背景:丙酮酸激酶(PK)缺乏症是一种罕见的遗传性疾病,其特征是慢性溶血性贫血和严重的后遗症,对患者的生活质量产生负面影响。这项研究旨在从心理上验证第一个疾病特异性患者报告的结果(PRO)工具:7项PK缺陷日记(PKDD)和12项PK缺陷影响评估(PKDIA)。旨在评估迹象,症状,和PK缺乏对参与Mitapivat与安慰剂的ACTIVATE全球3期研究的患者的影响(NCT03548220)。
方法:对PKDD和PKDIA的所有验证分析均对盲化数据进行,通过对项目完整性的分析,得分,可靠性,以及对筛查和基线数据的有效性。完成率和基线反应分布使用描述性统计进行表征。使用项目反应建模来告知加权评分系统。通过内部一致性和重测信度来评估信度;通过收敛和已知组分析来评估效度。
结果:在80名成年人中,PKDD和PKDIA患者的基线数据分别为77例(96.3%)和78例(97.5%),分别。项目响应向右倾斜,表明平均值超过了中值,特别是对于使用0-10数字刻度的项目,随后将其重新编码为0-4量表;由于冗余或与试验人群的相关性低,从PKDIA中删除了4个项目.PKDD和PKDIA都表现出很高的内部一致性(麦克唐纳系数ω分别为0.86和0.90)。重测可靠性(类内系数分别为0.94和0.87),以及与其他PRO的收敛有效性(线性相关系数[|r|]分别在0.30-0.73和0.50-0.82之间)。
结论:这些发现为PKDD和PKDIA提供了有效性和可靠性的证据,针对PK缺乏的第一个疾病特异性PRO措施,因此可以增加对,更准确地捕捉,PK缺乏对健康相关生活质量的更广泛影响。试用注册ClinicalTrials.gov,NCT03548220。2018年6月07日注册;https://www.
结果:gov/ct2/show/NCT03548220。
丙酮酸激酶(PK)缺乏症是一种罕见的遗传性血液疾病,具有广泛的体征和症状,可能对患者的生活质量产生负面影响。患者报告结果(PRO)工具是从患者的角度评估疾病如何影响患者的工具。这些仪器必须经过验证过程,以确保它们真正捕获患者的病情或治疗经验。本研究旨在在ACTIVATE临床试验(NCT03548220)的成年患者中验证两种新的PRO仪器,其中PK缺乏的患者接受了药物mitapivat或安慰剂。这两种新的PRO仪器是第一个专门针对PK缺陷开发的:PK缺陷日记(PKDD),每日日记,询问7个问题以测量PK缺乏的核心体征和症状,和PK缺陷影响评估(PKDIA),每周一份包含12个问题的问卷,以评估PK缺乏对患者生活的影响。这项研究的结果表明,PKDD和PKDIA正确可靠地测量了这些迹象,症状,以及他们旨在捕捉的PK缺陷的影响。这些发现表明,PKDD和PKDIA是第一个经过验证的针对PK缺乏的PRO,可以帮助提高对PK缺乏对患者生活质量影响的理解。
BACKGROUND: Pyruvate kinase (PK) deficiency is a rare hereditary disorder characterized by chronic hemolytic anemia and serious sequalae which negatively affect patient quality of life. This study aimed to psychometrically validate the first disease-specific patient-reported outcome (PRO) instruments: the 7-item PK Deficiency Diary (PKDD) and 12-item PK Deficiency Impact Assessment (PKDIA), designed to assess signs, symptoms, and impacts of PK deficiency in patients enrolled in the ACTIVATE global phase 3 study of mitapivat versus placebo (NCT03548220).
METHODS: All validation analyses for the PKDD and PKDIA were performed on blinded data, with analyses on item integrity, scoring, reliability, and validity conducted on data from screening and baseline. Completion rates and baseline response distributions were characterized using descriptive statistics. Item response modelling was used to inform a weighted scoring system. Reliability was assessed by internal consistency and test-retest reliability; and validity by convergent and known-groups analyses.
RESULTS: Of the 80 adults enrolled, baseline data were available for 77 (96.3%) and 78 (97.5%) patients for the PKDD and PKDIA, respectively. Item responses skewed right, indicating that mean values exceeded median values, especially for items utilizing a 0-10 numeric scale, which were subsequently recoded to a 0-4 scale; 4 items were removed from the PKDIA due to redundancy or low relevance to the trial population. Both the PKDD and PKDIA demonstrated high internal consistency (McDonald\'s coefficient ω = 0.86 and 0.90, respectively), test-retest reliability (intra-class coefficients of 0.94 and 0.87, respectively), and convergent validity with other PROs (linear correlation coefficients [|r|] between 0.30-0.73 and 0.50-0.82, respectively).
CONCLUSIONS: The findings provide evidence of validity and reliability for the PKDD and PKDIA, the first disease-specific PRO measures for PK deficiency, and can therefore increase understanding of, and more accurately capture, the wider impact of PK deficiency on health-related quality of life. Trial registration ClinicalTrials.gov, NCT03548220. Registered June 07, 2018; https://www.
RESULTS: gov/ct2/show/NCT03548220 .
Pyruvate kinase (PK) deficiency is a rare genetic blood disorder with a wide range of signs and symptoms that may have a negative impact on patients’ quality of life. Patient-reported outcome (PRO) instruments are tools that assess how a disease affects a patient from the patient’s perspective. These instruments must go through a validation process to make sure they truly capture the patient’s experience with their condition or its treatment. This study aimed to validate two new PRO instruments in adult patients enrolled in the ACTIVATE clinical trial (NCT03548220), where patients with PK deficiency received the drug mitapivat or a placebo. These two new PRO instruments are the first to be developed specifically for PK deficiency: the PK Deficiency Diary (PKDD), a daily diary that asks 7 questions to measure the core signs and symptoms of PK deficiency, and the PK Deficiency Impact Assessment (PKDIA), a weekly questionnaire with 12 questions to assess the impact of PK deficiency on a patient’s life. The results of this study showed that the PKDD and PKDIA properly and reliably measured the signs, symptoms, and impacts of PK deficiency that they aimed to capture. These findings indicate that the PKDD and PKDIA are the first validated PROs specifically for PK deficiency and can help improve the understanding of the impact of PK deficiency on patients’ quality of life.