Standardizing Clinically Meaningful Outcome Measures Beyond HbA1c for Type 1 Diabetes: A Consensus Report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange

Abstract

OBJECTIVETo identify and define clinically meaningful type 1 diabetes outcomes beyond hemoglobin A1c (HbA1c) based upon a review of the evidence, consensus from clinical experts, and input from researchers, people with type 1 diabetes, and industry. Priority outcomes include hypoglycemia, hyperglycemia, time in range, diabetic ketoacidosis (DKA), and patient-reported outcomes (PROs). While priority outcomes for type 1 and type 2 diabetes may overlap, type 1 diabetes was the focus of this work.RESEARCH AND METHODSA Steering Committee—comprising representatives from the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange—was the decision-making body for the Type 1 Diabetes Outcomes Program. Their work was informed by input from researchers, industry, and people with diabetes through Advisory Committees representing each stakeholder group. Stakeholder surveys were used to identify priority outcomes. The outcomes prioritized in the surveys were hypoglycemia, hyperglycemia, time in range, DKA, and PROs. To develop consensus on the definitions of these outcomes, the Steering Committee relied on published evidence, their clinical expertise, and feedback from the Advisory Committees.RESULTSThe Steering Committee developed definitions for hypoglycemia, hyperglycemia, time in range, and DKA in type 1 diabetes. The definitions reflect their assessment of the outcome’s short- and long-term clinical impact on people with type 1 diabetes. Knowledge gaps to be addressed by future research were identified. The Steering Committee discussed PROs and concluded that further type 1 diabetes–specific development is needed.CONCLUSIONSThe Steering Committee recommends use of the defined clinically meaningful outcomes beyond HbA1c in the research, development, and evaluation of type 1 diabetes therapies.

Beyond HbA1c: using continuous glucose monitoring metrics to enhance interpretation of treatment effect and improve clinical decision‐making

“…A common depiction of that type of data is time in range (TIR) based on various glycaemic cut-offs proposed by a variety of groups [9,10]. The central difference is the time scale of observation: HbA 1c changes slowly and reflects averages over months, whereas CGM reflects actual excursions in minutes.…”

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

“…While individualized ranges may be appropriate for some individuals and situations, we believe that a standard and universal definition range for glucose time in range (e.g., 70-180 mg/dL [3.9-10.0 mmo/L]) would be desirable as an end point for clinical trials. However, a number of other summary measures are in current use for characterization of: c glucose controldmean glucose (of all readings), median glucose for all readings, area under the curve (AUC) (for 24 h, normalized hourly, excess for 24 h), low blood glucose index (LBGI); and c glucose variabilitydtotal SD (withinday or between-day), interquartile range (IQR), coefficient of variation (CV), mean amplitude of glucose excursions (MAGE), mean of daily difference (MODD), continuous overall net glycemic action (CONGA), and others have been described (20,41,42).…”

“…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].…”

Defining outcomes for beta cell replacement therapy: a work in progress

“…First, continuous glucose monitoring (CGM) provides meaningful metrics for clinical research and diabetes care [15, 16]. The IPITA/EPITA consensus report takes into consideration the possibility of using CGM data, if available, to evaluate glycaemic variability, time in range and levels of hypoglycaemia instead of, or in combination with, more ‘traditional’ data derived from the self-monitoring of blood glucose (SMBG) and individual completed surveys.…”