The Meanings of “Pediatric Drug Development”

Rose K, Walson PD. Do paediatric investigation plans (PIPs) advance paediatric healthcare? Paediatr Drugs. 2017;19(6): 515–522.

Rose K, Grant-Kels JM. Pediatric melanoma and drug development. Children (Basel). 2018;5(3).

Janssen WM. A historical perspective on off-label medicine: from regulation, promotion, and the First Amendment to the next frontiers. In: Levy MC, ed. Off-Label Communications. Washington, DC: Food and Drug Law Institute; 2008.

Rägo L, Santo B. Drug regulation: history, present and future. In: van Boxtel CJ, Santo B, Edwards IR, eds. Drug Benefits and Risks: International Textbook of Clinical Pharmacology. Rev. 2nd ed. Uppsala, Sweden: IOS Press & Uppsala Monitoring Centre; 2008:65–77.

Hilts PJ. Protecting America’s Health: The FDA, Business, and One Hundred Years of Regulation. New York: Alfred A. Knopf; 2003.

Burns LE, Hodgman JE, Cass AB. Fatal circulatory collapse in premature infants receiving chloramphenicol. N EngI J Med. 1959 24;261:1318–1321.

Silverman WA, Andersen DH, Blanc WA, Crozier DN. A difference in mortality rate and incidence of kernicterus among premature infants allotted to two prophylactic antibacterial regimens. Pediatrics. 1956;18:614.

Shirkey H. Therapeutic orphans. J Pediatr. 1968;72(1):119–120.

Ward RM, Benjamin DK Jr, Davis JM, et al. The need for pediatric drug development. J Pediatr. 2018;192:13–21.

AAP 1977, Committee on Drugs. Guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations. Pediatrics. 1977;60(1):91–101.

Guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations. Committee on Drugs, American Academy of Pediatrics. Pediatrics. 1995;95(2):286–294.

Hirschfeld S. History of pediatric labeling. https://www.slideserve.com/marlin/history-of-pediatric-labeling.

Hirschfeld S, Saint-Raymond A. Pediatric regulatory initiatives. Handb Exp Pharmacol. 2011;205:245-268.

Field MJ, Boat TF, eds. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA). Washington, DC: National Academies Press, 2012. https://www.ncbi.nlm.nih.gov/books/NBK202043/#sec_0145.

Dunne J, Rodriguez WJ, Murphy MD, et al. Extrapolation of adult data and other data in pediatric drug-development programs. Pediatrics. 2011;128:e1242-e1249.

Sun H, Temeck JW, Chambers W, Perkins G, Bonnel R, Murphy D. Extrapolation of efficacy in pediatric drug development and evidence-based medicine: progress and lessons learned. Therapeutic Innovation & Regulatory Science. 2017;2017:1–7.

Adamson PC. Improving the outcome for children with cancer: development of targeted new agents. CA Cancer J Clin. 2015; 65(3):212–220.

Lee-Sherick AB, Linger RM, Gore L, Keating AK, Graham DK. Targeting paediatric acute lymphoblastic leukaemia: novel therapies currently in development. Br J Haematol. 2010;151(4): 295–311.

Wharton GT, Murphy MD, Avant D, et al. Impact of pediatric exclusivity on drug labeling and demonstrations of efficacy. Pediatrics. 2014;134(2):e512-e518.

Subbiah V. Fast-tracking novel drugs in pediatric oncology. Cell Cycle. 2015;14(8):1127–1128.

Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bitten-court H. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439–448.

Philip AG. The evolution of neonatology. Pediatr Res. 2005; 58(4):799–815.

Hardin AP, Hackell JM; Committee on Practice and Ambulatory Medicine. Age limit of pediatrics. Pediatrics. 2017;140(3).

Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Lee-der JS, Kauffman RE. Developmental pharmacology—drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349(12):1157–1167.

Berde C, Carins B. Developmental pharmacology across species: promise and problems. Anesth Analg. 2000;91(1):1–5.

Poole RL. The history of PPAG: the first 30 years. J Pediatr Pharmacol Ther. 2010;15:72–80.

25th Anniversary of the European Society of Developmental Perinatal and Paediatric Pharmacology. http://www.esdppp.org/site/wp-content/uploads/2013/10/Pharmacology-International-June-2013-pp-8-12.pdf.

Gören JL. Antidepressants use in pediatric populations. Expert Opin Drug Saf. 2008;7(3):223–225.

Hammad TA, Laughren T, Racoosin J. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry. 2006;63(3):332–339.

Varley CK. Treating depression in children and adolescents: what options now? CNS Drugs. 2006;20(1):1–13.

Dawson RS. Depression in children and adolescents: the pediatrician at the front lines. Pediatr Ann. 2018;47(7):e261-e265.

Healy D, Le Noury J, Jureidini J. Paediatric antidepressants: benefits and risks. Int J Risk Saf Med. 2019;30(1):1–7.

Henry A, Kisicki MD, Varley C. Efficacy and safety of antide-pressant drug treatment in children and adolescents. Mol Psychiatry. 2012;17(12):1186–1193.

Plate V. The impact of off-label, compassionate and unlicensed use on health care laws in preselected countries. http://hss.ulb.uni-bonn.de/2009/1936/1936.pdf.

Committee on Drugs. American Academy of Pediatrics. Uses of drugs not described in the package insert (off-label uses). Pediatrics. 2002;110(1, pt 1):181–183.

Blum A, Wolinsky H. AMA rewrites tobacco history. Lancet. 1995;346(29):261.

Declaration of the Rights of the Child. https://www.unicef.org/malaysia/1959-Declaration-of-the-Rights-of-the-Child.pdf.

FDA 2001. The Pediatric Exclusivity Provision. January 2001. Status Report to Congress. https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM049915.pdf.

FDA 2016. Best Pharmaceuticals for Children Act and Pediatric Research Equity Act. July 2016. Status Report to Congress. Department of Health and Human Services. Food and Drug Administration. https://www.fda.gov/downloads/ScienceResearch/SpecialTopics/PediatricTherapeuticsResearch/UCM509815.pdf.

FDA News Release. FDA approves Eucrisa for eczema. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm533371.htm.

EMA 2004. Evidence of harm from off-label or unlicensed medicines in children. http://www.ema.europa.eu/docs/en_GB/document_library/Other/2009/10/WC500004021.pdf.

Rose K, Walson PD. The contributions of the European Medicines Agency and its pediatric committee to the fight against childhood leukemia. Risk Manag Healthc Policy. 2015;8: 185-205.

Rose K, Happl R. The effect of regulation on pediatric psoriasis drug approvals: the challenge of the European Union (EU) Pediatric Investigation Plans. Pediatr Dermatol. 2017;34(3): e154–e159.

Rose K, Muller T. Children with multiple sclerosis should not become therapeutic hostages. Ther Adv Neurol Disord. 2016;9: 389–395.

Rose K, Grant-Kels JM. Questionable international pediatric studies with Swiss participation. Swiss Med Wkly. 2018, https://smw.ch/en/op-eds/post/questionable-pediatric-studies-with-swiss-participation/.

Rose K, Grant-Kels JM. Questionable international pediatric studies in the United States and Russia triggered by regulatory authorities. http://www.journalrepository.org/media/journals/AJRIMPS_63/2018/Apr/Rose332018AJRIMPS40776.pdf.

Rose K, Grant-Kels JM. Questionable industry-sponsored pediatric studies in China triggered by United States of America (US) and European Union (EU) regulatory authorities. SF Pharma J 2018,1:1. http://scifedpublishers.com/fulltext/questionable-industry-sponsored-pediatric-studies-in-china-triggeredby-united-states-of-america-us-and-european-union-eu-regulatoryauthorities/22070.

Rose K, Kopp MV. Pediatric investigation plans for specific immunotherapy: Questionable contributions to childhood health. Pediatr Allergy Immunol. 2015;26(8):695–701.

EMA 2007. The European Paediatric Initiative: history of the paediatric regulation. http://www.ema.europa.eu/docs/en_GB/document_library/Other/2009/09/WC500003693.pdf

Snyder KM, Reaman G, Avant D, Pazdur R. The impact of the written request process on drug development in childhood cancer. Pediatr Blood Cancer. 2013;60:531–537.

Gaspar N, Marshall LV, Binner D, et al. Joint adolescent–adult early phase clinical trials to improve access to new drugs for adolescents with cancer: proposals from the multi-stakeholder platform—ACCELERATE. Ann Oncol. 2018;29(3):766–771.

Christensen ML, Franklin BE, Momper JD, Reed MD. Pediatric drug development programs for type 2 diabetes: a review. J Clin Pharmacol. 2015;55(7):731–738.

Siegfried EC, Jaworski JC, Eichenfield LF, et al. Developing drugs for treatment of atopic dermatitis in children (≥3 months to <18 years of age): draft guidance for industry. Pediatr Dermatol. 2018;35(3):303–322.

Torok RD, Li JS, Kannankeril PJ, et al. Recommendations to enhance pediatric cardiovascular drug development: report of a multi-stakeholder think tank. J Am Heart Assoc. 2018;7(4).

Ruperto N, Vesely R, Saint-Raymond A, Martini A; Paediatric Rheumatology International Trials Organisation (PRINTO). Impact of the European paediatric legislation in paediatric rheumatology: past, present and future. Ann Rheum Dis. 2013;72(12): 1893–1896.

Benjamin DK Jr, Smith PB, Jadhav P, et al. Pediatric antihypertensive trial failures: analysis of end points and dose range. Hypertension. 2008;51(4):834–840.

Hoppu K, Anabwani G, Garcia-Bournissen F, et al. The status of paediatric medicines initiatives around the world—what has happened and what has not? Eur J Clin Pharmacol. 2012;68(1):1–10.

Turner MA, Catapano M, Hirschfeld S, Giaquinto C; Global Research in Paediatrics. Paediatric drug development: the impact of evolving regulations. Adv Drug Deliv Rev. 2014;73:2–13.

Turner MA, Attar S, de Wildt SN, Vassal G, Mangiarini L, Gia-quinto C. Roles of clinical research networks in pediatric drug development. Clin Ther. 2017;39(10):1939–1948.

Mentzer D. Progress review of the European Paediatric Regulatory Framework after six years of implementation. Int J Pharm. 2014;469(2):240–243.

Tomasi PA, Egger GF, Pallidis C, Saint-Raymond A. Enabling development of paediatric medicines in Europe: 10 years of the EU Paediatric Regulation. Pediatr Drugs. 2017;19(6): 505–513.

Tsukamoto K, Carroll KA, Onishi T, Matsumaru N, Brasseur D, Nakamura H. Improvement of pediatric drug development: regulatory and practical frameworks. Clin Ther. 2016;38(3): 574–581.

Onishi T, Tsukamoto K, Matsumaru N, Waki T. Industry perspective of pediatric drug development in the United States: involvement of the European Union Countries. Therapeutic Innovation & Regulatory Science. 2018;52(1):49–56.

EMA 2016: 10-year report to the European Commission. https://ec.europa.eu/health/sites/health/files/files/paediatrics/2016_pc_report_2017/ema_10_year_report_for_consultation.pdf.

Global Research in Pediatrics (GRiP). www.grip-network.org.

Saint-Raymond A, Brasseur D. Development of medicines for children in Europe: ethical implications. Paediatr Respir Rev. 2005;6(1):45–51.

European Network of Paediatric Research at the European Medicines Agency (ENPR-EMA) http://www.ema.europa.eu/ema/index.jsp?curl=pages/partners_and_networks/general/general_content_000303.jsp.

European Parliament resolution of 15 December 2016 on the regulation on paediatric medicines (2016/2902(RSP)). http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-//EP//TEXT+TA+P8-TA-2016-0511+0+DOC+XML+V0//EN.

Craft AW, Brocklebank JT, Hey EN, Jackson RH. The “grey toddler” chloramphenicol toxicity. Arch Dis Child. 1974;49(3): 235–237.

Wiest DB, Cochran JB, Tecklenburg FW. Chloramphenicol toxicity revisited: a 12-year-old patient with a brain abscess. J Pediatr Pharmacol Ther. 2012;17(2):182–188.

Laughon MM, Benjamin DK. Mechanisms to provide safe and effective drugs for children. Pediatrics. 2014;134(2):e562–e563.

Gonzalez D, Melloni C, Yogev R, et al. Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents. Clin Pharmacol Ther. 2014;96(4):429–437.

Beecher HK. Ethics and clinical research. N Engl J Med. 1966; 274(24):1354–1360.

Thomann KD. Die Contergan-Katastrophe. Die trügerische Sicherheit der “harten” Daten. Deutsches Ärzteblatt. 2007; 104(41):A2078–A2082.

Vargesson N. Thalidomide-induced teratogenesis: history and mechanisms. Birth Defects Res C Embryo Today. 2015;105(2): 140–156.

EMA pediatric website. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000023.jsp&mid=WC0b01ac0580b18c75.

Kim HC, Won Y-Y. Clinical, technological, and economic issues associated with developing new lung surfactant therapeutics. Biotechnol Adv. 2018;36(4):1185–1193.

Li JS, Eisenstein EL, Grabowski HG, et al. Economic return of clinical trials performed under the pediatric exclusivity program. JAMA. 2007;297(5):480–488.

Boots I, Sukhai RN, Klein RH, et al. Stimulation programs for pediatric drug research—do children really benefit? Eur J Pediatr. 2007;166(8):849–855.

Orlando A, Cazzaniga E, Giussani M, Palestini P, Genovesi S. Hypertension in children: role of obesity, simple carbohydrates, and uric acid. Front Public Health. 2018;6:129.

Falkner B. Monitoring and management of hypertension with obesity in adolescents. Integr Blood Press Control. 2017;10: 33–39.

PhRMA Research & Development Pediatrics. https://www.phrma.org/pediatrics.

EFPIA welcomes paediatric medicines regulation report and reiterates its commitment to progress in this area. https://www.efpia.eu/news-events/the-efpia-view/statements-press-releases/27102017-efpia-welcomes-paediatric-medicines-regulation-report-and-reiterates-its-commitment-to-progress-in-this-area/. Published October 27, 2017.

World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Revised by the 64th WMA General Assembly, Fortaleza, Brazil, October 2013. https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/.