Skip to main content
SpringerLink
Log in

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

  • Original Research Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

Introduction

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.

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Castellsague J, Riera-Guardia N, Calingaert B, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35:1127–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Andrade SE, Gurwitz JH, Chan KA, et al. Validation of diagnoses of peptic ulcers and bleeding from administrative databases: a multi-health maintenance organization study. J Clin Epidemiol. 2002;55:310–3.

    Article  PubMed  Google Scholar 

  3. Cattaruzzi C, Troncon MG, Agostinis L, Garcia Rodriguez LA. Positive predictive value of ICD-9th codes for upper gastrointestinal bleeding and perforation in the Sistema Informativo Sanitario Regionale database. J Clin Epidemiol. 1999;52:499–502.

    Article  CAS  PubMed  Google Scholar 

  4. Lopushinsky SR, Covarrubia KA, Rabeneck L, Austin PC, Urbach DR. Accuracy of administrative health data for the diagnosis of upper gastrointestinal diseases. Surg Endosc. 2007;21:1733–7.

    Article  CAS  PubMed  Google Scholar 

  5. Margulis AV, Garcia Rodriguez LA, Hernandez-Diaz S. Positive predictive value of computerized medical records for uncomplicated and complicated upper gastrointestinal ulcer. Pharmacoepidemiol Drug Saf. 2009;18:900–9.

    Article  PubMed  Google Scholar 

  6. Raiford DS, Perez Gutthann S, Garcia Rodriguez LA. Positive predictive value of ICD-9 codes in the identification of cases of complicated peptic ulcer disease in the Saskatchewan hospital automated database. Epidemiology. 1996;7:101–4.

    Article  CAS  PubMed  Google Scholar 

  7. Wahl PM, Rodgers K, Schneeweiss S, Gage BF, Butler J, Wilmer C, Nash M, Esper G, Gitlin N, Osborn N, Short LJ, Bohn RL. Validation of claims-based diagnostic and procedure codes for cardiovascular and gastrointestinal serious adverse events in a commercially-insured population. Pharmacoepidemiol Drug Saf. 2010;19:596–603.

    Article  PubMed  Google Scholar 

  8. Cunningham A, Stein CM, Chung CP, Daugherty JR, Smalley WE, Ray WA. An automated database case definition for serious bleeding related to oral anticoagulant use. Pharmacoepidemiol Drug Saf. 2011;20:560–6.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Platt R, Carnahan RM, Brown JS, Chrischilles E, Curtis LH, Hennessy S, Nelson JC, Racoosin JA, Robb M, Schneeweiss S, Toh S, Weiner MG. The U.S. Food and Drug Administration’s Mini-Sentinel program: status and direction. Pharmacoepidemiol Drug Saf. 2012;21(Suppl 1):1–8.

    PubMed  Google Scholar 

  10. Curtis LH, Weiner MG, Boudreau DM, Cooper WO, Daniel GW, Nair VP, Raebel MA, Beaulieu NU, Rosofsky R, Woodworth TS, Brown JS. Design considerations, architecture, and use of the Mini-Sentinel distributed data system. Pharmacoepidemiol Drug Saf. 2012;21(Suppl 1):23–31.

    Article  PubMed  Google Scholar 

  11. Raebel MA, Haynes K, Woodworth TS, Saylor G, Cavagnaro E, Coughlin KO, Curtis LH, Weiner MG, Archdeacon P, Brown JS. Electronic clinical laboratory test results data tables: lessons from Mini-Sentinel. Pharmacoepidemiol Drug Saf. 2014;23:609–18.

    Article  PubMed  Google Scholar 

  12. Mini-sentinel surveillance plan. Mini-sentinel prospective routine observational monitoring program tools (PROMPT): rivaroxaban surveillance. Version 3. 2015. http://www.mini-sentinel.org/work_products/Assessments/Mini-Sentinel_PROMPT_Rivaroxaban-Surveillance-Plan.pdf.

  13. Mini-sentinel medical product assessment. A protocol for assessment of dabigatran. Version 3. 2015. http://www.mini-sentinel.org/work_products/Assessments/Mini-Sentinel_Protocol-for-Assessment-of-Dabigatran.pdf. Accessed 3 Feb 2016.

  14. Sentinel Overview and Description of the Common Data Model v5.0.1. 2015. http://www.mini-sentinel.org/work_products/Data_Activities/Sentinel_Common-Data-Model.pdf.

  15. SCDM Clinical Data Elements Workgroup. Sentinel Common Data Model. Laboratory Result Table Documentation. Version 1.0. 2015. http://www.mini-sentinel.org/work_products/Data_Activities/Sentinel_Common-Data-Model_Laboratory-Result-Table-Documentation.pdf.

  16. Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011;123:2736–47.

    Article  PubMed  Google Scholar 

  17. Rao SV, O’Grady K, Pieper KS, Granger CB, Newby LK, Van de Werf F, Mahaffey KW, Califf RM, Harrington RA. Impact of bleeding severity on clinical outcomes among patients with acute coronary syndromes. Am J Cardiol. 2005;96:1200–6.

    Article  PubMed  Google Scholar 

  18. Bovill EG, Terrin ML, Stump DC, Berke AD, Frederick M, Collen D, Feit F, Gore JM, Hillis LD, Lambrew CT, Leiboff R, Mann KG, Markis JE, Pratt CM, Sharkey SW, Sopko G, Tracy RP, Chesebro JH, For the TIMI Investigators. Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial. Ann Intern Med. 1991;115:256–65.

  19. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM, TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001–15.

    Article  CAS  PubMed  Google Scholar 

  20. Moride Y, Abenhaim L. Evidence of the depletion of susceptibles effect in non-experimental pharmacoepidemiologic research. J Clin Epidemiol. 1994;47:731–7.

    Article  CAS  PubMed  Google Scholar 

  21. van Staa TP, Abenhaim L, Leufkens H. A study of the effects of exposure misclassification due to the time-window design in pharmacoepidemiologic studies. J Clin Epidemiol. 1994;47:183–9.

    Article  PubMed  Google Scholar 

  22. Ray WA. Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol. 2003;158:915–20.

    Article  PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 1620 Tremont Street (Suite 3030), Boston, MA, 02120, USA

    Elisabetta Patorno & Joshua J. Gagne

  2. Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA

    Christine Y. Lu

  3. HealthCore, Wilmington, DE, USA

    Kevin Haynes

  4. Kaiser Permanente Colorado Institute for Health Research, Denver, CO, USA

    Andrew T. Sterrett & Marsha A. Raebel

  5. University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Jason Roy & Xingmei Wang

Authors
  1. Elisabetta Patorno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joshua J. Gagne
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christine Y. Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kevin Haynes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrew T. Sterrett
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jason Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xingmei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marsha A. Raebel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elisabetta Patorno.

Ethics declarations

Funding

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.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 2882 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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). https://doi.org/10.1007/s40264-016-0472-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40264-016-0472-3

Keywords

Search

Navigation