Quality of life questionnaire specific to FAP, other ATTR forms created
44 patients aided in measure of 32 symptoms and their impact
Scientists have developed a first patient-reported questionnaire on quality of life that’s specific to transthyretin amyloidosis (ATTR).
Called the Transthyretin Amyloidosis – Quality of Life Questionnaire (ATTR-QOL), it was created with significant patient involvement and guidance from a multidisciplinary group of clinical specialists, led by scientists with the Amyloidosis Research Consortium, a Massachusetts-based nonprofit organization.
“With further refinement from psychometric testing, the ATTR-QOL will provide a standard, comprehensive measure for all ATTR-specific research including both clinical trials and clinical practice,” the researchers wrote.
Details of ATTR-QOL’s development are in the study “The Transthyretin Amyloidosis – Quality of Life (ATTR-QOL) Questionnaire: Development of a Conceptual Model and Disease-Specific Patient-Reported Outcome Measure,” published in the journal Patient Related Outcome Measures.
Effort to better understand how symptoms of FAP, other ATTR forms affect life
ATTR is a rare disease characterized by the toxic accumulation of clumps of misfolded transthyretin protein, called amyloid fibrils, in various tissues.
When such fibrils are caused by mutations in the TTR gene, which encodes transthyretin, patients have hereditary transthyretin amyloidosis (hATTR). Wild-type ATTR (ATTRwt) develops without known genetic mutations, with onset in older age.
hATTR with polyneuropathy, known as familial amyloid polyneuropathy (FAP), is a subtype marked mostly by damage to peripheral nerves, those outside the brain and spinal cord. When amyloid fibrils accumulate mostly in the heart muscle, damaging it, the disease is called hATTR with cardiomyopathy.
Patients often experience a wide range of disease symptoms, such as weakness, fatigue, numbness, tingling, dizziness, heart palpitations, shortness of breath, and difficulty swallowing. Such symptoms can impact daily activities and affect health-related quality of life (HRQoL).
However, “the lack of an ATTR-specific patient-reported outcome measure has made consistent measurement of HRQoL in ATTR challenging,” the researchers wrote, with “clinicians, researchers, drug developers, regulatory bodies, and payer evaluation organizations” relying on “a combination of [patient-reported outcome] measures intended for other conditions to measure symptoms, impacts, and overall HRQoL.”
Researchers at the Amyloidosis Research Consortium, in collaboration with QualityMetric, set out to develop an ATTR-specific outcome measure that reflects patient views of the disease’s symptoms and their impact. In total, 29 ATTR experts and 44 patients with FAP and other ATTR forms were involved in the process.
Following a literature review, the scientists developed a list of 23 ATTR symptoms that fell into three areas of life affected by the disease: physical health, emotional health, and work/productivity. Ten patient-reported outcomes previously used by ATTR researchers also were identified.
A group of patient representatives and clinicians then confirmed and further refined the symptoms list, and added as impact areas patients’ social life, independence, and finances.
Patient-reported measures ranging from heart and nerve health to memory
hATTR and ATTRwt patients who participated in a focus group next reviewed and supported the list of symptoms, and highlighted areas of daily life impacted by ATTR, including physical functioning, mental health/emotional well-being, social life, and finances.
Additional individual interviews were conducted with a larger group of hATTR and ATTRwt patients, who confirmed focus group findings. Further revisions ensured more patient-friendly word choices, as well as adding pastimes and planning to the list of daily life items.
“A recall period of 4 weeks was identified as appropriate” by both clinicians and patients, the researchers wrote. Feedback suggested that one patient-reported outcome measure, “with items addressing the full spectrum of symptoms and impacts across types and subtypes, could adequately cover both hATTR and ATTRwt,” they added.
A conceptual model with two components — symptoms and impacts — was used to generate an ATTR-QOL with 32 symptom items and 40 impact items. Further modifications were made, based on separate rounds of input from specialists and patients, to ensure clarity.
The final model’s 32 items cover symptoms occurring in the past four weeks related to the heart and nerves, and issues related to vision, skin, autonomic nervous system, and/or memory. The autonomic nervous system is responsible for the control of involuntary bodily functions, such as heart rate, blood flow, and gastrointestinal and bladder function.
Unintentional weight loss or gain over the past year was added to the symptom’s list.
40 items rank how disease symptoms affect patients’ daily life
Frequency is marked by responses ranging from “never,” “rarely,” and “sometimes,” to “often,” and “always,” while severity measures are marked by “not applicable,” “mild,” “moderate,” and “severe.”
The 40 impact-specific items focus on physical function, such as balance, motor function, activities of daily living, social life, mental health, and work and productivity. Answered on a five-point scale, responses range from “not at all,” “a little,” and “some,” to “a lot,” and “completely; I cannot do it at all” or “extremely.”
Finally, based on the administrator’s discretion, two optional items ask patients to identify their ATTR subtype and whether they had any of 11 common co-existing medical conditions (comorbidities).
“The ATTR-QOL, developed and refined based on expert and patient feedback, represents an important step forward in patient-centered care and research in ATTR,” the researchers wrote.
The questionnaire “will undergo psychometric testing with a large group of patients with ATTR (hATTR and ATTRwt) to further refine the measure,” they added.
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