title: Insulin pump risks and benefits: a clinical appraisal of pump safety standards, adverse event reporting, and research needs: a joint statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology Working Group.
abstract: Insulin pump therapy, also known as continuous subcutaneous insulin infusion (CSII), is an important and evolving form of insulin delivery, which is mainly used for people with type 1 diabetes. However, even with modern insulin pumps, errors of insulin infusion can occur due to pump failure, insulin infusion set (IIS) blockage, infusion site problems, insulin stability issues, user error, or a combination of these. Users are therefore exposed to significant and potentially fatal hazards: interruption of insulin infusion can result in hyperglycemia and ketoacidosis; conversely, delivery of excessive insulin can cause severe hypoglycemia. Nevertheless, the available evidence on the safety and efficacy of CSII remains limited. The European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) have therefore joined forces to review the systems in place for evaluating the safety of pumps from a clinical perspective. We found that useful information held by the manufacturing companies is not currently shared in a sufficiently transparent manner. Public availability of adverse event (AE) reports on the US Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database is potentially a rich source of safety information but is insufficiently utilized due to the current configuration of the system; the comparable database in Europe (European Databank on Medical Devices [EUDAMED]) is not publicly accessible. Many AEs appear to be attributable to human factors and/or user error, but the extent to which manufacturing companies are required by regulators to consider the interactions of users with the technical features of their products is limited. The clinical studies required by regulators prior to marketing are small and over-reliant on bench testing in relation to "predicate" products. Once a pump is available on the market, insufficient data are made publicly available on its long-term use in a real-world setting; such data could provide vital information to help health care teams to educate and support users and thereby prevent AEs. As well as requiring more from the manufacturing companies, we call for public funding of more research addressing clinically important questions in relation to pump therapy: both observational studies and clinical trials. At present, there are significant differences in the regulatory systems between the US and European Union at both pre- and postmarketing stages; improvements in the European system are more urgently required. This statement concludes with a series of recommended specific actions for "meknovigilance" (i.e., a standardized safety approach to technology) that could be implemented to address the shortcomings we highlight.
authors.affiliation: Science & Co, Düsseldorf, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Heinemann
authors.affiliation: Kinexum, Harpers Ferry, WV.
authors.forename: G Alexander
authors.initials: GA
authors.lastname: Fleming
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK john.petrie@glasgow.ac.uk.
authors.forename: John R
authors.initials: JR
authors.lastname: Petrie
authors.affiliation: Institute of Epidemiology and Medical Biometry, ZIBMT, University of Ulm, Ulm, Germany.
authors.forename: Reinhard W
authors.initials: RW
authors.lastname: Holl
authors.affiliation: International Diabetes Center at Park Nicollet, Minneapolis, MN.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Bergenstal
authors.affiliation: Keck School of Medicine of the University of Southern California, Los Angeles, CA.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Peters
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D018795:Device Approval / Q000592:standards; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000453:epidemiology; D004868:Equipment Failure; D005060:Europe; D006801:Humans; D006943:Hyperglycemia / Q000453:epidemiology / Q000209:etiology; D007003:Hypoglycemia / Q000453:epidemiology / Q000209:etiology; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects; D007332:Insulin Infusion Systems / Q000009:adverse effects* / Q000592:standards*; D057052:Medical Device Recalls; D018570:Risk Assessment; D014481:United States
chemical_list: D007328:Insulin