{"title":"为甲基丙二酸血症和丙酸血症患者护理人员开发体征和症状结果测量法(MMAPAQ)","authors":"","doi":"10.1016/j.ymgme.2024.108577","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and objective</h3><p>Methylmalonic acidemia (MMA) and propionic acidemia (PA) are rare inborn errors of metabolism with shared signs and symptoms that are associated with significant morbidity and mortality. No disease-specific clinical outcomes assessment instruments for MMA and/or PA currently exist to capture the patient perspective in clinical trials. Because patients with these conditions are generally young and have cognitive impairments, an observer-reported outcome (ObsRO) instrument is crucial. We report results from qualitative research supporting development of the Methylmalonic Acidemia and Propionic Acidemia Questionnaire (MMAPAQ), a signs and symptoms ObsRO measure for caregivers of patients with MMA and/or PA.</p></div><div><h3>Methods</h3><p>Concept elicitation (CE) interviews were conducted with 35 participants across 2 studies who were aged ≥18 years and caregivers of patients with a confirmed diagnosis of MMA or PA, and an additional 5 patients aged ≥6 years with MMA or PA in Study 1, to identify core signs/symptoms for inclusion in the MMAPAQ. All interviews were conducted in English. Study 2 included cognitive interviews (CI) with caregivers and clinical experts to further assess content validity. CE and a conceptual framework review were also conducted with clinical experts to further support findings.</p></div><div><h3>Results</h3><p>A consistent set of signs/symptoms of MMA and PA were reported by eligible caregivers interviewed in study 1 (<em>n</em> = 21) and study 2 (<em>n</em> = 14), representing 11 patients with MMA and 20 with PA. Based on concepts reported in study 1, a draft instrument was constructed and compared with the Pediatric Quality of Life Inventory™ (PedsQL™) and Family Impact module, demonstrating face validity for measuring key signs/symptoms important to patients and caregivers. The PedsQL™ and Family Impact modules were preferred to assess patient and caregiver impacts. Two waves of CE and CIs were conducted in study 2, with wave 1 resulting in removal of 7 items and other revisions to improve clarity, and wave 2 resulting in modification of examples used for 2 items. The final instrument consisted of the following 7 items assessed over the past 7 days using a Likert-type response scale ranging from “never” to “very often”: uncontrollable or involuntary movements, dehydration, rapid breathing at rest, appearing lethargic, appearing disinterested in eating, refusing to eat, and vomiting.</p></div><div><h3>Conclusions</h3><p>This study establishes the content validity of the MMAPAQ as the first ObsRO questionnaire for measuring core signs and symptoms of MMA and PA in clinical trials and community research. Scoring and psychometric measurement properties of the MMAPAQ will be established in future studies. The PedsQL™ was found to have face validity in measuring concepts that affect the MMA and PA patient populations and should also be considered for use in clinical trials in MMA and PA.</p></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S109671922400461X/pdfft?md5=2f6d364f0bed4c7573b3801b3060eed7&pid=1-s2.0-S109671922400461X-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Development of a signs and symptoms outcome measure for caregivers of patients with methylmalonic acidemia and propionic acidemia (MMAPAQ)\",\"authors\":\"\",\"doi\":\"10.1016/j.ymgme.2024.108577\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and objective</h3><p>Methylmalonic acidemia (MMA) and propionic acidemia (PA) are rare inborn errors of metabolism with shared signs and symptoms that are associated with significant morbidity and mortality. No disease-specific clinical outcomes assessment instruments for MMA and/or PA currently exist to capture the patient perspective in clinical trials. Because patients with these conditions are generally young and have cognitive impairments, an observer-reported outcome (ObsRO) instrument is crucial. We report results from qualitative research supporting development of the Methylmalonic Acidemia and Propionic Acidemia Questionnaire (MMAPAQ), a signs and symptoms ObsRO measure for caregivers of patients with MMA and/or PA.</p></div><div><h3>Methods</h3><p>Concept elicitation (CE) interviews were conducted with 35 participants across 2 studies who were aged ≥18 years and caregivers of patients with a confirmed diagnosis of MMA or PA, and an additional 5 patients aged ≥6 years with MMA or PA in Study 1, to identify core signs/symptoms for inclusion in the MMAPAQ. All interviews were conducted in English. Study 2 included cognitive interviews (CI) with caregivers and clinical experts to further assess content validity. CE and a conceptual framework review were also conducted with clinical experts to further support findings.</p></div><div><h3>Results</h3><p>A consistent set of signs/symptoms of MMA and PA were reported by eligible caregivers interviewed in study 1 (<em>n</em> = 21) and study 2 (<em>n</em> = 14), representing 11 patients with MMA and 20 with PA. Based on concepts reported in study 1, a draft instrument was constructed and compared with the Pediatric Quality of Life Inventory™ (PedsQL™) and Family Impact module, demonstrating face validity for measuring key signs/symptoms important to patients and caregivers. The PedsQL™ and Family Impact modules were preferred to assess patient and caregiver impacts. Two waves of CE and CIs were conducted in study 2, with wave 1 resulting in removal of 7 items and other revisions to improve clarity, and wave 2 resulting in modification of examples used for 2 items. The final instrument consisted of the following 7 items assessed over the past 7 days using a Likert-type response scale ranging from “never” to “very often”: uncontrollable or involuntary movements, dehydration, rapid breathing at rest, appearing lethargic, appearing disinterested in eating, refusing to eat, and vomiting.</p></div><div><h3>Conclusions</h3><p>This study establishes the content validity of the MMAPAQ as the first ObsRO questionnaire for measuring core signs and symptoms of MMA and PA in clinical trials and community research. Scoring and psychometric measurement properties of the MMAPAQ will be established in future studies. The PedsQL™ was found to have face validity in measuring concepts that affect the MMA and PA patient populations and should also be considered for use in clinical trials in MMA and PA.</p></div>\",\"PeriodicalId\":18937,\"journal\":{\"name\":\"Molecular genetics and metabolism\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S109671922400461X/pdfft?md5=2f6d364f0bed4c7573b3801b3060eed7&pid=1-s2.0-S109671922400461X-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular genetics and metabolism\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S109671922400461X\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular genetics and metabolism","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S109671922400461X","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
摘要
背景和目的甲基丙二酸血症(MMA)和丙酸血症(PA)是罕见的先天性代谢异常,具有共同的体征和症状,与严重的发病率和死亡率相关。目前还没有针对 MMA 和/或 PA 的特定疾病临床结果评估工具,无法在临床试验中从患者的角度进行评估。由于这些疾病的患者一般都很年轻,而且有认知障碍,因此观察者报告结果(ObsRO)工具至关重要。我们报告了支持甲基丙二酸血症和丙酸血症问卷(MMAPAQ)开发的定性研究结果,该问卷是针对甲基丙二酸血症和/或丙酸血症患者护理人员的体征和症状观察结果评估工具。方法在两项研究中,我们对年龄≥18岁的35名参与者和确诊为甲基丙二酸血症或丙酸血症患者的护理人员进行了概念激发(CE)访谈,并在研究1中对另外5名年龄≥6岁的甲基丙二酸血症或丙酸血症患者进行了访谈,以确定纳入MMAPAQ的核心体征/症状。所有访谈均以英语进行。研究 2 包括对护理人员和临床专家进行认知访谈 (CI),以进一步评估内容效度。结果在研究 1(n = 21)和研究 2(n = 14)中,符合条件的护理人员报告了一组一致的 MMA 和 PA 体征/症状,分别代表 11 名 MMA 患者和 20 名 PA 患者。根据研究 1 中报告的概念,我们构建了一个工具草案,并与儿科生活质量量表™ (PedsQL™) 和家庭影响模块进行了比较,结果表明该工具在测量对患者和护理人员非常重要的关键体征/症状方面具有表面效度。PedsQL™ 和家庭影响模块是评估患者和护理人员影响的首选。在研究 2 中进行了两波 CE 和 CI,第一波删除了 7 个项目,并进行了其他修改以提高清晰度,第二波修改了 2 个项目所用的示例。最终的问卷包括以下 7 个项目,采用李克特(Likert)式反应量表,从 "从不 "到 "非常频繁 "对过去 7 天的情况进行评估:无法控制或不自主的运动、脱水、休息时呼吸急促、昏昏欲睡、对进食不感兴趣、拒绝进食和呕吐。MMAPAQ 的评分和心理测量特性将在今后的研究中确定。研究发现 PedsQL™ 在测量影响 MMA 和 PA 患者群体的概念方面具有表面效度,因此也应考虑用于 MMA 和 PA 的临床试验。
Development of a signs and symptoms outcome measure for caregivers of patients with methylmalonic acidemia and propionic acidemia (MMAPAQ)
Background and objective
Methylmalonic acidemia (MMA) and propionic acidemia (PA) are rare inborn errors of metabolism with shared signs and symptoms that are associated with significant morbidity and mortality. No disease-specific clinical outcomes assessment instruments for MMA and/or PA currently exist to capture the patient perspective in clinical trials. Because patients with these conditions are generally young and have cognitive impairments, an observer-reported outcome (ObsRO) instrument is crucial. We report results from qualitative research supporting development of the Methylmalonic Acidemia and Propionic Acidemia Questionnaire (MMAPAQ), a signs and symptoms ObsRO measure for caregivers of patients with MMA and/or PA.
Methods
Concept elicitation (CE) interviews were conducted with 35 participants across 2 studies who were aged ≥18 years and caregivers of patients with a confirmed diagnosis of MMA or PA, and an additional 5 patients aged ≥6 years with MMA or PA in Study 1, to identify core signs/symptoms for inclusion in the MMAPAQ. All interviews were conducted in English. Study 2 included cognitive interviews (CI) with caregivers and clinical experts to further assess content validity. CE and a conceptual framework review were also conducted with clinical experts to further support findings.
Results
A consistent set of signs/symptoms of MMA and PA were reported by eligible caregivers interviewed in study 1 (n = 21) and study 2 (n = 14), representing 11 patients with MMA and 20 with PA. Based on concepts reported in study 1, a draft instrument was constructed and compared with the Pediatric Quality of Life Inventory™ (PedsQL™) and Family Impact module, demonstrating face validity for measuring key signs/symptoms important to patients and caregivers. The PedsQL™ and Family Impact modules were preferred to assess patient and caregiver impacts. Two waves of CE and CIs were conducted in study 2, with wave 1 resulting in removal of 7 items and other revisions to improve clarity, and wave 2 resulting in modification of examples used for 2 items. The final instrument consisted of the following 7 items assessed over the past 7 days using a Likert-type response scale ranging from “never” to “very often”: uncontrollable or involuntary movements, dehydration, rapid breathing at rest, appearing lethargic, appearing disinterested in eating, refusing to eat, and vomiting.
Conclusions
This study establishes the content validity of the MMAPAQ as the first ObsRO questionnaire for measuring core signs and symptoms of MMA and PA in clinical trials and community research. Scoring and psychometric measurement properties of the MMAPAQ will be established in future studies. The PedsQL™ was found to have face validity in measuring concepts that affect the MMA and PA patient populations and should also be considered for use in clinical trials in MMA and PA.
期刊介绍:
Molecular Genetics and Metabolism contributes to the understanding of the metabolic and molecular basis of disease. This peer reviewed journal publishes articles describing investigations that use the tools of biochemical genetics and molecular genetics for studies of normal and disease states in humans and animal models.