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Clinical Trial Design in Juvenile Idiopathic Arthritis

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Abstract

Randomized clinical trials provide the gold standard evidence base to guide clinical practice. Despite major advances in trial design, pediatric clinical trials are still difficult to perform and pose unique challenges, including the need to consider the impact of developmental changes in trial design. Advances within pediatric rheumatology combined with the need to comply with legislative requirements have driven new approaches to performing pediatric clinical trials such as utilization of large research networks, incorporation of patient and family stakeholders in the planning and implementation of clinical trials, and the development of novel trial designs. The expansion of available biological therapeutics that now includes biosimilar drugs highlights the important and difficult balance of providing new and cost-effective drugs to children while ensuring safety in a vulnerable population. Future advances in juvenile idiopathic arthritis (JIA) clinical trials will likely be the application of precision medicine based on biologic, rather than phenotypic, classification of JIA, with improved understanding of pediatric clinical pharmacology. Clinical trial simulations and comparative effectiveness studies are important supplements to traditional clinical trials, permitting efficient studies and results that are more generalizable.

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References

  1. Ruperto N, Giannini EH, Pistorio A, Brunner HI, Martini A, Lovell DJ. Is it time to move to active comparator trials in juvenile idiopathic arthritis?: a review of current study designs. Arthritis Rheum. 2010;62(11):3131–9.

    Article  PubMed  Google Scholar 

  2. Lovell DJ, Ruperto N, Giannini EH, Martini A. Advances from clinical trials in juvenile idiopathic arthritis. Nat Rev Rheumatol. 2013;9(9):557–63.

    Article  PubMed  Google Scholar 

  3. Ilowite NT, Prather K, Lokhnygina Y, Schanberg LE, Elder M, Milojevic D, et al. Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis. Arthritis Rheumatol. 2014;66(9):2570–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. European Medicines Agency: EMEA/H/C/000992 -II-0071-G. Simponi EPAR Product Information. 2009. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000992/WC500052368.pdf. Accessed 8 Nov 2016.

  5. United States Food and Drug Administration. Scientific Considerations in Demonstrating Biosimilarity to a Reference Product. Guidance for Industry. 2015. http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/UCM291128.pdf. Accessed 17 Apr 2017.

  6. Zimmerman K, Gonzalez D, Swamy GK, Cohen-Wolkowiez M. Pharmacologic studies in vulnerable populations: using the pediatric experience. Semin Perinatol. 2015;39(7):532–6.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Institute of Medicine (US) Forum on Drug Discovery, Development, and Translation. Addressing the Barriers to Pediatric Drug Development: Workshop Summary. Washington (DC): National Academies Press (US). 2008. 2, Regulatory Framework.

  8. Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006. http://ec.europa.eu/health//sites/health/files/files/eudralex/vol-1/reg_2006_1901/reg_2006_1901_en.pdf. Accessed 14 Dec 2016.

  9. Frattarelli DA, Galinkin JL, Green TP, Johnson TD, Neville KA, Paul IM, et al. Off-label use of drugs in children. Pediatrics. 2014;133(3):563–7.

    Article  PubMed  Google Scholar 

  10. World Medical Association declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA. 1997;277(11):925–6.

    Article  Google Scholar 

  11. Duke E. US Department of Health and Human Services. Report to Congress. 2007. The Pediatric Rheumatology Workforce: A Study of the Supply and Demand for Pediatric Rheumatologists. https://pdfs.semanticscholar.org/4f1d/41eec3b2ecbe7e529efb169cdb0d82c0a951.pdf. Accessed 1 Apr 2017.

  12. Childhood Arthritis and Rheumatology Research Alliance. STOP JIA Prezi. 2016. https://www.youtube.com/watch?v=oI2_j3ZDDDE. Accessed 17 Apr 2017.

  13. Patient-Centered Outcomes Research Institute. Research Funding. 2017. http://www.pcori.org/sites/default/files/PCORI-Research-Funding.pdf. Accessed 1 Apr 2017.

  14. Hudson K, Lifton R, Patrick-Lake B et al. Precision Medicine Initiative Working Group. The Precision Medicine Initiative Cohort Program- Building a Research Foundation for 21st Century Medicine. 2015. https://www.nih.gov/sites/default/files/research-training/initiatives/pmi/pmi-working-group-report-20150917-2.pdf. Accessed 1 May 2017.

  15. Cummings SR, Grady DG, Hulley SB. Designing a randomized trial. In: Hulley SB, Browner WS, Grady DB, Newman TB, editors. Designing clinical research. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2007. p. 147–61.

    Google Scholar 

  16. Feldman B, Wang E, Willan A, Szalai JP. The randomized placebo-phase design for clinical trials. J Clin Epidemiol. 2001;54(6):550–7.

    Article  CAS  PubMed  Google Scholar 

  17. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med. 1987;317(3):141–5.

    Article  CAS  PubMed  Google Scholar 

  18. Shaddy RE, Denne SC. Clinical report–guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations. Pediatrics. 2010;125(4):850–60.

    Article  PubMed  Google Scholar 

  19. European Medicines Agency: EMA/CHMP/239770/2014 Rev. 2- Guideline on clinical investigation of medicinal products for the treatment of juvenile idiopathic arthritis. 2015. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/11/WC500196719.pdf. Accessed 15 Nov 2016.

  20. Friedman, et al. Issues in data analysis. In: Friedman LM, Furberg CD, DeMets DL, Reboussin DM, Granger CB, editors. Fundamentals of clinical trials. Cham: Springer International Publishing; 2015. p. 403–62.

    Chapter  Google Scholar 

  21. A study of the safety and efficacy of CNTO 148 (Golimumab) in children with juvenile idiopathic arthritis (JIA) and multiple joint involvement who have poor response to methotrexate (GO KIDS). https://clinicaltrials.gov/ct2/show/study/NCT01230827. Accessed 8 November 2016.

  22. Brunner H, Ruperto N, Tzaribachev N, et al. A multi-center, double-blind, randomized-withdrawal trial of subcutaneous golimumab in pediatric patients with active polyarticular course juvenile idiopathic arthritis despite methotrexate therapy: week 48 results. Arthritis Rheumatol. 2014. doi:10.1002/art.38569.

    Google Scholar 

  23. Lovell DJ, Giannini EH, Reiff A, Cawkwell GD, Silverman ED, Nocton JJ et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N Engl J Med. 2000;342(11):763–769.

  24. Lovell DJ, Ruperto N, Goodman S, Reiff A, Jung L, Jarosova K, et al. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med. 2008;359(8):810–20.

    Article  CAS  PubMed  Google Scholar 

  25. Weinblatt ME, Bingham CO 3rd, Mendelsohn AM, Kim L, Mack M, Lu J, et al. Intravenous golimumab is effective in patients with active rheumatoid arthritis despite methotrexate therapy with responses as early as week 2: results of the phase 3, randomised, multicentre, double-blind, placebo-controlled GO-FURTHER trial. Ann Rheum Dis. 2013;72(3):381–9.

    Article  CAS  PubMed  Google Scholar 

  26. United States food and drug administration. General clinical pharmacology considerations for pediatric studies for drugs and biologic products. Guidance for Industry. 2014. https://www.fda.gov/downloads/drugs/guidances/ucm425885.pdf. Accessed 1 Apr 2017.

  27. European Medicines Agency. EMA/199678/2016. Reflection paper on extrapolation of efficacy and safety in paediatric medicine development. 2016. http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2016/04/WC500204187.pdf. Accessed 1 Apr 2017.

  28. European Medicines Agency: CHMP/437/04 Rev 1. Guidelines on similar biological medicinal products. 2014. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/10/WC500176768.pdf. Accessed 15 Nov 2016.

  29. United States food and drug administration. Information for healthcare professionals (Biosimilars). http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm241719.htm. Accessed 17 Jan 2017.

  30. McCamish M, Woollett G. The state of the art in the development of biosimilars. Clin Pharmacol Ther. 2012;91(3):405–17.

    Article  CAS  PubMed  Google Scholar 

  31. de Ridder L, Waterman M, Turner D, Bronsky J, Hauer AC, Dias JA, et al. Use of biosimilars in paediatric inflammatory bowel disease: a position statement of the ESPGHAN paediatric IBD porto group. J Pediatr Gastroenterol Nutr. 2015;61(4):503–8.

    Article  PubMed  Google Scholar 

  32. Lakhanpal A, Brahn E. Biosimilars in rheumatic diseases: structural and functional variability that may impact clinical and regulatory decisions. Clin Rheumatol. 2016. doi:10.1007/s10067-016-3430-7.

    PubMed  Google Scholar 

  33. Mielke J, Jilma B, Koenig F, Jones B. Clinical trials for authorized biosimilars in the European Union: a systematic review. Br J Clin Pharmacol. 2016. doi:10.1111/bcp.13076.

    PubMed Central  Google Scholar 

  34. Park W, Hrycaj P, Jeka S, Kovalenko V, Lysenko G, Miranda P, et al. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis. 2013;72(10):1605–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Yoo DH, Hrycaj P, Miranda P, Ramiterre E, Piotrowski M, Shevchuk S, et al. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis. 2013;72(10):1613–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. European Medicines Agency: EMA/CHMP/589317/2013. Assessment Report. Remsima. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002576/WC500151486.pdf. Accessed 15 Nov 2016.

  37. United States Food and Drug Administration. Briefing Document. Arthritis Advisory Committee Meeting. July 12, 2016. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM510293.pdf. Accessed 15 Nov 2016.

  38. United States Food and Drug Administration. Briefing Document. Arthritis Advisory Committee Meeting. July 13, 2016. http://www.fda.gov/downloads/%20AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/%20ArthritisAdvisoryCommittee/UCM510493.%20pdf. Accessed 15 Nov 2016.

  39. Singh SC, Bagnato KM. The economic implications of biosimilars. Am J Manag Care. 2015;21(16 Suppl):s331–40.

    PubMed  Google Scholar 

  40. Benjamin DK Jr, Smith PB, Jadhav P, Gobburu JV, Murphy MD, Hasselblad V, et al. Pediatric antihypertensive trial failures: analysis of end points and dose range. Hypertension. 2008;51(4):834–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ruperto N, Lovell DJ, Cuttica R, Wilkinson N, Woo P, Espada G, et al. A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum. 2007;56(9):3096–106.

    Article  CAS  PubMed  Google Scholar 

  42. Laughon MM, Benjamin DK Jr, Capparelli EV, Kearns GL, Berezny K, Paul IM, et al. Innovative clinical trial design for pediatric therapeutics. Expert Rev Clin Pharmacol. 2011;4(5):643–52.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lima A, Bernardes M, Azevedo R, Seabra V, Medeiros R. Moving toward personalized medicine in rheumatoid arthritis: SNPs in methotrexate intracellular pathways are associated with methotrexate therapeutic outcome. Pharmacogenomics. 2016;17(15):1649–74.

    Article  CAS  PubMed  Google Scholar 

  44. Dervieux T, Furst D, Lein DO, Capps R, Smith K, Walsh M, et al. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum. 2004;50(9):2766–74.

    Article  CAS  PubMed  Google Scholar 

  45. Becker ML, Gaedigk R, van Haandel L, Thomas B, Lasky A, Hoeltzel M, et al. The effect of genotype on methotrexate polyglutamate variability in juvenile idiopathic arthritis and association with drug response. Arthritis Rheum. 2011;63(1):276–85.

    Article  CAS  PubMed  Google Scholar 

  46. Hicks JK, Bishop JR, Sangkuhl K, Muller DJ, Ji Y, Leckband SG, et al. Clinical pharmacogenetics implementation consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015;98(2):127–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Gammal RS, Court MH, Haidar CE, Iwuchukwu OF, Gaur AH, Alvarellos M, et al. Clinical pharmacogenetics implementation consortium (CPIC) guideline for UGT1A1 and Atazanavir prescribing. Clin Pharmacol Ther. 2016;99(4):363–9.

    Article  CAS  PubMed  Google Scholar 

  48. Birdwell KA, Decker B, Barbarino JM, Peterson JF, Stein CM, Sadee W, et al. Clinical pharmacogenetics implementation consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing. Clin Pharmacol Ther. 2015;98(1):19–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Saito Y, Stamp LK, Caudle KE, Hershfield MS, McDonagh EM, Callaghan JT, et al. Clinical pharmacogenetics implementation consortium (CPIC) guidelines for human leukocyte antigen B (HLA-B) genotype and allopurinol dosing: 2015 update. Clin Pharmacol Ther. 2016;99(1):36–7.

    Article  CAS  PubMed  Google Scholar 

  50. Scott SA, Sangkuhl K, Stein CM, Hulot JS, Mega JL, Roden DM, et al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther. 2013;94(3):317–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, et al. Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing: 2013 update. Clin Pharmacol Ther. 2013;93(4):324–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Becker ML. Pharmacogenomics in pediatric rheumatology. Curr Opin Rheumatol. 2012;24(5):541–7.

    Article  CAS  PubMed  Google Scholar 

  53. Polk BI, Becker ML. Pharmacogenomics in childhood rheumatic disorders: a foundation for future individualized therapy. Discov Med. 2013;16(90):267–75.

    PubMed  Google Scholar 

  54. Ma Q, Lu AY. Pharmacogenetics, pharmacogenomics, and individualized medicine. Pharmacol Rev. 2011;63(2):437–59.

    Article  CAS  PubMed  Google Scholar 

  55. Daly AK. Genome-wide association studies in pharmacogenomics. Nat Rev Genet. 2010;11(4):241–6.

    Article  CAS  PubMed  Google Scholar 

  56. Roden DM, Pulley JM, Basford MA, Bernard GR, Clayton EW, Balser JR, et al. Development of a large-scale de-identified DNA biobank to enable personalized medicine. Clin Pharmacol Ther. 2008;84(3):362–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Stockmann C, Barrett JS, Roberts JK, Sherwin C. Use of modeling and simulation in the design and conduct of pediatric clinical trials and the optimization of individualized dosing regimens. CPT Pharmacometrics Syst Pharmacol. 2015;4(11):630–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. McMahon AW, Watt K, Wang J, Green D, Tiwari R, Burckart GJ. Stratification, hypothesis testing, and clinical trial simulation in pediatric drug development. Ther Innov Regul Sci. 2016;50(6):817–22.

    Article  Google Scholar 

  59. Bhattaram VA, Booth BP, Ramchandani RP, Beasley BN, Wang Y, Tandon V, et al. Impact of pharmacometrics on drug approval and labeling decisions: a survey of 42 new drug applications. AAPS J. 2005;7(3):E503–12.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Thorpe KE, Zwarenstein M, Oxman AD, Treweek S, Furberg CD, Altman DG, et al. A pragmatic-explanatory continuum indicator summary (PRECIS): a tool to help trial designers. J Clin Epidemiol. 2009;62(5):464–75.

    Article  PubMed  Google Scholar 

  61. Friedman, et al. Basic study design. In: Friedman LM, Furberg CD, DeMets DL, Reboussin DM, Granger CB, editors. Fundamentals of clinical trials. Cham: Springer International Publishing; 2015. p. 89–123.

    Chapter  Google Scholar 

  62. Friedman, et al. Study population. In: Friedman LM, Furberg CD, DeMets DL, Reboussin DM, Granger CB, editors. Fundamentals of clinical trials. Cham: Springer International Publishing; 2015. p. 73–88.

    Chapter  Google Scholar 

  63. Aspirin dosing: a patient-centric trial assessing benefits and long term (ADAPTABLE). https://clinicaltrials.gov/ct2/show/NCT02697916?term=adaptable+trial&rank=1. Accessed 15 Apr 2017.

  64. ADAPTABLE, the aspirin study- a patient-centered trial. http://theaspirinstudy.org/. Accessed 15 Apr 2017.

  65. Chow SC. Adaptive clinical trial design. Annu Rev Med. 2014;65:405–15.

    Article  CAS  PubMed  Google Scholar 

  66. United States Food and Drug Administration. Draft guidance for industry: adaptive design clinical trials for drugs and biologics. 2010. https://www.fda.gov/downloads/Drugs/…/Guidances/UCM201790.pdf. Accessed 1 May 2017.

  67. European medicines agency. Reflection paper on methodological issues in confirmatory clinical trials planned with an adaptive design. 2007. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003616.pdf. Accessed 1 May 2017.

  68. Ringold S, Weiss PF, Colbert RA, DeWitt EM, Lee T, Onel K, et al. Childhood arthritis and rheumatology research alliance consensus treatment plans for new-onset polyarticular juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2014;66(7):1063–72.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Ruperto N, Pistorio A, Oliveira S, Zulian F, Cuttica R, Ravelli A, et al. Prednisone versus prednisone plus ciclosporin versus prednisone plus methotrexate in new-onset juvenile dermatomyositis: a randomised trial. Lancet. 2016;387(10019):671–8.

    Article  PubMed  Google Scholar 

  70. Grady DG, Cummings SR, Hulley SB. Alternative trial designs and implementation issues. In: Hulley SB, Browner WS, Grady DB, Newman TB, editors. Designing clinical research. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2007. p. 163–82.

    Google Scholar 

  71. Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Perez N, Silva CA, et al. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. Lancet. 2008;372(9636):383–91.

    Article  CAS  PubMed  Google Scholar 

  72. Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat N, Horneff G, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367(25):2396–406.

    Article  CAS  PubMed  Google Scholar 

  73. Brunner HI, Ruperto N, Zuber Z, Keane C, Harari O, Kenwright A, et al. Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. Ann Rheum Dis. 2015;74(6):1110–7.

    Article  CAS  PubMed  Google Scholar 

  74. De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367(25):2385–95.

    Article  PubMed  Google Scholar 

  75. Quartier P, Allantaz F, Cimaz R, Pillet P, Messiaen C, Bardin C, et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis. 2011;70(5):747–54.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Michael Cohen-Wolkowiez receives support for research from the National Institutes of Health (1R01-HD076676-01A1), the National Institute of Allergy and Infectious Disease (HHSN272201500006I and HHSN272201300017I), the National Institute of Child Health and Human Development (HHSN275201000003I), the Biomedical Advanced Research and Development Authority (HHSO100201300009C), and Industry for drug development in adults and children.

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Authors and Affiliations

  1. Division of Pediatric Rheumatology, Duke University Medical Center, 2301 Erwin Road, CHC, T-Level, Durham, NC, 27710, USA

    Stephen J. Balevic & Laura E. Schanberg

  2. Department of Pediatrics, Children’s Mercy Kansas City, UMKC School of Medicine, 2401 Gillham Road, Kansas City, MO, 64108, USA

    Mara L. Becker

  3. Pharmacometrics Center, Duke Clinical Research Institute, 2400 Pratt St., Durham, NC, 27710, USA

    Michael Cohen-Wolkowiez

  4. Immunology and Inflammation Medicine, Duke Clinical Research Institute, Duke University Medical Center, 2400 Pratt St., Durham, NC, 27710, USA

    Laura E. Schanberg

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Correspondence to Stephen J. Balevic.

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Stephen J. Balevic receives salary and research support from the National Institute of General Medical Sciences and the National Institute of Child Health and Human Development (2T32GM086330-06). The National Institutes of Health sponsor Open Access. Laura E. Schanberg receives research support from the National Institutes of Health (5R01-AR063890-02), Patient-Centered Outcomes Research Institute (CER-1408-20534 and PPRN-1306-04601), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (1U19AR069522-01), and participates in the Data Safety and Monitoring Board for Sanofi, and the Swedish Orphan Biovitrum AB. Mara L. Becker and Michael Cohen-Wolkowiez have no conflicts of interest that are directly relevant to this article. This article did not involve the use of human participants or animals.

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Balevic, S.J., Becker, M.L., Cohen-Wolkowiez, M. et al. Clinical Trial Design in Juvenile Idiopathic Arthritis. Pediatr Drugs 19, 379–389 (2017). https://doi.org/10.1007/s40272-017-0244-2

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