Table 6.
Risk of bias in case-control studies of incretin treatment and pancreatitis in patients with type 2 diabetes mellitus
| Author (year) | Ascertainment of type 2 diabetes conditions | Is case definition adequate | Selection of controls | Definition of controls | Ascertainment of exposure to incretin agents | Ascertainment of other confounding variables | Same method of ascertainment for exposure to incretin agents | Comparability of study controls for important factors | Completeness of data within database |
|---|---|---|---|---|---|---|---|---|---|
| Singh (2013)94 | Type 2 diabetes mellitus identified as 1 relevant inpatient code of ICD-9 or 2 outpatient ICD-9 codes separated by at least 30 days (250.xx, 648.0, 362.0, and 266.41) | Yes, presumptive cases identified with validated algorithm of ICD-9 and Current Procedural Terminology codes for acute pancreatitis |
Each case randomly selected 1 control subject from same population matched on age within 10 years, sex, insurance plan site, diabetes complication severity index (0, 1, 2, 3, or more), and enrolment pattern or duration of follow-up |
Patients with no acute pancreatitis | Drug exposure defined as having filled prescription for sitagliptin or exenatide before first observed diagnosis of pancreatitis, and prescription data used as indicator of drug exposure | Ascertainment of risk factors for acute pancreatitis not mentioned | Yes, both groups used drug use information from computerised pharmacy database containing date of prescription filled and supplied to determine exposure to sitagliptin or exenatide, and patient with exposure after index diagnosis of acute pancreatitis counted as unexposed | Logistic regression model used control for matching variables, potential confounders specified a priori and identifiable in claims data, and metformin exposure during same period | Both groups had same rate of missing information on sex |
| Giorda (2013)95 | Patients with type 2 diabetes identified as at least 1 dose of any drug to treat diabetes and patients with type 1 diabetes excluded by ICD-9 code ( 250.x1 or 250.x3) | Yes, cases identified by having at least one discharge for acute pancreatitis (ICD-9 code 577.0 discharge diagnosis at any time after first exposure to antidiabetic drugs) | Each case randomly selected four controls from same population source, matched for year of birth, sex, and year of first exposure to antidiabetic drugs | Patients with no acute pancreatitis | Incretins selected by anatomical therapeutic chemical (ATC) classification system (ATC codes A10BH01 and A10BD07 (sitagliptin), A10BH02 and A10BD08 (vildagliptin), A10BH03 (saxagliptin), A10BX04 (exenatide), and A10BX07 (liraglutide)) | Potential confounders identified from ICD-9 codes, such as chronic or acute pancreatitis (excluding episode of index case (ICD-9 code 577.0)), gallstones, alcohol misuse, hypertriglyceridaemia, obesity, biliary tract or pancreatic cancers, cardio vascular diseases, and diabetic retinopathy | Yes, both cases and controls who had been prescribed incretins identified with regional drug database | Logistic regression model built to control for confounders, including past history of pancreatitis, gallstones, alcohol use, hypertrigly ceridaemia, obesity, biliary tract or pancreatic cancer, cardiovascular disease, and metformin or glibenclamide use | Authors did not mention completeness of outcome and exposure variable data in database |