NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
Queensland Centre for Gynaecological Cancer Research, University of Queensland, Brisbane, Queensland, Australia.
J Clin Oncol. 2022 Jul 20;40(21):2378-2388. doi: 10.1200/JCO.21.02750. Epub 2022 May 16.
Besides morbidity and mortality, quality of life (QoL) is a key outcome of cancer treatments. Trials on the basis of clinical outcomes have expectations that QoL outcomes can be either tolerated or improved. Simultaneously considering QoL and clinical outcomes is challenging with lack of suitable metrics allowing incorporation of QoL as coprimary end points in clinical trial design and utilization of hierarchical hypothesis testing.
We propose combining time to achieving a minimal clinically important difference (MCID) and probabilities of a MCID occurring in each QoL domain to provide QoL metrics analogous to those used for clinical end points. For QoL domains of interest, these yield QoL profiles, time to MCID, and number needed to treat. Incorporation of QoL as coprimary end points in clinical trial designs through hierarchical hypothesis testing can easily be achieved. The noninferiority designed Laparoscopic Approach to Carcinoma of the Endometrium trial, evaluating laparoscopic versus open abdominal surgery for endometrial cancer with Functional Assessment of Cancer Therapy-General QoL domains, is used to illustrate the usefulness of these metrics.
This analysis revealed that laparoscopic surgery had a significant shorter time to MCID for physical and functional well-being QoL domains (physical mean: 1.5 months, 95% CI, 0.5 to 2.6; = .002; and functional mean: 1.4 months; 95% CI, 0.4 to 2.4; = .003) than abdominal surgery, but little difference between the two approaches for psychologic social and emotion well-being. Probability profile plots show a consistent > 2-fold higher chance of attaining a MCID for physical and functional well-being over time for laparoscopic compared with abdominal surgery.
This analysis reinforces the potential value of novel MCID metrics and their usefulness in raising the profile of QoL outcomes to complement clinical end points. The methods will allow health professionals to counsel patients about QoL outcomes and clinical outcomes simultaneously.
除了发病率和死亡率外，生活质量（QoL）也是癌症治疗的关键结果。基于临床结果的试验预计 QoL 结果可以耐受或改善。同时考虑 QoL 和临床结果具有挑战性，因为缺乏合适的指标来将 QoL 作为共同主要终点纳入临床试验设计，并利用分层假设检验。
我们建议将达到最小临床重要差异（MCID）的时间与每个 QoL 域中 MCID 发生的概率相结合，以提供类似于用于临床终点的 QoL 指标。对于感兴趣的 QoL 域，这会产生 QoL 概况、达到 MCID 的时间和需要治疗的人数。通过分层假设检验将 QoL 作为共同主要终点纳入临床试验设计可以很容易地实现。非劣效设计的腹腔镜子宫内膜癌试验，评估腹腔镜与开放腹部手术治疗子宫内膜癌与癌症治疗功能评估-一般 QoL 域，用于说明这些指标的有用性。
该分析显示，腹腔镜手术在身体和功能健康 QoL 域（身体平均：1.5 个月，95%CI，0.5 至 2.6； =.002；和功能平均：1.4 个月；95%CI，0.4 至 2.4； =.003）达到 MCID 的时间明显短于腹部手术，但两种方法在心理社会和情感健康方面差异不大。概率概况图显示，随着时间的推移，腹腔镜手术达到 MCID 的机会始终比腹部手术高 2 倍以上。
这项分析加强了新型 MCID 指标的潜在价值及其在提高 QoL 结果的重要性以补充临床终点的有用性。这些方法将使医疗保健专业人员能够同时向患者咨询 QoL 结果和临床结果。
