Comparison of Different Case-Crossover Variants in Handling Exposure-Time Trend or Persistent-User Bias: Using Dipeptidyl Peptidase-4 Inhibitors and the Risk of Heart Failure as an Example
Journal
Value in Health
Journal Volume
23
Journal Issue
2
Pages
217-226
Date Issued
2020
Author(s)
Abstract
Objectives: Inappropriate use of the case-crossover design, which is efficient for examining associations between brief exposure and abrupt outcomes, in evaluating the effects of medications in the presence of exposure-time trends or persistent drug use may generate spurious associations. We compared different approaches to adjusting for these sources of bias by examining the risk of heart failure hospitalization (HFH) associated with dipeptidyl peptidase-4 (DPP-4) inhibitors. Overall, existing evidence does not suggest a higher risk of HFH associated with DPP-4 inhibitors; however, case-crossover analyses of these medications may be susceptible to bias. Methods: We conducted case-crossover; age, sex, risk-set (ASR) matched case-time-control; disease risk score (DRS)-matched case-time-control; and case-case-time-control analyses to assess the association between DPP-4 inhibitors and HFH among patients with diabetes mellitus (DM) in a population-based Taiwanese database. We also examined metformin and sulfonylureas, both with assumed null associations. Results: Among 362 022 DM patients, 4105 (case-crossover), 4103 (ASR-matched case-time-control), 3957 (DRS-matched case-time-control), and 2812 (case-case-time-control) HFH cases were identified. The OR for DPP-4 inhibitors and HFH was elevated in the case-crossover analysis (1.52; 95% confidence interval [95% CI] 0.95–2.42). The ASR-matched case-time control, DRS-matched case-time-control, and case-case-time control analyses yielded near-null associations (0.90 [95% CI 0.45–1.83], 0.96 [95% CI 0.46–2.02], and 0.92 [95% CI 0.39–2.21], respectively). Null effects were observed for metformin across designs and for sulfonylureas in the case-case-time control analysis. Conclusions: Our case-crossover analysis suggested DPP-4 inhibitors may be associated with HFH; however, each method for adjusting for exposure-time and persistent user bias attenuated the findings. The case-case-time-control analysis had the least precision. ? 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research
Subjects
case-crossover variant designs; diabetes; dipeptidyl peptidase-4 inhibitors; heart failure; pharmacoepidemiology; self-controlled study design
SDGs
Other Subjects
acetylsalicylic acid; alpha adrenergic receptor blocking agent; alpha glucosidase inhibitor; angiotensin receptor antagonist; antibiotic agent; antidepressant agent; antidiabetic agent; beta adrenergic receptor blocking agent; beta adrenergic receptor stimulating agent; calcium channel blocking agent; cholinergic receptor blocking agent; clopidogrel; corticosteroid; digitalis glycoside; dipeptidyl carboxypeptidase inhibitor; dipeptidyl peptidase IV inhibitor; diuretic agent; fibric acid derivative; hydroxymethylglutaryl coenzyme A reductase inhibitor; insulin; linagliptin; metformin; nitric acid derivative; nonsteroid antiinflammatory agent; pioglitazone; saxagliptin; sulfonylurea derivative; vildagliptin; warfarin; xanthine derivative; dipeptidyl peptidase IV inhibitor; metformin; sulfonylurea derivative; age; aged; Article; cardiovascular risk; case control study; case crossover design; cohort analysis; controlled study; data base; diabetic patient; disease association; disease risk assessment; drug exposure; evidence based practice; female; first wave bias; heart failure; high risk population; hospitalization; human; intermethod comparison; major clinical study; male; methodology; non insulin dependent diabetes mellitus; persistent user bias; priority journal; sex; statistical bias; susceptible population; Taiwan; trend study; comparative study; factual database; heart failure; hospitalization; incidence; middle aged; non insulin dependent diabetes mellitus; pathophysiology; pharmacoepidemiology; risk assessment; risk factor; statistical bias; time factor; treatment outcome; very elderly; Aged; Aged, 80 and over; Bias; Case-Control Studies; Databases, Factual; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Heart Failure; Hospitalization; Humans; Incidence; Male; Metformin; Middle Aged; Pharmacoepidemiology; Risk Assessment; Risk Factors; Sulfonylurea Compounds; Taiwan; Time Factors; Treatment Outcome
Publisher
Elsevier Ltd
Type
journal article