{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:09:05Z","timestamp":1789193345436,"version":"build-2803163510"},"reference-count":24,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"unspecified","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre, Poland","award":["UMO-2021\/41\/B\/HS1\/01123"],"award-info":[{"award-number":["UMO-2021\/41\/B\/HS1\/01123"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,8,20]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Paediatric phase I oncology trials establish safe dosing and provide preliminary efficacy data for investigational anti-cancer agents in children. The aim of the proposed systematic review is to identify the risk and benefit ratio for targeted therapy agents in paediatric Phase I trials in oncology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We will search Embase and PubMed for paediatric Phase I cancer trials published from 2 March 2015 to 30 June 2026. Eligible studies are dose-escalation trials enrolling participants under 21 years with solid or haematological malignancies, testing targeted therapy agents. We will measure two co-primary outcomes: (1) risk\u2014proportion of participants experiencing drug-related adverse events of grade 3, 4 or 5; and (2) benefit\u2014objective response rate. Where data permit, proportions will be pooled using random-effects meta-analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study will use publicly available data; therefore, ethics committee approval is not required. Results from the systematic review will be published in a peer-reviewed journal and presented at relevant conferences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD420261408673.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-123756","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:15:30Z","timestamp":1789190130000},"page":"e123756","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Risk and benefit for targeted therapy agents in paediatric phase I trials in oncology: a systematic review and meta-analysis protocol"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8718-2609","authenticated-orcid":false,"given":"Joanna","family":"Ostrowska","sequence":"first","affiliation":[{"name":"REMEDY, Research Ethics in Medicine Study Group, Department of Bioethics and Health Psychology, Jagiellonian University Medical College, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2652-2635","authenticated-orcid":false,"given":"Karolina","family":"Strzebonska","sequence":"additional","affiliation":[{"name":"REMEDY, Research Ethics in Medicine Study Group, Department of Bioethics and Health Psychology, Jagiellonian University Medical College, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1553-1416","authenticated-orcid":false,"given":"Marcin","family":"Waligora","sequence":"additional","affiliation":[{"name":"REMEDY, Research Ethics in Medicine Study Group, Department of Bioethics and Health Psychology, Jagiellonian University Medical College, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"2026091122152011000_16.9.e123756.1","doi-asserted-by":"crossref","DOI":"10.1186\/1472-6939-15-44","article-title":"Child\u2019s assent in research: age threshold or personalisation?","volume":"15","author":"Waligora","year":"2014","journal-title":"BMC Med Ethics"},{"key":"2026091122152011000_16.9.e123756.2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1001\/jamapediatrics.2018.3629","article-title":"Participant protection in phase 1 pediatric cancer trials","volume":"173","author":"Kimmelman","year":"2019","journal-title":"JAMA Pediatr"},{"key":"2026091122152011000_16.9.e123756.3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02125"},{"key":"2026091122152011000_16.9.e123756.4","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1200\/JCO.2016.67.9902","article-title":"Is Participation in Cancer Phase I Trials Really Therapeutic?","volume":"35","author":"Kimmelman","year":"2017","journal-title":"J Clin Oncol"},{"key":"2026091122152011000_16.9.e123756.5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1002505","article-title":"Risk and surrogate benefit for pediatric Phase I trials in oncology: A systematic review with meta-analysis","volume":"15","author":"Waligora","year":"2018","journal-title":"PLoS Med"},{"key":"2026091122152011000_16.9.e123756.6","unstructured":"World Medical Association . Declaration of helsinki \u2013 ethical principles for medical research involving human participants. 2024."},{"key":"2026091122152011000_16.9.e123756.7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1200\/PO.20.00214","article-title":"Revisiting Risk and Benefit in Early Oncology Trials in the Era of Precision Medicine: A Systematic Review and Meta-Analysis of Phase I Trials of Targeted Single-Agent Anticancer Therapies","volume":"5","author":"Mackley","year":"2021","journal-title":"JCO Precis Oncol"},{"key":"2026091122152011000_16.9.e123756.8","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1634\/theoncologist.2019-0615","article-title":"A Systematic Review of Pediatric Phase I Trials in Oncology: Toxicity and Outcomes in the Era of Targeted Therapies","volume":"25","author":"Cohen","year":"2020","journal-title":"Oncologist"},{"key":"2026091122152011000_16.9.e123756.9","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jpeds.2021.06.009","article-title":"Do the Potential Medical Benefits of Phase 1 Pediatric Oncology Trials Justify the Risks? Views of the United States Public","volume":"238","author":"Schupmann","year":"2021","journal-title":"J Pediatr"},{"key":"2026091122152011000_16.9.e123756.10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0234911","article-title":"Clinical development success rates and social value of pediatric Phase 1 trials in oncology","volume":"15","author":"Wasylewski","year":"2020","journal-title":"PLoS One"},{"key":"2026091122152011000_16.9.e123756.11","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s11523-021-00822-5","article-title":"Risk and benefit for targeted therapy agents in pediatric phase II trials in oncology: a systematic review with a meta-analysis","volume":"16","author":"Strzebonska","year":"2021","journal-title":"Target Oncol"},{"key":"2026091122152011000_16.9.e123756.12","doi-asserted-by":"crossref","first-page":"113705","DOI":"10.1016\/j.jpeds.2023.113705","article-title":"Timing for First-in-Minor Clinical Trials of New Cancer Drugs","volume":"263","author":"Bicer","year":"2023","journal-title":"J Pediatr"},{"key":"2026091122152011000_16.9.e123756.13","doi-asserted-by":"crossref","DOI":"10.1186\/2046-4053-4-1","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement","volume":"4","author":"Moher","year":"2015","journal-title":"Syst Rev"},{"key":"2026091122152011000_16.9.e123756.14","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2026091122152011000_16.9.e123756.15","unstructured":"Ostrowska J , Strzebonska K , Waligora M . n.d. Risk and Benefit for Targeted Therapy Agents in Pediatric Phase I Trials in Oncology: A Systematic Review and Meta-Analysis."},{"key":"2026091122152011000_16.9.e123756.16","doi-asserted-by":"crossref","unstructured":"Eisenhauer EA , Twelves C , Buyse M . Phase I Cancer Clinical Trials: A Practical Guide. 2nd edn. Oxford: Oxford University Press, 2015.","DOI":"10.1093\/med\/9780199359011.001.0001"},{"key":"2026091122152011000_16.9.e123756.17","unstructured":"Karp DD , Falchook GS , Lim JD . Handbook of Targeted Cancer Therapy and Immunotherapy. 3rd edn. Singapore: Lippincott Williams & Wilkins (Wolters Kluwer), 2023."},{"key":"2026091122152011000_16.9.e123756.18","unstructured":"National Cancer Institute . Definition of targeted therapy. nci dictionary of cancer terms. National Institutes of Health. n.d. Available: https:\/\/www.cancer.gov\/publications\/dictionaries\/cancer-terms\/def\/targeted-therapy"},{"key":"2026091122152011000_16.9.e123756.19","unstructured":"National cancer institute . Common terminology criteria for adverse events (ctcae), version 6.0. U.S. Department of Health and Human Services, National Institutes of Health, 2025."},{"key":"2026091122152011000_16.9.e123756.20","unstructured":"49. Regulation (EC) no 1901\/2006 of the european parliament and of the council of 12 december 2006 on medicinal products for paediatric use. Official Journal of the European Union; 2006.1\u201319."},{"key":"2026091122152011000_16.9.e123756.21","unstructured":"U.S. food and drug administration . In: Pediatric Research Equity Act (PREA). Silver Spring, MD: FDA, 2024."},{"key":"2026091122152011000_16.9.e123756.22","doi-asserted-by":"crossref","DOI":"10.1016\/S2352-4642(23)00125-6","article-title":"Clinical trials for paediatric cancers under new legislation in the USA","volume":"7","author":"Hwang","year":"2023","journal-title":"Lancet Child Adolesc Health"},{"key":"2026091122152011000_16.9.e123756.23","doi-asserted-by":"crossref","first-page":"e368","DOI":"10.1016\/S1470-2045(22)00376-X","article-title":"New legislation to promote paediatric studies for new cancer medicines","volume":"23","author":"Hwang","year":"2022","journal-title":"Lancet Oncol"},{"key":"2026091122152011000_16.9.e123756.24","doi-asserted-by":"crossref","first-page":"3408","DOI":"10.1200\/JCO.22.02430","article-title":"Combination Early-Phase Trials of Anticancer Agents in Children and Adolescents","volume":"41","author":"Moreno","year":"2023","journal-title":"J Clin Oncol"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2026-123756","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:15:36Z","timestamp":1789190136000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2026-123756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":24,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,11]]},"published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1136\/bmjopen-2026-123756"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2026-123756","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]}}}