Bose Mousumi, Anglade Tahra C, Donlon Chelsea I, Kerrihard Adrian L, Berger Hila F, Berkowitz Ariel S, Ritchie Shawn A, Smith Tara M
Department of Nutrition and Food Studies, College for Community Health, Montclair State University, 1 Normal Avenue, UN 2154, Montclair, NJ 07043, USA.
Department of Psychology, College of Arts and Sciences, Howard University, 2400 Sixth Street NW, Washington, DC, 20059, USA.
Orphanet J Rare Dis. 2025 Mar 31;20(1):147. doi: 10.1186/s13023-025-03660-0.
Rhizomelic chondrodysplasia punctata (RCDP) is a rare genetic disorder characterized by symptoms such as respiratory dysfunction, seizures, orthopedic issues, and neurodevelopmental delay. Potential therapeutics for RCDP warrant the development of clinical outcome assessments to assess the efficacy of treatment and the well-being of patients. Our study aimed to develop a valid quality-of-life (QOL) caregiver-reported survey instrument, RhizoQOL, to be used as a supportive endpoint in RCDP clinical trials.
Development of the RhizoQOL survey tool included three RCDP caregiver focus groups to elicit concepts to serve as potential domains in a QOL survey instrument for RCDP, pilot survey development and initial testing, cognitive interviewing of revised survey drafts to determine content validity, as well as a three-month longitudinal study for reliability and internal consistency of the survey instrument.
Twenty-eight caregivers participated in the focus groups, reporting that concepts that could be appropriate domains of QOL in RCDP include psychosocial behavior, feeding symptoms, mobility symptoms, respiratory symptoms, seizures and related activity, and impact of treatment. Following pilot survey testing (n = 22) and stakeholder feedback, a revised pilot survey instrument was administered to five caregivers for cognitive interviewing. This resulted in a revised survey instrument with 31 question items, six domains, and a 1-5 Likert scale item response assessing frequency or severity of event in the question item. Longitudinal testing (n = 18) of the revised survey instrument found the average response score was 1.98 ± 0.97 for all question items, and a Cronbach's alpha value of 0.856, suggesting strong intra-survey question reliability. Using individual question item results from reliability testing, linear regression modeling, and testing for required magnitude of significant treatment effects, eight question items were removed from the survey instrument, resulting in a total of 23 question items within 6 discrete domains.
The final RhizoQOL survey instrument, consisting of 23 questions, assesses the symptoms and experiences of RCDP patients as observed by caregivers and serves as a novel clinical outcome assessment for RCDP therapeutic clinical trials to assess the impacts of RCDP and support the overall effectiveness of treatments.
肢根型点状软骨发育不良（RCDP）是一种罕见的遗传性疾病，其特征包括呼吸功能障碍、癫痫发作、骨科问题和神经发育迟缓等症状。RCDP的潜在治疗方法需要开发临床结局评估方法，以评估治疗效果和患者的健康状况。我们的研究旨在开发一种有效的生活质量（QOL）照顾者报告调查工具RhizoQOL，用作RCDP临床试验的支持性终点。
RhizoQOL调查工具的开发包括三个RCDP照顾者焦点小组，以引出可作为RCDP生活质量调查问卷潜在领域的概念；进行试点调查工具的开发和初步测试；对修订后的调查问卷草稿进行认知访谈以确定内容效度；以及进行为期三个月的纵向研究，以评估调查工具的信度和内部一致性。
28名照顾者参与了焦点小组，报告称RCDP生活质量的合适领域概念包括心理社会行为、喂养症状、活动症状、呼吸症状、癫痫发作及相关活动，以及治疗影响。在试点调查测试（n = 22）和利益相关者反馈之后，向五名照顾者发放了修订后的试点调查问卷以进行认知访谈。这产生了一份修订后的调查问卷，包含31个问题项、六个领域，以及一个1-5李克特量表项反应，用于评估问题项中事件的频率或严重程度。对修订后的调查问卷进行纵向测试（n = 18）发现，所有问题项的平均反应得分为1.98 ± 0.97，克朗巴哈系数值为0.856，表明调查内问题信度较高。利用信度测试、线性回归建模的单个问题项结果以及对显著治疗效果所需幅度的测试，从调查问卷中删除了八个问题项，最终在六个离散领域内共有23个问题项。
最终的RhizoQOL调查问卷由23个问题组成，评估照顾者观察到的RCDP患者的症状和经历，作为RCDP治疗性临床试验的一种新型临床结局评估，以评估RCDP的影响并支持治疗的整体有效性。
