Research and Reporting Methods

12 March 2019

Graphical Depiction of Longitudinal Study Designs in Health Care Databases

Authors: Sebastian Schneeweiss, MD, ScD, Jeremy A. Rassen, ScD, Jeffrey S. Brown, PhD, Kenneth J. Rothman, DrPH, Laura Happe, PharmD, MPH, Peter Arlett, MD, Gerald Dal Pan, MD, MHS, Wim Goettsch, PhD, William Murk, PhD, and Shirley V. Wang, PhDAuthor, Article, & Disclosure Information

Publication: Annals of Internal Medicine

Volume 170, Number 6

https://doi.org/10.7326/M18-3079

Abstract

Pharmacoepidemiologic and pharmacoeconomic analysis of health care databases has become a vital source of evidence to support health care decision making and efficient management of health care organizations. However, decision makers often consider studies done in nonrandomized health care databases more difficult to review than randomized trials because many design choices need to be considered. This is perceived as an important barrier to decision making about the effectiveness and safety of medical products. Design flaws in longitudinal database studies are avoidable but can be unintentionally obscured in the convoluted prose of methods sections, which often lack specificity. We propose a simple framework of graphical representation that visualizes study design implementations in a comprehensive, unambiguous, and intuitive way; contains a level of detail that enables reproduction of key study design variables; and uses standardized structure and terminology to simplify review and communication to a broad audience of decision makers. Visualization of design details will make database studies more reproducible, quicker to review, and easier to communicate to a broad audience of decision makers.

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References

1.

Ball R, Robb M, Anderson SA, Dal Pan G. The FDA's sentinel initiative—a comprehensive approach to medical product surveillance. Clin Pharmacol Ther. 2016;99:265-8. [PMID: 26667601] doi: 10.1002/cpt.320

2.

Makady A, Ham RT, de Boer A, Hillege H, Klungel O, Goettsch W; GetReal Workpackage 1. Policies for use of real-world data in health technology assessment (HTA): a comparative study of six HTA agencies. Value Health. 2017;20:520-32. [PMID: 28407993] doi: 10.1016/j.jval.2016.12.003

3.

Hampson G, Towse A, Dreitlein B, Henshall C, Pearson SD. Real world evidence for coverage decisions: opportunities and challenges. A report from the 2017 ICER membership policy summit. Boston: Institute for Clinical and Economic Review; 2018.

4.

Malone DC, Brown M, Hurwitz JT, Peters L, Graff JS. Real-world evidence: useful in the real world of US payer decision making? How? When? And what studies? Value Health. 2018;21:326-33. [PMID: 29566840] doi: 10.1016/j.jval.2017.08.3013

5.

Hemkens LG, Contopoulos-Ioannidis DG, Ioannidis JP. Agreement of treatment effects for mortality from routinely collected data and subsequent randomized trials: meta-epidemiological survey. BMJ. 2016;352:i493. [PMID: 26858277] doi: 10.1136/bmj.i493

6.

Maclure M, Schneeweiss S. Causation of bias: the episcope. Epidemiology. 2001;12:114-22. [PMID: 11138805]

7.

Suissa S. Immortal time bias in observational studies of drug effects. Pharmacoepidemiol Drug Saf. 2007;16:241-9. [PMID: 17252614]

8.

Gruber S, Chakravarty A, Heckbert SR, Levenson M, Martin D, Nelson JC, et al. Design and analysis choices for safety surveillance evaluations need to be tuned to the specifics of the hypothesized drug-outcome association. Pharmacoepidemiol Drug Saf. 2016;25:973-81. [PMID: 27418432] doi: 10.1002/pds.4065

9.

Jena AB, Goldman D, Weaver L, Karaca-Mandic P. Opioid prescribing by multiple providers in Medicare: retrospective observational study of insurance claims. BMJ. 2014;348:g1393. [PMID: 24553363] doi: 10.1136/bmj.g1393

10.

Suissa S. Immeasurable time bias in observational studies of drug effects on mortality. Am J Epidemiol. 2008;168:329-35. [PMID: 18515793] doi: 10.1093/aje/kwn135

11.

Moride Y, Abenhaim L, Yola M, Lucein A. Evidence of the depletion of susceptibles effect in non-experimental pharmacoepidemiologic research. J Clin Epidemiol. 1994;47:731-7. [PMID: 7722586]

12.

Hernán MA, Alonso A, Logan R, Grodstein F, Michels KB, Willett WC, et al. Observational studies analyzed like randomized experiments: an application to postmenopausal hormone therapy and coronary heart disease. Epidemiology. 2008;19:766-79. [PMID: 18854702] doi: 10.1097/EDE.0b013e3181875e61

13.

Goodman SN, Schneeweiss S, Baiocchi M. Using design thinking to differentiate useful from misleading evidence in observational research [Editorial]. JAMA. 2017;317:705-7. [PMID: 28241335] doi: 10.1001/jama.2016.19970

14.

Langan SM, Schmidt SA, Wing K, Ehrenstein V, Nicholls SG, Filion KB, et al. The reporting of studies conducted using observational routinely collected health data statement for pharmacoepidemiology (RECORD-PE). BMJ. 2018;363:k3532. [PMID: 30429167] doi: 10.1136/bmj.k3532

15.

Berger ML, Sox H, Willke RJ, Brixner DL, Eichler HG, Goettsch W, et al. Good practices for real-world data studies of treatment and/or comparative effectiveness: recommendations from the joint ISPOR-ISPE Special Task Force on real-world evidence in health care decision making. Pharmacoepidemiol Drug Saf. 2017;26:1033-9. [PMID: 28913966] doi: 10.1002/pds.4297

16.

Wang SV, Schneeweiss S, Berger ML, Brown J, de Vries F, Douglas I, et al; joint ISPE-ISPOR Special Task Force on Real World Evidence in Health Care Decision Making. Reporting to improve reproducibility and facilitate validity assessment for healthcare database studies V1.0. Pharmacoepidemiol Drug Saf. 2017;26:1018-32. [PMID: 28913963] doi: 10.1002/pds.4295

17.

Rothman KJ, Greenland S, Lash TL. Modern Epidemiology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2008.

18.

Gini R, Schuemie M, Brown J, Ryan P, Vacchi E, Coppola M, et al. Data extraction and management in networks of observational health care databases for scientific research: a comparison of EU-ADR, OMOP, Mini-Sentinel and MATRICE strategies. EGEMS (Wash DC). 2016;4:1189. [PMID: 27014709] doi: 10.13063/2327-9214.1189

19.

Curtis LH, Weiner MG, Boudreau DM, Cooper WO, Daniel GW, Nair VP, et al. Design considerations, architecture, and use of the Mini-Sentinel distributed data system. Pharmacoepidemiol Drug Saf. 2012;21 Suppl 1:23-31. [PMID: 22262590] doi: 10.1002/pds.2336

20.

Matcho A, Ryan P, Fife D, Reich C. Fidelity assessment of a Clinical Practice Research Datalink conversion to the OMOP common data model. Drug Saf. 2014;37:945-59. [PMID: 25187016] doi: 10.1007/s40264-014-0214-3

21.

Schneeweiss S. Automated data-adaptive analytics for electronic healthcare data to study causal treatment effects. Clin Epidemiol. 2018;10:771-88. [PMID: 30013400] doi: 10.2147/CLEP.S166545

22.

Hartzema AG, Racoosin JA, MaCurdy TE, Gibbs JM, Kelman JA. Utilizing Medicare claims data for real-time drug safety evaluations: is it feasible? Pharmacoepidemiol Drug Saf. 2011;20:684-8. [PMID: 21847800]

23.

Hernán MA, Hernández-Díaz S. Beyond the intention-to-treat in comparative effectiveness research. Clin Trials. 2012;9:48-55. [PMID: 21948059] doi: 10.1177/1740774511420743

24.

Schneeweiss S. A basic study design for expedited safety signal evaluation based on electronic healthcare data. Pharmacoepidemiol Drug Saf. 2010;19:858-68. [PMID: 20681003] doi: 10.1002/pds.1926

25.

Brunelli SM, Gagne JJ, Huybrechts KF, Wang SV, Patrick AR, Rothman KJ, et al. Estimation using all available covariate information versus a fixed look-back window for dichotomous covariates. Pharmacoepidemiol Drug Saf. 2013;22:542-50. [PMID: 23526818] doi: 10.1002/pds.3434

26.

Nakasian SS, Rassen JA, Franklin JM. Effects of expanding the look-back period to all available data in the assessment of covariates. Pharmacoepidemiol Drug Saf. 2017;26:890-9. [PMID: 28397352] doi: 10.1002/pds.4210

27.

Rassen JA, Choudhry NK, Avorn J, Schneeweiss S. Cardiovascular outcomes and mortality in patients using clopidogrel with proton pump inhibitors after percutaneous coronary intervention or acute coronary syndrome. Circulation. 2009;120:2322-9. [PMID: 19933932] doi: 10.1161/CIRCULATIONAHA.109.873497

28.

Suissa S. Immortal time bias in pharmaco-epidemiology. Am J Epidemiol. 2008;167:492-9. [PMID: 18056625]

29.

Rothman KJ. Induction and latent periods. Am J Epidemiol. 1981;114:253-9. [PMID: 7304560]

30.

Layton JB, Kshirsagar AV, Simpson RJ Jr, Pate V, Jonsson Funk M, Stürmer T, et al. Effect of statin use on acute kidney injury risk following coronary artery bypass grafting. Am J Cardiol. 2013;111:823-8. [PMID: 23273532] doi: 10.1016/j.amjcard.2012.11.047

31.

Kim SC, Solomon DH, Rogers JR, Gale S, Klearman M, Sarsour K, et al. Cardiovascular safety of tocilizumab versus tumor necrosis factor inhibitors in patients with rheumatoid arthritis: a multi-database cohort study. Arthritis Rheumatol. 2017;69:1154-64. [PMID: 28245350] doi: 10.1002/art.40084

32.

Bykov K, Schneeweiss S, Glynn RJ, Mittleman MA, Bates DW, Gagne JJ. Updating the evidence of the interaction between clopidogrel and CYP2C19-inhibiting selective serotonin reuptake inhibitors: a cohort study and meta-analysis. Drug Saf. 2017;40:923-32. [PMID: 28623527] doi: 10.1007/s40264-017-0556-8

33.

Brookhart MA. Counterpoint: the treatment decision design. Am J Epidemiol. 2015;182:840-5. [PMID: 26507307] doi: 10.1093/aje/kwv214

34.

Douglas IJ, Langham J, Bhaskaran K, Brauer R, Smeeth L. Orlistat and the risk of acute liver injury: self controlled case series study in UK Clinical Practice Research Datalink. BMJ. 2013;346:f1936. [PMID: 23585064] doi: 10.1136/bmj.f1936

35.

Toh S, Reichman ME, Houstoun M, Ross Southworth M, Ding X, Hernandez AF, et al. Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system. Arch Intern Med. 2012;172:1582-9. [PMID: 23147456] doi: 10.1001/2013.jamainternmed.34

36.

Gagne JJ, Wang SV, Fox M, Lash T, Eddings W, Dublin S, et al. Mini-Sentinel methods: analytical methods to assess robustness of drug safety monitoring results. 2015. Accessed at www.sentinelinitiative.org/sites/default/files/Methods/Mini-Sentinel_Methods_Analytical-Methods-to-Assess-Robustness-of-Drug-Safety-Monitoring-Results_0.pdf on 14 January 2019.

37.

Schneeweiss S, Patrick AR, Stürmer T, Brookhart MA, Avorn J, Maclure M, et al. Increasing levels of restriction in pharmacoepidemiologic database studies of elderly and comparison with randomized trial results. Med Care. 2007;45:S131-42. [PMID: 17909372]

38.

Azoulay L, Yin H, Filion KB, Assayag J, Majdan A, Pollak MN, et al. The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study. BMJ. 2012;344:e3645. [PMID: 22653981] doi: 10.1136/bmj.e3645

39.

Gagne JJ, Glynn RJ, Avorn J, Levin R, Schneeweiss S. A combined comorbidity score predicted mortality in elderly patients better than existing scores. J Clin Epidemiol. 2011;64:749-59. [PMID: 21208778] doi: 10.1016/j.jclinepi.2010.10.004

40.

Romano PS, Roos LL, Jollis JG. Adapting a clinical comorbidity index for use with ICD-9-CM administrative data: differing perspectives. J Clin Epidemiol. 1993;46:1075-9. [PMID: 8410092]

41.

Maclure M, Fireman B, Nelson JC, Hua W, Shoaibi A, Paredes A, et al. When should case-only designs be used for safety monitoring of medical products? Pharmacoepidemiol Drug Saf. 2012;21 Suppl 1:50-61. [PMID: 22262593] doi: 10.1002/pds.2330

42.

Maclure M. The case-crossover design: a method for studying transient effects on the risk of acute events. Am J Epidemiol. 1991;133:144-53. [PMID: 1985444]

43.

Baker MA, Lieu TA, Li L, Hua W, Qiang Y, Kawai AT, et al. A vaccine study design selection framework for the postlicensure rapid immunization safety monitoring program. Am J Epidemiol. 2015;181:608-18. [PMID: 25769306] doi: 10.1093/aje/kwu322

44.

Whitaker HJ, Farrington CP, Spiessens B, Musonda P. Tutorial in biostatistics: the self-controlled case series method. Stat Med. 2006;25:1768-97. [PMID: 16220518]

45.

Hallas J. Evidence of depression provoked by cardiovascular medication: a prescription sequence symmetry analysis. Epidemiology. 1996;7:478-84. [PMID: 8862977]

46.

Meier CR, Jick SS, Derby LE, Vasilakis C, Jick H. Acute respiratory-tract infections and risk of first-time acute myocardial infarction. Lancet. 1998;351:1467-71. [PMID: 9605802]

47.

Wang SV, Abdurrob A, Spoendlin J, Lewis E, Newcomer SR, Fireman B, et al. Methods for addressing “innocent bystanders” when evaluating safety of concomitant vaccines. Pharmacoepidemiol Drug Saf. 2018;27:405-12. [PMID: 29441647] doi: 10.1002/pds.4399

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Information & Authors

Information

Published In

cover image Annals of Internal Medicine

Annals of Internal Medicine

Volume 170 • Number 6 • 19 March 2019

Pages: 398 - 406

History

Published online: 12 March 2019

Published in issue: 19 March 2019

Keywords

Copyright

© 2019 American College of Physicians.

Authors

Affiliations

Sebastian Schneeweiss, MD, ScD

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (S.S., S.V.W.)

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Jeremy A. Rassen, ScD

Aetion, New York, New York (J.A.R., W.M.)

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Jeffrey S. Brown, PhD

Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, Massachusetts (J.S.B.)

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Kenneth J. Rothman, DrPH

RTI Health Solutions, Durham, North Carolina (K.J.R.)

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Laura Happe, PharmD, MPH

Journal of Managed Care and Specialty Pharmacy, Alexandria, Virginia (L.H.)

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Peter Arlett, MD

European Medicines Agency, London, United Kingdom (P.A.)

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Gerald Dal Pan, MD, MHS

U.S. Food and Drug Administration, Silver Spring, Maryland (G.D.)

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Wim Goettsch, PhD

The National Health Care Institute, Diemen, and Utrecht University, Utrecht, the Netherlands (W.G.)

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William Murk, PhD

Aetion, New York, New York (J.A.R., W.M.)

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Shirley V. Wang, PhD

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (S.S., S.V.W.)

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Disclaimer: The views expressed in this article are those of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or the U.S. Food and Drug Administration.

Financial Support: Writing of this manuscript was supported by internal funds from the Division of Pharmacoepidemiology and Pharmacoeconomics of the Department of Medicine at Brigham and Women's Hospital and Harvard Medical School.

Disclosures: Dr. Schneeweiss reports grants from the U.S. Food and Drug Administration, the Patient-Centered Outcomes Research Institute, and the National Institutes of Health during the conduct of the study and personal fees from WHISCON, equity in Aetion, and being principal investigator of research contracts to Brigham and Women's Hospital from Bayer, Vertex, Boehringer Ingelheim, and the Arnold Foundation outside the submitted work. In addition, Dr. Schneeweiss has a patent for a database system for analysis of longitudinal data sets, with no royalties paid. Dr. Rassen reports that he is an employee of and has an ownership stake in Aetion outside the submitted work. Dr. Murk reports that he is an employee of and holds stock options in Aetion outside the submitted work. Dr. Wang reports being principal investigator on research contracts to Brigham and Women's Hospital from Boehringer Ingelheim, Novartis, and Johnson & Johnson, and the Arnold Foundation outside the submitted work. She is also a consultant to Aetion for unrelated work. Dr. Arlett is a full-time employee of the European Medicines Agency. Dr. Dal Pan is a full-time employee of the Food and Drug Administration. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-3079.

Corresponding Author: Shirley V. Wang, PhD, 1620 Tremont Street, Suite 303, Boston, MA 02120; e-mail, [email protected].

Current Author Addresses: Drs. Schneeweiss and Wang: 1620 Tremont Street, Suite 303, Boston, MA 02120.

Drs. Rassen and Murk: 1441 Broadway 20th Floor, New York, NY 10018.

Dr. Brown: 401 Park Drive, Suite 401 East, Boston, MA 02215.

Dr. Rothman: 307 Waverley Oaks Road, Suite 101, Waltham, MA 02452-8413.

Dr. Happe: JMCP, 675 North Washington Street, Suite 220, Alexandria, VA 22314.

Dr. Arlett: Department of Pharmacovigilance and Epidemiology, European Medicines Agency, 30 Churchill Place, London E14 5EU, United Kingdom.

Dr. Dal Pan: 10903 New Hampshire Avenue, Silver Spring, MD 20993.

Dr. Goettsch: Zorginstituut Nederland, Health Care Insurance Board Health Care TA Program, Postbus 320, NL-1110 AH Diemen, the Netherlands.

Author Contributions: Conception and design: S. Schneeweiss, S.V. Wang, J.A. Rassen.

Analysis and interpretation of the data: S. Schneeweiss, S.V. Wang.

Drafting of the article: S. Schneeweiss, J.A. Rassen, J.S. Brown, K.J. Rothman, L. Happe, P. Arlett, G. Dal Pan, W. Goettsch, W. Murk, S.V. Wang.

Critical revision of the article for important intellectual content: S. Schneeweiss, J.A. Rassen, J.S. Brown, K.J. Rothman, L. Happe, P. Arlett, G. Dal Pan, W. Goettsch, W. Murk, S.V. Wang.

Final approval of the article: S. Schneeweiss, J.A. Rassen, J.S. Brown, K.J. Rothman, L. Happe, P. Arlett, G. Dal Pan, W. Goettsch, W. Murk, S.V. Wang.

This article was published at Annals.org on 12 March 2019.

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Sebastian Schneeweiss, Jeremy A. Rassen, Jeffrey S. Brown, et al. Graphical Depiction of Longitudinal Study Designs in Health Care Databases. Ann Intern Med.2019;170:398-406. [Epub 12 March 2019]. doi:10.7326/M18-3079

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