{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:47:16Z","timestamp":1790689636477,"version":"4.1.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2010,6,20]],"date-time":"2010-06-20T00:00:00Z","timestamp":1276992000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Epidemiol"],"published-print":{"date-parts":[[2010,8]]},"DOI":"10.1007\/s10654-010-9480-2","type":"journal-article","created":{"date-parts":[[2010,6,21]],"date-time":"2010-06-21T00:16:31Z","timestamp":1277079391000},"page":"593-601","source":"Crossref","is-referenced-by-count":6,"title":["Fewer infants than older patients in paediatric randomised controlled trials"],"prefix":"10.1007","volume":"25","author":[{"given":"Fran\u00e7ois","family":"Angoulvant","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florentia","family":"Kaguelidou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Dauger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Alberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,6,20]]},"reference":[{"key":"9480_CR1","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1053\/j.seminoncol.2008.07.008","volume":"35","author":"M O\u2019Leary","year":"2008","unstructured":"O\u2019Leary M, Krailo M, Anderson JR, Reaman GH. Progress in childhood cancer: 50\u00a0years of research collaboration, a report from the Children\u2019s Oncology Group. Semin Oncol. 2008;35:484\u201393.","journal-title":"Semin Oncol"},{"key":"9480_CR2","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0140-6736(04)16942-0","volume":"364","author":"PH Caldwell","year":"2004","unstructured":"Caldwell PH, Murphy SB, Butow PN, Craig JC. Clinical trials in children. Lancet. 2004;364:803\u201311.","journal-title":"Lancet"},{"key":"9480_CR3","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1136\/bmj.320.7227.79","volume":"320","author":"S Conroy","year":"2000","unstructured":"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\u201382.","journal-title":"BMJ"},{"key":"9480_CR4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2005.12.001","volume":"58","author":"NY Rakhmanina","year":"2006","unstructured":"Rakhmanina NY, van den Anker JN. Pharmacological research in pediatrics: from neonates to adolescents. Adv Drug Deliv Rev. 2006;58:4\u201314.","journal-title":"Adv Drug Deliv Rev"},{"key":"9480_CR5","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1001\/archpedi.161.3.282","volume":"161","author":"SS Shah","year":"2007","unstructured":"Shah SS, Hall M, Goodman DM, Feuer P, Sharma V, Fargason C Jr, et al. Off-label drug use in hospitalized children. Arch Pediatr Adolesc Med. 2007;161:282\u201390.","journal-title":"Arch Pediatr Adolesc Med"},{"key":"9480_CR6","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1542\/peds.104.S3.585","volume":"104","author":"JT Wilson","year":"1999","unstructured":"Wilson JT. An update on the therapeutic orphan. Pediatrics. 1999;104:585\u201390.","journal-title":"Pediatrics"},{"key":"9480_CR7","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1097\/01.inf.0000101847.22501.e7","volume":"22","author":"JC Salazar","year":"2003","unstructured":"Salazar JC. Pediatric clinical trial experience: government, child, parent and physician\u2019s perspective. Pediatr Infect Dis J. 2003;22:1124\u20137.","journal-title":"Pediatr Infect Dis J"},{"key":"9480_CR8","unstructured":"Best Pharmaceuticals for Children Act. 107th Cong (January 4, 2002) ed."},{"key":"9480_CR9","unstructured":"Better Medicines for Children\u2014proposed regulatory actions in paediatric medicinal products. Brussels: European Commission; 2002."},{"key":"9480_CR10","unstructured":"AAMC. Principles for protecting integrity in the conduct and reporting of clinical trials. Approved by AAMC Executive Committee; 2005."},{"key":"9480_CR11","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1542\/peds.2007-2849","volume":"122","author":"C Martinez-Castaldi","year":"2008","unstructured":"Martinez-Castaldi C, Silverstein M, Bauchner H. Child versus adult research: the gap in high-quality study design. Pediatrics. 2008;122:52\u20137.","journal-title":"Pediatrics"},{"key":"9480_CR12","doi-asserted-by":"crossref","first-page":"e172","DOI":"10.1371\/journal.pmed.0050172","volume":"5","author":"TP Klassen","year":"2008","unstructured":"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.","journal-title":"PLoS Med"},{"key":"9480_CR13","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1001\/archpediatrics.2009.291","volume":"164","author":"E Cohen","year":"2010","unstructured":"Cohen E, Goldman RD, Ragone A, Uleryk E, Atenafu EG, Siddiqui U, et al. Child vs adult randomized controlled trials in specialist journals: a citation analysis of trends, 1985\u20132005. Arch Pediatr Adolesc Med. 2010;164:283\u20138.","journal-title":"Arch Pediatr Adolesc Med"},{"key":"9480_CR14","doi-asserted-by":"crossref","first-page":"e166","DOI":"10.1371\/journal.pmed.0050166","volume":"5","author":"S Rheims","year":"2008","unstructured":"Rheims S, Cucherat M, Arzimanoglou A, Ryvlin P. Greater response to placebo in children than in adults: a systematic review and meta-analysis in drug-resistant partial epilepsy. PLoS Med. 2008;5:e166.","journal-title":"PLoS Med"},{"key":"9480_CR15","unstructured":"EMEA. Note for guidance on clinical investigation of medicinal products in the paediatric population (E11): the international conference on harmonisation of technical requirements for registration of pharmaceuticals for human use; 2002."},{"key":"9480_CR16","unstructured":"ICH. U.S. Department of Health. FDA. Guidance for Industry E11 Clinical investigation of medicinal products in the Pediatric Population. The international conference on harmonisation of technical requirements for registration of pharmaceuticals for human use; 2000."},{"key":"9480_CR17","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1001\/archpediatrics.2009.573","volume":"164","author":"FP Rivara","year":"2010","unstructured":"Rivara FP, Alexander D. Randomized controlled trials and pediatric research. Arch Pediatr Adolesc Med. 2010;164:296\u20137.","journal-title":"Arch Pediatr Adolesc Med"},{"key":"9480_CR18","unstructured":"The International Forum of Standards for Research with Children. [cited December 7, 2009]; Available from: http:\/\/www.ifsrc.org\/ ."},{"key":"9480_CR19","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1001\/jama.287.21.2805","volume":"287","author":"KP Lee","year":"2002","unstructured":"Lee KP, Schotland M, Bacchetti P, Bero LA. Association of journal quality indicators with methodological quality of clinical research articles. Jama. 2002;287:2805\u20138.","journal-title":"Jama"},{"key":"9480_CR20","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jclinepi.2007.05.010","volume":"61","author":"RM Gow","year":"2008","unstructured":"Gow RM, Barrowman NJ, Lai L, Moher D. A review of five cardiology journals found that observer variability of measured variables was infrequently reported. J Clin Epidemiol. 2008;61:394\u2013401.","journal-title":"J Clin Epidemiol"},{"key":"9480_CR21","unstructured":"WHO. International Statistical Classification of Diseases and Related Health Problems 10th Revision Version for 2006. Available from: http:\/\/apps.who.int\/classifications\/apps\/icd\/icd10online2006\/ ."},{"key":"9480_CR22","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0300-483X(03)00249-X","volume":"192","author":"TN Johnson","year":"2003","unstructured":"Johnson TN. The development of drug metabolising enzymes and their influence on the susceptibility to adverse drug reactions in children. Toxicology. 2003;192:37\u201348.","journal-title":"Toxicology"},{"key":"9480_CR23","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1056\/NEJM196004212621601","volume":"262","author":"CF Weiss","year":"1960","unstructured":"Weiss CF, Glazko AJ, Weston JK. Chloramphenicol in the newborn infant. A physiologic explanation of its toxicity when given in excessive doses. N Engl J Med. 1960;262:787\u201394.","journal-title":"N Engl J Med"},{"key":"9480_CR24","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1183\/09031936.04.00015404","volume":"23","author":"GW 't Jong","year":"2004","unstructured":"'t Jong GW, Eland IA, Sturkenboom MC, van den Anker JN, Strickerf BH. Unlicensed and off-label prescription of respiratory drugs to children. Eur Respir J. 2004;23:310\u20133.","journal-title":"Eur Respir J"},{"key":"9480_CR25","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1542\/peds.111.2.291","volume":"111","author":"E Schirm","year":"2003","unstructured":"Schirm E, Tobi H, den Berg LT. Risk factors for unlicensed and off-label drug use in children outside the hospital. Pediatrics. 2003;111:291\u20135.","journal-title":"Pediatrics"},{"key":"9480_CR26","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1055\/s-2002-23557","volume":"19","author":"J Barr","year":"2002","unstructured":"Barr J, Brenner-Zada G, Heiman E, Pareth G, Bulkowstein M, Greenberg R, et al. Unlicensed and off-label medication use in a neonatal intensive care unit: a prospective study. Am J Perinatol. 2002;19:67\u201372.","journal-title":"Am J Perinatol"},{"key":"9480_CR27","unstructured":"Freid VM, Makuc DM, Rooks RN. Ambulatory health care visits by children: principal diagnosis and place of visit. Vital Health Stat. 1998:1\u201323."},{"key":"9480_CR28","doi-asserted-by":"crossref","unstructured":"Akinbami LJ, Moorman JE, Garbe PL, Sondik EJ. Status of childhood asthma in the United States, 1980\u20132007. Pediatrics. 2009;123(Suppl 3):S1:31\u201345.","DOI":"10.1542\/peds.2008-2233C"},{"key":"9480_CR29","unstructured":"DeFrances CJ, Cullen KA, Kozak LJ. National Hospital Discharge Survey: 2005 annual summary with detailed diagnosis and procedure data. Vital Health Stat. 2007:1\u2013209."},{"key":"9480_CR30","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1001\/jama.2010.104","volume":"303","author":"J Cleave Van","year":"2010","unstructured":"Van Cleave J, Gortmaker SL, Perrin JM. Dynamics of obesity and chronic health conditions among children and youth. Jama. 2010;303:623\u201330.","journal-title":"Jama"},{"key":"9480_CR31","unstructured":"WHO. Global health risks: mortality and burden of disease attributable to selected major risks; 2009."},{"key":"9480_CR32","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1542\/peds.2005-0620C","volume":"117","author":"KJ Anand","year":"2006","unstructured":"Anand KJ, Aranda JV, Berde CB, Buckman S, Capparelli EV, Carlo W, et al. Summary proceedings from the neonatal pain-control group. Pediatrics. 2006;117:S9\u201322.","journal-title":"Pediatrics"},{"key":"9480_CR33","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1001\/jama.296.10.1266","volume":"296","author":"DK Benjamin Jr","year":"2006","unstructured":"Benjamin DK Jr, 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\u201373.","journal-title":"Jama"},{"key":"9480_CR34","doi-asserted-by":"crossref","first-page":"e124","DOI":"10.1371\/journal.pmed.0020124","volume":"2","author":"JP Ioannidis","year":"2005","unstructured":"Ioannidis JP. Why most published research findings are false. PLoS Med. 2005;2:e124.","journal-title":"PLoS Med"},{"issue":"Suppl 2","key":"9480_CR35","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1038\/sj.jp.7211423","volume":"26","author":"RM Ward","year":"2006","unstructured":"Ward RM, Lane RH, Albertine KH. Basic and translational research in neonatal pharmacology. J Perinatol. 2006;26(Suppl 2):S8\u201312.","journal-title":"J Perinatol"},{"key":"9480_CR36","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.drudis.2008.07.007","volume":"14","author":"SN Wildt de","year":"2009","unstructured":"de Wildt SN, Ito S, Koren G. Challenges for drug studies in children: CYP3A phenotyping as example. Drug Discov Today. 2009;14:6\u201315.","journal-title":"Drug Discov Today"},{"key":"9480_CR37","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.jpeds.2008.04.060","volume":"153","author":"ES Thingvoll","year":"2008","unstructured":"Thingvoll ES, Guillet R, Caserta M, Dicenzo R. Observational trial of a 48-hour gentamicin dosing regimen derived from Monte Carlo simulations in infants born at less than 28\u00a0weeks\u2019 gestation. J Pediatr. 2008;153:530\u20134.","journal-title":"J Pediatr"},{"key":"9480_CR38","first-page":"271","volume":"12","author":"P Politis","year":"2005","unstructured":"Politis P. Transition from the carrot to the stick: the evolution of pharmaceutical regulations concerning pediatric drug testing. Widener Law Rev. 2005;12:271.","journal-title":"Widener Law Rev"},{"key":"9480_CR39","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1001\/jama.297.5.480","volume":"297","author":"JS Li","year":"2007","unstructured":"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\u20138.","journal-title":"Jama"},{"key":"9480_CR40","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/S0091-6749(99)70075-8","volume":"104","author":"P Lozano","year":"1999","unstructured":"Lozano P, Sullivan SD, Smith DH, Weiss KB. The economic burden of asthma in US children: estimates from the National Medical Expenditure Survey. J Allergy Clin Immunol. 1999;104:957\u201363.","journal-title":"J Allergy Clin Immunol"},{"key":"9480_CR41","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1183\/09031936.03.00057002","volume":"21","author":"CA Stevens","year":"2003","unstructured":"Stevens CA, Turner D, Kuehni CE, Couriel JM, Silverman M. The economic impact of preschool asthma and wheeze. Eur Respir J. 2003;21:1000\u20136.","journal-title":"Eur Respir J"},{"key":"9480_CR42","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1001\/jama.1996.03540080059030","volume":"276","author":"C Begg","year":"1996","unstructured":"Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I, et al. Improving the quality of reporting of randomized controlled trials. The CONSORT statement. Jama. 1996;276:637\u20139.","journal-title":"Jama"}],"container-title":["European Journal of Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10654-010-9480-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10654-010-9480-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10654-010-9480-2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T17:19:08Z","timestamp":1685639948000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10654-010-9480-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,20]]},"references-count":42,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2010,8]]}},"alternative-id":["9480"],"URL":"https:\/\/doi.org\/10.1007\/s10654-010-9480-2","relation":{},"ISSN":["0393-2990","1573-7284"],"issn-type":[{"value":"0393-2990","type":"print"},{"value":"1573-7284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,20]]}}}