超越危险比:量化免疫肿瘤疗法临床疗效的适当统计方法--以荷兰为例。

IF 3.9 3区 医学 Q1 HEALTH CARE SCIENCES & SERVICES
Isaac Corro Ramos, Venetia Qendri, Maiwenn Al
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引用次数: 0

摘要

背景:荷兰肿瘤药物评估委员会(Dutch Committee for the Evaluation of Oncological Drugs)负责评估肿瘤新疗法的有效性。该委员会将生存期终点与所谓的 PASKWIL-2023 缓解治疗标准进行比较,该标准规定了治疗效果是否具有临床相关性。积极推荐取决于参照组的中位总生存期(OS)是低于还是高于12个月。如果是前者,则要求至少有12周的OS获益,且危险比(HR)小于0.7。如果是后者,则要求 OS 或无进展生存期(PFS)至少达到 16 周,HR 小于 0.7。尽管如此,免疫肿瘤(IO)疗法可能无法达到中位生存时间,而且以HR量化的比例危险(PH)假设也可能被违反,因此这些标准并不合适:我们进行了一项系统性的文献综述,以确定用于根据试验数据表示 IO 疗法临床疗效的统计方法。我们检索了从开始到 2022 年 8 月 31 日的 MEDLINE 和 EMBASE 数据库,仅限于英文论文。方法学研究、随机对照试验,以及认识到IO疗法生存数据分析关键问题的讨论性论文均符合纳入条件:结果:共发现 1,035 篇独特的参考文献。在对所有论文进行筛选后,有 17 篇论文被纳入综述。此外,通过 "滚雪球 "的方式还发现了 43 篇论文。我们的结论是,目前的 PASKWIL-2023 标准在非 PH 的情况下在方法上是不正确的。在这种情况下,单一的总结性统计无法捕捉治疗效果,任何测量方法都应结合卡普兰-梅耶曲线进行解释。我们建议采用 "无参数 "指标,如受限平均生存时间的差异,避免对基本生存时间进行假设:结论:HR 通常用于评估治疗效果,而不对 PH 假设的有效性进行调查。这种情况发生在应用 PASKWIL-2023 标准进行姑息性肿瘤治疗时,该标准只能在 PH 环境下有效。在非 PH 条件下,建议采用其他治疗效果衡量标准。我们提出了一种循序渐进的方法,支持选择最合适的方法来量化治疗效果,该方法可用于重新定义 PASKWIL-2023 标准或其他临床领域的类似标准。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Beyond hazard ratios: appropriate statistical methods for quantifying the clinical effectiveness of immune-oncology therapies - the example of the Netherlands.

Background: The Dutch Committee for the Evaluation of Oncological Drugs evaluates the effectiveness of new oncological treatments. The committee compares survival endpoints to the so-called PASKWIL-2023 criteria for palliative treatments, which define if treatment effects are considered clinically relevant. A positive recommendation depends on whether the median overall survival (OS) is below or above 12 months in the comparator arm. If the former applies, an OS benefit of at least 12 weeks, and a hazard ratio (HR) smaller than 0.7 are required. If the latter applies, an OS or progression free survival (PFS) benefit of at least 16 weeks, and an HR smaller than 0.7 are required. Nonetheless, the median survival time may not be reached and the proportional hazards (PH) assumption, quantified by the HR, is likely violated for immuno-oncology (IO) therapies, deeming these criteria inappropriate.

Methods: We conducted a systematic literature review to identify statistical methods used to represent the clinical effectiveness of IO therapies based on trial data. We searched MEDLINE and EMBASE databases from inception to August 31, 2022, limited to English papers. Methodological studies, randomized controlled trials, and discussion papers recognising key issues of survival data analysis of IO therapies were eligible for inclusion.

Results: A total of 1,035 unique references were identified. After full paper screening, 17 publications were included in the review. Additionally, 43 papers were identified through 'snowballing'. We conclude that the current PASKWIL-2023 criteria are methodologically incorrect under non-PH. In that case, single summary statistics fail to capture the treatment effect and any measure should be interpreted in combination with the Kaplan-Meier curves. We recommend 'parameter-free' measures, such as the difference in restricted mean survival time, avoiding assumptions on the underlying survival.

Conclusions: The HR is commonly used to assess treatment effectiveness, without investigating the validity of the PH assumption. This happens with the application of the PASKWIL-2023 criteria for palliative oncology treatments, which can only be valid under a PH setting. Under non-PH, alternative treatment effect measures are suggested. We propose a step-by-step approach supporting the choice of the most appropriate methods to quantify treatment effectiveness that can be used to redefine the PASKWIL-2023 criteria, or similar criteria in other clinical areas.

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来源期刊
BMC Medical Research Methodology
BMC Medical Research Methodology 医学-卫生保健
CiteScore
6.50
自引率
2.50%
发文量
298
审稿时长
3-8 weeks
期刊介绍: BMC Medical Research Methodology is an open access journal publishing original peer-reviewed research articles in methodological approaches to healthcare research. Articles on the methodology of epidemiological research, clinical trials and meta-analysis/systematic review are particularly encouraged, as are empirical studies of the associations between choice of methodology and study outcomes. BMC Medical Research Methodology does not aim to publish articles describing scientific methods or techniques: these should be directed to the BMC journal covering the relevant biomedical subject area.
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