A Holistic Approach to Sickle Cell Disease Severity Using Patient-Reported Outcomes
Authors: Minniti Caterina P. , Buscetta Ashley , Ramirez Hasmin C. , Seddighi Diba , Farmer Nicole , Bonham Vence L. 
Published: December 2024

Introduction
In this era of advanced therapies for sickle cell disease (SCD), it is imperative to accurately assess individual disease severity to inform and guide therapeutic approaches. Currently, indicators of severity are mostly restricted to clinical measures, such as genotype, medical history, and hematological indexes. Clinical-based measures to determine severity do not adequately capture the lived experience of a person with SCD and assess mortality more than morbidity. A large body of research has demonstrated that psychosocial and mental health factors have a large impact on one's disease severity and quality of life. Quality of life metrics and patient-reported outcomes (PROs) have become increasingly adopted into clinical trials and healthcare practice; however, consensus on which measures to use has not been established. This study aims to explore the relationship between psychosocial and clinical predictors of global health in adults living with SCD.
Methods
This cross-sectional, prospective research study included 276 participants from the INSIGHTS study (NCT02156102), which examines phenotypic variation in adults (18 years or older) living with SCD in the United States. We set out to create a holistic approach to assess disease severity by examining the role of psychosocial measures, such as measures of stress (Cohen stress and Global Financial Stress surveys), depression (Beck questionnaire), pain (ASCQ-Me Pain Frequency measure) and sleep (ASCQ-Me Sleep Measure). Disease severity was measured using the Sebastiani sickle cell disease severity score and the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS GH) measures for adults. The Sebastiani disease severity score utilizes a network of interactions among 14 clinical variables to measure clinical severity on a range of 0 (least severe) to 1 (most severe). The PROMIS GH measure is an overall evaluation of one's physical and mental health, with higher scores indicating better global health. Statistical analyses were conducted between global health, clinical severity, and psychosocial measures using two-sample t-tests/ANOVA for binary/multinomial predictors and Fisher's z-test for numeric predictors.
Results
A majority of participants identified as female (55%), Black/African American (97%), were college educated (79% with an associate degree or higher), not married (78%), with genotype HbSS/HbSB0 (82%), and a median age of 37 years (IQR 29, 47). Median Sebastiani clinical severity score was 0.53 (IQR 0.41, 0.73) and median PROMIS GH score was 40 (IQR 37, 48). Preliminary results indicated that worse sleep, higher levels of stress (general and financial), depression, and pain frequency were all significantly correlated with lower PROMIS GH (p &lt;0.001). These correlations were maintained when examining the two components (i.e. physical and mental health) of the PROMIS GH measure separately (p &lt;0.001). In comparison, clinical disease severity was not significantly correlated with any of the psychosocial measures (p &gt;0.05).
Conclusion
A holistic approach to assessing severity is important for risk stratification, counseling, and determining therapeutic interventions. It is imperative to evaluate the influence of PROs on SCD severity, as this can impact the consideration and determination of eligibility for potentially transformative therapies and affect long-term outcomes. The PROMIS GH measurement design is conducive to use in a clinic- and research-based setting and can be easily integrated into these healthcare settings. Quality of life factors, such as stress, sleep, and pain frequency, correlate with PROMIS GH scores, which are a reliable assessment of physical and mental health and disease severity. Our research suggests that the inclusion of PROs when determining overall SCD severity provides essential additional information for clinicians and patients alike.