Investigating patients' experiences with dyspnea associated with warm antibody hemolytic anemia (wAIHA) and cognitive debriefing of the FACIT-dyspnea 10 item short form: A qualitative patient interview study Free

Introduction:Dyspnea is considered a prominent symptom in patients with warm autoimmune hemolytic anemia (wAIHA). However, there is a lack of existing research into how patients experience this symptom and how it impacts their lives. Dyspnea is not routinely assessed in wAIHA clinical trials, and there is an absence of patient-reported outcomes (PROs) developed or validated for use in this population despite its clinical significance. This study therefore aimed to: i) explore patients' experience of wAIHA-related dyspnea, ii) identify the most bothersome impacts of dyspnea on daily life, and iii) gather evidence of content validity of the Functional Assessment of Chronic Illness Therapy-Dyspnea (FACIT-Dyspnea) 10-item Short Form (SF) in wAIHA patients. The overarching aim was to generate evidence to support the use of patient-centric endpoints for evaluating dyspnea in wAIHA clinical trials.

Methods:Hybrid concept elicitation and cognitive debriefing interviews were conducted with adults diagnosed with wAIHA in the United States. The study was approved by an Institutional Review Board and participants were recruited through recruitment vendors and a patient advocacy group. Semi-structured interviews using a discussion guide were conducted online via teleconferencing software. Interviews were transcribed and analyzed using a combination of inductive and deductive coding approaches.

Results:Participants (n=15) ranged in age from 35 to 74 years old, with varying educational backgrounds; 80% of the sample were female. The majority were of White ethnicity and had been diagnosed with wAIHA within the past 6 years. Three participants were on treatment for wAIHA at the time of interview.

All 15 participants reported experiencing wAIHA-related dyspnea, typically triggered by physical exertion and alleviated by rest. Many participants spontaneously described a relationship between dyspnea and fatigue, noting that each symptom could exacerbate the other. Thirty-three distinct impacts of dyspnea were identified, with the most frequently reported relating to physical functioning or activities of daily living (ADLs). These included difficulty walking (n=14/15), difficulty with instrumental activities (n=13/15), difficulty climbing stairs (n=11/15), needing frequent rests/take breaks (n=11/15), and difficulty with or avoiding physical activity (n=11/15). Emotional impacts were reported by 12 participants, including feelings of anxiety, panic, anger or frustration. Eight patients reported occupational impacts, such as reduced productivity or needing to take breaks during the workday. Together, these findings indicate that dyspnea has a salient impact on health-related quality of life (HRQoL) for patients with wAIHA.

Participants overall found the FACIT-Dyspnea 10-item SF relevant and were able to comprehend the items correctly. Items related to physical functioning, especially walking, or strenuous ADLs were considered most relevant and aligned with participant's frequently reported impacts. Less strenuous items (e.g., dressing, washing dishes) were seen as less relevant by some, but still appropriate for broader use given the varying severity of dyspnea experienced by wAIHA patients. Items involving lifting and carrying (items 8 and 9) were sometimes interpreted similarly and sweeping/mopping (item 6) was sometimes equated with vacuuming. All participants found the instructions to be clear, and most felt that the response options were distinct and easy to use. However, 3 participants noted some overlap between the options ‘some’ and ‘a little’ in part II of the questionnaire. Nearly all participants indicated that they found it easy to recall their experience over the past 7 days. Notably, all participants were able to complete the questionnaire as intended.Conclusions:This study confirms dyspnea as a key symptom of wAIHA, with substantial and wide-ranging impacts on patients' HRQoL. The FACIT-Dyspnea 10-item SF demonstrated evidence of content validity, with participants confirming its relevance and clarity in capturing their experience with dyspnea. The measure was well understood, easy to complete, and its content closely aligned with the most frequently reported impacts of dyspnea on physical functioning and ADLs. These findings support the content validity of the FACIT-Dyspnea 10-item SF. Psychometric evaluation is required to further establish this PRO as fit-for-purpose for use in patients with wAIHA.