The Journal of Pediatrics
Volume 157, Issue 2 , Pages 322-330.e17 , August 2010

Comparative Effectiveness of Medical Interventions in Adults Versus Children

  • Despina G. Contopoulos-Ioannidis, MD

      Affiliations

    • Department of Pediatrics, University of Ioannina School of Medicine, Ioannina, Greece
    • ,
  • Maria S. Baltogianni, MD

      Affiliations

    • Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
    • Neonatal Intensive Care Unit, University Hospital, Ioannina, Greece
    • ,
  • John P.A. Ioannidis, MD

      Affiliations

    • Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
    • Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, MA
    • Biomedical Research Institute, Foundation for Research and Technology-Hellas, Ioannina, Greece
    • Department of Epidemiology, Harvard School of Public Health, Boston, MA
    • Corresponding Author InformationReprint requests: Dr John P.A. Ioannidis, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece, 45110.

Received 14 August 2009 ,Revised 15 January 2010 ,Accepted 9 February 2010.

References 

  1. Budetti PP. Ensuring safe and effective medications for children. JAMA. 2003;290:950–951
  2. Roberts R, Rodriguez W, Murphy D, Crescenzi T. Pediatric drug labeling: improving the safety and efficacy of pediatric therapies. JAMA. 2003;290:905–911
  3. Conroy S, Choonara I, Impicciatore P, Mohn A, Arnell H, Rane A, et al. Survey of unlicensed and off label drug use in paediatric wards in European countries. European Network for Drug Investigation in Children. BMJ. 2000;320:79–82
  4. Ceci A, Felisi M, Catapano M, Baiardi P, Cipollina L, Ravera S, et al. Medicines for children licensed by the European Agency for the Evaluation of Medicinal Products. Eur J Clin Pharmacol. 2002;58:495–500
  5. Milne CP, Bruss JB. The economics of pediatric formulation development for off-patent drugs. Clin Ther. 2008;30:2133–2145
  6. Specific requirements on content and format of labeling for human prescription drugs: revision of "pediatric use: subsection in the labeling, 59 Federal Register 64240 (1994).
  7. Mullen CA, Petropoulos D, Roberts WM, Rytting M, Zipf T, Chan KW, et al. Outpatient treatment of fever and neutropenia for low risk pediatric cancer patients. Cancer. 1999;86:126–134
  8. Macfadyen C, Gamble C, Garner P, Macharia I, Mackenzie I, Mugwe P, et al. Topical quinolone vs antiseptic for treating chronic suppurative otitis media: a randomized controlled trial. Trop Med Int Health. 2005;10:190–197
  9. http://www.childrenshospital.org/.
  10. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188
  11. Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127:820–826
  12. Ioannidis JP, Patsopoulos NA, Evangelou E. Uncertainty in heterogeneity estimates in meta-analyses. BMJ. 2007;335:914–916
  13. Sterne JA, Jüni P, Schulz KF, Altman DG, Bartlett C, Egger M. Statistical methods for assessing the influence of study characteristics on treatment effects in ‘meta-epidemiological’ research. Stat Med. 2002;21:1513–1524
  14. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–1558
  15. Ni Chroinin M, Lasserson TJ, Greenstone I, Ducharme FM. Addition of long-acting beta-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2009;3;(CD007949)
  16. Molyneux EM, Walsh AL, Forsyth H, Tembo M, Mwenechanya J, Kayira K, et al. Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial. Lancet. 2002;360:211–218
  17. Mongelluzzo J, Mohamad Z, Ten Have TR, Shah SS. Corticosteroids and mortality in children with bacterial meningitis. JAMA. 2008;299:2048–2055
  18. 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;60:118–123
  19. Martinez-Castaldi C, Silverstein M, Bauchner H. Child versus adult research: the gap in high-quality study design. Pediatrics. 2008;122:52–57
  20. Sinha G. EU law mandates drug testing in children. J Natl Cancer Inst. 2008;100:84–85
  21. World Health Organization. Make medicines child size. 2007. Available at: www.who.int/childmedicines/en/.
  22. Choonara I. Regulation of drugs for children in Europe. BMJ. 2007;335:1221–1222
  23. Benjamin DK, Smith PB, Murphy MD, Roberts R, Mathis L, Avant D, et al. Peer-reviewed publication of clinical trials completed for pediatric exclusivity. JAMA. 2006;296:1266–1273
  24. Pandolfini C, Bonati M. A literature review on off-label drug use in children. Eur J Pediatr. 2005;164:552–558
  25. Boots I, Sukhai RN, Klein RH, Holl RA, Wit JM, Cohen AF, et al. Stimulation programs for pediatric drug research: do children really benefit?. Eur J Pediatr. 2007;166:849–855
  26. Bazzano AT, Mangione-Smith R, Schonlau M, Suttorp MJ, Brook RH. Off-label prescribing to children in the United States outpatient setting. Acad Pediatr. 2009;9:81–88
  27. Pandolfini C, Bonati M. European paediatric research and children's therapeutic needs: a trial review. Acta Paediatr. 2008;97:1232–1237
  28. Benjamin DK, 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;51:834–840
  29. Caldwell PH, Murphy SB, Butow PN, Craig JC. Clinical trials in children. Lancet. 2004;364:803–811
  30. Food and Drug Administration. Breakdown of requested studies report (as of March 31, 2009) at: www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm050001.htm.
  31. Cramer K, Wiebe N, Moyer V, Hartling L, Williams K, Swingler G, et al. Children in reviews: methodological issues in child-relevant evidence syntheses. BMC Pediatr. 2005;5:38
  32. Rodriguez W, Selen A, Avant D, Chaurasia C, Crescenzi T, Gieser G, et al. Improving pediatric dosing through pediatric initiatives: what we have learned. Pediatrics. 2008;121:530–539
  33. Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology-drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349:1157–1167
  34. Shaddy RE, Boucek MM, Hsu DT, Boucek RJ, Canter CE, Mahony L, et al. Carvedilol for children and adolescents with heart failure: a randomized controlled trial. JAMA. 2007;298:1171–1179
  35. Olsen O, Middleton P, Ezzo J, Gøtzsche PC, Hadhazy V, Herxheimer A, et al. Quality of Cochrane reviews: assessment of sample from 1998. BMJ. 2001;323:829–832
  36. Jüni P, Witschi A, Bloch R, Egger M. The hazards of scoring the quality of clinical trials for meta-analysis. JAMA. 1999;282:1054–1060
  37. Ioannidis JP, Lau J. Can quality of clinical trials and meta-analyses be quantified?. Lancet. 1998;352:590–591
  38. Ioannidis JP, Lau J. Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas. JAMA. 2001;285:437–443
  39. Ioannidis JP, Evans SJ, Gøtzsche PC, O'Neill RT, Altman DG, Schulz K, et al. Better reporting of harms in randomized trials: an extension of the CONSORT statement. Ann Intern Med. 2004;141:781–788
  40. Ioannidis JP. Adverse events in randomized trials: neglected, restricted, distorted, and silenced. Arch Intern Med. 2009;169:1737–1739
  41. Papanikolaou PN, Ioannidis JP. Availability of large-scale evidence on specific harms from systematic reviews of randomized trials. Am J Med. 2004;117:582–589
  42. European Medicines Agency. Evidence of harm from off-label or unlicensed medicines in children. European Medicines Agency preauthorisation evaluation of medicines for human use. London: EMA; 2004;(EMEA /126327/2004)
  43. Strom BL. How the US drug safety system should be changed. JAMA. 2006;295:2072–2075
  44. Fontanarosa PB, Rennie D, DeAngelis CD. Postmarketing surveillance: lack of vigilance, lack of trust. JAMA. 2004;292:2647–2650
  45. Smith PB, Benjamin DK, Murphy MD, Johann-Liang R, Iyasu S, Gould B, et al. Safety monitoring of drugs receiving pediatric marketing exclusivity. Pediatrics. 2008;122:e628–e633
  46. Li JS, Eisenstein EL, Grabowski HG, Reid ED, Mangum B, Schulman KA, et al. Economic return of clinical trials performed under the pediatric exclusivity program. JAMA. 2007;297:480–488
  47. Sturkenboom MC, Verhamme KM, Nicolosi A, Murray ML, Neubert A, Caudri D, et al. Drug use in children: cohort study in three European countries. BMJ. 2008;337:a2245
  48. Klassen TP, Hartling L, Craig JC, Offringa M. Children are not just small adults: the urgent need for high-quality trial evidence in children. PLoS Med. 2008;5:e172

 The authors declare no conflicts of interest.

PII: S0022-3476(10)00121-6

doi: 10.1016/j.jpeds.2010.02.011

The Journal of Pediatrics
Volume 157, Issue 2 , Pages 322-330.e17 , August 2010

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