INTRODUCTION: Cold agglutinin disease (CAD) is a rare disorder (a prevalence of 16 cases per 1 million people), accounting for approximately 15%–25% of all autoimmune hemolytic anemias (Berentsen. Semin Hematol. 2018). Currently, there is no approved drug for the treatment of CAD. Debilitating fatigue that greatly affects quality of life is common among patients with CAD (Roth et al. Blood. 2019). The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale has recently been used to quantify fatigue in patients with CAD (Roth et al. Blood. 2019). However, the appropriateness of FACIT-F in these patients has not been assessed. In-depth individual interviews of adults with CAD were conducted primarily to identify the symptoms and effects of CAD reported as important by patients and to better understand their experiences with CAD. The secondary objective was to obtain patient feedback regarding the relevance and importance of the items on the FACIT-F.
METHODS: Participants were identified and recruited from a proprietary panel of patients with CAD. Of 1,250 panel members, approximately 600 members from the United States (US) were invited to participate in an in-depth interview. Systematic random sampling was used to select every nth panel member from each of 4 US regions to receive an email invitation. A semi-structured interview guide was used to ensure consistent systematic collection of data pertaining to study objectives, while maintaining a conversational tone and encouraging spontaneity of answers.
RESULTS: Twenty-two members expressed interest in participating; of these, 18 could be reached for screening and 16 were eligible for interview. The sample was 100% White and non-Hispanic, 62.5% female, and had an average age of 67.8 years. Participants resided in the West (37.5%), Midwest and South (both 25%), and Northeast (12.5%). The date of CAD diagnosis averaged 6 years before the interview, and 68.8% of patients had received their diagnosis within the last 1.5 years. Seven (43.8%) patients reported that they were not taking any prescription or over-the-counter (OTC) medication for CAD, whereas 9 (56.3%) were taking prescribed or OTC folic acid for CAD (of these, 4 also took prescription strength vitamin B12). In this sample, no patient reported current use of other prescription medications for CAD. A few patients spontaneously reported previous treatments for CAD (eg, transfusions and rituximab or other injections). However, previous CAD treatment was not systematically collected for all subjects and is a limitation of the study.
Concept-elicitation of symptoms: The most frequently reported symptoms were fatigue/tiredness/lack of energy (93.8%), reaction to cold environments (93.8%), breathlessness (68.8%), and trouble thinking/concentrating (68.8%). When probed, 43.8% of patients reported sleep disturbances).
Concept-elicitation of effects: Most participants (68.8%) reported lifestyle or behavioral changes to help treat CAD symptoms (eg, taking gloves/extra clothing to places that may be cold). Others reported giving up/limiting enjoyable or outdoor activities and making major changes (eg, discontinuing outdoor activities, restricting travel). Other CAD-related effects included impairment in daily activities, overall health/physical activities, and social/leisure activities/relationships . For the evaluation of the FACIT-F in this CAD population, participants reported that FACIT-F instructions and items were clear and easy to understand, response options were distinct from each other, and they could recall their fatigue over the previous 7 days. They reported that FACIT-F measured one or more concepts personally important to them and important concepts were not missing. This provides support for the content validity of the FACIT-F in patients with CAD.
CONCLUSIONS: Patients with CAD experienced negative effects on daily activities, physical health/activities, social/ leisure activities/relationships, the ability to concentrate/recall, and mood/emotions mostly owing to fatigue/lack of energy and reactions to cold environments. Most patients required modifying their lifestyle/behavior to manage CAD symptoms. FACIT-F measured concepts important to patients with CAD, which supports its content validity and use in this patient population.
