by academic institutions to comply with the tremendous logistic and financial consequences. This situation seems to be unique to the US, in contrast to Canada and most countries in the rest of the world, where allogeneic islets are considered as cell therapy products and fall under organ transplant regulations. The US regulation implies that a Biologics License must be obtained for an institution or a company to be authorized to manufacture and administer allogeneic islets to patients with type 1 diabetes and to secure third party reimbursement. No such license has been granted so far, resulting in the absence of health care coverage in the United States. Many other countries currently have islet transplantation considered as standard-of-care and reimbursed, but there are still several instances in which the classification of allogeneic islets as “basic" cell therapy products has not led to their recognition as standard-of-care treatment of type 1 diabetes and/or to full or even partial insurance coverage.