{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T12:51:32Z","timestamp":1776257492090,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T00:00:00Z","timestamp":1606435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pediatric anticancer drug development has numerous challenges. The Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA) were passed to address pediatric drug development deficiencies in general. Until recently, the requirements for pediatric evaluation of most oncology products developed for adult cancers have been waived. Because children typically do not have the same type of cancers, which occur commonly in adults, or the indication or drug had been granted an orphan designation, PREA therefore has had no impact. Pediatric studies for labeling updates are largely done through BPCA by a written request (WR) issued by the Food and Drug Administration (FDA). Because the cancers that occur in pediatric and adult populations do not share the same etiology or natural history, there are limited opportunities to extrapolate adult efficacy and safety to the pediatric population. The characteristics of individual pediatric studies included in WRs have varied greatly over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>In this study, we searched WRs that were issued by the FDA since 2001. We found 40 such requests issued for oncology drugs and biologics, which had been accepted by sponsors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Clinical trials included in 23 of the WRs have been concluded, 19 have resulted in exclusivity, and three drugs that were studied have been approved for use in pediatric populations. Herein, we present the spectrum of WRs from a regulatory, study design, dosing, formulation, analysis plan, evidentiary standard of efficacy, and safety perspective.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This provides information on requests issued in the past nearly 20\u00a0years and studies that are completed. As WRs have provided the only regulatory mechanism to assure pediatric cancer drug development, this can potentially provide insight on how pediatric cancer drug development may change in the future.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.28828","type":"journal-article","created":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T12:59:51Z","timestamp":1606481991000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["A review of the experience with pediatric written requests issued for oncology drug products"],"prefix":"10.1002","volume":"68","author":[{"given":"Alemayehu Y.","family":"Akalu","sequence":"first","affiliation":[{"name":"Office of Oncologic Diseases Office of New Drugs Center for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration (FDA)  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics School of Public Health and Health Sciences University of Massachusetts  Amherst Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory H.","family":"Reaman","sequence":"additional","affiliation":[{"name":"Office of Oncologic Diseases Office of New Drugs Center for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration (FDA)  Silver Spring Maryland"},{"name":"Oncology Center of Excellence (OCE) U.S. Food and Drug Administration (FDA)  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Pharmacometrics (DPM) Office of Clinical Pharmacology (OCP) Center for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration (FDA)  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weishi","family":"Yuan","sequence":"additional","affiliation":[{"name":"Division of Biostatistics IX (DBIX) Office of Biostatistics (OB) Office of Translational Sciences (OTS) Center for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration (FDA)  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0086-2228","authenticated-orcid":false,"given":"Jingjing","family":"Ye","sequence":"additional","affiliation":[{"name":"Division of Biostatistics IX (DBIX) Office of Biostatistics (OB) Office of Translational Sciences (OTS) Center for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration (FDA)  Silver Spring Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(68)80414-7"},{"key":"e_1_2_8_3_1","volume-title":"Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act","author":"Institute of Medicine","year":"2012"},{"key":"e_1_2_8_4_1","unstructured":"Institute of Medicine (US) Forum on Drug Discovery Development and Translation.Pediatric Research Equity Act (PREA).https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK3997\/. Accessed November 19 2020."},{"key":"e_1_2_8_5_1","unstructured":"NIH.Best Pharmaceuticals for Children's Act (BPCA).https:\/\/bpca.nichd.nih.gov\/Pages\/default.aspx. Accessed November 19 2020."},{"key":"e_1_2_8_6_1","unstructured":"FDA.Yondelis. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/207953s005lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_7_1","unstructured":"FDA.Abraxane. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/021660s046lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_8_1","unstructured":"FDA.Jevtana. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/201023s023lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_9_1","unstructured":"FDA.Velcade. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/021602s044lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_10_1","unstructured":"FDA.Afinitor. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/022334s044 203985s016lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_11_1","unstructured":"FDA.Treanda. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/022249s024lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_12_1","unstructured":"FDA.Tasigna. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/022068s031lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_13_1","unstructured":"FDA.Taxotere. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/020449s083lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_14_1","unstructured":"FDA.Sutent. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/021938s036lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_15_1","unstructured":"FDA.Methotrexate Injection USP.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/011719s125lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_16_1","unstructured":"FDA.Xeloda. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/020896Orig1s042lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_17_1","unstructured":"FDA.Eloxatin. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/021759s023lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_18_1","unstructured":"FDA.Zometa. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/021223s041lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_19_1","unstructured":"FDA.phosphate. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2011\/022137s003lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_20_1","unstructured":"FDA.Arimidex. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/020541s031lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_21_1","unstructured":"FDA.Camptosar. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/020571s051lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_22_1","unstructured":"FDA.Temodar. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/022277s013lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_23_1","unstructured":"FDA.Navelbine. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/020388s037lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_24_1","unstructured":"FDA.Gemzar. United States prescribing information (USPI).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/020509s082lbl.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_25_1","unstructured":"HonigS.Medical Review for Navelbine (Vinorelbine). NDA 20388\/S014. November 2002. Silver Spring MD: Food and Drug Administration 2002.http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2002\/020388_S014_NAVELBINE_INJECTION_AP.pdf. Accessed April 3 2012."},{"key":"e_1_2_8_26_1","unstructured":"FDA.Gemzar (Gemcitabine HCL) Pediatric Written Request. January 2001. Silver Spring MD: Food and Drug Administration.https:\/\/www.fda.gov\/media\/88726\/download. Accessed November 19 2020."},{"key":"e_1_2_8_27_1","unstructured":"FDA.Pediatric Exclusivity Granted April 2016. Silver Spring MD: Food and Drug Administration.https:\/\/www.fda.gov\/media\/79154\/download. Accessed November 19 2020."},{"key":"e_1_2_8_28_1","unstructured":"ShapiroA.Medical Review for Temodar (Temozolomide). NDA 21029\/S005. March 2003. Silver Spring MD: Food and Drug Administration 2003.https:\/\/www.fda.gov\/media\/92216\/download. Accessed November 19 2020."},{"key":"e_1_2_8_29_1","unstructured":"IbrahimA.Medical Review for Camptosar (Irinotecan). NDA 20571\/S021. December 2003. Silver Spring MD: Food and Drug Administration 2003.https:\/\/www.fda.gov\/files\/drugs\/published\/N20-571S023-Irinotecan-Clinical-BPCA.pdf. Accessed November 19 2020."},{"key":"e_1_2_8_30_1","unstructured":"VaidyanathanJ.Clinical Pharmacology Review for Anastrozole (Arimidex). NDA22214. February 2008. Silver Spring MD: Food and Drug Administration 2008.https:\/\/www.fda.gov\/media\/75522\/download. 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