Dept. of Philosophy and Bioethics, REMEDY, Research Ethics in Medicine Study Group, Jagiellonian University Medical College, Krakow, Poland.
Dept. of Epidemiology and Population Studies, Jagiellonian University Medical College, Krakow, Poland.
PLoS One. 2020 Jun 24;15(6):e0234911. doi: 10.1371/journal.pone.0234911. eCollection 2020.
Drug development trials must fulfill social value requirement but no estimates of value provided by pediatric Phase 1 trials in oncology exist. These trials involve a particularly vulnerable population. Our objective was to assess of surrogates of social value of Phase 1 trials performed in pediatric oncology: rates of approval of tested interventions, transition to further phases of testing and citation in subsequent primary research reports.
We performed an analysis on a subset of eligible trials included in a previous meta-analysis. That study systematically searched EMBASE and PubMed for small sample size, non-randomized, dose escalation pediatric cancer Phase 1 studies of any malignancy, assessing chemotherapy and/or targeted therapy and looked at risk and benefit. The current analysis assessed all studies in that review published between January 1st 2004 and December 31st 2013 for predictors of social value. This time range allowed for at least five years of subsequent development activity. Sources of data included FDA and EMA medicine databases (for approval), ClinicalTrials.gov and EU Clinical Trials Register (for transition) and Google Scholar (for citation).
One hundred thirty-nine trials enrolling 3814 patients met the eligibility criteria. Seven trials (5%) led to drugs being registered for pediatric use in therapy of cancer. Fifty-two (37%) transitioned to later phases of pediatric oncology trials according to ClinicalTrials.gov and/or EU Register. Over 90% of trials were cited by at least one subsequent primary research report or systematic review. Most of the citations were preclinical studies.
Our analysis shows that treatments tested in pediatric Phase 1 trials in oncology have low rates of regulatory approval. However, a large proportion of Phase 1 trials inform further testing and development of tested interventions.
药物开发试验必须满足社会价值要求，但目前尚无肿瘤儿科 I 期试验提供的价值估计。这些试验涉及到特别脆弱的人群。我们的目的是评估儿科肿瘤学中 I 期试验的社会价值替代指标：已测试干预措施的批准率、向进一步测试阶段的转化以及后续主要研究报告中的引用率。
我们对之前荟萃分析中包含的合格试验的一个子集进行了分析。该研究系统地在 EMBASE 和 PubMed 中搜索小样本量、非随机、剂量递增的儿科癌症 I 期研究，评估化疗和/或靶向治疗的风险和益处。目前的分析评估了该综述中所有发表于 2004 年 1 月 1 日至 2013 年 12 月 31 日的研究，以预测社会价值。这个时间范围允许至少有五年的后续开发活动。数据来源包括 FDA 和 EMA 药品数据库（用于批准）、ClinicalTrials.gov 和欧盟临床试验注册中心（用于转化）以及 Google Scholar（用于引用）。
139 项试验共纳入 3814 名患者，符合入选标准。7 项试验（5%）导致药物在癌症治疗中被注册用于儿科使用。根据 ClinicalTrials.gov 和/或欧盟注册，52 项（37%）试验转化为儿科肿瘤学试验的后期阶段。超过 90%的试验至少被一篇后续的主要研究报告或系统评价引用。大多数引文是临床前研究。
我们的分析表明，在肿瘤学儿科 I 期试验中测试的治疗方法的监管批准率较低。然而，很大一部分 I 期试验为测试干预措施的进一步测试和开发提供了信息。
