Department of Equity, Ethics and Policy, McGill University School of Population and Global Health, 2001 McGill College Avenue, Montreal, QC, H3A 1G1, Canada.
CARE Advocates Network, Boston, MA, USA.
Sci Rep. 2023 Sep 26;13(1):16138. doi: 10.1038/s41598-023-42213-y.
Patients endure risk and uncertainty when they participate in clinical trials. We previously estimated that 12,217 patient-participants are required to bring a new cancer drug to market. However, many development efforts are aimed at extending the label of already approved drugs. Herein, we estimate the number of patients required to extend the indication of an FDA approved cancer drug. We identified all anti-cancer drugs approved by the FDA 2012 to 2015. We searched clinicaltrials.gov to identify all drug development trajectories (i.e., a series of one or more clinical trials testing a unique drug-indication pairing) launched after FDA approval for each drug. We identified which trajectories produced the following milestones: secondary FDA approvals, secondary FDA approvals achieving substantial clinical benefit in ESMO-MCBS, and recommendations in NCCN clinical practice guidelines. Using the total enrollment, we estimated the number of patients needed to reach each milestone. Forty-two drugs were approved by the FDA between 2012 and 2015, leading to 451 post-approval trajectories enrolling 129,548 patients. Fourteen secondary FDA approvals were identified, of which 4 met the ESMO-MCBS definition of substantial clinical benefit. Fourteen NCCN off-label recommendations were obtained. A total of 9253, 32,387 and 4627 patients were needed to attain an FDA approval, an approval with substantial clinical benefit on ESMO-MCBS, and an NCCN guideline recommendation, respectively. The number of patients needed to obtain a first secondary FDA approval was 16,596. Large numbers of patients are needed to extend the label of prior FDA approved drugs. Label extension after approval entails lower marginal costs for developers. However, extra knowledge available to researchers about a drug's safety and pharmacology after FDA approval does not appear to translate into reduced patient numbers required for developing new cancer applications.
患者在参与临床试验时会承受风险和不确定性。我们之前估计，需要 12217 名患者参与才能将一种新的癌症药物推向市场。然而，许多研发工作的目标是扩大已批准药物的标签。在此，我们估计扩大 FDA 批准的癌症药物适应证所需的患者数量。我们确定了 2012 年至 2015 年期间 FDA 批准的所有抗癌药物。我们在 clinicaltrials.gov 上搜索了所有在 FDA 批准后启动的药物开发轨迹（即一系列测试独特药物-适应证配对的一个或多个临床试验）。我们确定了哪些轨迹产生了以下里程碑：FDA 的二次批准、在 ESMO-MCBS 中具有实质性临床获益的 FDA 二次批准，以及 NCCN 临床实践指南中的建议。我们使用总入组人数估计达到每个里程碑所需的患者数量。2012 年至 2015 年间，FDA 批准了 42 种药物，随后批准了 451 个后续批准的治疗方案，共招募了 129548 名患者。确定了 14 项 FDA 的二次批准，其中 4 项符合 ESMO-MCBS 对实质性临床获益的定义。获得了 14 项 NCCN 标签外推荐。分别需要 9253、32387 和 4627 名患者才能获得 FDA 批准、具有 ESMO-MCBS 实质性临床获益的批准和 NCCN 指南建议。获得首次 FDA 二次批准所需的患者人数为 16596 名。需要大量患者来扩大之前 FDA 批准药物的标签。批准后扩大标签对开发者来说意味着边际成本较低。然而，FDA 批准后，研究人员对药物安全性和药理学的了解似乎并没有转化为开发新癌症应用所需的患者数量减少。
