Academic Journal
How Negative Controls Are Used in Pharmacoepidemiology: A Methodological Scoping Review of Real-World Observational Studies of Glucagon-Like Peptide-1 Receptor Agonists.
| Τίτλος: | How Negative Controls Are Used in Pharmacoepidemiology: A Methodological Scoping Review of Real-World Observational Studies of Glucagon-Like Peptide-1 Receptor Agonists. |
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| Συγγραφείς: | Li Z; Department of Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, Houston, Texas, USA., Huang Y; Department of Pharmacy Administration, School of Pharmacy, University of Mississippi, Mississippi, USA.; Center for Pharmaceutical Marketing & Management, School of Pharmacy, University of Mississippi, Mississippi, USA., Chen H; Department of Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, Houston, Texas, USA., Li J; Department of Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, Houston, Texas, USA. |
| Πηγή: | Pharmacoepidemiology and drug safety [Pharmacoepidemiol Drug Saf] 2026 Jul; Vol. 35 (7), pp. e70420. |
| Τύπος έκδοσης: | Journal Article; Scoping Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley Country of Publication: England NLM ID: 9208369 Publication Model: Print Cited Medium: Internet ISSN: 1099-1557 (Electronic) Linking ISSN: 10538569 NLM ISO Abbreviation: Pharmacoepidemiol Drug Saf Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Chichester, West Sussex : Wiley, 1992- |
| Ιατρικοί όροι (MeSH): | Pharmacoepidemiology*/methods , Pharmacoepidemiology*/standards , Observational Studies as Topic*/methods , Observational Studies as Topic*/standards , Hypoglycemic Agents*/therapeutic use , Glucagon-Like Peptide-1 Receptor Agonists*, Humans ; Bias ; Confounding Factors, Epidemiologic ; Research Design |
| Περίληψη: | Negative controls (NCs) are increasingly used in real-world observational studies to detect residual confounding and systematic bias, but their implementation and reporting remain heterogeneous in applied pharmacoepidemiology. We conducted a methodological scoping review to characterize how NCs were selected, implemented, reported, and interpreted in real-world studies evaluating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for non-indicated clinical outcomes. We systematically searched PubMed and Embase from database inception through November 2025 and additionally screened reference lists of included studies. Eligible studies used real-world data, applied an observational analytic framework to evaluate GLP-1 RAs, focused on non-indicated outcomes, and explicitly incorporated NCs for bias detection, falsification, validation, or empirical calibration. Among 489 records identified, 42 studies met the inclusion criteria. Most studies were cohort-based and were conducted in diabetes-related populations using electronic health records or administrative claims. Negative control outcomes (NCOs) were the dominant approach, whereas negative control exposures (NCEs), positive controls, and empirical calibration were less common. An explicit rationale for NC selection was reported in most studies, but none of the included studies explicitly discussed the assumptions underlying NC analysis. Most NC findings were reported as null or consistent with expectations, and were primarily used to support validity or robustness rather than to materially alter interpretation. Overall, our findings suggest that the current use of NCs in GLP-1 RA observational research has increased, while standardized implementation and reporting have lagged. Greater transparency regarding why NCs were selected, what source of bias they were intended to probe, how results were interpreted, and whether they changed analytic conclusions may improve the credibility and interpretability of real-world evidence in this rapidly evolving therapeutic area. (© 2026 John Wiley & Sons Ltd.) |
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| Contributed Indexing: | Keywords: GLP‐1 receptor agonists; empirical calibration; negative controls; pharmacoepidemiology; real‐world evidence; residual confounding; scoping review Local Abstract: [plain-language-summary] Studies that use real‐world health data are increasingly relied upon to evaluate the benefits and risks of medications, but these studies can be affected by hidden sources of bias. One approach to detecting such bias is the use of “negative controls,” which are outcomes or exposures that are not expected to be causally related to the treatment being studied but may still reflect similar sources of confounding or bias. In this review, we examined how negative controls have been used in observational studies of glucagon‐like peptide‐1 receptor agonists, a widely prescribed class of medications for diabetes and obesity. We found that negative control outcomes were commonly used, but negative control exposures, positive controls, and empirical calibration were much less common. Although many studies briefly explained why negative control was chosen, none explicitly discussed the assumptions required for interpreting negative control findings. In most studies, negative control results were used mainly to support the credibility of the main findings rather than to change conclusions. These results suggest that negative controls are increasingly used in GLP‐1 RA research, but clearer and more consistent reporting is needed to improve how readers interpret these analyses. |
| Substance Nomenclature: | 0 (Glucagon-Like Peptide-1 Receptor Agonists) 0 (Hypoglycemic Agents) |
| Entry Date(s): | Date Created: 20260710 Date Completed: 20260711 Latest Revision: 20260731 |
| Update Code: | 20260801 |
| PubMed Central ID: | PMC13354716 |
| DOI: | 10.1002/pds.70420 |
| PMID: | 42432825 |
| Βάση Δεδομένων: | MEDLINE |
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