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Abstract：
BACKGROUND: Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA) are rare inherited retinal degenerative disorders. The associated visual impairments have significant impacts on patients\' vision-dependent activities of daily living (ADL), mobility, and distal health-related quality of life (HRQoL). To adequately capture patient and caregiver perspectives in clinical trials, patient and observer-reported outcome instruments must demonstrate sufficient evidence of content validity in the target population. This study aimed to explore the patient experience of RP/LCA and assess the content validity of the Visual Symptom and Impact Outcomes PRO (ViSIO-PRO) and ObsRO (ViSIO-ObsRO) instruments in RP/LCA.
METHODS: A total of 66 qualitative, combined concept elicitation (CE) and cognitive debriefing (CD) interviews were conducted (33 adults, 10 adolescents, 8 children and 15 caregivers of children) in the US, France, Germany, and Canada. Patients had a clinical and genetic diagnosis of RP/LCA from a range of genotypes. CE results were used to further inform the development of a conceptual model and CD interviews assessed the relevance and understanding of the 44-item ViSIO-PRO and 26-item ViSIO-ObsRO instruments. Interviews were conducted across two iterative rounds to allow item modifications.
RESULTS: Findings were consistent across RP/LCA genotypes. Night blindness, reduced peripheral vision, vision in very bright lighting and light/dark adaptation were the most frequently reported visual function symptoms impacting vision-dependent ADL and mobility. Impacts on distal HRQoL domains were also reported. The ViSIO-PRO and ObsRO items were well understood by participants and relevant across genotypes. The instructions, 7-day recall period and response scales were well understood and endorsed. Participant and expert clinician feedback supported modifications to item wording, the addition of six new ViSIO-PRO items and one new ViSIO-ObsRO item, and the removal of one ViSIO-PRO item due to lack of relevance.
CONCLUSIONS: Findings support the content validity of the ViSIO-PRO and ViSIO-ObsRO instruments for use across RP/LCA genotypes. Ongoing research to evaluate the psychometric validity of the instruments will support future use of the instruments as efficacy endpoints in clinical trials and in general clinical practice to track disease severity and impact of disease on functioning.
METHODS: A total of 66 qualitative, combined concept elicitation (CE) and cognitive debriefing (CD) interviews were conducted (33 adults, 10 adolescents, 8 children and 15 caregivers of children) in the US, France, Germany, and Canada. Patients had a clinical and genetic diagnosis of RP/LCA from a range of genotypes. CE results were used to further inform the development of a conceptual model and CD interviews assessed the relevance and understanding of the 44-item ViSIO-PRO and 26-item ViSIO-ObsRO instruments. Interviews were conducted across two iterative rounds to allow item modifications.
RESULTS: Findings were consistent across RP/LCA genotypes. Night blindness, reduced peripheral vision, vision in very bright lighting and light/dark adaptation were the most frequently reported visual function symptoms impacting vision-dependent ADL and mobility. Impacts on distal HRQoL domains were also reported. The ViSIO-PRO and ObsRO items were well understood by participants and relevant across genotypes. The instructions, 7-day recall period and response scales were well understood and endorsed. Participant and expert clinician feedback supported modifications to item wording, the addition of six new ViSIO-PRO items and one new ViSIO-ObsRO item, and the removal of one ViSIO-PRO item due to lack of relevance.
CONCLUSIONS: Findings support the content validity of the ViSIO-PRO and ViSIO-ObsRO instruments for use across RP/LCA genotypes. Ongoing research to evaluate the psychometric validity of the instruments will support future use of the instruments as efficacy endpoints in clinical trials and in general clinical practice to track disease severity and impact of disease on functioning.
摘要：
背景：视网膜色素变性（RP）和Leber先天性黑蒙（LCA）是罕见的遗传性视网膜退行性疾病。相关的视觉障碍对患者的视觉依赖性日常生活活动（ADL）有显著影响，移动性,和远端健康相关生活质量（HRQoL）。为了在临床试验中充分捕捉患者和护理人员的观点，患者和观察者报告的结果工具必须在目标人群中证明足够的内容有效性.本研究旨在探索RP/LCA的患者体验，并评估RP/LCA中视觉症状和影响结果PRO（ViSIO-PRO）和ObsRO（ViSIO-ObsRO）仪器的内容有效性。
方法：共66个定性，进行了概念启发(CE)和认知汇报(CD)相结合的访谈(33名成年人，10名青少年,8名儿童和15名儿童看护人）在美国，法国,德国,和加拿大。患者有一系列基因型的RP/LCA的临床和遗传诊断。CE结果用于进一步为概念模型的开发提供信息，CD访谈评估了44项ViSIO-PRO和26项ViSIO-ObsRO仪器的相关性和理解。在两轮迭代中进行了访谈，以允许对项目进行修改。
结果：研究结果在RP/LCA基因型之间是一致的。夜盲症,周边视力降低，在非常明亮的照明和明暗适应下的视觉是最常见的视觉功能症状,影响视觉依赖性ADL和活动能力.还报告了对远端HRQoL域的影响。参与者很好地理解了ViSIO-PRO和ObsRO项目，并且跨基因型相关。指示,7天召回期和反应量表得到了充分理解和认可。参与者和专家临床医生反馈支持对项目措辞的修改，增加了六个新的ViSIO-PRO项目和一个新的ViSIO-ObsRO项目，由于缺乏相关性而删除了一个ViSIO-PRO项目。
结论：研究结果支持ViSIO-PRO和ViSIO-ObsRO仪器在RP/LCA基因型中使用的内容有效性。正在进行的评估工具的心理测量有效性的研究将支持将来在临床试验和一般临床实践中使用该工具作为疗效终点，以跟踪疾病的严重程度和疾病对功能的影响。
方法：共66个定性，进行了概念启发(CE)和认知汇报(CD)相结合的访谈(33名成年人，10名青少年,8名儿童和15名儿童看护人）在美国，法国,德国,和加拿大。患者有一系列基因型的RP/LCA的临床和遗传诊断。CE结果用于进一步为概念模型的开发提供信息，CD访谈评估了44项ViSIO-PRO和26项ViSIO-ObsRO仪器的相关性和理解。在两轮迭代中进行了访谈，以允许对项目进行修改。
结果：研究结果在RP/LCA基因型之间是一致的。夜盲症,周边视力降低，在非常明亮的照明和明暗适应下的视觉是最常见的视觉功能症状,影响视觉依赖性ADL和活动能力.还报告了对远端HRQoL域的影响。参与者很好地理解了ViSIO-PRO和ObsRO项目，并且跨基因型相关。指示,7天召回期和反应量表得到了充分理解和认可。参与者和专家临床医生反馈支持对项目措辞的修改，增加了六个新的ViSIO-PRO项目和一个新的ViSIO-ObsRO项目，由于缺乏相关性而删除了一个ViSIO-PRO项目。
结论：研究结果支持ViSIO-PRO和ViSIO-ObsRO仪器在RP/LCA基因型中使用的内容有效性。正在进行的评估工具的心理测量有效性的研究将支持将来在临床试验和一般临床实践中使用该工具作为疗效终点，以跟踪疾病的严重程度和疾病对功能的影响。
