Background

The extent to which patients with cancer are willing to accept uncertainty about the clinical benefit of new cancer drugs in exchange for faster access is not known. This study aims to examine preferences for access versus certainty, and to understand factors that influence these preferences.

Methods

A US nationally representative sample of older adults were recruited via Cint, an online platform for survey research, to take part in an online discrete choice experiment. To be eligible, respondents had to self-report some experience with cancer—ie, they themselves, a close friend or a family member, previously or currently diagnosed with cancer. In the experiment, respondents chose between two cancer drugs, considering five attributes: functional status, life expectancy, certainty of the survival benefit of a new drug, effect of the drug on a surrogate endpoint, and delay in US Food and Drug Administration (FDA) approval time. The first primary outcome was the relative importance of certainty of survival benefit and wait time to respondents. The second primary outcome was willingness to wait for greater certainty of survival benefit, including subgroup analysis by cancer experience, age, education status, race or ethnicity and income. Secondary outcomes were changes in sensitivity to certainty and wait time, depending on the drug's effect on a surrogate endpoint, respondents' functional status, and life expectancy. The study plan was registered with ClinicalTrials.gov, NCT05936632.

Findings

Between July 7 and July 20, 2023, 998 eligible respondents completed the survey. 870 respondents (461 [53%] male, 406 [47%] female, and three [<1%] other) were included in the final analysis. Respondents showed strong preferences for high certainty of survival benefit (coefficient 2·61, 95% CI 2·23 to 2·99), and strong preferences against a 1-year delay in FDA approval time (coefficient –1·04, 95% CI –1·31 to –0·77). Given very low certainty a drug would provide survival benefit (no evidence linking a surrogate endpoint to overall survival), respondents were willing to wait up to 21·68 months (95% CI 17·61 to 25·74) for high certainty (strong evidence) of survival benefit. A drug's effect on a surrogate endpoint had no significant impact on drug choices (coefficient 0·02, 95% CI –0·21 to 0·25). Older respondents (aged ≥55 years), non-White, lower-income (<$40 000 per year) individuals, and those with the lowest life expectancy, were most sensitive to wait time.

Interpretation

Many cancer drugs approved through the FDA's accelerated approval pathway do not offer any survival benefit to patients. In this study, individuals expressed strong preferences for certainty that a cancer drug would offer survival benefit. Some individuals also expressed a higher willingness to wait for greater certainty than would be necessary to assess the survival benefit (over progression-free survival benefit) of most cancer drugs used in the metastatic setting.

Funding

The London School of Economics and Political Science Phelan United States Centre.

中文翻译：

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对新癌症药物的获取速度与生存获益确定性的偏好：一项离散选择实验

 背景

癌症患者在多大程度上愿意接受新癌症药物临床益处的不确定性以换取更快的可及性尚不清楚。本研究旨在检查对访问的偏好与确定性，并了解影响这些偏好的因素。

 方法

通过在线调查研究平台 Cint 招募了具有美国全国代表性的老年人样本，以参加在线离散选择实验。要获得资格，受访者必须自我报告一些癌症经历——即他们自己、亲密的朋友或家人，以前或现在被诊断出患有癌症。在实验中，受访者在两种癌症药物之间进行选择，考虑五个属性：功能状态、预期寿命、新药生存获益的确定性、药物对替代终点的影响以及美国食品和药物管理局 （FDA） 批准时间的延迟。第一个主要结局是生存获益确定性和等待时间对受访者的相对重要性。第二个主要结局是愿意等待更高的生存获益确定性，包括按癌症经历、年龄、教育状况、种族或民族和收入进行亚组分析。次要结局是对确定性和等待时间的敏感性的变化，这取决于药物对替代终点、受访者的功能状态和预期寿命的影响。该研究计划已在 ClinicalTrials.gov， NCT05936632 注册。

 发现

在 2023 年 7 月 7 日至 7 月 20 日期间，998 名符合条件的受访者完成了调查。870 名受访者 （461 名 [53%] 男性，406 名 [47%] 女性和 3 名 [<1%] 其他）被纳入最终分析。受访者强烈偏好生存获益的高质量（系数 2·61,95% CI 2·23 至 2·99），强烈反对 FDA 批准时间延迟 1 年（系数 -1·04,95% CI -1·31 至 -0·77）。鉴于药物将提供生存获益的确定性极低（没有证据将替代终点与总生存期联系起来），受访者愿意等待长达 21·68 个月（95% CI 17·61 至 25·74）以获得生存获益的高质量（强证据）。药物对替代终点的影响对药物选择没有显著影响（系数 0·02,95% CI -0·21 至 0·25）。年长的受访者（年龄≥55岁）、非白人、低收入（x3C$ 每年40 000）的人以及预期寿命最低的人对等待时间最敏感。

 解释

许多通过 FDA 加速批准途径批准的癌症药物不会为患者提供任何生存益处。在这项研究中，个人对确定癌症药物会提供生存益处表示强烈偏好。一些人还表示，与评估转移性中使用的大多数癌症药物的生存获益 （超过无进展生存期获益） 相比，他们更愿意等待更高的确定性。

 资金

伦敦政治经济学院 Phelan 美国中心。