Medialis Ltd, 13 Horse Fair, Banbury, OX16 0AH, UK.
Centre for Pharmaceutical Medicine Research, Institute of Pharmaceutical Science, Faculty of Life Science and Medicine, King's College University, London, UK.
Orphanet J Rare Dis. 2022 Feb 23;17(1):81. doi: 10.1186/s13023-022-02250-8.
Accurate measurement of any constructs in clinical studies is of critical importance, especially if the adoption of an intervention relies on detecting a significant treatment effect where one exists. Under Neutral theory, the amount of relevant and irrelevant indicators selected to operationalise the construct contribute equally to the accuracy of the observation. The Neutral or accurate observation is achieved by observing all relevant indicators only. Generic QoL instruments such as EQ-5D are increasingly being accepted as imprecise, especially in rare diseases, based on the relevance of their indicators. QoL is a construct that embodies a patient's subjectivity, individuality, and local circumstances at measurement. SEIQoL-DW is an instrument designed to respect these characteristics of QoL through eliciting indicators or cues directly from the subject along with the proportion of the overall QoL they contribute. EQ-5D and SEIQoL can therefore be considered as being at opposing ends of accuracy in QoL measurement. XLH is a hereditary, progressive, rare disease characterised by phosphate wasting, affecting both children and adults and impacting their QoL. The purpose of this study was to observe if any change in QoL of adult XLH patients were detectable using EQ-5D, SEIQoL eliciting new cues at each visit, and SEIQoL administering baseline cues overall visits (thereby silencing its time-dependency) versus baseline over 12 months. In addition, any association between the three sets of observations was explored.
All quality of life scores were observed to decrease from baseline by 13.36%, 7.32% and 2.7% based on SEIQoL, SEIQoL, and EQ-5D assessments, respectively. The decrease in the quality of life scores was only statistically significant (p = 0.037) for SEIQoL. Beyond the baseline visit, the only highly positive and statistically significant pairwise association was between SEIQoL and SEIQoL at M6 (ρ = 0.782, P value < 0.05) and M9 (ρ = 0.879, P value < 0.05).
EQ-5D and SEIQoL failed to detect the same statistically significant decrease in QoL observed by SEIQoL. Both sets of SEIQoL observations were more closely associated with each other than with EQ-5D. Observing constructs such as QoL in rare diseases benefit from a Neutrality in indicator selection and respecting variation in dominance of various indicators over time.
在临床研究中，对任何构建体的准确测量都至关重要，尤其是在依赖于检测存在的显著治疗效果来采用干预措施的情况下。根据中性理论，用于实现构建体的相关和不相关指标的数量对观察的准确性同样有贡献。中性或准确的观察是通过仅观察所有相关指标来实现的。基于其指标的相关性，通用的 QoL 工具（如 EQ-5D）在罕见疾病中越来越被认为是不精确的。QoL 是一个体现患者在测量时的主观性、个体性和局部环境的构建体。SEIQoL-DW 是一种通过直接从受试者那里引出指标或线索，并根据它们对整体 QoL 的贡献比例来设计的工具，旨在尊重 QoL 的这些特征。因此，EQ-5D 和 SEIQoL 可以被认为是在 QoL 测量的准确性上处于对立的两端。XLH 是一种遗传性、进行性的罕见疾病，其特征是磷酸盐丢失，影响儿童和成人，并影响他们的 QoL。本研究的目的是观察使用 EQ-5D 时是否可以检测到成年 XLH 患者的 QoL 变化，SEIQoL 在每次就诊时引出新的线索，以及 SEIQoL 在整个就诊期间（从而使其不受时间依赖性的影响）管理基线线索与 12 个月的基线相比。此外，还探讨了三组观察结果之间的任何关联。
根据 SEIQoL、SEIQoL 和 EQ-5D 评估，所有生活质量评分均观察到从基线下降 13.36%、7.32%和 2.7%。生活质量评分的下降仅在 SEIQoL 上具有统计学意义（p=0.037）。除了基线就诊外，唯一高度正相关且具有统计学意义的成对关联是 SEIQoL 与 M6（ρ=0.782，P 值<0.05）和 M9（ρ=0.879，P 值<0.05）之间的关联。
EQ-5D 和 SEIQoL 未能检测到 SEIQoL 观察到的相同具有统计学意义的 QoL 下降。两组 SEIQoL 观察结果彼此之间的相关性比对 EQ-5D 的相关性更强。在罕见疾病中观察 QoL 等构建体时，从指标选择的中立性和随时间变化的各种指标主导地位的变化中受益。
