Biomedical Ethics Unit, McGill University, Montreal, Quebec, Canada.
Pediatr Blood Cancer. 2022 Aug;69(8):e29534. doi: 10.1002/pbc.29534. Epub 2022 Jan 14.
Approximately 5% of adult cancer interventions put into clinical testing attain regulatory approval. Little is known about corresponding rates for pediatric cancer.
Our primary outcomes were the proportion of interventions graduating to the next trial phase, randomized trials, and/or clinical practice. We created a saturation sample of clinical trials by searching ClinicalTrials.gov for all pediatric anticancer trials in the United States or Canada. Trial characteristics were extracted automatically from ClinicalTrials.gov records, and cancer indication/drug class categorization, biomarker enrichment, and Food and Drug Administration (FDA) approval status at time of recruitment were double-extracted from each record. Regulatory approval status and labeling modifications for each intervention were determined by searching Drugs@FDA and the New Pediatric Labeling Information Database.
Five hundred eighty-nine pediatric trials launched between 1987 and 2019 were captured. The overall probability of graduation was 17.0%; 18.9% of interventions graduated from phase 1 to phase 2 trials, and 1.6% of interventions graduated from phase 2 to phase 3 trials. The proportion of interventions advancing from phase 1 to FDA approval was 3.6%, and 1.9% of interventions tested in phase 1 advanced to a randomized phase 2 trial. Only biomarker enrichment was significantly predictive of graduation from phase 1 to phase 2 trials (p = .011).
The proportion of interventions advancing from phase 1 testing to FDA approval was similar to estimates for adult oncology. Our findings highlight the challenges for current paradigms of pediatric anticancer drug development.
大约有 5%的成人癌症干预措施进入临床测试并获得监管部门的批准。对于儿科癌症，相应的比例则知之甚少。
我们的主要结局指标是干预措施进入下一个试验阶段、随机试验和/或临床实践的比例。我们通过在美国或加拿大的临床试验搜索临床Trials.gov，创建了一个儿科抗癌试验的饱和样本。从临床Trials.gov 记录中自动提取试验特征，并从每个记录中提取癌症指征/药物类别分类、生物标志物富集和招募时的食品和药物管理局（FDA）批准状态的双提取。通过搜索 Drugs@FDA 和新儿科标签信息数据库，确定每个干预措施的监管批准状态和标签修改。
共捕获了 1987 年至 2019 年期间启动的 589 项儿科试验。总体毕业率为 17.0%；18.9%的干预措施从 1 期试验毕业到 2 期试验，1.6%的干预措施从 2 期试验毕业到 3 期试验。从 1 期试验进展到 FDA 批准的干预措施比例为 3.6%，在 1 期试验中测试的 1.9%的干预措施进展到随机 2 期试验。只有生物标志物富集是从 1 期试验到 2 期试验毕业的显著预测因素（p = 0.011）。
从 1 期测试到 FDA 批准的干预措施的比例与成人肿瘤学的估计值相似。我们的研究结果强调了当前儿科抗癌药物开发范式所面临的挑战。
