Variation in methods, results and reporting in electronic health record-based studies evaluating routine care in gout: A systematic review

Autoři: Samantha S. R. Crossfield aff001;  Lana Yin Hui Lai aff001;  Sarah R. Kingsbury aff001;  Paul Baxter aff003;  Owen Johnson aff004;  Philip G. Conaghan aff001;  Mar Pujades-Rodriguez aff005
Působiště autorů: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom aff001;  NIHR Leeds Biomedical Research Centre, Leeds, United Kingdom aff002;  Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom aff003;  School of Computing, University of Leeds, Leeds, United Kingdom aff004;  Leeds Institute of Health Sciences, University of Leeds, Leeds, United Kingdom aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224272



To perform a systematic review examining the variation in methods, results, reporting and risk of bias in electronic health record (EHR)-based studies evaluating management of a common musculoskeletal disease, gout.


Two reviewers systematically searched MEDLINE, Scopus, Web of Science, CINAHL, PubMed, EMBASE and Google Scholar for all EHR-based studies published by February 2019 investigating gout pharmacological treatment. Information was extracted on study design, eligibility criteria, definitions, medication usage, effectiveness and safety data, comprehensiveness of reporting (RECORD), and Cochrane risk of bias (registered PROSPERO CRD42017065195).


We screened 5,603 titles/abstracts, 613 full-texts and selected 75 studies including 1.9M gout patients. Gout diagnosis was defined in 26 ways across the studies, most commonly using a single diagnostic code (n = 31, 41.3%). 48.4% did not specify a disease-free period before ‘incident’ diagnosis. Medication use was suboptimal and varied with disease definition while results regarding effectiveness and safety were broadly similar across studies despite variability in inclusion criteria. Comprehensiveness of reporting was variable, ranging from 73% (55/75) appropriately discussing the limitations of EHR data use, to 5% (4/75) reporting on key data cleaning steps. Risk of bias was generally low.


The wide variation in case definitions and medication-related analysis among EHR-based studies has implications for reported medication use. This is amplified by variable reporting comprehensiveness and the limited consideration of EHR-relevant biases (e.g. data adequacy) in study assessment tools. We recommend accounting for these biases and performing a sensitivity analysis on case definitions, and suggest changes to assessment tools to foster this.

Klíčová slova:

Data management – Diagnostic medicine – Drug therapy – Electronic medical records – Gout – Longitudinal studies – Nephrology – Systematic reviews


1. Murdoch TB, Detsky AS. The inevitable application of big data to health care. JAMA. 2013;309(13):1351–2. doi: 10.1001/jama.2013.393 23549579

2. Kuo CF, Grainge MJ, Zhang W, Doherty M. Global epidemiology of gout: prevalence, incidence and risk factors. Nature reviews Rheumatology. 2015 Nov;11(11):649–62. doi: 10.1038/nrrheum.2015.91 26150127

3. Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis care & research. 2012 Oct;64(10):1431–46.

4. Hui M, Carr A, Cameron S, Davenport G, Doherty M, Forrester H, et al. The British Society for Rheumatology Guideline for the Management of Gout. Rheumatology. 2017;56(7):1056–9. doi: 10.1093/rheumatology/kex150 28549195

5. Richette P, Doherty M, Pascual E, Barskova V, Becce F, Castaneda-Sanabria J, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Annals of the rheumatic diseases. 2016 Jul 25;76(1):29–42. doi: 10.1136/annrheumdis-2016-209707 27457514

6. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Eligibility for and prescription of urate-lowering treatment in patients with incident gout in England. JAMA. 2014;312(24):2684–6. doi: 10.1001/jama.2014.14484 25536262

7. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Annals of the rheumatic diseases. 2014 Apr;74(4):661–7. doi: 10.1136/annrheumdis-2013-204463 24431399

8. Oderda GM, Shiozawa A, Walsh M, Hess K, Brixner DI, Feehan M, et al. Physician adherence to ACR gout treatment guidelines: perception versus practice. Postgraduate medicine. 2014 May;126(3):257–67. doi: 10.3810/pgm.2014.05.2774 24918810

9. Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Impact of gout on the risk of atrial fibrillation. Rheumatology. 2016 Apr;55(4):721–8. doi: 10.1093/rheumatology/kev418 26683193

10. Crossfield S, Lai L, Kingsbury S. Systematic review of variation in gout medication exposure and its definition and measurement in studies using electronic health records data. PROSPERO. 2017.

11. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009 Jul 21;339:b2535. doi: 10.1136/bmj.b2535 19622551

12. Denison HJ, Dodds R, Ntani G, Cooper R, Cooper C, Sayer AA, et al. How to get started with a systematic review in epidemiology: an introductory guide for early career researchers. Archives of Public Health. 2013;71(21).

13. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—A web and mobile app for systematic reviews. Systematic Reviews. 2016(5):210.

14. Centre for Reviews and Dissemination. Systematic Reviews: CRD’s guidance for undertaking reviews in health care. 2009 [cited 23.03.2017];

15. Neogi T, Jansen TLTA, Dalbeth N, Fransen J, Schumacher HR, Berendsen D, et al. 2015 gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis & rheumatology. 2015;67(10):2557–68.

16. Benchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, et al. The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement. 2015;12(10):e1001885.

17. Cochrane Collaboration. Tool to Assess Risk of Bias in Cohort Studies. [cited 22.01.2018];

18. Care Quality Commission. NHS Patient Survey Programme: Survey scoring method.; 2015.

19. Ramke J, Palagyi A, Jordan V, Petkovic J, Gilbert CE. Using the STROBE statement to assess reporting in blindness prevalence surveys in low and middle income countries. PLoS One. 2017;12(5):e0176178-e.

20. Rothenbacher D, Primatesta P, Ferreira A, Cea-Soriano L, Rodriguez LAG. Frequency and risk factors of gout flares in a large population-based cohort of incident gout. Rheumatology (Oxford). 2011;50(5):973–81.

21. Keenan RT, O’Brien WR, Lee K, Crittenden DB, Fisher MC, Goldfarb DS, et al. Prevalence of contraindications and prescription of pharmacologic therapies for gout. Am J Med. 2011;124(2):155–63. doi: 10.1016/j.amjmed.2010.09.012 21295195

22. Kuo C-F, Grainge MJ, Mallen C, Zhang W, Doherty M. Eligibility for and prescription of urate-lowering treatment in patients with incident gout in England. JAMA. 2014;312(24):2684–6. doi: 10.1001/jama.2014.14484 25536262

23. Scheepers LEJM, Burden AM, Arts ICW, Spaetgens B, Souverein P, de Vries F, et al. Medication adherence among gout patients initiated allopurinol: a retrospective cohort study in the Clinical Practice Research Datalink (CPRD). Rheumatology (Oxford). 2018 2018-1-1;57(9):1641–50.

24. Roddy E, Mallen CD, Hider SL, Jordan KP. Prescription and comorbidity screening following consultation for acute gout in primary care. Rheumatology (Oxford). 2010;49(1):105–11.

25. Rothenbacher D, Primatesta P, Ferreira A, Cea-Soriano L, Rodriguez LA. Frequency and risk factors of gout flares in a large population-based cohort of incident gout. Rheumatology. 2011 May;50(5):973–81. doi: 10.1093/rheumatology/keq363 21228059

26. Dehlin M, Ekström EH, Petzold M, Strömberg U, Telg G, Jacobsson LTH. Factors associated with initiation and persistence of urate-lowering therapy. Arthritis Res Ther. 2017;19(1):6. doi: 10.1186/s13075-016-1211-y 28095891

27. Kuo C-F, Grainge MJ, Mallen C, Zhang W, Doherty M. Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Ann Rheum Dis. 2014;74(4):661–7. doi: 10.1136/annrheumdis-2013-204463 24431399

28. Sigurdardottir V, Drivelegka P, Svard A, Jacobsson LTH, Dehlin M. Work disability in gout: a population-based case-control study. Ann Rheum Dis. 2017;77(3):399–404. doi: 10.1136/annrheumdis-2017-212063 29170202

29. Kapetanovic MC, Hameed M, Turkiewicz A, Neogi T, Saxne T, Jacobsson L, et al. Prevalence and incidence of gout in southern Sweden from the socioeconomic perspective. RMD Open. 2016;2(2):e000326. doi: 10.1136/rmdopen-2016-000326 27933209

30. Mikuls TR, Farrar JT, Bilker WB, Fernandes S, Schumacher HR Jr., Saag KG. Gout epidemiology: results from the UK General Practice Research Database, 1990–1999. Annals of the rheumatic diseases. 2005 Feb;64(2):267–72. doi: 10.1136/ard.2004.024091 15647434

31. Rai SK, Avina-Zubieta JA, McCormick N, De Vera MA, Shojania K, Sayre EC, et al. The rising prevalence and incidence of gout in British Columbia, Canada: Population-based trends from 2000 to 2012. Semin Arthritis Rheum. 2017;46(4):451–6. doi: 10.1016/j.semarthrit.2016.08.006 28040245

32. Fisher MC, Rai SK, Lu N, Zhang YQ, Choi HK. The unclosing premature mortality gap in gout: a general population-based study. Ann Rheum Dis. 2017;76(7):1289–94. doi: 10.1136/annrheumdis-2016-210588 28122760

33. Arromdee E, Michet CJ, Crowson CS, O’Fallon WM, Gabriel SE. Epidemiology of gout: is the incidence rising? J Rheumatol. 2002;29(11):2403–6. 12415600

34. Wahedduddin S, Singh JA, Culhane-Pera KA, Gertner E. Gout in the Hmong in the United States. J Clin Rheumatol. 2010;16(6):262–6. doi: 10.1097/RHU.0b013e3181eeb487 20808166

35. Rashid N, Coburn BW, Wu Y-L, Cheetham TC, Curtis JR, Saag KG, et al. Modifiable factors associated with allopurinol adherence and outcomes among patients with gout in an integrated healthcare system. J Rheumatol. 2014;42(3):504–12. doi: 10.3899/jrheum.140588 25512479

36. Harrold LR, Andrade SE, Briesacher B, Raebel MA, Fouayzi H, Yood RA, et al. The Dynamics of Chronic Gout Treatment: Medication Gaps and Return to Therapy. Am J Med. 2010;123(1):54–9. doi: 10.1016/j.amjmed.2009.05.026 20102992

37. Singh JA, Hodges JS, Asch SM. Opportunities for improving medication use and monitoring in gout. Ann Rheum Dis. 2008;68(8):1265–70. doi: 10.1136/ard.2008.092619 18701554

38. Coburn BW, Michaud K, Bergman DA, Mikuls TR. Allopurinol Dose Escalation and Mortality Among Patients With Gout: A National Propensity-Matched Cohort Study. Arthritis Rheumatol. 2018 2018-1-1;70(8):1298–307. doi: 10.1002/art.40486 29513934

39. Mantarro S, Capogrosso-Sansone A, Tuccori M, Blandizzi C, Montagnani S, Convertino I, et al. Allopurinol adherence among patients with gout: an Italian general practice database study. International journal of clinical practice. 2015 Jul;69(7):757–65. doi: 10.1111/ijcp.12604 25683693

40. Coburn BW, Bendlin KA, Sayles H, Meza J, Russell CL, R MT. Allopurinol Medication Adherence as a Mediator of Optimal Outcomes in Gout Management. J Clin Rheumatol. 2017;23(6):317–23. doi: 10.1097/RHU.0000000000000561 28816767

41. Hughes JC, Wallace JL, Bryant CL, Salvig BE, Fourakre TN, Stone WJ. Monitoring of Urate-Lowering Therapy Among US Veterans Following the 2012 American College of Rheumatology Guidelines for Management of Gout. Ann Pharmacother. 2017;51(4):301–6. doi: 10.1177/1060028016679848 27881692

42. Maravic M, Hincapie N, Pilet S, Flipo RM, Lioté F. Persistent clinical inertia in gout in 2014: An observational French longitudinal patient database study. Joint Bone Spine. 2018 2018-1-1;85(3):311–5. doi: 10.1016/j.jbspin.2017.03.013 28478208

43. Cottrell E, Crabtree V, Edwards JJ, Roddy E. Improvement in the management of gout is vital and overdue: an audit from a UK primary care medical practice. BMC Fam Pract. 2013;14(170).

44. Rashid N, Levy GD, Wu YL, Zheng CY, Koblick R, Cheetham TC. Patient and clinical characteristics associated with gout flares in an integrated healthcare system. Rheumatol Int. 2015;35(11):1799–807. doi: 10.1007/s00296-015-3284-3 25991397

45. Landgren AJ, Jacobsson LTH, Lindstrom U, Sandstrom TZS, Drivelegka P, Bjorkman L, et al. Incidence of and risk factors for nephrolithiasis in patients with gout and the general population, a cohort study. Arthritis Res Ther. 2017;19(1).

46. Pui K, Gow PJ, Dalbeth N. Efficacy and tolerability of probenecid as urate-lowering therapy in gout; clinical experience in high-prevalence population. J Rheumatol. 2013;40(6):872–6. doi: 10.3899/jrheum.121301 23457380

47. Morlock R, Chevalier P, Horne L, Nuevo J, Storgard C, Aiyer L, et al. Disease Control, Health Resource Use, Healthcare Costs, and Predictors in Gout Patients in the United States, the United Kingdom, Germany, and France: A Retrospective Analysis. Rheumatol Ther. 2016;3(1):53–75. doi: 10.1007/s40744-016-0033-3 27747520

48. Ryu H, Song R, Kim H, Kim J, Lee EY, Lee YJ, et al. Clinical risk factors for adverse events in allopurinol users. J Clin Pharmacol. 2013;53(2):211–6. doi: 10.1177/0091270012439715 23436266

49. Hatoum H, Khanna D, Lin SJ, Akhras KS, Shiozawa A, Khanna P. Achieving Serum Urate Goal: A Comparative Effectiveness Study Between Allopurinol and Febuxostat. Postgrad Med. 2014;126(2):65–75. doi: 10.3810/pgm.2014.03.2741 24685969

50. Mikuls TR, Cheetham TC, Levy GD, Rashid N. Adherence and Outcomes with Urate-Lowering Therapy: A Site-Randomized Trial. Am J Med. 2019:354–61. doi: 10.1016/j.amjmed.2018.11.011 30503879

51. Singh JA, Hodges JS, Toscano JP, Asch SM. Quality of care for gout in the US needs improvement. Arthritis Rheum. 2007;57(5):822–9. doi: 10.1002/art.22767 17530682

52. Mikuls TR, Farrar JT, Bilker WB, Fernandes S, Saag KG. Suboptimal physician adherence to quality indicators for the management of gout and asymptomatic hyperuricaemia: results from the UK General Practice Research Database (GPRD). Rheumatology. 2005 Aug;44(8):1038–42. doi: 10.1093/rheumatology/keh679 15870145

53. Janssen CA, Jansen T, Voshaar M, Vonkeman HE, van de Laar M. Quality of care in gout: a clinical audit on treating to the target with urate lowering therapy in real-world gout patients. Rheumatol Int. 2017;37(9):1435–40. doi: 10.1007/s00296-017-3777-3 28748426

54. Crittenden DB, Lehmann RA, Schneck L, Keenan RT, Shah B, Greenberg JD, et al. Colchicine Use Is Associated with Decreased Prevalence of Myocardial Infarction in Patients with Gout. J Rheumatol. 2012;39(7):1458–64. doi: 10.3899/jrheum.111533 22660810

55. Solomon DH, Liu CC, Kuo IH, Zak A, Kim SC. Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: a cohort study using electronic medical records linked with Medicare claims. Ann Rheum Dis. 2016;75(9):1674–9. doi: 10.1136/annrheumdis-2015-207984 26582823

56. Kwon OC, Hong S, Ghang B, Kim YG, Lee CK, Yoo B. Risk of Colchicine-Associated Myopathy in Gout: Influence of Concomitant Use of Statin. Am J Med. 2016;130(5):583–7.

57. Kuo CF, Grainge MJ, Mallen C, Zhang WY, Doherty M. Effect of allopurinol on all-cause mortality in adults with incident gout: propensity score-matched landmark analysis. Rheumatology (Oxford). 2015;54(12):2145–50.

58. Meier CR, Jick H. Omeprazole, other antiulcer drugs and newly diagnosed gout. British Journal of Clinical Pharmacology. 1997;44:4.

59. Herrett E, Gallagher AM, Bhaskaran K, Forbes H, Mathur R, van Staa T, et al. Data Resource Profile: Clinical Practice Research Datalink (CPRD). International journal of epidemiology. 2015 Jun;44(3):827–36. doi: 10.1093/ije/dyv098 26050254

60. Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. Newcastle-Ottawa quality assessment scale: Cohort studies. 2014.

61. Sterne JA, Hernan MA, Reeves BC, Savovic J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016 Oct 12;355:i4919. doi: 10.1136/bmj.i4919 27733354

62. Schinasi LH, Auchincloss AH, Forrest CB, Diez Roux AV. Using electronic health record data for environmental and place based population health research: a systematic review. Ann Epidemiol. 2018 2018/07/01/;28(7):493–502. doi: 10.1016/j.annepidem.2018.03.008 29628285

Článek vyšel v časopise


2019 Číslo 10