Hanbury Andria, Smith Adam B, Buesch Katharina
York Health Economics Consortium, University of York, York YO10 5NQ, UK.
PTC Therapeutics, Zug 6300, Switzerland.
Patient Relat Outcome Meas. 2021 Jan 7;12:1-12. doi: 10.2147/PROM.S278258. eCollection 2021.
Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare genetic condition, characterised by movement disorder, and speech and cognitive functioning impairment. To enable economic evaluation of treatments, health-related quality of life or utilities need to be derived. These are currently lacking in the literature. This is challenging, where patient numbers are small, particularly in paediatric populations. This study outlines the 5-stage development of vignettes describing AADC, for use in a subsequent health-state utility elicitation study, with an emphasis on caregiver and clinician engagement.
To align with the economic model, 5 vignettes describing 5 AADC deficiency motor milestones were developed, ranging from "bedridden" to "walking with assistance". Stage 1 comprised identification of symptoms/impairments from the literature and AADC deficiency charity websites. Stage 2 comprised group discussion with 3 caregivers. A symptoms matrix was developed, followed by draft vignettes (Stage 3). Eight clinicians reviewed these, alongside the same 3 caregivers via a survey (Stage 4). The vignettes were revised at stage 5.
There was high consensus regarding symptoms at Stages 1 and 2, although the literature highlighted behavioural and autonomic symptoms, which caregivers did not. The symptoms were grouped into neuromuscular, autonomic, cognitive, behavioural and functional impairments. Clinician and caregiver vignette feedback highlighted the idiopathic nature of AADC. Despite this, clinicians suggested only 2 additional symptoms. Similarly, caregivers suggested 4 symptoms and a change to the wording used for the cognitive symptoms. Not all changes were included.
The differing focus of caregivers, clinicians and the literature reinforces the importance of patient/caregiver engagement. The vignettes need to comprehensively capture what it is like to live with AADC deficiency, in order for the subsequent utilities to be robust. A focus on evidence triangulation, especially for idiopathic conditions, and how engagement is sought from caregivers are important future avenues of research.
芳香族L-氨基酸脱羧酶（AADC）缺乏症是一种罕见的遗传病，其特征为运动障碍以及言语和认知功能受损。为了能够对治疗方法进行经济学评估，需要得出与健康相关的生活质量或效用值。目前文献中缺乏这些内容。在患者数量较少的情况下，尤其是儿科人群，这具有挑战性。本研究概述了用于描述AADC的案例的五阶段开发过程，以用于后续的健康状态效用值获取研究，重点是照顾者和临床医生的参与。
为了与经济模型保持一致，开发了5个描述AADC缺乏症运动里程碑的案例，范围从“卧床不起”到“在协助下行走”。第一阶段包括从文献和AADC缺乏症慈善网站中识别症状/损伤。第二阶段包括与3名照顾者进行小组讨论。制定了症状矩阵，随后形成案例草稿（第三阶段）。8名临床医生以及同样的3名照顾者通过一项调查对这些案例进行了评审（第四阶段）。案例在第五阶段进行了修订。
在第一阶段和第二阶段，对于症状存在高度共识，尽管文献强调了行为和自主神经症状，而照顾者并未提及。这些症状被分为神经肌肉、自主神经、认知、行为和功能损伤。临床医生和照顾者对案例的反馈突出了AADC的特发性本质。尽管如此，临床医生仅建议增加2种症状。同样，照顾者建议增加4种症状，并对认知症状所用措辞进行修改。并非所有更改都被采纳。
照顾者、临床医生和文献的不同关注点强化了患者/照顾者参与的重要性。案例需要全面反映患有AADC缺乏症的生活状况，以便后续的效用值可靠。关注证据三角验证，尤其是对于特发性疾病，以及如何寻求照顾者的参与是未来重要的研究方向。
