Key Information
Background
The diversity of disease phenotypes associated with transthyretin (ATTR) amyloidosis poses challenges for measurement of health outcomes. The Transthyretin Amyloidosis – Quality of Life (ATTR-QOL) Questionnaire is a disease-specific patient-reported outcome (PRO) measure of the symptoms and impacts of ATTR amyloidosis. The objective of this study was to evaluate the structural validity, reliability, and construct validity of the ATTR-QOL Impact scales.
Methodology
This was a non-interventional, online survey study of adults with self-reported diagnosis of symptomatic ATTR amyloidosis. The survey included the ATTR-QOL and additional criterion measures. A scoring algorithm was proposed and tested. Factor structure, differential item functioning, and psychometric properties were explored.
Results
The analytic sample included 233 patients. Satisfactory fit was found for a 4-factor model of disease impacts (including Daily Activities, Physical Functioning, Social/Role Functioning, and Emotional Wellbeing) and a scoring algorithm was developed. Twelve impact items were dropped from the ATTR-QOLv2 as a result of factor and differential item functioning analyses. Each scale showed evidence of satisfactory internal consistency reliability (Cronbach’s α range = 0.85–0.97) and test-retest reliability at 1 week (intraclass coefficient range = 0.84–0.97). Convergent validity was supported by correlations ≥ 0.30 between ATTR-QOL Impact scale scores and other PRO measures of related constructs. The ATTR-QOL Impact scales showed greater impact among patients with worse symptom severity, cardiac functioning, or unemployment due to ATTR amyloidosis (all p < 0.05), supporting known-groups validity.
Conclusion
The ATTR-QOL is a reliable and valid measure of impacts meaningful to patients with ATTR amyloidosis. This study resulted in updates to the ATTR-QOL for item reduction and the development of a scoring algorithm. Ongoing studies are collecting data to evaluate the symptom scales of the ATTR-QOL.
Background
Transthyretin (ATTR) amyloidosis is a rare disease characterized by the deposition of amyloids in organ tissues throughout the body, particularly affecting the cardiac and/or nervous systems [1external link, opens in a new tab, 2external link, opens in a new tab], and causing progressive damage over time if untreated [3external link, opens in a new tab, 4external link, opens in a new tab]. Between the wild-type (ATTRwt) and over 140 known genetic variants of ATTR amyloidosis (ATTRv) [5external link, opens in a new tab], there is substantial diversity in the affected systems, symptoms, and patients’ overall experiences of the disease [6external link, opens in a new tab, 7external link, opens in a new tab]. The heterogeneity of disease phenotypes associated with ATTR amyloidosis poses a challenge for clinicians and researchers who aim to measure the various symptoms and impacts on health-related quality of life (HRQOL) from the patient’s perspective. The conventional use of either generic instruments or those specific to other diseases may fail to capture concepts that are important to patients with ATTR amyloidosis (or capture irrelevant concepts) and therefore undermine the validity, responsiveness, interpretability, and utility of these instruments in clinical settings [8external link, opens in a new tab, 9external link, opens in a new tab]. Survey items that attribute health impacts to other conditions, or lack a disease attribution altogether, can lack sensitivity and precision in the measurement of outcomes that patients attribute to ATTR amyloidosis.
The Transthyretin Amyloidosis – Quality of Life (ATTR-QOL) Questionnaire was recently developed as a disease-specific measure of the symptoms and impacts of ATTR amyloidosis from the patient’s perspective [10external link, opens in a new tab]. The decision to develop the ATTR-QOL followed calls from stakeholders for a standard measure of relevant health outcomes across types of ATTR amyloidosis, that is not only able to overcome the practical and psychometric limitations of using measures intended for the general population or for patients with other health conditions, but also fit-for-purpose in both clinical research and practice. A rigorous and iterative process was used to establish the content validity of the ATTR-QOL, involving a literature review, concept elicitation interviews with patients and clinical experts, a series of Delphi expert panel reviews, translatability assessments, informal reviews by drug developers, and cognitive debriefing interviews [10external link, opens in a new tab]. The objective of this study was to evaluate the reliability, structural validity, and construct validity of the ATTR-QOL Impact scales.
Methods
Study design and procedures
This was a non-interventional, online survey study of adults in the United States (US) with self-reported diagnosis of ATTR amyloidosis. Study participants completed an initial survey that included the ATTR-QOL and additional patient-reported outcome (PRO) measures of HRQOL, as well as questions pertaining to treatment history and clinical characteristics. A follow-up survey including only the ATTR-QOL and items evaluating change in health status was administered to study participants 1 week later.
Study population and recruitment
Participants were recruited using convenience sampling and targeted outreach. Scripted recruitment messages were disseminated on multiple platforms managed by the Amyloidosis Research Consortium (ARC), including the organization’s website, social media, and electronic mailing lists. Individuals interested in participating were directed to an online screener used to determine eligibility and collect basic sociodemographic and clinical information. Participation in the study was limited to English-speaking adults residing in the US who reported having been diagnosed with ATTR amyloidosis by a healthcare provider, and had experienced symptoms clinically related to the condition. Informed consent was obtained from those determined to be eligible and participants were directed to the initial survey. All study materials were approved by the Western Institutional Review Board (WIRB) Copernicus Group (WCG IRB).