Outcome Measures for Artificial Pancreas Clinical Trials: A Consensus Report

Abstract

Research on and commercial development of the artificial pancreas (AP) continue to progress rapidly, and the AP promises to become a part of clinical care. In this report, members of the JDRF Artificial Pancreas Project Consortium in collaboration with the wider AP community 1) advocate for the use of continuous glucose monitoring glucose metrics as outcome measures in AP trials, in addition to HbA1c, and 2) identify a short set of basic, easily interpreted outcome measures to be reported in AP studies whenever feasible. Consensus on a broader range of measures remains challenging; therefore, reporting of additional metrics is encouraged as appropriate for individual AP studies or study groups. Greater consistency in reporting of basic outcome measures may facilitate the interpretation of study results by investigators, regulatory bodies, health care providers, payers, and patients themselves, thereby accelerating the widespread adoption of AP technology to improve the lives of people with type 1 diabetes.

Closed-loop glucose control in young people with type 1 diabetes during and after unannounced physical activity: a randomised controlled crossover trial

“…The study endpoints are in line with recommendations for outcome measurements for artificial pancreas clinical trials [22].…”

Improving the Clinical Value and Utility of CGM Systems: Issues and Recommendations

“…The FDA's Center for Devices and Radiological Health (CDRH), which regulates devices and diagnostics, is supportive of the use of data from appropriately standardized CGM devices for clinical trials, as it has approved numerous trials using devices that regulate insulin delivery based on CGM values (36,39,59). The CDRH has generally requested that investigators utilize the key glucose outcome metrics outlined by Maahs et al (21) in the Consensus Report on artificial pancreas outcome measures for clinical trials.…”

“…For example, the frequency of nocturnal or total daily hypoglycemic events as determined by CGM could be used as a clinical trial end point [1d]: no other feasible alternative technology for accessing nocturnal hypoglycemia is available. For CGM to provide evaluable end points, consensus on definitions of the various levels of time in range and hypoglycemia (in clinical practice and by CGM) is urgently required among payers and providers (21,43). There has been some very recent progress on this topic (58).…”

“…A virtuous cycle could be created with increasing evidence for the value of monitoring technologies, improvement in these technologies, and demonstration of the favorable economics of wider availability. The FDA's Center for Drug Evaluation and Research, which regulates drug therapies, recently examined new definitions and standards for measuring glucose control and other patient-reported outcomes beyond HbA 1c in clinical trials and expressed willingness to continue a series of meetings in an attempt to reach a consensus (21). The FDA's Center for Devices and Radiological Health (CDRH), which regulates devices and diagnostics, is supportive of the use of data from appropriately standardized CGM devices for clinical trials, as it has approved numerous trials using devices that regulate insulin delivery based on CGM values (36,39,59).…”

“…However, if there is an undetected malfunction, missing data transfer, or the algorithms do not handle the CGM data adequately, a clinically relevant adverse event can clearly ensue [3a]. As with CGM, there are likely to be rapid improvements in AID systems from one generation to the next that will challenge the pace of clinical evaluation (see above) and demand standardized outcome measures (19)(20)(21) [1c].…”