{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:25:02Z","timestamp":1793330702172,"version":"4.5.0"},"reference-count":34,"publisher":"American Academy of Pediatrics (AAP)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,9,1]]},"abstract":"<jats:p>OBJECTIVES. The Food and Drug Administration Modernization Act provided for an additional 6-month period of marketing exclusivity to companies that perform pediatric drug trials in response to a Food and Drug Administration\u2013issued written request. Because many safety concerns cannot be detected until after the introduction of a product to a larger and more diverse market, the Best Pharmaceuticals for Children Act required the Food and Drug Administration to report to the Pediatric Advisory Committee on adverse events occurring during the 1-year period after granting pediatric exclusivity. We sought to describe the Pediatric Advisory Committee's recommendations made in response to safety reviews informed by data from the Food and Drug Administration Adverse Event Reporting System in 67 drugs granted exclusivity.<\/jats:p><jats:p>PATIENTS AND METHODS. Pediatric Advisory Committee meetings and data presented by the Food and Drug Administration for all drugs were reviewed from June 2003 through April 2007. We divided the drugs into 2 groups: those that were returned to routine adverse event monitoring and those that had specific Pediatric Advisory Committee recommendations.<\/jats:p><jats:p>RESULTS. Forty-four (65.7%) drugs were returned to routine monitoring for adverse events. The Pediatric Advisory Committee, sometimes working with other advisory committees, recommended label changes for 12 (17.9%) drugs, continued monitoring for 10 (14.9%), production of MedGuides for 9 (13.4%), and an update on label changes resulting from discussions with the sponsor for 1 (1.5%) drug. Some drugs had &amp;gt;1 action. Several of the adverse events revealed during this process were rare and life-threatening.<\/jats:p><jats:p>CONCLUSIONS. Safety monitoring during the early postmarketing period is crucial to detect rare, serious, or pediatric-specific adverse events. Fortunately, the majority of drugs given exclusivity had no adverse events of a frequency or severity that prevented a return to routine adverse event monitoring.<\/jats:p>","DOI":"10.1542\/peds.2008-0585","type":"journal-article","created":{"date-parts":[[2008,9,1]],"date-time":"2008-09-01T13:27:57Z","timestamp":1220275677000},"page":"e628-e633","source":"Crossref","is-referenced-by-count":36,"title":["Safety Monitoring of Drugs Receiving Pediatric Marketing Exclusivity"],"prefix":"10.1542","volume":"122","author":[{"given":"P. Brian","family":"Smith","sequence":"first","affiliation":[{"name":"Food and Drug Administration, Rockville, Maryland"},{"name":"Departments of Pediatrics and Medicine and Duke Clinical Research Institute, Duke University, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Daniel K.","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Food and Drug Administration, Rockville, Maryland"},{"name":"Departments of Pediatrics and Medicine and Duke Clinical Research Institute, Duke University, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Dianne","family":"Murphy","sequence":"additional","affiliation":[{"name":"Food and Drug Administration, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Johann-Liang","sequence":"additional","affiliation":[{"name":"Food and Drug Administration, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon","family":"Iyasu","sequence":"additional","affiliation":[{"name":"Food and Drug Administration, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Gould","sequence":"additional","affiliation":[{"name":"Food and Drug Administration, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Califf","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Medicine and Duke Clinical Research Institute, Duke University, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Li","sequence":"additional","affiliation":[{"name":"Food and Drug Administration, Rockville, Maryland"},{"name":"Departments of Pediatrics and Medicine and Duke Clinical Research Institute, Duke University, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Food and Drug Administration, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2008,9,1]]},"reference":[{"key":"2021120905250317000_R1","unstructured":"Food and Drug Administration Modernization Act of 1997, 111 Stat 2296, 105th Congress;1997:107\u2013109"},{"key":"2021120905250317000_R2","doi-asserted-by":"crossref","unstructured":"Benjamin DK Jr, Smith PB, Murphy MD, et al. Peer-reviewed publication of clinical trials completed for pediatric exclusivity. JAMA.\u20082006;296(10):1266\u20131273","DOI":"10.1001\/jama.296.10.1266"},{"key":"2021120905250317000_R3","doi-asserted-by":"crossref","unstructured":"Li JS, Eisenstein EL, Grabowski HG, et al. Economic return of clinical trials performed under the pediatric exclusivity program. JAMA.\u20082007;297(5):480\u2013488","DOI":"10.1001\/jama.297.5.480"},{"key":"2021120905250317000_R4","unstructured":"Best Pharmaceuticals for Children Act, Vol115, Stat 1408;2002:107\u2013109. Available at: www.fda.gov\/opacom\/laws\/pharmkids\/pharmkids.html. Accessed September 1,2007"},{"key":"2021120905250317000_R5","unstructured":"Food and Drug Administration. Drugs granted pediatric exclusivity. Available at: www.fda.gov\/CDER\/pediatric\/exgrant.htm. Accessed September 1,2007"},{"key":"2021120905250317000_R6","unstructured":"Food and Drug Administration. Safety reporting. Available at: www.fda.gov\/oc\/opt\/pediatricsafety.html. Accessed September 1,2007"},{"key":"2021120905250317000_R7","unstructured":"Iyasu S; Food and Drug Administration. One year post-pediatric postmarketing adverse event review. Available at: www.fda.gov\/ohrms\/dockets\/ac\/03\/slides\/3965S2_01_Iyasu_files\/frame.htm. Accessed September 1,2007"},{"key":"2021120905250317000_R8","unstructured":"Iyasu S; Food and Drug Administration. One year post exclusivity adverse event review: fentanyl transdermal system. Available at: www.fda.gov\/ohrms\/dockets\/ac\/04\/slides\/2004-4050S1_08_McNeil.ppt. Accessed September 1,2007"},{"key":"2021120905250317000_R9","unstructured":"Phelan KM; Food and Drug Administration. Executive summary. Available at: www.fda.gov\/ohrms\/dockets\/ac\/05\/briefing\/2005-4152b2_01_01_01_Concerta%20AE.pdf. Accessed September 1,2007"},{"key":"2021120905250317000_R10","unstructured":"Truffa MM; Food and Drug Administration. One year post-exclusivity adverse event review for Tamiflu (oseltamivir). Available at: www.fda.gov\/ohrms\/dockets\/ac\/05\/slides\/2005-4180s_03_truffa_files\/frame.htm. Accessed on September 1,2007"},{"key":"2021120905250317000_R11","doi-asserted-by":"crossref","unstructured":"Bruno I, Pennesi M, Marchetti F. ACE-inhibitors-induced metabolic acidosis in a child with nephrotic syndrome. Pediatr Nephrol.\u20082003;18(12):1293\u20131294","DOI":"10.1007\/s00467-003-1282-2"},{"key":"2021120905250317000_R12","unstructured":"Grylack L; Food and Drug Administration. One year post-exclusivity adverse event review: benazepril. Available at: www.fda.gov\/ohrms\/dockets\/ac\/05\/slides\/2005-4089s1_01_Benazepril.pdf. Accessed September 1,2007"},{"key":"2021120905250317000_R13","unstructured":"Grylack L; Food and Drug Administration. One year post-exclusivity adverse event review: esmolol. Available at: www.fda.gov\/ohrms\/dockets\/ac\/05\/slides\/2005-4089s1_02_Esmolol.pdf. Accessed September 1,2007"},{"key":"2021120905250317000_R14","unstructured":"Wassel R; Food and Drug Administration. Executive summary. Available at: www.fda.gov\/ohrms\/dockets\/ac\/06\/briefing\/2006-4254b_02_01_LinezolidSafetyReview%20Redacted_D50101_06232.pdf. Accessed September 1,2007"},{"key":"2021120905250317000_R15","doi-asserted-by":"crossref","unstructured":"Truong U, Moon-Grady AJ, Butani L. Cardiac tamponade in a pediatric renal transplant recipient on sirolimus therapy. Pediatr Transplant.\u20082005;9(4):541\u2013544","DOI":"10.1111\/j.1399-3046.2005.00323.x"},{"key":"2021120905250317000_R16","unstructured":"Farinas ER; Food and Drug Administration. Executive summary. Available at: www.fda.gov\/ohrms\/dockets\/ac\/06\/briefing\/2006-4254b_04_02_Sirolimus%20Safety%20Review%20Redacted_D040771_02.pdf. Accessed September 1,2007"},{"key":"2021120905250317000_R17","doi-asserted-by":"crossref","unstructured":"Strom BL. Potential for conflict of interest in the evaluation of suspected adverse drug reactions: a counterpoint. JAMA.\u20082004;292(21):2643\u20132646","DOI":"10.1001\/jama.292.21.2643"},{"key":"2021120905250317000_R18","unstructured":"Iyasu S, Murphy MD. Pharmacovigilance. 2nd ed. Waterlooville, United Kingdom: John Wiley & Sons, Ltd;2007"},{"key":"2021120905250317000_R19","doi-asserted-by":"crossref","unstructured":"Andersen DH, Blanc WA, Crozier DN, Silverman WA. A difference in mortality rate and incidence of kernicterus among premature infants allotted to two prophylactic antibacterial regimens. Pediatrics.\u20081956;18(4):614\u2013625","DOI":"10.1542\/peds.18.4.614"},{"key":"2021120905250317000_R20","doi-asserted-by":"crossref","unstructured":"Gilman JT, Gal P. Pharmacokinetic and pharmacodynamic data collection in children and neonates. A quiet frontier. Clin Pharmacokinet.\u20081992;23(1):1\u20139","DOI":"10.2165\/00003088-199223010-00001"},{"key":"2021120905250317000_R21","doi-asserted-by":"crossref","unstructured":"Wilson JT. An update on the therapeutic orphan. Pediatrics.\u20081999;104(3 pt 2):585\u2013590","DOI":"10.1542\/peds.104.S3.585"},{"key":"2021120905250317000_R22","doi-asserted-by":"crossref","unstructured":"Moore TJ, Psaty BM, Furberg CD. Time to act on drug safety. JAMA.\u20081998;279(19):1571\u20131573","DOI":"10.1001\/jama.279.19.1571"},{"key":"2021120905250317000_R23","doi-asserted-by":"crossref","unstructured":"Brewer T, Colditz GA. Postmarketing surveillance and adverse drug reactions: current perspectives and future needs. JAMA.\u20081999;281(9):824\u2013829","DOI":"10.1001\/jama.281.9.824"},{"key":"2021120905250317000_R24","doi-asserted-by":"crossref","unstructured":"Fontanarosa PB, Rennie D, DeAngelis CD. Postmarketing surveillance: lack of vigilance, lack of trust. JAMA.\u20082004;292(21):2647\u20132650","DOI":"10.1001\/jama.292.21.2647"},{"key":"2021120905250317000_R25","doi-asserted-by":"crossref","unstructured":"Psaty BM, Charo RA. FDA responds to institute of medicine drug safety recommendations\u2014in part. JAMA.\u20082007;297(17):1917\u20131920","DOI":"10.1001\/jama.297.17.1917"},{"key":"2021120905250317000_R26","unstructured":"Department of Health and Human Services. Report on the performance of drug and biologics firms in conducting postmarketing commitment studies. Available at: http:\/\/a257.g.akamaitech.net\/7\/257\/2422\/01jan20071800\/edocket.access.gpo.gov\/2007\/E7-1749.htm. Accessed September 1,2007"},{"key":"2021120905250317000_R27","doi-asserted-by":"crossref","unstructured":"Wysowski DK, Swartz L. Adverse drug event surveillance and drug withdrawals in the United States, 1969\u20132002: the importance of reporting suspected reactions. Arch Intern Med.\u20082005;165(12):1363\u20131369","DOI":"10.1001\/archinte.165.12.1363"},{"key":"2021120905250317000_R28","doi-asserted-by":"crossref","unstructured":"Kessler DA. Introducing MEDWatch. A new approach to reporting medication and device adverse effects and product problems. JAMA.\u20081993;269(21):2765\u20132768","DOI":"10.1001\/jama.269.21.2765"},{"key":"2021120905250317000_R29","doi-asserted-by":"crossref","unstructured":"Nebeker JR, Barach P, Samore MH. Clarifying adverse drug events: a clinician's guide to terminology, documentation, and reporting. Ann Intern Med.\u20082004;140(10):795\u2013801","DOI":"10.7326\/0003-4819-140-10-200405180-00009"},{"key":"2021120905250317000_R30","unstructured":"General Accounting Office. FDA drug review: postapproval risks 1976\u20131985. Available at: www.mindfully.org\/Health\/FDA-Postapproval-RisksGAOApr1990.htm. Accessed September 1,2007"},{"key":"2021120905250317000_R31","doi-asserted-by":"crossref","unstructured":"Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH. Timing of new black box warnings and withdrawals for prescription medications. JAMA.\u20082002;287(17):2215\u20132220","DOI":"10.1001\/jama.287.17.2215"},{"key":"2021120905250317000_R32","unstructured":"Food and Drug Administration. Postmarketing study commitments introduction. Available at: www.fda.gov\/cder\/pmc. Accessed March 19,2008"},{"key":"2021120905250317000_R33","doi-asserted-by":"crossref","unstructured":"American Academy of Pediatrics, Committee on Drugs. Guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations. Pediatrics.\u20081995;95(2):286\u2013294","DOI":"10.1542\/peds.95.2.286"},{"key":"2021120905250317000_R34","doi-asserted-by":"crossref","unstructured":"Roberts R, Rodriguez W, Murphy D, Crescenzi T. Pediatric drug labeling: improving the safety and efficacy of pediatric therapies. JAMA.\u20082003;290(7):905\u2013911","DOI":"10.1001\/jama.290.7.905"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/122\/3\/e628\/1175873\/zpe0090800e628.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/122\/3\/e628\/1175873\/zpe0090800e628.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T20:29:09Z","timestamp":1684528149000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/122\/3\/e628\/72277\/Safety-Monitoring-of-Drugs-Receiving-Pediatric"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9,1]]},"references-count":34,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2008,9,1]]},"published-print":{"date-parts":[[2008,9,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2008-0585","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9,1]]}}}