Pediatric Drugs

, Volume 17, Issue 5, pp 401–410 | Cite as

Comparison of Drug Utilization Patterns in Observational Data: Antiepileptic Drugs in Pediatric Patients

  • Florence T. Bourgeois
  • Karen L. Olson
  • Annapurna Poduri
  • Kenneth D. Mandl
Original Research Article
First Online:

Abstract

Purpose

Physicians require information on the comparative benefits and harms of medications for optimal treatment decisions. However, this type of data is limited, especially for pediatric patients.

Objective

Our aim was to use observational data to measure and compare medication utilization patterns in a pediatric patient population.

Methods

Using pharmacy claims data from a large, national-scale insurance program in the USA, we identified all patients with a diagnosis of epilepsy treated with a first-generation antiepileptic drug (carbamazepine, ethosuximide, phenobarbital, phenytoin, or valproate) or a second-generation antiepileptic drug [carbamazepine extended release (XR), gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, valproate XR, or zonisamide]. Treatment periods were defined on the basis of prescription fill dates and medication days supplied. Medication use was measured for individual antiepileptic drugs and for first-generation and second-generation drugs as groups.

Results

There were 2527 patients (54 %) who initiated therapy with first-generation antiepileptics and 2139 patients (46 %) who initiated therapy with second-generation antiepileptics. First- and second-generation drugs had the same 1-year retention rates [26 % (95 % confidence interval (CI) 24–28) and 26 % (95 % CI 25–28), respectively], and 26 % of patients (95 % CI 25–28) and 29 % of patients (95 % CI 27–31) who started on a first- or second-generation antiepileptic medication, respectively, resumed treatment with the initial drug after discontinuation. Overall, 73 % of patients (95 % CI 71–74) were treated with only one antiepileptic drug, with similar rates for patients started on first- and second-generation drugs [71 % (95 % CI 69–73) versus 74 % (95 % CI 72–76)].

Conclusion

Comparing drug utilization patterns in a pediatric population using observational data, we found similar rates of retention and therapeutic changes. These findings are consistent with the available comparative data and demonstrate an approach that could be extended to other drug classes and conditions in pediatric populations to examine drug effectiveness.

Keywords

Antiepileptic Drug Topiramate Oxcarbazepine Zonisamide Tiagabine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Notes

Funding support

Drs. Bourgeois and Mandl were supported by a Grant (Number 1R01GM104303-01) from the National Institute of General Medical Sciences. Dr. Bourgeois was supported by a training Grant (Number 5T32HD040128) from the National Institute of Child Health and Human Development, and Dr. Mandl by a Grant (Number 5G08LM009778) from the National Library of Medicine, National Institutes of Health. No funding was specifically received for this study.

Conflicts of interest

Drs. Bourgeois, Olson, Poduri, and Mandl do not have any conflicts of interest to disclose.

References

  1. 1.
    Zhang Y, Baicker K, Newhouse JP. Geographic variation in the quality of prescribing. N Engl J Med. 2010;363(21):1985–8.CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Mittler JN, Landon BE, Fisher ES, Cleary PD, Zaslavsky AM. Market variations in intensity of Medicare service use and beneficiary experiences with care. Health Serv Res. 2010;45(3):647–69.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Bourgeois FT, Murthy S, Pinto C, Olson KL, Ioannidis JP, Mandl KD. Pediatric versus adult drug trials for conditions with high pediatric disease burden. Pediatrics. 2012;130(2):285–92.CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Cohen E, Goldman RD, Ragone A, et al. Child vs adult randomized controlled trials in specialist journals: a citation analysis of trends, 1985–2005. Arch Pediatr Adolesc Med. 2010;164(3):283–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Cohen E, Uleryk E, Jasuja M, Parkin PC. An absence of pediatric randomized controlled trials in general medical journals, 1985–2004. J Clin Epidemiol. 2007;60(2):118–23.CrossRefPubMedGoogle Scholar
  6. 6.
    Hamm MP, Hartling L, Milne A, et al. A descriptive analysis of a representative sample of pediatric randomized controlled trials published in 2007. BMC Pediatr. 2010;10:96.CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    Martinez-Castaldi C, Silverstein M, Bauchner H. Child versus adult research: the gap in high-quality study design. Pediatrics. 2008;122(1):52–7.CrossRefPubMedGoogle Scholar
  8. 8.
    ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):2981–97.CrossRefGoogle Scholar
  9. 9.
    Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet. 2009;373(9665):746–58.CrossRefPubMedGoogle Scholar
  10. 10.
    Tsai AC, Rosenlicht NZ, Jureidini JN, Parry PI, Spielmans GI, Healy D. Aripiprazole in the maintenance treatment of bipolar disorder: a critical review of the evidence and its dissemination into the scientific literature. PLoS Med. 2011;8(5):e1000434.CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Chokshi DA, Avorn J, Kesselheim AS. Designing comparative effectiveness research on prescription drugs: lessons from the clinical trial literature. Health Aff (Millwood). 2010;29(10):1842–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Stafford RS, Wagner TH, Lavori PW. New, but not improved? Incorporating comparative-effectiveness information into FDA labeling. N Engl J Med. 2009;361(13):1230–3.CrossRefPubMedGoogle Scholar
  13. 13.
    O’Connor AB. Building comparative efficacy and tolerability into the FDA approval process. JAMA. 2010;303(10):979–80.CrossRefPubMedGoogle Scholar
  14. 14.
    Hollingworth SA, Eadie MJ. Antiepileptic drugs in Australia: 2002–2007. Pharmacoepidemiol Drug Saf. 2010;19(1):82–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Weijenberg A, Offringa M, Brouwer OF, Callenbach PM. RCTs with new antiepileptic drugs in children: a systematic review of monotherapy studies and their methodology. Epilepsy Res. 2010;91(1):1–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Hansen RA, Dusetzina SB, Dominik RC, Gaynes BN. Prescription refill records as a screening tool to identify antidepressant non-adherence. Pharmacoepidemiol Drug Saf. 2010;19(1):33–7.CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    Norris SL, Atkins D, Bruening W, et al. Observational studies in systemic reviews of comparative effectiveness: AHRQ and the Effective Health Care Program. J Clin Epidemiol. 2011;64(11):1178–86.CrossRefPubMedGoogle Scholar
  18. 18.
    Shcherbakova N, Rascati K, Brown C, et al. Factors associated with seizure recurrence in epilepsy patients treated with antiepileptic monotherapy: a retrospective observational cohort study using US administrative insurance claims. CNS Drugs. 2014;28(11):1047–58.CrossRefPubMedGoogle Scholar
  19. 19.
    Cerner Multum Drug Products. http://www.multum.com/lexicon.html. Accessed 31 Oct 2011.
  20. 20.
    Pellock JM, Bourgeois BFD, Dodson WE, editors. Pediatric epilepsy: diagnosis and therapy. 3rd ed. New York: Demos Medical Publishing; 2008.Google Scholar
  21. 21.
    Andrade SE, Kahler KH, Frech F, Chan KA. Methods for evaluation of medication adherence and persistence using automated databases. Pharmacoepidemiol Drug Saf. 2006;15(8):565–74 (discussion 575–567).Google Scholar
  22. 22.
    Vink NM, Klungel OH, Stolk RP, Denig P. Comparison of various measures for assessing medication refill adherence using prescription data. Pharmacoepidemiol Drug Saf. 2009;18(2):159–65.CrossRefPubMedGoogle Scholar
  23. 23.
    Hudson M, Rahme E, Richard H, Pilote L. Comparison of measures of medication persistency using a prescription drug database. Am Heart J. 2007;153(1):59–65.CrossRefPubMedGoogle Scholar
  24. 24.
    SAS Institute Inc. SAS/STAT 9.3 user’s guide. 2011. http://support.sas.com/documentation/cdl/en/statug/63962/PDF/default/statug.pdf. Accessed 21 Oct 2014.
  25. 25.
    Guerreiro MM, Vigonius U, Pohlmann H, et al. A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in children and adolescents with epilepsy. Epilepsy Res. 1997;27(3):205–13.CrossRefPubMedGoogle Scholar
  26. 26.
    Nieto-Barrera M, Brozmanova M, Capovilla G, et al. A comparison of monotherapy with lamotrigine or carbamazepine in patients with newly diagnosed partial epilepsy. Epilepsy Res. 2001;46(2):145–55.CrossRefPubMedGoogle Scholar
  27. 27.
    Resendiz-Aparicio JC, Rodriguez-Rodriguez E, Contreras-Bernal J, et al. A randomised open trial comparing monotherapy with topiramate versus carbamazepine in the treatment of paediatric patients with recently diagnosed epilepsy. Rev Neurol. 2004;39(3):201–4.Google Scholar
  28. 28.
    Wheless JW, Neto W, Wang S. Topiramate, carbamazepine, and valproate monotherapy: double-blind comparison in children with newly diagnosed epilepsy. J Child Neurol. 2004;19(2):135–41.PubMedGoogle Scholar
  29. 29.
    Thomson D, Hartling L, Cohen E, Vandermeer B, Tjosvold L, Klassen TP. Controlled trials in children: quantity, methodological quality and descriptive characteristics of pediatric controlled trials published 1948–2006. PLoS One. 2010;5(9):e13106.CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Demauro SB, Giaccone A, Kirpalani H, Schmidt B. Quality of reporting of neonatal and infant trials in high-impact journals. Pediatrics. 2011;128(3):e639–44.PubMedGoogle Scholar
  31. 31.
    Lindkvist J, Airaksinen M, Kaukonen AM, Klaukka T, Hoppu K. Evolution of paediatric off-label use after new significant medicines become available for adults: a study on triptans in Finnish children 1994–2007. Br J Clin Pharmacol. 2011;71(6):929–35.CrossRefPubMedCentralPubMedGoogle Scholar
  32. 32.
    Waller DG. Off-label and unlicensed prescribing for children: have we made any progress? Br J Clin Pharmacol. 2007;64(1):1–2.CrossRefPubMedCentralPubMedGoogle Scholar
  33. 33.
    Viner RM, Hsia Y, Tomsic T, Wong IC. Efficacy and safety of anti-obesity drugs in children and adolescents: systematic review and meta-analysis. Obes Rev. 2010;11(8):593–602.CrossRefPubMedGoogle Scholar
  34. 34.
    Murray ML, de Vries CS, Wong IC. A drug utilisation study of antidepressants in children and adolescents using the General Practice Research Database. Arch Dis Child. 2004;89(12):1098–102.CrossRefPubMedCentralPubMedGoogle Scholar
  35. 35.
    Gartlehner G, Hansen RA, Nissman D, Lohr KN, Carey TS. A simple and valid tool distinguished efficacy from effectiveness studies. J Clin Epidemiol. 2006;59(10):1040–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Sorenson C, Naci H, Cylus J, Mossialos E. Evidence of comparative efficacy should have a formal role in European drug approvals. BMJ. 2011;343:d4849.CrossRefPubMedGoogle Scholar
  37. 37.
    Travers J, Marsh S, Williams M, et al. External validity of randomised controlled trials in asthma: to whom do the results of the trials apply? Thorax. 2007;62(3):219–23.CrossRefPubMedCentralPubMedGoogle Scholar
  38. 38.
    Tunis SR, Stryer DB, Clancy CM. Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy. JAMA. 2003;290(12):1624–32.CrossRefPubMedGoogle Scholar
  39. 39.
    Smith B. Comparative-effectiveness research as it affects clinical pharmacology. Clin Pharmacol Ther. 2011;90(6):751–4.CrossRefPubMedGoogle Scholar
  40. 40.
    Dreyer NA, Tunis SR, Berger M, Ollendorf D, Mattox P, Gliklich R. Why observational studies should be among the tools used in comparative effectiveness research. Health Aff (Millwood). 2010;29(10):1818–25.CrossRefPubMedGoogle Scholar
  41. 41.
    Concato J, Lawler EV, Lew RA, Gaziano JM, Aslan M, Huang GD. Observational methods in comparative effectiveness research. Am J Med. 2010;123(12 Suppl 1):e16–23.CrossRefPubMedGoogle Scholar
  42. 42.
    Schneeweiss S, Gagne JJ, Glynn RJ, Ruhl M, Rassen JA. Assessing the comparative effectiveness of newly marketed medications: methodological challenges and implications for drug development. Clin Pharmacol Ther. 2011;90(6):777–90.CrossRefPubMedGoogle Scholar
  43. 43.
    Chung S, Wang N, Hank N. Comparative retention rates and long-term tolerability of new antiepileptic drugs. Seizure. 2007;16(4):296–304.CrossRefPubMedGoogle Scholar
  44. 44.
    Wong IC, Mawer GE, Sander JW, Lhatoo SD. A pharmacoepidemiologic study of factors influencing the outcome of treatment with lamotrigine in chronic epilepsy. Epilepsia. 2001;42(10):1354–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Bootsma HP, Ricker L, Diepman L, et al. Long-term effects of levetiracetam and topiramate in clinical practice: a head-to-head comparison. Seizure. 2008;17(1):19–26.CrossRefPubMedGoogle Scholar
  46. 46.
    Ben-Menachem E, Sander JW, Privitera M, Gilliam F. Measuring outcomes of treatment with antiepileptic drugs in clinical trials. Epilepsy Behav. 2010;18(1–2):24–30.CrossRefPubMedGoogle Scholar
  47. 47.
    Lhatoo SD, Wong IC, Polizzi G, Sander JW. Long-term retention rates of lamotrigine, gabapentin, and topiramate in chronic epilepsy. Epilepsia. 2000;41(12):1592–6.CrossRefPubMedGoogle Scholar
  48. 48.
    Sander JW. New antiepileptic drugs in practice—how do they perform in the real world? Acta Neurol Scand Suppl. 2005;181:26–9.CrossRefPubMedGoogle Scholar
  49. 49.
    Simister RJ, Sander JW, Koepp MJ. Long-term retention rates of new antiepileptic drugs in adults with chronic epilepsy and learning disability. Epilepsy Behav. 2007;10(2):336–9.CrossRefPubMedGoogle Scholar
  50. 50.
    Bootsma HP, Ricker L, Hekster YA, et al. The impact of side effects on long-term retention in three new antiepileptic drugs. Seizure. 2009;18(5):327–31.CrossRefPubMedGoogle Scholar
  51. 51.
    Bourgeois FT, Murthy S, Mandl KD. Comparative effectiveness research: an empirical study of trials registered in ClinicalTrials.gov. PLoS One. 2012;7(1):e28820.CrossRefPubMedCentralPubMedGoogle Scholar
  52. 52.
    Dunn AG, Bourgeois FT, Murthy S, Mandl KD, Day RO, Coiera E. The role and impact of research agendas on the comparative-effectiveness research among antihyperlipidemics. Clin Pharmacol Ther. 2012;91(4):685–91.CrossRefPubMedGoogle Scholar
  53. 53.
    van Luijn JC, Stolk P, Gribnau FW, Leufkens HG. Gap in publication of comparative information on new medicines. Br J Clin Pharmacol. 2008;65(5):716–22.CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Florence T. Bourgeois
    • 1
    • 2
    • 3
  • Karen L. Olson
    • 1
    • 2
    • 3
  • Annapurna Poduri
    • 2
    • 4
  • Kenneth D. Mandl
    • 1
    • 2
    • 3
  1. 1.Division of Emergency MedicineBoston Children’s HospitalBostonUSA
  2. 2.Department of PediatricsHarvard Medical SchoolBostonUSA
  3. 3.Children’s Hospital Informatics ProgramBoston Children’s HospitalBostonUSA
  4. 4.Department of NeurologyHarvard Medical SchoolBostonUSA

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