Therapeutic Intervention and Decision-Making by Primary Caregivers of Children with Severe Sickle Cell Anemia.
Authors: Hankins Jane , Day Sara , Carroll Yvonne , Naidu Paula , Li Chin-Shang , Hinds Pamela , Garvie Patricia , Wang Winfred 
Published: October 2019

Abstract
Recurrent vaso-occlusive events (VOE) in children with severe sickle cell anemia (SCA) prompt consideration of therapeutic intervention with one of three treatments: hydroxyurea (HU), chronic red cell transfusion (CT) or hematopoietic stem cell transplantation (SCT). Differing benefits and risks and a lack of randomized trials make it difficult to determine the best treatment strategy. The preferences of primary caregivers (PC) are an important element in the decision process. Our goal was to explore factors that influence decision-making (DM) in PC regarding the available interventions. Secondary goals were to examine the relationships between treatment preference and both health-related quality of life (HRQOL) and the prior frequency of VOE. Patients were defined as severe if they had ≥ 3 painful events requiring ER visits or hospitalization within 12 months, ≥ 2 acute chest syndrome (ACS) events within 24 months, or a combination. PC were given literature in non-technical language describing the three interventions and 1 to 2 weeks later participated in a standardized discussion about interventions with a designated sickle cell nurse educator. During this meeting, risks and benefits of each intervention were conveyed. PC then completed a 10-minute survey, which explored factors influencing treatment preference, and the HRQOL Peds QL 4.0 inventory. The survey had 40 items grouped in eight categories: treatment efficacy, safety, practicability, infertility risk, emotional factors, religious factors, extraneous influence, and child’s preference. The measurement of HRQOL included four domains: physical, emotional, social and school functioning, and was completed by PC. Differences among the three treatment preference groups were calculated using the Fisher exact test for categorical variables and Kruskal-Wallis test for discrete or continuous variables. Seventeen patients were enrolled based on recurrent painful events (8), recurrent ACS events (8), or both (1). PC were mostly female (88 %) with a median age of 37 years (range 25 – 49). Patients had a median age of 8 years (range 4 – 17); all had Hb SS and were African-American. Fourteen (82 %) PC felt they had received enough information to make a treatment decision. Twelve (70%, CI 0.39 – 0.91) PC expressed preference for HU, three (18%, CI 0.03 – 0.46) for CT, two (12%, 0.01 – 0.39) for SCT, and none preferred no treatment. None of the 40 items listed as possible factors influencing preference were significantly different among the treatment groups, although safety approached significance (p = 0.09). The HRQOL mean scores, on a zero to 100 scale, were 57.2 ± 4.8, 65.2 ± 1.0, and 60.0 ± 4.2 among the HU, SCT, and CT groups respectively (p = 0.61). The number of VOE within 2 years prior to study among the HU, SCT, and CT groups was not significantly different. We conclude that: 1. HU was the most frequently preferred treatment option of PC of children with severe SCA. 2. The proportion of PC preferring HU was significantly higher than that of SCT, but not of CT. 3. No distinguishing influential factors among treatment groups have been identified as of yet. 4. There were no significant differences in HRQOL and preceding VOE among the groups. Improved understanding of caregivers’ preferences and DM process should aid in the design of future clinical trials.