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The Role of Hemoglobin Laboratory Test Results for the Detection of Upper Gastrointestinal Bleeding Outcomes Resulting from the Use of Medications in Observational Studies

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The identification of upper gastrointestinal (UGI) bleeding and perforated ulcers in claims data typically relies on inpatient diagnoses. The use of hemoglobin laboratory results might increase the detection of UGI events that do not lead to hospitalization.


Our objective was to evaluate whether hemoglobin results increase UGI outcome identification in electronic databases, using non-steroidal anti-inflammatory drugs (NSAIDs) as a test case.


From three data partner sites within the Mini-Sentinel Distributed Database, we identified NSAID initiators aged ≥18 years between 2008 and 2013. Numbers of events and risks within 30 days after NSAID initiation were calculated for four mutually exclusive outcomes: (1) inpatient UGI diagnosis of bleeding or gastric ulcer (standard claims-based definition without laboratory results); (2) non-inpatient UGI diagnosis AND ≥3 g/dl hemoglobin decrease; (3) ≥3 g/dl hemoglobin decrease without UGI diagnosis in any clinical setting; (4) non-inpatient UGI diagnosis, without ≥3 g/dl hemoglobin decrease.


We identified 2,289,772 NSAID initiators across three sites. Overall, 45.3% had one or more hemoglobin result available within 365 days before or 30 days after NSAID initiation; only 6.8% had results before and after. Of 7637 potential outcomes identified, outcome 1 accounted for 21.7%, outcome 2 for 0.8%, outcome 3 for 34.3%, and outcome 4 for 43.3%. Potential cases identified by outcome 3 were largely not suggestive of UGI events. Outcomes 1, 2, and 4 had similar distributions of specific UGI diagnoses.


Using available hemoglobin result values combined with non-inpatient UGI diagnoses identified few additional UGI cases. Non-inpatient UGI diagnostic codes may increase outcome detection but would require validation.

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Author contributions

EP, JJG, and MAR were involved in all parts of the study. CYL and KH were involved in designing the study and revising the manuscript. ATS, JR, and XW were involved in data analysis and revising the manuscript.

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Correspondence to Elisabetta Patorno.

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The Mini-Sentinel program is funded by the US FDA through contract HHSF22301012T-0008 under Master Agreement HHSF223020091006I from the Department of Health and Human Services.

Conflict of interest

The following authors received salary support from their institutions for this work conducted under contract HHSF22301012T-0008: Elisabetta Patorno, Josh J. Gagne, Christine Y. Lu, Kevin Haynes, Andrew T. Sterrett, Jason Roy, Xingmei Wang, and Marsha A. Raebel.

Ethical approval

The Health and Human Services Office of Human Research Protections determined that the Common Rule does not apply to activities included in the FDA’s Sentinel Initiative. This assessment also applies to Mini-Sentinel activities such as the work detailed in this paper, as Mini-Sentinel is part of the Sentinel Initiative. Because Mini-Sentinel activities are public health activities in support of FDA’s public health mission, they are not under the purview of institutional review boards or privacy boards.

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Patorno, E., Gagne, J.J., Lu, C.Y. et al. The Role of Hemoglobin Laboratory Test Results for the Detection of Upper Gastrointestinal Bleeding Outcomes Resulting from the Use of Medications in Observational Studies. Drug Saf 40, 91–100 (2017).

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