Novel precision oncology trial designs, such as basket and umbrella trials, are designed to test new anticancer agents in more effective and affordable ways. However, they present some ethical concerns referred to scientific validity, risk-benefit balance and informed consent. Our aim is to discuss these issues in basket and umbrella trials, giving examples of two ongoing cancer trials: NCI-MATCH (National Cancer Institute – Molecular Analysis for Therapy Choice) and Lung-MAP (Lung Cancer Master Protocol) study. We discuss three ethical requirements for clinical trials which may be challenged in basket and umbrella trial designs. Firstly, we consider scientific validity. Thanks to the new trial designs, patients with rare malignancies have the opportunity to be enrolled and benefit from the trial, but due to insufficient accrual, the trial may generate clinically insignificant findings. Inadequate sample size in study arms and the use of surrogate endpoints may result in a drug approval without confirmed efficacy. Moreover, complexity, limited quality and availability of tumor samples may not only introduce bias and result in unreliable and unrepresentative findings, but also can potentially harm patients and assign them to an inappropriate therapy arm. Secondly, we refer to benefits and risks. Novel clinical trials can gain important knowledge on the variety of tumors, which can be used in future trials to develop effective therapies. However, they offer limited direct benefits to patients. All potential participants must wait about 2 weeks for the results of the genetic screening, which may be stressful and produce anxiety. The enrollment of patients whose tumors harbor multiple mutations in treatments matching a single mutation may be controversial. As to informed consent – the third requirement we discuss, the excessive use of phrases like “personalized medicine”, “tailored therapy” or “precision oncology” might be misleading and cause personal convictions that the study protocol is designed to fulfill the individual health-related needs of participants. We suggest that further approaches should be implemented to enhance scientific validity, reduce misunderstandings and risks, thus maximizing the benefits to society and to trial participants.

中文翻译：

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肿瘤学中的伞式和篮式试验：伦理挑战

新颖的精准肿瘤学试验设计，例如篮式试验和伞式试验，旨在以更有效和更实惠的方式测试新的抗癌药物。然而，他们提出了一些涉及科学有效性、风险收益平衡和知情同意的伦理问题。我们的目的是在篮子试验和伞式试验中讨论这些问题，并给出两个正在进行的癌症试验的例子：NCI-MATCH（国家癌症研究所 - 治疗选择的分子分析）和 Lung-MAP（肺癌主方案）研究。我们讨论了临床试验的三个伦理要求，这些要求可能在篮子和伞式试验设计中受到挑战。首先，我们考虑科学有效性。由于新的试验设计，患有罕见恶性肿瘤的患者有机会参加试验并从试验中受益，但由于应计人数不足，该试验可能会产生临床意义不大的结果。研究组中的样本量不足以及替代终点的使用可能会导致药物在未确认疗效的情况下获得批准。此外，肿瘤样本的复杂性、有限的质量和可用性不仅可能引入偏差并导致不可靠和不具有代表性的结果，而且还可能伤害患者并将他们分配到不适当的治疗组。其次，我们提到利益和风险。新颖的临床试验可以获得有关各种肿瘤的重要知识，可用于未来的试验以开发有效的疗法。然而，它们为患者提供的直接益处有限。所有潜在参与者必须等待大约两周的基因筛查结果，这可能会带来压力并产生焦虑。将具有多个突变的肿瘤患者纳入与单个突变相匹配的治疗可能存在争议。至于知情同意——我们讨论的第三个要求，过度使用“个性化医疗”、“定制治疗”或“精准肿瘤学”等短语可能会产生误导，并导致个人相信研究方案旨在满足个人健康需求——参与者的相关需求。我们建议采取进一步的方法来提高科学有效性，减少误解和风险，从而最大限度地提高社会和试验参与者的利益。