Forrest Robin, Lagarde Mylene, Aggarwal Ajay, Naci Huseyin
Department of Health Policy, London School of Economics and Political Science, London, UK.
Department of Health Policy, London School of Economics and Political Science, London, UK.
Lancet Oncol. 2024 Dec;25(12):1635-1643. doi: 10.1016/S1470-2045(24)00596-5. Epub 2024 Nov 18.
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.
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.
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.
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.
The London School of Economics and Political Science Phelan United States Centre.
癌症患者愿意在多大程度上接受新癌症药物临床获益的不确定性以换取更快获取尚不清楚。本研究旨在探讨获取与确定性之间的偏好，并了解影响这些偏好的因素。
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成年人样本，以参与在线离散选择实验。符合条件的受访者必须自我报告有一些癌症经历，即他们自己、亲密朋友或家庭成员曾被诊断患有癌症，无论是过去还是现在。在实验中，受访者在两种癌症药物之间进行选择，同时考虑五个属性：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药品监督管理局（FDA）批准时间的延迟。第一个主要结果是生存获益确定性和等待时间对受访者的相对重要性。第二个主要结果是愿意等待更高的生存获益确定性，包括按癌症经历、年龄、教育程度、种族或族裔以及收入进行亚组分析。次要结果是根据药物对替代终点的影响、受访者的功能状态和预期寿命，对确定性和等待时间的敏感度变化。该研究计划已在ClinicalTrials.gov（NCT05936632）上注册。
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。最终分析纳入了870名受访者（461名[53%]男性，406名[47%]女性，3名[<1%]其他）。受访者对高生存获益确定性表现出强烈偏好（系数2.61，95%置信区间2.23至2.99），对FDA批准时间延迟1年表现出强烈反感（系数 -1.04，95%置信区间 -1.31至 -0.77）。鉴于药物提供生存获益的确定性非常低（没有证据将替代终点与总生存相关联），受访者愿意等待长达21.68个月（95%置信区间17.61至25.74）以获得高生存获益确定性（有力证据）。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%置信区间 -0.21至0.25）。年龄较大的受访者（≥55岁）、非白人、低收入（每年<$40000）个体以及预期寿命最低的个体对等待时间最为敏感。
许多通过FDA加速批准途径获批的癌症药物并未给患者带来任何生存获益。在本研究中，个体对癌症药物能提供生存获益的确定性表现出强烈偏好。一些个体还表示，为了获得更高的确定性，他们愿意等待的时间比评估大多数用于转移性疾病的癌症药物的生存获益（相对于无进展生存获益）所需的时间更长。
伦敦政治经济学院费兰美国中心。
