Introduction and Objective: AL amyloidosis (AL) is a rare, complex, and progressive disease in which an abnormal protein, amyloid, misfolds and deposits in organs. AL can affect one or many organs, such as the heart, kidneys, liver, nervous system, and digestive tract, leading to organ dysfunction and death. AL symptoms and treatments are known to impact health-related quality of life (HRQoL), but little research has been conducted to establish which HRQoL concepts are relevant for AL patients before and during treatment. The objective of this study was to identify the most important HRQoL concepts to measure in clinical trials of AL patients through in-depth interviews with physicians and patients.

Methods: This qualitative study was conducted from March to May 2015 through in-depth, 1-hour telephone interviews using a concept elicitation method and semistructured interview guides. In phase 1, interviews were conducted with three hematologists and one nephrologist on (a) journey to diagnosis, including how HRQoL is evaluated in everyday practice, and (b) HRQoL concepts that impact how AL patients feel and function. In phase 2, interviews were conducted with 10 AL patients who varied in terms of organ involvement, years since diagnosis, and response to treatment. Patients provided input on journey to diagnosis and impact of AL and treatment on their HRQoL. All interviews were audiotaped, transcribed, coded, and analyzed using NVivo software and a grounded theory approach. Physician interviews were coded and analyzed by one researcher. Patient interviews were coded and analyzed by four researchers, with dual coding and review meetings to ensure agreement between coders. Transcripts were divided into four groups (interviews 1-3, 4-6, 7-9, 10) and were coded one group at a time to demonstrate saturation (saturation reflects the point at which no new relevant information emerges and interviewing can stop).

Results/Physician Interviews: Physicians reported an average time to diagnosis of at least 10 months, during which patients consulted three or four different physician specialists to reach a diagnosis. Respondents called AL "a great masquerader" because AL presents in different organs and because many AL symptoms are common to other diseases. Physicians did not use any standardized assessments for HRQoL with AL patients; instead, they asked generally about fatigue, sleep, pain, and impact on work. They agreed to the usefulness of a standard HRQoL assessment but worried about the time it would require. They recommended patients complete HRQoL assessment every 3 months, using a recall period of "past month." After complete hematologic response, assessment could slow to every 6 months. Physicians agreed the most important HRQoL concepts were physical functioning, vitality/fatigue, pain, ability to work and perform other roles, general health, and sleep. They also noted an impact on mental health, such as depression and anxiety.

Results/Patient Interviews: Patients reported a variety of experiences on their journey to diagnosis in terms of time to diagnosis, number and types of doctors seen, and number of tests/examinations. The average time to diagnosis was 2 years and ranged from 3 months to 4 years, during which they consulted, on average, three different physician specialists to reach a diagnosis. The type of physician specialist consulted depended on the organ involved. Patients reported a broad range of serious HRQoL impacts from AL, spanning physical disability to emotional distress. Specifically, impairments were noted in physical function and mobility, energy level, ability to work, participation in leisure activities, role in family, social relationships, mental health, sleep, cognitive function, ability to exercise, and ability to perform activities of daily living. The level of impairment was severe in many areas. Saturation analysis confirmed no new information emerged in the later interviews.

Conclusions: Physicians and patients reported significant challenges in diagnosing AL and severe impairments across a broad range of HRQoL concepts. Because developers of new drugs are expected to provide direct evidence of the treatment benefit experienced by patients, these concepts should be measured in clinical trials with AL patients to demonstrate meaningful treatment benefits to patients.


White:Prothena Biosciences Inc: Consultancy. Bayliss:Prothena Biosciences Inc: Consultancy. Guthrie:Prothena Biosciences Inc: Employment, Other: Stock.

Author notes


Asterisk with author names denotes non-ASH members.